Abstract: Aging produces a simultaneous thoracic aorta (TA) enlargement and unfolding. We sought to analyze the impact of hypertension on these geometric changes. Non-contrast computed tomography images were obtained from coronary artery calcium scans, including the entire aortic arch, in 200 normotensive and 200 hypertensive asymptomatic men. An automated algorithm reconstructed the vessel in three-dimensions, estimating orthogonal aortic sections along the whole TA pathway, and calculated several geometric descriptors to assess TA morphology. Hypertensive patients were older with respect to normotensive (P<0.001). Diameter and volume of TA ascending, arch and descending segments were higher in hypertensive patients with respect to normotensive (P<0.001) and differences persisted after adjustment for age. Hypertension produced an accelerated unfolding effect on TA shape. We found increments in aortic arch width (P<0.001), radius of curvature (P<0.001) and area under the arch curve (P<0.01) with a concomitant tortuosity decrease (P<0.05) and no significant change in aortic arch height. Overall, hypertension produced an equivalent effect of 2-7-years of aging. In multivariate analysis adjusted for age and hypertension treatment, diastolic pressure was more associated to TA size and shape changes than systolic pressure. These data suggest that hypertension accelerates TA enlargement and unfolding deformation with respect to the aging effect.Journal of Human Hypertension advance online publication, 24 January 2013; doi:10.1038/jhh.2012.69.
Abstract: Measures of atherosclerosis burden like coronary artery calcification are performed using non-contrast heart CT. However, additional information can be derived from these studies, looking beyond the coronary arteries without exposing the patients to further radiation. We present a semi-automated method to assess ascending, arch and descending aorta geometry from non-contrast CT datasets in 250 normotensive patients. We investigated the effect of aging on thoracic aorta morphometry. The algorithm identifies the aortic centerline coordinates following a toroidal path for the curvilinear portion and axial planes for descending aorta. Then it reconstructs oblique planes orthogonal to the centerline direction and a circle fitting process estimates the vessel cross-section. Finally, global thoracic aorta dimensions (diameter, volume and length) and shape (vessel curvature and tortuosity, aortic arch width and height) are calculated. From a multivariate analysis, adjusted for gender and body-size area, aortic volume and arch width were the descriptors that better represented the aortic size and shape alterations with aging. The thoracic aorta suffers an expanding and unfolding process with aging that deserves further attention to prevent aortic aneurisms.
Abstract: An increasing number of intermediate risk asymptomatic subjects benefit from measures of atherosclerosis burden like coronary artery calcification studies with non-contrast heart computed tomography (CT). However, additional information can be derived from these studies, looking beyond the coronary arteries and without exposing the patients to further radiation. We report a semi-automatic method that objectively assesses ascending, arch and descending aorta dimension and shape from non-contrast CT datasets to investigate the effect of aging on thoracic aorta geometry. First, the segmentation process identifies the vessel centerline coordinates following a toroidal path for the curvilinear portion and axial planes for descending aorta. Then, reconstructing oblique planes orthogonal to the centerline direction, it iteratively fits circles inside the vessel cross-section. Finally, regional thoracic aorta dimensions (diameter, volume and length) and shape (vessel curvature and tortuosity) are calculated. A population of 200 normotensive men was recruited. Length, mean diameter and volume differed by 1.2 cm, 0.13 cm and 21 cm(3) per decade of life, respectively. Aortic shape uncoiled with aging, reducing its tortuosity and increasing its radius of curvature. The arch was the most affected segment. In conclusion, non-contrast cardiac CT imaging can be successfully employed to assess thoracic aorta 3D morphometry.
Abstract: Membrane-shed submicron microparticles (MPs) are released after cell activation or apoptosis. High levels of MPs circulate in the blood of patients with atherothrombotic diseases, where they could serve as a useful biomarker of vascular injury and a potential predictor of cardiovascular mortality and major adverse cardiovascular events. Atherosclerotic lesions also accumulate large numbers of MPs of leukocyte, smooth muscle cell, endothelial, and erythrocyte origin. A large body of evidence supports the role of MPs at different steps of atherosclerosis development, progression, and complications. Circulating MPs impair the atheroprotective function of the vascular endothelium, at least partly, by decreased nitric oxide synthesis. Plaque MPs favor local inflammation by augmenting the expression of adhesion molecule, such as intercellular adhesion molecule -1 at the surface of endothelial cell, and monocyte recruitment within the lesion. In addition, plaque MPs stimulate angiogenesis, a key event in the transition from stable to unstable lesions. MPs also may promote local cell apoptosis, leading to the release and accumulation of new MPs, and thus creating a vicious circle. Furthermore, highly thrombogenic plaque MPs could increase thrombus formation at the time of rupture, together with circulating MPs released in this context by activated platelets and leukocytes. Finally, MPs also could participate in repairing the consequences of arterial occlusion and tissue ischemia by promoting postischemic neovascularization.
Abstract: Epidemiological studies suggest that apple consumption is associated with a reduction in cardiovascular disease risk. Apple polyphenols may contribute to explain these effects. Endothelial dysfunction has been associated with early stage of atherosclerosis and polyphenols from various dietary sources have been shown to reverse it. The aim of the present study was to investigate the effect of the consumption of a polyphenol-rich apple on endothelial function.
Abstract: BACKGROUND: Application of coronary artery calcium (CAC) for stratifying coronary heart disease (CHD) risk may change the proportion of subjects eligible for risk reduction treatment and decrease cost-effectiveness of primary prevention. We therefore aimed to analyze the impact of CAC on CHD risk categorization. METHODS: We measured CAC with electron beam computed tomography in 500 asymptomatic untreated hypercholesterolemic men and re-calibrated 10-year Framingham CHD risk by adding CAC score information (post CAC test risk) via an algorithm integrating relative risk and expected distribution of CAC in the population tested. Proportions of low (<10%), intermediate (10-20%) and high (>20%) risk categories, and of eligibility for lipid-lowering treatment, were compared between Framingham risk and post CAC test risk. RESULTS: In the overall population, post CAC test risk calculation changed risk categorization defined by Framingham assessment alone, with 10% more low risk and 10% less intermediate risk (p<0.01). Risk reclassifications were bidirectional since 30% of high and 30% of intermediate Framingham risk were downgraded to intermediate and low risk categories respectively, while 11% of low and 14% of intermediate Framingham risk were upgraded to intermediate and high-risk categories respectively. Post CAC test risk did not change the proportion of Framingham-based lipid-lowering treatment eligibility in the overall population but decreased it by 8% in intermediate Framingham risk subgroup (p<0.05). CONCLUSIONS: Addition of CAC to risk prediction resulted rather in downgrading than in upgrading risk and did not change treatment eligibility, except in intermediate risk subjects, less frequently eligible for treatment.
Abstract: We reviewed prospective epidemiological data in the general population, mostly middle-aged to older persons, to determine the association of carotid intima-media thickness (CIMT) (assessed by B-mode ultrasonography) with cardiovascular risk. Reported risks were expressed as absolute (event risk per persons-years in subjects with a high CIMT) and relative (hazard ratio of high vs low CIMT). They were hardly comparable as the result of differences between the analyzed studies, including the site and procedure of CIMT measurement, the report of adjusted or unadjusted models, and the arbitrary cutoff point to evaluate the CIMTAEs ability to predict risk. Despite these heterogeneities, the following four main conclusions emerged: (1) CIMT was an independent but relatively modest (as judged by absolute risk) predictor of coronary heart disease (CHD); (2) CIMT was an independent predictor for stroke, slightly better than for CHD as judged by the relative risks of both events; (3) CIMT added little to the CHD prediction by risk factors, as judged by c statistic and receiver operating characteristic curve analysis (however, appropriate data for stroke on this important issue were lacking); and (4) the CHD prediction by CIMT was inferior to that by ultrasonography-assessed carotid plaque because plaque may be more representative of atherosclerosis than CIMT.
Abstract: The ambulatory arterial stiffness index (AASI) is claimed to be a new estimator for arterial rigidity. It was recently defined as one minus the slope of the linear regression of systolic to diastolic ambulatory pressure during 24 h. Although several reports testify its clinical relevance, the explanation of how this new index is conceptually associated with arterial stiffness remains controversial. In this work we hypothesize that nonlinear arterial elasticity is behind AASI physiological principles. To that end, random number generators were used to emulate arterial cross-sectional area (CSA) during 24 h. Pressure values were calculated using linear and nonlinear elasticity models for rigid and compliant arteries. The AASI was calculated from simulated pressures and also analytically predicted for each model. Additionally, invasive aortic pressure and CSA were continuously measured in a conscious sheep during 24 h to test the nonlinear model. We found that analytical solutions agreed with simulation outcomes; for the nonlinear model, the AASI was higher in rigid arteries with respect to compliant arteries (0.51 versus 0.38) and the linear model systematically predicted AASI = 0. For in vivo pressure measurements, AASI was 0.31. Using the measured pulsatile CSA and an estimation of the elastic constant for the nonlinear model, the AASI was accurately predicted with errors below 5%. We conclude that the AASI is higher in stiffer arteries due to the nonlinear behavior of the arterial wall. With a nonlinear arterial function, the slope of the linear regression of diastolic to systolic pressures during 24 h depends on the product of an elastic constant by the pulsatile CSA. As the elastic constant dominates the product, the reported associations between the AASI and arterial stiffness indices now have a consistent explanation.
Abstract: Microparticles are submicron vesicles shed from plasma membranes in response to cell activation, injury, and/or apoptosis. The measurement of the phospholipid content (mainly phosphatidylserine; PSer) of microparticles and the detection of proteins specific for the cells from which they are derived has allowed their quantification and characterization. Microparticles of various cellular origin (platelets, leukocytes, endothelial cells) are found in the plasma of healthy subjects, and their amount increases under pathological conditions. Endothelial microparticles (EMP) not only constitute an emerging marker of endothelial dysfunction, but are also considered to play a major biological role in inflammation, vascular injury, angiogenesis, and thrombosis. Although the mechanisms leading to their in vivo formation remain obscure, the release of EMP from cultured cells can be caused in vitro by a number of cytokines and apoptotic stimuli. Recent studies indicate that EMP are able to decrease nitric-oxide-dependent vasodilation, increase arterial stiffness, promote inflammation, and initiate thrombosis at their PSer-rich membrane, which highly co-expresses tissue factor. EMP are known to be elevated in acute coronary syndromes, in severe hypertension with end organ damage, and in thrombotic thrombocytopenic purpura, all conditions associated with endothelial injury and pro-thrombotic state. The release of EMP has also been associated with endothelial dysfunction of patients with multiple sclerosis and lupus anticoagulant. More recent studies have focused on the role of low shear stress leading to endothelial cell apoptosis and subsequent EMP release in end-stage renal disease. Improved knowledge of EMP composition, their biological effects, and the mechanisms leading to their clearance will probably open new therapeutic approaches in the treatment of atherothrombosis.
Abstract: In symptom-free subjects, exercise tolerance testing (ETT) has a doubtful utility for detecting latent coronary heart disease (CHD) because of frequent false positives, but it may be valuable for predicting future CHD. To clarify the latter question, we calculated CHD incidence associated with presence or absence of ETT-induced abnormalities of ST-segment depression, exercise capacity, and heart rate using published prospective ETT studies in primary prevention populations. Based on 5-23 years of follow-up, yearly incidence of fatal and non-fatal CHD ranged from 0.9 to 5.8% in the presence of ST-segment depression and from 1.2 to 1.7% in the presence of impaired maximal heart rate, and pooling of all data provided a linear positive relationship between pre- and post-test CHD incidence. Yearly incidence of CHD death was 0.8% in the presence of ST-segment depression, 0.2-0.3% in the presence of impaired heart rate recovery, and 0.5% in the presence of low exercise capacity. Absence of ST-segment depression was associated with <1.5% yearly incidence of fatal and non-fatal CHD events, except for one study and <0.2% yearly incidence of CHD or CVD death in all populations analyzed. Lastly ETT-induced ST-segment depression conveys a CHD risk superior to that associated with ETT-induced heart rate and exercise capacity abnormalities. This may be due to difference in pretest CHD incidences in ETT studies.
Abstract: BACKGROUND: Patients with type IIb, or mixed, dyslipidemia have high levels of low-density lipoprotein cholesterol (LDL-C) with predominance of small dense LDL particles, high levels of triglycerides (TG), and low levels of high-density lipoprotein cholesterol (HDL-C). Fenofibrate significantly reduces TG and, more moderately, LDL-C, increases HDL-C and produces a shift from small to large LDL particle size; the main effect of ezetimibe is a reduction in LDL-C levels. Combined treatment with fenofibrate and ezetimibe may correct all the abnormalities of type IIb dyslipidemia. OBJECTIVE: To assess the efficacy and safety of coadministration of fenofibrate (NanoCrystal(R)) and ezetimibe in patients with type IIb dyslipidemia and the metabolic syndrome compared with administration of fenofibrate and ezetimibe alone (ClinicalTrials.gov Identifier: NCT00349284; Study ID: CLF178P 04 01). METHODS: This was a prospective, randomized, double-blind, three-parallel arm, multicenter, comparative study. Sixty ambulatory patients (mean age 56 years; 50% women, 50% men) were treated in each group. For inclusion in the study, patients were required to have LDL-C >or=4.13 mmol/L (>or=160 mg/dL), TG >or=1.71 mmol/L and <or=4.57 mmol/L (>or=150 mg/dL and <or=405 mg/dL), and at least two of the following National Cholesterol Education Program Adult Treatment Panel III criteria for the metabolic syndrome: low HDL-C or increased fasting plasma glucose, blood pressure, or waist circumference. Patients received fenofibrate 145 mg, ezetimibe 10 mg, or coadministration of both (fenofibrate/ezetimibe) daily for 12 weeks. The outcome measures were changes in lipids and related parameters, apolipoproteins, glucose metabolism parameters, and high-sensitivity C-reactive protein (hsCRP). Fenofibrate/ezetimibe was more effective than either fenofibrate or ezetimibe in reducing LDL-C (-36.2% vs -22.4% and -22.8%, respectively), non-HDL-C (-36.2% vs -24.8% and -20.9%, respectively), total cholesterol (TC) [-27.9% vs -18.9% and -17.1%, respectively], apolipoprotein B (-33.3% vs -24.5% and -18.7%, respectively), TC/HDL-C ratio (-34.2% vs -23.0% and -17.0%, respectively), and apolipoprotein B/apolipoprotein AI ratio (-37.5% vs -27.0% and -17.7%, respectively) [p < 0.001 for all comparisons between fenofibrate/ezetimibe and monotherapies]. RESULTS: Fenofibrate/ezetimibe was as effective as fenofibrate and more effective than ezetimibe in reducing remnant-like particle cholesterol (-36.2% and -30.7% vs -17.3%, respectively), and in increasing LDL size (+2.1% and +1.9% vs + 0.7%, respectively), apolipoprotein AI (+7.9% and +5.1% vs +0.2%, respectively) and apolipoprotein AII (+24.2% and +21.2% vs +2.7%, respectively). Fenofibrate/ezetimibe and fenofibrate were equally effective in reducing TG (both -38.3%) and in increasing HDL-C (+11.5% and + 7.9%, respectively; p = 0.282). Ezetimibe had minor effects on TG (-10.4%) and HDL-C (+2.2%). Among patients with low HDL-C at baseline (<1.29 mmol/L [<50 mg/dL] in women, <1.03 mmol/L [<40 mg/dL] in men), normalization of HDL-C was observed in 52.9% with fenofibrate/ezetimibe and in 58.8% with fenofibrate, compared with 20.0% with ezetimibe. Changes in hsCRP were -25.9% with fenofibrate/ezetimibe, -27.8% with fenofibrate, and -10.2% with ezetimibe (not statistically significant). None of the treatments altered glucose metabolism parameters. CONCLUSION: In patients with type IIb dyslipidemia and features of the metabolic syndrome, coadministration of fenofibrate 145 mg and ezetimibe 10 mg daily was more effective than either monotherapy in reducing LDL-C, non-HDL-C, apolipoprotein B, and cardiovascular risk ratios, and was as effective as fenofibrate 145 mg alone in reducing TG and in increasing HDL-C in patients with low baseline HDL-C levels.
Abstract: Medical prevention consists to identify as soon as possible apparently healthy individuals who develop a disease and to engage them for active preventive treatment. Several cross-sectional studies of general populations or high cardiovascular risk have shown that coronary calcium score (coronary artery calcium, CAC) was positively associated with traditional risk factors (hypertension, dyslipidemia, diabetes, and smoking) and some new risk factors (fibrinogen). In this work, we first calculated, among 618 men, the risk of 10-years cardiovascular heart disease (CHD) according to the Framingham risk model, and then we calculated the probability that the CAC score of an individual falls in all four CAC categories (0, 1-100, 101-400 and > 400). We obtained risk factors adjusted relative risk (RR) estimates from a meta-analysis comparing the risk of coronary heart disease in individuals with CAC scores of 1-100 (RR = 1.7), 101 - 400 (RR = 3.0) and > 400 (RR = 4.3) with the risk of a person with a CAC score zero. The new model for the risk of CHD for each CAC score category were then calculated assuming an average 1-year risk of CHD and risk assessment of the four CAC score categories, weighted by the probability that scores fall into each category. The combination of modeling the CCA with the modeling of conventional risk factors allows obtaining a remarkable predictive value that can improve the assessment of overall risk Framingham through the reclassification of the risk of CHD to an extent which may be clinically important.
Abstract: PURPOSE: Early artery wall-thickening detected by ultrasound-assessed increased carotid intima-media thickness (IMT) may reflect atherosclerosis or represent an adaptive response to keep homeostasis tensile stress that is related inversely to wall thickness by Laplace's equation. We attempted to discriminate between both mechanisms by correcting IMT for its inverse association with tensile stress. METHODS: Common carotid IMT and lumen diameter (D) where determined in 40 healthy controls and 119 never-treated asymptomatic patients with >or=1 traditional cardiovascular risk factor. The cross-sectional area (CSA) was calculated as pi x IMT x (IMT + D). Tensile stress was approximated by [mean blood pressure x (D/2 x IMT)], and wall shear stress by [(blood viscosity) x 4 x (mean blood velocity/D)]. Inverse regression line relating IMT and tensile stress in controls (p < 0.001) was used as a reference to determine in an individual at-risk patient the IMT deviation, defining DeltaIMT from the regression line of controls at the measured patient's tensile stress. RESULTS: DeltaIMT correlated positively with age (p < 0.05), body mass index (p < 0.05), blood pressure (p < 0.001), and glucose (p < 0.001). In multivariate analysis, DeltaIMT was independently associated with age (p < 0.01), male gender (p < 0.001), and blood pressure (p < 0.001). IMT showed positive association with age (p < 0.001) but not with other risk factors. Also, DeltaIMT, like CSA, correlated positively with tensile stress (p < 0.001) and negatively with wall shear stress (p < 0.05, p < 0.01), whereas IMT correlated negatively with tensile stress (p < 0.001) but not with wall shear stress. CONCLUSION: Correcting IMT for adaptive association with tensile stress may give more strength to carotid evaluation for assessing cardiovascular risk.
Abstract: INTRODUCTION AND OBJECTIVES: Echographic studies of the composition of atheromatous plaque make use of the median gray level, which provides an overall measure of echogenicity. We propose adding an additional dimension to this approach by dividing the lesion into layers and generating a curve that shows the variation in echolucency with depth. METHODS: Femoral and carotid plaque in asymptomatic patients was investigated using both the median gray level and new layer METHODS: Interobserver variability was assessed for both METHODS: Three risk factors were studied: age, gender and smoking status. Differences in echogenicity-depth curves between different groups were assessed using two-way ANOVA. RESULTS: The two methods gave similar results for the mean echogenicity of carotid and femoral plaque. Echogenicity increased as a function of depth (r=0.96; P< .001). With the median gray level method, none of the risk factors produced a change in echogenicity. However, with the layer method, the echogenicity of femoral plaque was found to increase with age (P< .001), though gender had no effect. Moreover, the echogenicity of superficial layers was less in smokers than nonsmokers (P< .01). In carotid plaque, echogenicity increased with age (P< .01) and was higher in men (P< .01). The echogenicity of deep plaque was greater in smokers than nonsmokers (P< .05). The reproducibility of the two methods was similar. CONCLUSIONS: The layer method was more effective than the median gray level method for identifying the effect of age, sex and smoking status on the echogenicity of atheromatous plaque.
Abstract: BACKGROUND: Postulating that serotonin (5-HT), released from smoking-activated platelets could be involved in smoking-induced vascular modifications, we studied its catabolism in a series of 115 men distributed as current smokers (S), never smokers (NS) and former smokers (FS) who had stopped smoking for a mean of 13 years. METHODOLOGY/PRINCIPAL FINDINGS: 5-HT, monoamine oxidase (MAO-B) activities and amounts were measured in platelets, and 5-hydroxyindolacetic acid (5-HIAA)--the 5-HT/MAO catabolite--in plasma samples. Both platelet 5-HT and plasma 5-HIAA levels were correlated with the 10-year cardiovascular Framingham relative risk (P<0.01), but these correlations became non-significant after adjustment for smoking status, underlining that the determining risk factor among those taken into account in the Framingham risk calculation was smoking. Surprisingly, the platelet 5-HT content was similar in S and NS but lower in FS with a parallel higher plasma level of 5-HIAA in FS. This was unforeseen since MAO-B activity was inhibited during smoking (P<0.00001). It was, however, consistent with a higher enzyme protein concentration found in S and FS than in NS (P<0.001). It thus appears that MAO inhibition during smoking was compensated by a higher synthesis. To investigate the persistent increase in MAO-B protein concentration, a study of the methylation of its gene promoter was undertaken in a small supplementary cohort of similar subjects. We found that the methylation frequency of the MAOB gene promoter was markedly lower (P<0.0001) for S and FS vs. NS due to cigarette smoke-induced increase of nucleic acid demethylase activity. CONCLUSIONS/SIGNIFICANCE: This is one of the first reports that smoking induces an epigenetic modification. A better understanding of the epigenome may help to further elucidate the physiopathology and the development of new therapeutic approaches to tobacco addiction. The results could have a larger impact than cardiovascular damage, considering that MAO-dependent 5-HT catabolism is also involved in addiction, predisposition to cancer, behaviour and mental health.
Abstract: Hypertriglyceridemia being an independent cardiovascular risk factor, we have compared the potential of sera from asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP) subjects to promote both fractional cholesterol efflux and cellular cholesterol mass changes using macrophage foam cells. The J774 cells loaded with cholesterol by incubation with acetylated LDL were incubated in the absence or presence of cAMP to upregulate ABCA1 (ATP binding cassette transporter A1) and then incubated for 24h with 1% serum. Compared with NLP, type IV sera exhibited a major increase in ABCA1-dependent efflux while type IIb sera exhibited a moderate but not significant increased ABCA1-mediated efflux. Moreover, positive correlations were established between ABCA1-dependent efflux and the serum prebeta-HDL or TG concentrations. The major finding was that the sera from type IV induced higher total cholesterol and cholesteryl ester mass depletions from ABCA1-expressing cells compared with other groups. Moreover, negative correlations were obtained between total cholesterol or cholesteryl ester mass changes and serum prebeta-HDL levels. In conclusion, we demonstrated for the first time that the serum prebeta-HDL present in high proportions in type IV HTG subjects are not only responsible for higher cholesterol efflux potential but also for increased abilities to promote net removal of cholesterol from macrophage foam cells.
Abstract: BACKGROUND: Obesity increases the risk of cardiovascular diseases and diabetes. OBJECTIVE: To determine which measure of adiposity, body mass index (BMI), waist circumference (WC) or body fat mass (BFM) is the most predictive of the coronary heart disease (CHD) risk and of the presence of the metabolic syndrome. METHODS: A cross-sectional study of 649 consecutive men and women aged 22-79 years, in primary prevention. RESULTS: BMI, WC and BFM were strongly associated with conventional cardiometabolic risk factors. For a 1-S.D. increase in BMI, WC and BFM, the odds ratios (95% CIs) of having the metabolic syndrome after adjustment for age, gender, and drug treatments were as follows: BMI, 3.40 (2.68-4.37); WC, 4.79 (3.61-6.53); and BFM, 3.19 (2.49-4.16). WC annihilated the association of BMI and BFM with the metabolic syndrome when measures of adiposity were introduced two by two. For CHD risk, the odds ratios (95% CIs) were as follows: 1.62 (1.16-2.24), 1.72 (1.22-2.42), and 1.92 (1.40-2.62) respectively. BFM annihilated the associations of BMI and WC with CHD risk when measures of adiposity were introduced two by two. CONCLUSIONS: WC shows the best association with the metabolic syndrome, while BFM shows the best association with high CHD risk. BMI shows weaker relationships with the metabolic syndrome, and high CHD risk. Our findings suggest that BFM can be used as a complementary measure to identify CHD risk in adult subjects.
Abstract: OBJECTIVES: Our aim was to analyze flow-mediated dilation (FMD) time-course in response to forearm occlusion in the clinical setting. METHODS AND RESULTS: In 50 asymptomatic subjects, monitoring software measuring continuous beat-to-beat change in brachial artery diameter was used to determine FMD magnitude in percentage change in peak diameter from baseline (FMD-DeltaD), time to peak diameter after occlusion release (FMD-t(peak)), integrated FMD response calculated as area under dilation curve (FMD-AUC), maximum FMD rate calculated as maximal slope of dilation (FMD-MDR). FMD-DeltaD and FMD-MDR correlated positively with peak wall shear stress (P < 0.05, P < 0.01). FMD-MDR correlated negatively with age (P < 0.001), Framingham risk score (P < 0.01) and carotid intima-media thickness (P < 0.05), while FMD-DeltaD correlated negatively with Framingham risk score only (P < 0.01). After adjustment, all these correlations were independent of antihypertensive, lipid-lowering and antidiabetic therapies. All but that of FMD-MDR with intima-media thickness were also found in a subgroup of 29 untreated subjects and in a subgroup of 24 untreated and low-risk (FRS < 10%) subjects. FMD-t(peak) and FMD-AUC were not associated with shear stimulus, Framingham risk score, and intima-media thickness. CONCLUSION: The kinetics of dilation (maximum rate) seem more sensitive than their magnitude in assessing FMD performance and its determinants.
Abstract: In this study we evaluate early atherosclerotic changes and determine whether anti-HSP-60, anti-HSP-65 and anti-oxLDL autoantibodies are elevated in systemic necrotizing vasculitis. Thirty-two patients having systemic necrotizing vasculitis were compared with normal controls and patients with systemic lupus erythematosus (SLE). The antibodies against human HSP-60, HSP-65 and oxLDL were measured by antihuman ELISA kit. All patients underwent non-invasive measurements of carotid artery intima-media thickness (IMT). In a comparison between carotid IMT extent between vasculitis patients and SLE, no significant differences were noted. Levels of anti-HSP-60, anti-HSP-65 IgG and anti-oxLDL autoantibodies were similar among patients compared to controls. IgM anti-HSP-60 antibody levels were significantly lower in patients compared to controls and a similar trend was found regarding IgM anti-HSP-65. As a group, patients having various necrotizing vasculitis have similar extent of early atherosclerotic changes regardless of the vasculitis type, and these levels are similar to those found in SLE.
Abstract: The vascular endothelium plays an important role in the regulation of vascular tone, cell growth, inflammation, and thrombogenicity. Endothelium dysfunction, then, is considered to promote several disorders that initiate the atherosclerosis process. Vascular tone dysfunction can be determined by high-resolution ultrasonographic imaging of the brachial artery, enabling one to assess endothelium-dependent flow-mediated dilation (FMD). It is based on the principle that an increase in blood flow, specifically in shear stress, provokes the release of nitric oxide and then a vasodilation that can be quantified. In this study, brachial artery diameter evolution was continuously followed during baseline and hyperemia after forearm occlusion using a custom designed software. Some techniques used to measure FMD are limited by operator dependence. We present a new, automated, and versatile method of FMD quantification based on B-mode echographic images and edge detection algorithms. Edges for each image in the acquired sequences are recognized as interfaces based on the grey-level profiles of the averaged pixel values. Within-reading and within-subject FMD% coefficients of variation were 7% and 10%, respectively. This technique largely improves manual measurements and was shown to be appropriate for wide clinical use.
Abstract: AIMS: Measurement of change in carotid intima-media thickness (CIMT) has been proposed as an alternative for the occurrence of cardiovascular (CV) events in the assessment of therapeutic interventions. Nevertheless, criticism has been voiced based on observations indicating a weak relation between CIMT and coronary atherosclerosis as well as on the virtual absence of data showing that progression of CIMT indeed predicts coronary artery disease (CAD) and stroke. METHODS AND RESULTS: We set out to review the evidence on these issues by performing a literature search on these topics. Of the 34 studies on the relation of CIMT with coronary atherosclerosis, as assessed by angiography (n=33) or intravascular ultrasound (n=1), 30 showed a modest positive relationship; the magnitude of which was similar to that found in autopsy studies. Of all studies on CIMT and future CV events (n=18), 17 showed graded positive relationships. At present, only one study has provided evidence on the relation of change in CIMT and future CV events, showing an increased risk with CIMT progression. The paucity of data on progression and future CV risk is partly attributable to time windows required to complete these studies. CONCLUSION: The modest relation between CIMT and coronary atherosclerosis most likely reflects variability in atherosclerosis development between the vascular beds rather than limitations of CIMT measurements. Additional data on the relation between change in CIMT and future CV events is required and currently is in progress.
Abstract: The prognostic performance of subclinical atherosclerosis in predicting coronary heart disease (CHD) needs to be clarified because of the existence of many non-invasive tests available for its detection in the clinical setting: ultrasound measurement of carotid intima-media thickness (IMT) and plaque, cardiac computed tomography assessment of coronary artery calcium, Doppler stethoscope measurement of ankle-arm index pressure (AAI), and mechanographic or Doppler determination of aortic pulse wave velocity (PWV). Data analysis of the main prospective studies in asymptomatic populations allows the establishment of a dose-response relationship between subclinical atherosclerosis burden and cumulative incidence of future CHD event (absolute risk). Negative subclinical atherosclerosis testing conveys a low 10-year CHD risk inferior to 10% whatever the test considered, i.e. IMT less than the 1st tertile or 1st quintile, AAI > or = 0.90, PWV less than the first tertile, no discernible carotid plaque, or zero coronary calcium score. Positive testing for IMT (>95th percentile or 5th quintile), AAI (<0.90), or PWV (>3rd tertile) conveys a moderately high 10-year CHD risk between 10 and 20%. Positive testing for carotid plaque (focal protrusion >1.5 mm or mineralization) or coronary calcium (total score >300 or 400 units) conveys a high 10-year CHD risk superior to 20%. Therefore, positive subclinical atherosclerosis measurement seems to have its place in the context of existing prediction models, namely for intermediate risk classification. It also remains to be established whether individuals with negative subclinical atherosclerosis may be considered at low CHD risk and receive conservative management.
Abstract: It is currently accepted that atherosclerosis is rather, or also, an inflammatory disease and, indeed, vasculitis is defined by inflammatory infiltrates in blood vessel walls, albeit initially by different predominant cell populations and in arteries of different calibers. As for other chronic systemic inflammatory diseases, premature and accelerated atherosclerosis has emerged during the last 5-10 years as an important facet of vasculitides, independently of the other risk factors of cardiovascular disease and also, apparently, corticosteroids. Chronic systemic inflammation, like persistently active vasculitis, might play a role in early atherosclerosis, through the actions of C-reactive protein (CRP), some adhesion molecules, and/or cytokines, as well as local inflammation, perhaps through locally secreted TNF-alpha and/or upregulation of matrix metalloproteinases and oxidative stress. Endothelial cell dysfunction and increased arterial stiffness have also been found in vasculitis patients. Notably, some vasculitis treatments were able to reverse some of these endothelial cell anomalies. Unlike antineutrophil cytoplasm autoantibodies (ANCA), which were not shown to correlate with a higher risk of atherosclerosis or cardiovascular events, autoantibodies to endothelial cells, heat-shock proteins, or oxidized-LDL may also be implicated, although these latter are now thought to protect against atherosclerosis. It is likely that other, as yet unidentified, factors facilitating atherosclerosis may play more important roles in vasculitides. Until their precise identification, it remains important to take into consideration and treat, every time it is necessary and possible, the other well-known cardiovascular risk factors.
Abstract: BACKGROUND: The reproducibility of brachial artery flow-mediated vasodilatation (FMD) is limited by the operator dependence of most measurement methods. METHODS: A new automated computerized analysis of brachial artery ultrasound scan providing a continuous evolution of the diameter during acute hyperemia, reactive to short hyperemia of the forearm and hand, was tested in 10 normal volunteers and 26 asymptomatic patients with cardiovascular risk factors such as hypertension, hypercholesterolemia, heavy smoking, history of premature coronary heart disease and the metabolic syndrome. FMD was the percentage of the maximum hyperemic diastolic diameter from baseline. Within-reading variations in FMD and diameters were assessed by reading one scan from the same subject twice by two observers. The within-subject variability of FMD was assessed by analysing two repeated measurements in the same subject by the same operator 1 h, 1 week or 1 month apart. RESULTS: Coefficients of variation (CV) of repeated FMD readings were 7.5% in normal volunteers and 6.9% in patients with risk factors. CV of repeated FMD measurements 1 h apart were 7.8% in normal volunteers and 16.5% in patients with risk factors. In normal volunteers, CV of repeated FMD measurements 1 week apart was 9.6%, and in patients with risk factors CV of repeated FMD measurement 1 month apart was 18.1%. CONCLUSION: This method overcomes the variability of FMD measurement seen with conventional manual analysis in normal volunteers, and to a lesser extent in patients with major cardiovascular risk factors, thus supporting its clinical applicability to patients with disease conditions.
Abstract: OBJECTIVES: To assess whether circulating endothelial progenitor cells (CEPCs) can be considered as a cardiovascular risk marker before event has occurred, that is less firmly established than in clinically overt atherosclerosis. METHODS: Number of CD34+KDR+ cell number per ml blood was measured by flow cytometry in 84 untreated subjects without cardiovascular disease. Atherosclerotic plaque was detected by ultrasound in carotid, abdominal aortic and femoral sites and the number of sites affected by plaque among these three sites was counted as 0, 1, 2 or 3. Additionally, intima-media thickness (IMT) was measured by computerized ultrasound imaging of both common carotid segments. RESULTS: CD34+KDR+ cell number decreased by 48, 29 or 30% in the presence of carotid, aortic or femoral plaque (p<0.001, 0.05, 0.05, respectively) as compared to the absence of plaque and by 70% in the presence of three sites affected with plaque as compared with 0 site with plaque (p<0.01) but did not change with increasing IMT tertiles. Adjustment for Framingham risk score, that was also associated with decreased CD34+KDR+ cell number (p<0.001), made CD34+KDR+ cell number associations with plaque insignificant, except at the carotid site (p<0.01). CONCLUSIONS: Reduced CEPC number may participate to preclinical stage of atherosclerosis and provide additional information to traditional risk factors as regards global risk assessment.
Abstract: BACKGROUND AND OBJECTIVE: Although changes in smaller vessels is the hallmark of medium-sized and small-vessel vasculitis, it has been suggested that large arteries of such patients may also be affected by the early atherosclerotic process because of coexisting risk factors or systemic inflammation. This study aimed to bring additional arguments supporting this hypothesis. DESIGN, SETTING AND PATIENTS: 50 consecutive patients with primary systemic necrotising vasculitis and 100 controls matched for age and sex underwent ultrasonic detection of plaque in three peripheral vessels (carotid and femoral arteries and abdominal aorta). Cardiovascular risk factors and inflammation (C reactive protein (CRP)) were concomitantly measured in all participants, and diagnosis of high-risk status was defined by the presence of known history of cardiovascular disease, type 2 diabetes or 10-year-Framingham Risk Score > or =20%. RESULTS: Patients had higher frequency of plaque than controls in the carotid arteries (p<0.05), in the aorta (p<0.01) and in the three vessels examined (p<0.001), and adjustment for high-risk status did not confound such difference in the aorta and in the three vessels. In the overall population of patients and controls, vasculitis was associated with a higher frequency of three-vessel plaques (p<0.05), independently of high-risk status and CRP. In patients, the higher frequency of three-vessel plaques was associated with high-risk status (p<0.05) but not with CRP, or disease and treatment characteristics. CONCLUSIONS: Small-vessel vasculitis is associated with more frequent subclinical atherosclerosis, especially extended to multiple peripheral vessels, and such association is not entirely explained by cardiovascular risk factors and systemic inflammation.
Abstract: BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive method previously shown to improve measures of myocardial ischemia in patients with coronary artery disease. However, the concomitant effects of EECP on large and small arterial properties have been poorly examined. In a randomized controlled study, we investigated whether arterial stiffness and resistance of the carotid circulation are altered by EECP. METHODS: Thirty patients with angiographically demonstrated coronary artery disease were randomized into two groups to receive either 'sham' or active EECP therapy for 35 1-hour sessions. The beta stiffness index was calculated by the ln(Ps/Pd)/DD equation where Ps and Pd = systolic and diastolic blood pressure, and DD = the ratio between carotid pulse and diastolic diameter, measured by ultrasound sequential frames during the cardiac cycle. Carotid vascular resistance was calculated as the ratio between mean arterial pressure and mean common carotid blood flow. RESULTS: No significant between-group differences were seen in clinical characteristics or carotid hemodynamics at baseline. The beta stiffness index and carotid vascular resistance were significantly reduced after 35 h of active EECP (p < 0.01), and the decrease was significantly different when compared with controls (p < 0.05 for beta stiffness index and p < 0.001 for carotid vascular resistance). These reductions persisted after multiple covariate adjustment. CONCLUSIONS: This study suggests that EECP exerts clear arterial effects on large and small vessels of the carotid circulation. The combined effects on arterial stiffness and vascular resistance are of particular interest in cardiovascular disease involving reduction in blood flow, in which techniques that increase regional blood flow may be beneficial.
Abstract: OBJECTIVE: To clarify circulating microparticles (MP) relationships with preclinical atherosclerosis. METHODS AND RESULTS: In 216 subjects without cardiovascular disease, we assessed: (1) annexin V-positive, platelet-derived, endothelium-derived and leukocyte-derived circulating MP by capture on annexin V, anti-GPIb, anti-CD105, and anti-CD11a antibody-coated wells, respectively; (2) Framingham risk, metabolic syndrome, and low-grade inflammation by risk factors measurement including hsCRP; and (3) subclinical atherosclerosis by ultrasound examination of carotid, abdominal aorta, and femoral arteries. Number of sites with plaque ranged from 0 to 3 and plaque burden was classified into 0 to 1 or 2 to 3 sites disease. Leukocyte-derived MP level was higher in the presence than in the absence of moderate to high Framingham risk (P<0.05), metabolic syndrome (P<0.01), high C-reactive protein (CRP) (P<0.05), or 2- to 3-sites disease (P<0.01), and correlated positively with number of metabolic syndrome components (P<0.001), tertiles of fibrinogen (P<0.001), and number of diseased sites (P<0.01). In multivariate analysis, 2- to 3-sites disease was independently associated with leukocyte-derived MP level (P<0.05), Framingham risk (P<0.001), and metabolic syndrome (P<0.01). None of the other MP types correlated with risk markers or atherosclerosis. CONCLUSIONS: Leukocyte-derived MP, identified by affinity for CD11a, are increased in subjects with ultrasound evidence of subclinical atherosclerosis, unveiling new directions for atherosclerosis research.
Abstract: BACKGROUND: Relations of mediators of inflammation and hemostasis with preclinical atherosclerosis have been poorly analyzed. The aim of this study was to test potential associations of these blood markers with indicators of cardiovascular risk and atherosclerotic burden in asymptomatic, nonsmoking, hypercholesterolemic men. METHODS: A total of 87 men underwent cardiovascular risk assessment by means of 10-year Framingham risk calculation (median 9%) and atherosclerotic burden evaluation by means of ultrasonographic measurement of common carotid intima-media thickness and assessment of atherosclerotic plaques at three arterial sites (three-site plaques). RESULTS: Of the markers C-reactive protein, tumor necrosis factor-alpha, interleukin-10, factor VIIc, fibrinogen, plasminogen activator inhibitor-activator, soluble intercellular adhesion molecule-1, soluble P-selectin (sP-selectin), and von Willebrand factor, only sP-selectin was positively and independently associated with high Framingham risk score (>9%) (71.7 +/- 3.6 ng/mL, n = 33 v 59.6 +/- 2.8, n = 54; mean +/- SEM; P < .05) and with three-site plaques (75.4 +/- 5.7 ng/mL, n = 14 v 62.0 +/- 2.5, n = 73; P < .05). After adjustment for all of the above markers and for cardiovascular risk factors, odd ratios of having high Framingham risk and three-site plaques were 3.38 (1.43 to 10.21) and 5.23 (1.74 to 23.52) respectively, per 1-standard deviation increase in sP-selectin. CONCLUSIONS: These results confirm that among several hemostasis and inflammation mediators, only sP-selectin blood level was associated with preclinical atherosclerosis. It might confer to sP-selectin measurement a clinical usefulness for detecting and managing high cardiovascular risk in primary prevention.
Abstract: Current possibilities for better detecting high risk of coronary heart disease (CHD) and stroke and peripheral arterial disease are described in this review. A first step is based on risk factors assessment that allows establishing high-risk diagnostic, either by detecting a condition termed as "CHD risk equivalent" and defined by one or more severe major risk factor, or by calculating multifactorial risk in asymptomatic subjects with a global risk score integrating several moderate risk factors. A second diagnostic step, concerning subjects not considered at high-risk by risk factors assessment, is based on non-invasive detection of sub clinical atherosclerosis via a wide variety of structural and functional arterial markers. A third step focuses on detection of myocardial ischemia that may add diagnostic and prognostic information in subjects with high CHD risk. The implementation of high-risk strategy is not yet standardized but it should allow improving cost-effectiveness of cardiovascular prevention, particularly in asymptomatic subjects.
Abstract: BACKGROUND: Fu5AH rat hepatoma cells and cAMP (cyclic AMP)-pretreated J774 mouse macrophages are commonly used as models for SR-BI (scavenger receptor class B type I) and ABCA1 (ATP binding cassette transporter 1)-mediated free cholesterol efflux to whole serum, respectively. However, the responsiveness of Fu5AH, control or cAMP pretreated J774 cells to the various lipids and HDL (high-density lipoprotein)-parameters from both normo- and dyslipidaemic subjects has never been compared within the same study. MATERIALS AND METHODS: Fifty-eight men were classified into four groups: type IIa hypercholesterolaemic (n = 12), type IIb dyslipidaemic (n = 13), type IV hypertriglyceridaemic (n = 18) and normolipidaemic (n = 15) were recruited. A complete lipid profile including prebeta-HDL was performed. Cholesterol efflux from Fu5AH cells as well as from control or cAMP pretreated J774 cells were measured; the difference between these two latter values being taken as the ABCA1-mediated efflux. RESULTS: The Fu5AH and the control J774 cells delivered cholesterol to mature HDLs, especially to phospholipid (PL)-rich HDL. Using cAMP pretreated cells, the ABCA1-dependent efflux was highly sensitive to prebeta-HDL, which appeared to be a factor in determining the efflux. Consistent with the dependence of the SR-BI-mediated efflux on HDL-PL levels, which are not different between groups, all sera displayed similar efflux capacities from the Fu5AH cells. Conversely, in accordance with their high prebeta-HDL levels, the ABCA1-dependent efflux highlighted the efficiency of type IV sera. CONCLUSION: Two complementary cellular models providing SR-BI and ABCA1-dependent efflux should be used to measure the capacity of a biological fluid which contains a wide variety of components to promote cholesterol efflux.
Abstract: BACKGROUND: Enhanced external counterpulsation (EECP) is a noninvasive, pneumatic technique that provides favorable effects in patients with coronary artery disease and heart failure. The mechanisms by which EECP exerts its beneficial effects remain poorly understood. Cyclic GMP (cGMP) regulates vascular smooth muscle tone that may improve arterial function. We investigated the effect of a single session of EECP on plasma and platelet cGMP in asymptomatic subjects with cardiovascular risk factors (HCVR) and in patients with coronary artery disease (CAD). METHODS: Fifty-five subjects were included (25 HCVR and 30 CAD) and randomized into two groups to receive either sham (control) or active EECP during 1 h. Plasma and platelet cGMP were measured immediately before and after EECP by radioimmunoassay. RESULTS: One hour of EECP increased cGMP plasma concentration by 52% +/- 66% (SD) (P < .001) and platelet content by 19% +/- 28% (P < .01). The increase in plasma cGMP was particularly marked in CAD patients receiving active EECP (P < .01), mainly in those with low LDL-cholesterol. Platelets, inhibition of nitric oxide synthesis by N(G)-monomethyl-l-arginine (L-NMMA) reduced cGMP by 23% +/- 31% (P < .001), whereas presence of superoxide dismutase and inhibition of phosphodiesterase-5 increased cGMP by 46% +/- 49% and 70% +/- 77%, respectively (P < .001). In all of the cases EECP increased additional platelet cGMP content, which suggests nitric oxide synthase activation. CONCLUSIONS: Acute external counterpulsation showed that very early treatment increases the cGMP production that may participate in the mechanism by which EECP exerts its clinical benefit. Analysis of the modulation of platelet cGMP content suggests that EECP activated the nitric oxide-dependent pathways.
Abstract: Traditional risk factors are poor screening tests for coronary heart disease, whereas clinical arterial disease represents its strongest predictor. This raises the question whether subclinical arterial disease may also predict coronary disease. Using published data of prospective studies of subclinical arterial disease, we calculated the incidence of coronary event associated with the absence or presence of atherosclerosis as defined by dichotomous characterization of the following markers: low or high intima-media thickness or the absence or presence of plaque, assessed by carotid ultrasound; zero or high total coronary artery calcium score assessed by computed tomography; normal or decreased ankle-arm index pressure assessed by Doppler stethoscope; and low or high aortic pulse wave velocity assessed by mecanography. A dose-response relationship was found between the absence and presence of atherosclerosis and coronary event incidence. Yearly incidence was <1% in the absence of atherosclerosis regardless of the marker used. Coronary event incidence was >1% in the presence of atherosclerosis and increased in a gradual way, depending on the marker tested, to reach 3% maximum with massive coronary calcifications. The relation between clinically overt arterial disease, such as angina, transient ischemic attack, stroke, or myocardial infarct, and yearly incidence of subsequent events reported in the literature prolonged the dose-response curve of subclinical disease. Therefore, detection of arterial disease, not only clinically overt but also subclinical asymptomatic, is a worthwhile screening test for future coronary event.
Abstract: OBJECTIVE: As main markers of atherogenic lipoproteins, apolipoprotein B (apoB), non-HDL cholesterol (non-HDLC), and LDL cholesterol (LDLC) do not seem equipotent to predict cardiovascular complications, we have compared simultaneously their capacity to predict high cardiovascular risk and subclinical atherosclerosis in a primary prevention population. METHODS: In 723 asymptomatic men, we measured apoB, non-HDLC, and LDLC, and we determined concomitantly coronary heart disease (CHD) risk equivalent defined by National Cholesterol Education Program guidelines, ultrasound-assessed extra-coronary plaques at multiple sites, and electron beam computed tomography-assessed high coronary calcium. RESULTS: Odds ratios (95% confidence interval) per standard deviation of apoB, non-HDLC, and LDLC of having: (i) CHD risk equivalent were 1.90 (1.53-2.37), 1.78 (1.43-2.21), 1.47 (1.19-1.81); (ii) extra-coronary plaques were 1.37 (1.16-1.61), 1.31 (1.11-1.56), 1.19 (1.01-1.39); (iii) high coronary calcium were 1.35 (1.09-1.68), 1.33 (1.07-1.64), 1.26 (1.01-1.39), respectively. Risk factors and treatment did not confound the above associations, except triglycerides for which adjustment weakened the risk predictions of lipids and annihilated lipids differences in predicting CHD risk equivalent and atherosclerosis markers. CONCLUSIONS: ApoB was the best predictor, non-HDLC the second best predictor, and LDLC the poorest predictor of high cardiovascular risk and subclinical extra-coronary and coronary atherosclerosis, and triglycerides participated to these differences.
Abstract: BACKGROUND: The effects of statins on intima-media thickness (IMT) are well documented, whereas those of fibrates are unknown. Therefore we compared IMT under treatment with each class of drugs. METHODS: We studied a cohort of consecutive dyslipidemic subjects treated with statin (n = 291) or fibrate (n = 82) drugs. Fibrate-treated subjects were matched with the same number of statin-treated subjects to obtain two subgroups of similar demographic and risk factors including LDL cholesterol. Common carotid far wall IMT and lumen diameter were measured by ultrasonography. RESULTS: In the entire study population, IMT was greater in the fibrate group than in the statin group (P < .001), even after adjustment for LDL cholesterol and other covariates (P < .05). In the matched groups, IMT was greater in fibrate group than in the statin group (P < .01), even after adjustment for LDL cholesterol and other covariates including treatment duration (P < .01). The IMT correlated positively with treatment duration in the fibrate group (P < 0.05) but not in the statin group. In addition, IMT correlated positively with carotid lumen diameter in both the fibrate and statin groups (P < .05, P < .01) but with a lower slope in the former (P < .05). CONCLUSIONS: In this study fibrate treatment was associated with greater IMT, steeper IMT-time relationship, and lower compensatory carotid enlargement than was statin treatment. These differences were not explained by differences in LDL cholesterol.
Abstract: The diagnosis of high risk of cardiovascular disease (CVD) in subjects without clinically overt CVD has been somewhat improved by integrating multiple traditional risk factors via appropriate risk score programs. Nevertheless, novel measures of CVD risk are being proposed and debated to further improve high-risk detection by their addition to, or their use in place of, traditional risk factors. Among such measures, non-invasive detection of subclinical arterial disease is a subject of growing interest. It may improve CVD risk evaluation and enable more intensive risk-reduction therapy in subjects judged to be at intermediate risk after preliminary risk factor assessment. However, the clinical utility and cost-effectiveness of high-risk diagnostic and therapeutic strategy guided by subclinical arterial disease remain untested. This uncertainty precludes systematic detection of subclinical arterial disease in routine clinical management for primary prevention, but such detection may be used at the discretion of the physician as a part of CVD risk assessment.
Abstract: BACKGROUND: Calcium antagonists retard progression of intima-media thickness (IMT), but whether this retardation covers heterogeneous individual patient responses of IMT change is unknown. METHODS: Hypertensive patients treated for 4 years with nifedipine (n = 115) or coamilozide (n = 127) underwent ultrasound measurements of carotid IMT at baseline, 4 months later, and then every year. RESULTS: A histogram of individual slopes of IMT change (least square regression of IMT to time) during treatment identified three categories of slopes according to the 20th and 80th percentiles of distribution: lower, intermediate and higher percentiles of IMT slope; the proportion of categories of IMT slope differed between treatments (P < 0.05), due to a more frequent lower slope percentile under nifedipine (27%) than under coamilozide (14%); within-group differences between IMT slope categories were: (i) increased baseline IMT associated with lower IMT slope percentile in nifedipine group (P < 0.001) and (ii) more frequent carotid plaque associated with higher IMT slope percentile in both treatment groups (P < 0.05). Analysis of overall patients showed that IMT slope was associated negatively with nifedipine treatment (P < 0.01) and baseline IMT (P < 0.001) and positively with carotid plaque (P < 0.01); the relationship between IMT slope and baseline IMT was negative under nifedipine and flat under coamilozide, and the presence of plaque reset both relationships towards a higher IMT slope; the between-treatment difference in IMT slope was different between tertiles of baseline IMT (P = 0.016). CONCLUSIONS: The differences in IMT slope between nifedipine and coamilozide increase with increasing baseline IMT.
Abstract: cGMP regulates vascular smooth muscle tone and arterial wall response to proliferative signals. We determined plasma cGMP and carotid artery intima-media thickness (IMT) and diameter in 84 asymptomatic men submitted to investigation of their cardiovascular risk profiles. Plasma cGMP was positively associated with IMT (P<0.01) and diameter (P<0.05), independently of coexisting risk factors. These associations were reinforced in the subgroup of subjects with high-sensitivity C-reactive protein level or multiple atherosclerotic plaques. A positive relationship existed between diameter and IMT (P<0.01) and disappeared after cGMP adjustment. This suggests a link between cGMP pathway and arterial wall geometry that is revealed by vascular injury conditions and may participate in early large artery remodeling.
Abstract: AIM: We determined the wall mechanical response of the pulmonary artery (PA) to acute pulmonary hypertension induced pharmacologically and by an occlusion maneuver, to study the vascular response of the local segment and its influence in the whole pulmonary circulation. METHODS: Pulmonary pressure and diameter were measured in six anaesthetized sheep under steady-state conditions. Transient hypertension in the PA was induced by phenylephrine (PHE) and a high pressure (HP) mechanical occlusion aimed at producing the same pulse and mean pressure responses. A viscoelastic arterial wall model was applied and the elastic (E(pd)) and viscous (micro) indexes were obtained. The micro/E(pd) ratio was adopted to quantify the damping performance of the arterial wall segment. The diastolic time constant was used as an indicator of the whole pulmonary buffering function. The systemic pressure was always measured. RESULTS: The pulmonary mean, systolic and pulse pressure increases (P < 0.05) were similar during PHE and HP, with respect to control. PHE also induced a systemic pressure rise (P < 0.05). The E(pd) elastic index increased during HP (P < 0.05) and tended to increase during PHE with respect to control. The viscous index micro only increased with PHE (P < 0.05) with respect to control and occlusion. The diastolic time constant increased with PHE with respect to control (P < 0.05). CONCLUSIONS: A pressure rise in the PA, induced by an occlusion maneuver, increased local stiffness. Similar pressure rises with smooth muscle activation (PHE), produced both a stiffness and viscous index increase. In PHE resistance increases more than compliance decreases so that the global net effect is a longer decay time. Smooth-muscle activation enhances the local damping effect (micro/E(pd)), concomitant with the buffering function improvement.
Abstract: BACKGROUND AND PURPOSE: Several epidemiological studies have suggested a U-shaped association between alcohol consumption and cardiovascular risk. However, the modifications of vascular structure associated with alcohol consumption are largely unknown. METHODS: The study population sample comprised 6216 subjects (3780 women and 2436 men) aged 65 years or older who were recruited from 3 French cities (Bordeaux, Dijon, and Montpellier, which are located in the 3 principal wine-growing regions). Usual alcohol consumption was assessed by a standardized questionnaire. Carotid ultrasound examination included measurements (at sites free of plaques) of intima-media thickness (IMT) at the common carotid arteries (CCA), CCA-lumen diameter, and assessment of atherosclerotic plaques in the extracranial carotid arteries. RESULTS: Neither CCA-IMT nor carotid plaques were associated with alcohol consumption categories in the overall population. Weak and marginal positive associations were observed between categories of alcohol consumption and carotid plaques in men (P=0.02 for linear trend). CCA-lumen diameter was positively and independently associated with alcohol consumption in overall population and in men and in women. Similar results were found between alcohol consumption and carotid measurements in subjects free of cardiovascular disease (90.1% of the population). CONCLUSIONS: This very large population sample of French older adults shows no marked relationships of alcohol consumption with atherosclerosis. The positive association of alcohol intake with carotid arterial diameter may reflect the ability of alcohol to maintain adaptive enlargement to preserve lumen area.
Abstract: OBJECTIVE: We aimed to analyze the influence of hypertension on early large artery remodeling. METHODS AND RESULTS: Carotid intima-media thickness (IMT) and diameter were measured ultrasonographically in 394 normotensive subjects and 327 untreated and 528 treated hypertensive patients. IMT and diameter were increased in hypertensive groups, treated or untreated, compared with the normotensive group (P<0.001). Positive association existed between diameter and IMT in the overall study population (P<0.001), and this association interacted with the category of clinical groups (P<0.01). The slope of the diameter-IMT relationship was different between normotensive, untreated hypertensive, and treated hypertensive groups (P<0.01), with higher value in the treated hypertensive group than in untreated hypertensive and normotensive groups (P<0.05, P<0.01). Adjustment for blood pressure, lipid-lowering therapy, or multiple covariates (age, sex, systolic and diastolic blood pressures, body mass index, lipid-lowering therapy, smoking, and previous cardiovascular disease) did not abolish the diameter-IMT slope difference between clinical groups (P<0.01). CONCLUSIONS: The sensitivity of carotid artery enlargement in response to increase in wall thickness was unchanged in untreated hypertension but altered by antihypertensive therapy compared with the normotensive condition.
Abstract: Since elevated plasma triglycerides (TGs) are an independent cardiovascular risk factor, we have compared the cholesterol efflux potential of sera from asymptomatic hypertriglyceridemic (HTG) type IIb, type IV or normolipidemic (NLP) individuals using two different cell systems. In both type IIb and IV HTG, the efflux of cholesterol from SR-BI-rich Fu5AH cells was similar to that obtained with NLP. The maintenance of efflux efficiency in spite of reduced HDL-cholesterol levels can be mainly attributed to the relative enrichment of HDL with phospholipid. In the J774 macrophage cell system, pretreatment with cAMP, which upregulates ABCA1, induced a markedly higher increase in efflux to type IV sera compared with type IIb or NLP. In addition, type IV sera exhibited two-fold higher pre-beta HDL relative concentration (percentage of total apo AI) compared with NLP. Moreover, positive correlations were established between ABCA1-mediated efflux and the serum pre-beta HDL levels or TG concentrations. Thus, the hyperTGemia is associated with a higher fraction of apo AI recovered as pre-beta HDL which appear to be partly responsible for enhanced efflux obtained upon the cAMP stimulation of J774 cells. In conclusion, we demonstrated for the first time that the ABCA1-expressing J774 cell system is responsive to the percent of apo AI present in human serum as pre-beta HDL. Our results suggest that high-plasma TG, accompanied by low HDL may not result in an impaired cholesterol efflux capacity.
Abstract: Sterol regulatory element binding proteins (SREBPs) are membrane-bound transcription factors that control the metabolism of cholesterol and fatty acids in mammalian cells. We postulated that polymorphisms (SNPs) in SREBP-2 gene might influence lipid parameters and the risk of coronary atherosclerosis. PCR-SSCP analysis and direct sequencing of DNA from 64 asymptomatic hypercholesterolemic men revealed seven genetic SREBP-2 SNPs. The genotype distribution of four of these SNPs (1668G>T, 1784G>C, 3474T>C and 3705C>T), and their influence on plasma lipid values and clinical parameters was studied in 655 asymptomatic men previously selected for the presence of at least one cardiovascular risk factor (hypertension, hypercholesterolemia, tobacco consumption). No significant relation was found with lipid parameters but there was a significant association between the 1784G>C polymorphism and intima-media thickness (IMT) measured in 497 subjects. Thus, a common variation in the SREBP-2 gene is related with early-stage carotid atherosclerosis in subjects with a risk of cardiovascular events without detectable change in plasma lipid levels.
Abstract: The authors used ultrasonography to measure carotid artery intima-media thickness (IMT) in 36 HIV-infected patients taking highly active antiretroviral therapy (cases) and in two control groups without (control group 1) or with (control group 2) blood lipid and glucose disturbances similar to those of the patients. Case IMT values were 8% higher than control group 1 IMT values (p <.05) but not different from control group 2 IMT values. Positive independent associations of IMT with the total-to-HDL cholesterol ratio and waist circumference existed for cases (p <.05) but not for controls. Case IMT did not correlate with parameters of HIV infection and antiretroviral treatment. This case-control study suggests that lipid disturbances, mainly hypoHDLemia, may be involved in the early atherosclerotic process in HIV-infected patients.
Abstract: Given the major role of elevated blood pressure in the pathogenesis of both stroke and coronary heart disease, one of the biggest challenges facing public health authorities and medical practitioners is the control of hypertension worldwide, both in individual patients and at the population level. The prevalence of hypertension increases with age and is nearly 60% in people aged 65 - 74 years. With increasing age, polymorbidity and polypharmacy usually contribute to an increasingly complex approach to manage the respective clinical conditions, including the treatment of hypertension. All subgroups of calcium channel blockers are effective and well-tolerated in lowering blood pressure. They are of demonstrated benefit for the prevention of stroke in elderly patients with systolic hypertension. Calcium channel blockers are particularly recommended for elderly patients with systolic hypertension and for black patients. The nifedipine gastrointestinal therapeutic system (GITS) formulation provides a once-daily dosing regimen with a continuous and slow release of the drug, resulting in a smooth plasma concentration/time profile. The INSIGHT study established that nifedipine GITS decreased mortality and morbidity at the same level as standard diuretic treatment in hypertensive patients with additional risk factors. A subgroup analysis showed that the long-term protective effects of nifedipine GITS extended to hypertensive patients with diabetes mellitus and with previous myocardial infarction. Two substudies of INSIGHT showed that nifedipine slowed the progression of atherosclerosis in carotid arteries (intima-media thickness) and coronary arteries (coronary calcium) as compared to diuretic.
Abstract: OBJECTIVES: To assess the incidence and the clinical features of coronary heart disease in HIV-infected patients. To assess atherosclerosis risk factors in this population. METHODS: A review of our experience consisting of 16 patients with acute myocardial infarction (AMI) was the basis of our retrospective analysis of two cohorts in France. Incidence was compared with the national database on the incidence of AMI in the general population. RESULTS: Incidence appears to be between 5 and 5.5 per 1000 person-years among HIV-infected patients. This accounts for at least a threefold increase in incidence (1.52 per 1000 person-years reported in the Monica database registry in France). Age of onset of AMI in HIV-infected patients (younger than 50 years in most cases) is a point of major concern and is an indirect way to confirm the increased incidence. AMI was typically of sudden onset without prior history of angina pectoris. Treatment and prognosis of AMI in this population has no specificity. Patients with coronary heart disease present several risk factors such as tobacco smoking, hypertension, diabetes mellitus and low high-density lipoprotein level. The links between AMI and protease inhibitor exposure is still a matter of debate, and longer duration of follow-up is needed in order to reach any conclusion. CONCLUSIONS: Coronary heart disease is of a higher than expected incidence in HIV-infected patients. The limitation of risk factors (mainly tobacco smoking) is a new challenge. An adaptation of the Framingham score is necessary to state the individual risk. Prospective, controlled studies are necessary to assess new strategies such as the role of statins and switching therapeutic regimens.
Abstract: OBJECTIVE: To assess the incidence, clinical features, treatment, and follow-up of coronary events in HIV-infected patients over a period of 5 years. PATIENTS AND PARTICIPANTS: A cohort of 840 patients. MEASUREMENTS AND RESULTS: A coronary event occurred in 17 patients (5.9/1000 persons-years). Sixteen of them were exposed to highly active antiretroviral therapy (HAART). Patients with coronary events differed in age (48.3 vs. 43 years), CD4 T-cell count (284 vs. 486/mm(3)), total cholesterol (6.2 vs. 5.3 mmol/l), HDL cholesterol (0.72 vs. 1.16 mmol/l), and LDL cholesterol (4.95 vs. 3.391.61 mmol/l). No difference was observed regarding duration of HAART, weight, glucose level, or smoking status between the two groups. Acute coronary syndrome was the first manifestation in 14 patients. Coronary angiography showed 2.56 stenosis per patient, with a single vessel involvement in one-half. Percutaneous angioplasty was performed in all cases, with stenting in 11. After a mean follow-up of 36 months, 14 patients remain alive. Restenosis ( n=4) occurred in 3 patients (PTCA 3; stenting 4). All 14 patients are free of heart failure symptoms. Their mean left ventricular ejection fraction is 61%. CONCLUSIONS: A higher coronary-event rate is observed among HIV-infected patients, associated with drug-induced metabolic disturbances and a high prevalence of tobacco smoking. However, treatment and prognosis of acute myocardial infarction has no specificity.
Abstract: Increased intima-media thickness (IMT) is a non-invasive marker of early arterial wall alteration, which is easily assessed in the carotid artery by B-mode ultrasound, and more and more widely used in clinical research. Methods of IMT measurement can be categorized by two approaches: (i) measurement at multiple extracranial carotid sites in near and far walls and (ii) computerized measurement restricted to the far wall of the distal common carotid artery. Because IMT reflects global cardiovascular risk, its normal value might be better defined in terms of increased risk rather than in terms of statistical distribution within a healthy population. The available epidemiological data indicate that increased IMT (at or above 1 mm) represents a risk of myocardial infarction and/or cerebrovascular disease. Close relationships have been shown between: (i) most traditional cardiovascular risk factors; (ii) certain emerging risk factors such as lipoproteins, psychosocial status, plasma viscosity, or hyperhomocysteinemia; and (iii) various cardiovascular or organ damages such as white matter lesion of the brain, left ventricular hypertrophy, microalbuminuria or decreased ankle to brachial systolic pressure index. Thus, IMT gives a comprehensive picture of the alterations caused by multiple risk factors over time on arterial walls. Prospective primary and secondary prevention studies have also shown that increased IMT is a powerful predictor of coronary and cerebrovascular complications (risk ratio from 2 to 6) with a higher predictive value when IMT is measured at multiple extracranial carotid sites than solely in the distal common carotid artery. Therapeutic double-blind trials have shown that lipid-lowering drugs, such as resin and overall statines, and to a lesser extent antihypertensive drugs, such as calcium antagonists, may have a beneficial effect on IMT progression in asymptomatic or in coronary patients. However, methodological standardization of IMT measurement still needs to be implemented before routine measurement of IMT can be proposed in clinical practice as a diagnostic tool for stratifying cardiovascular risk in primary prevention and for aggressive treatment decision. It can be anticipated however, that the presence of increased carotid IMT in one individual with intermediate cardiovascular risk would lead to his classification into the high-risk category and thus influence the aggressiveness of risk factor modifications.
Abstract: The role of blood viscosity on arterial wall elasticity before and after deendothelization (DE) was studied. Seven ovine brachiocephalic arteries were studied in vitro under physiological pulsatile flow conditions achieved by a mock circulation loop. Instantaneous pressure and diameter signals were assessed in each arterial segment. Incremental elastic modulus (E(inc)) was calculated using the slope of the pure elastic stress-strain relationship. There was no significant difference between E(inc) values before and after DE (3.11 vs. 3.16 10(7) dyn/cm(2)) at a blood viscosity of 2.00 mPa. s. Increases in blood viscosity (2.50, 3.00, 3.50, and 4.00 mPa. s) always resulted in decreases of E(inc) before DE; inversely, increases in blood viscosity resulted in increases of E(inc) after DE. These values of E(inc), for identical levels of blood viscosity, were always significantly lower (P < 0.05) before DE than those obtained after DE. Arterial wall elasticity assessed through E(inc) was strongly influenced by blood viscosity, probably due to presence or absence of endothelium relaxing factors or to direct shear smooth muscle activation when endothelial cells are removed.
Abstract: Extended coronary artery calcifications (CAC) are predictive for cardiovascular complications but little is known about factors likely to influence CAC deposit. An analysis was undertaken to assess the cardiovascular risk factors that are capable of predicting CAC change over time. A retrospective analysis of CAC change was carried out in 55 asymptomatic men who underwent sequential electron beam computed tomographic measurement of CAC score a mean of 3.3 years apart. To ensure maximal accuracy in CAC change analysis, patients were included who had an initial CAC score of 10 or greater and with difference between both scores of 20% or greater of the initial score. The annual change rate in CAC score was calculated by dividing the change in CAC score by the interval between scores. Subjects' risk factors were analyzed and included body mass index, blood pressure, blood lipids and glucose, plasma lipoprotein(a) and fibrinogen, smoking status, and family history of coronary heart disease. The annual change rate in CAC score correlated positively with lipoprotein(a) (r = 0.42, p<0.01) and with initial CAC score (r = 0.46, p<0.001) and these associations persisted in multivariate analysis (p = 0.01, p = 0.001 respectively, R2 = 0.31). In contrast, no association existed between annual CAC change and baseline values and follow-up changes of other risk factors. The association of lipoprotein(a) with CAC progression in symptom-free patients with preexisting coronary calcifications provides new insights into the progression of coronary artery disease and may be useful for planning therapy and follow-up.
Abstract: Atherosclerotic disease is the most frequent cause of death in the western world.The key role of calcium ions in atherogenesis has created interest in the antiatherogenic potential of calcium channel blockers. Nifedipine, administered in a long-acting gastrointestinal transport system (GITS) formulation, was shown to have similar efficacy to the diuretic co-amilozide in the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT).Two side-arm studies of INSIGHT suggest that nifedipine GITS has a greater antiatherosclerotic effect than diuretic therapy, which may signal additional cardiovascular protection in the long term. This paper reviews the evidence for the antiatherogenic properties of calcium channel blockers and discusses their clinical implication.
Abstract: The high triglyceride/low HDL-cholesterol trait is a common finding in the general population. The aim of the present study was to analyze and interpret the relationships between triglycerides (TG), HDL-related parameters and serum cholesterol efflux potential in an asymptomatic population including both normo- and hyperlipidemic individuals. In a large sample (n = 1143) of this population, there was a negative correlation between TG and HDL-cholesterol (HDL-C) (r = -0.49, P<0.0001) whereas the negative correlation between TG and HDL-phospholipid (HDL-PL) (r = -0.29, P<0.0001) was weaker, leading to a strong positive correlation between TG and HDL-PL/C ratio (r = 0.58, P<0.0001). Thus, increased TG concentrations were associated with an enrichment of HDL with PL. Since we have demonstrated previously that HDL-PL is the major determinant for cholesterol efflux potential from Fu5AH rat hepatoma cells, we determined the effect of the variations in HDL lipid composition on the cholesterol efflux capacity in a subsample of 198 subjects. Compared with normolipidemic subjects (NLP) (TG< or = 1.7 mmol/l; LDL-C< or = 4.1 mmol/l, n=58), hypertriglyceridemic subjects (HTG) (TG>1.7 mmol/l, n=63) exhibited lower HDL-C levels (1.08+/-0.21 vs. 1.25+/-0.32, P=0.0003) whereas they showed similar HDL-PL concentrations (1.25+/-0.21 vs. 1.25+/-2.7) and, thus, higher HDL-PL/C ratio (1.17+/-0.15 vs. 1.02+/-0.14, P=0.0001). The relative efflux capacity of serum measured in the Fu5AH system (5% serum, 4 h incubation at 37 degrees C) was on average identical in the HTG and NLP groups. Thus, this study provides evidence that despite decreased HDL concentrations, as determined routinely by the HDL-C assay, some HTG subjects maintained serum cholesterol efflux capacity thanks to the enrichment of HDL with PL.
Abstract: BACKGROUND: Haemochromatosis is a common genetic disorder, inherited as an autosomal recessive trait that results in a progressive accumulation of iron in most tissues of the body. Positive association studies have been recently published between cardiovascular diseases and heterozygosity for the major mutation C282Y in the haemochromatosis gene HFE. METHODS: In the present work, we have determined the HFE genotypes for C282Y and H63D in subjects from two case-control studies: the ECTIM and GENIC studies, designed to identify genetic variants associated with myocardial and brain infarction, respectively. In addition, we tested whether HFE mutations were associated with the degree of arteriosclerosis assessed non-invasively by Doppler ultrasonography on the carotid and femoral arteries, in a group of apparently healthy individuals (the AXA Study). RESULTS: The prevalence of 282Y, and 63D allele carriers, did not differ between cases and controls in the ECTIM and in the GENIC studies, while 63D but not 282Y carriers were more numerous among subjects with atherosclerotic plaques in the AXA Study. CONCLUSIONS: These three studies do not provide consistent evidence supporting the hypothesis that HFE mutations are associated with an increased risk of cardiovascular disease and with the development of arteriosclerosis.
Abstract: BACKGROUND: Common carotid artery intima-media thickness (IMT) progression was compared between 4 years of treatment with nifedipine and diuretic. METHODS AND RESULTS: This study, ancillary to the International Nifedipine GITS Study: Intervention as a Goal in Hypertension Treatment (INSIGHT), involved nifedipine 30 mg or co-amilozide (hydrochlorothiazide 25 mg and amiloride 2.5 mg) with optional subsequent titration. Among 439 randomized hypertensive patients, 324 had >/=1 year of follow-up (intent-to-treat group), and 242 completed follow-up (until-end-of-study group). Ultrasonography was performed at baseline, 4 months later, and then every year. Central computerized reading provided far-wall IMT, diameter, and cross-sectional area IMT (CSA-IMT). The primary outcome was IMT progression rate (slope of IMT-time regression). Secondary outcomes were changes from baseline (Delta) in IMT, diameter, and CSA-IMT. In the until-end-of-study population, between-treatment differences existed in IMT progression rate (P=0.002), Delta IMT (P=0.001), and Delta CSA-IMT (P=0.006), because IMT progressed on co-amilozide but not on nifedipine. In the intent-to-treat population, treatment differences existed in Delta IMT (P=0.004) and Delta CSA-IMT (P=0.04) but not in IMT progression rate (P=0.09). Patients with >/=2, 3, or 4 years of follow-up showed treatment differences in IMT progression rate (P=0.04, 0.004, 0.007, respectively), Delta IMT (P=0.005, 0.001, 0.005), and Delta CSA-IMT (P=0.025, 0.013, 0.015). Diameter decreased more on co-amilozide than on nifedipine in the intent-to-treat population (P<0.05), whereas blood pressure decreased similarly on both treatments. CONCLUSIONS: A difference in early carotid wall changes is shown between 2 equally effective antihypertensive treatments.
Abstract: Two traditional methodologic approaches, the analysis of the arterial pressure waveform in the time domain and the measurement of pulse wave velocity along the arterial tree, have been extensively used to determine the distensibility of large arteries in humans. They have shown that large artery walls are stiffened in the presence of hypertension. However, several methodologic limitations, especially the incapability of these methods to take into account the physiologic pressure-dependence of arterial distensibility, have led to the development of new approaches for characterizing more in depth the elastic and viscous properties of large arteries. The noninvasive recording of instantaneous pressure and diameter waveforms in superficial arteries (carotid or femoral) by means of tonometry and ultrasonography allows, via appropriate model of the arterial wall, determination of the pure elastic properties as well as the wall viscosity of the vessel. Using case (hypertensive)-control (normotensive) studies it has been found that elastic alteration (stiffening) was preferential in the femoral artery rather than in the carotid artery and that viscous alteration (increased wall viscosity) was relatively uniform in both arteries. This topographic dissociation between elastic and viscous responses of the arterial wall to hypertension suggests that the elastic alteration might be a local phenomena dependent on the singularities of the arterial system, whereas abnormal wall viscosity may reflect a more general influence of hypertension on large artery smooth muscle, the likely determinant factor of viscosity. Therefore, the elastic and viscous components of the arterial walls should be considered independently when assessing the development of hypertensive vascular change and its response to antihypertensive treatment.
Abstract: Epidemiological data regarding the preventive role of vitamin E in the pathogenesis of atherosclerosis have yielded conflicting results, possibly because endpoints considered were clinical events but not detection of atherosclerosis per se. Otherwise, it has been suggested that the measure of the erythrocyte alpha-tocopherol level may be more suitable to assess the human tocopherol status than its plasma level. We investigated the association between early atherosclerosis in superficial arteries assessed noninvasively and the alpha-tocopherol status in 261 asymptomatic men at risk for cardiovascular disease. alpha-Tocopherol concentrations in plasma, HDL, and erythrocytes were determined using a reverse-phase HPLC method. Detection of carotid plaques and measure of carotid intima-media thickness (IMT) were performed using high-resolution B-mode ultrasonography. The main result of this study is the observation of a negative correlation (P<0.01) between carotid IMT and erythrocyte alpha-tocopherol concentration, independently of conventional cardiovascular risk factors, whereas no such association has been found with plasma (total or HDL) alpha-tocopherol concentrations. No association has been evidenced between alpha-tocopherol concentrations and carotid plaques. These results emphasize the primary protective role of vitamin E in the early phases of atherosclerosis and the significance of the erythrocyte alpha-tocopherol concentration as a marker of atherosclerosis.
Abstract: BACKGROUND AND PURPOSE: We attempted to detect a group-specific north-south difference in carotid artery intima-media thickness (IMT), a marker of subsequent cardiovascular complication, by means of a case (high risk)-control (low risk) study in French and Swedish men. METHODS: The selection of high-risk and low-risk subjects was performed within the lower and upper percentiles of the Framingham risk distribution of 2 samples of 1000 white, male auto workers (45 to 50 years of age) in France (Renault) and Sweden (Volvo). In total, 299 men at low risk (79 French, 76 Swedish) and high risk (61 French, 83 Swedish), free from sustained hypertension, definite hypercholesterolemia, and cardiovascular disease, were included. Both common carotid arteries, by ultrasonography and central off-line computerized analysis, provided measurements of far wall media thickness, lumen diameter, and cross-sectional area IMT (CSA-IMT). RESULTS: As compared with low-risk status, high-risk status was associated with higher IMT (P<0.001), diameter (P<0.01), and CSA-IMT (P<0.001) in French men and higher CSA-IMT (P<0.05) in Swedish men. IMT, diameter, and CSA-IMT were higher in Swedish than in French men in the low-risk group (P<0.001) and in the high-risk group (P<0.01, P<0.001, P<0.001). The multivariate analysis of the whole population showed that IMT, diameter, and CSA-IMT were associated with risk status (P<0.01, P<0.01, P<0.001) and geographic status (P<0.001). CONCLUSIONS: These findings show that the geographic status influences carotid artery structure independent of traditional cardiovascular risk factors and that this may affect the mortality and morbidity gradient between Northern and Southern Europe.
Abstract: Viscoelastic properties determine the dynamic behaviour of the arterial wall under pulsatile pressure and flow, suggesting time- or frequency-dependent responses to changes in wall stress and strain. The objectives of the present study were: (i) to develop a simplified model to derive simultaneously the elastic, viscous and inertial wall moduli; (ii) to assess Young's modulus as a function of frequency, in conscious, chronically instrumented dogs. Parametric discrete time models were used to characterise the dynamics of the arterial system based on thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements in control steady state and during activation of smooth muscle with the alpha-adrenoceptor agonist phenylephrine (5 microg kg(-1) min(-1), I.V.), in eight conscious dogs. The linear autoregressive model and a physically motivated non-linear model were fitted to the input-output (stress-strain) relationship. The aortic buffering function (complex Young's modulus) was obtained in vivo from the identified linear model. Elastic, viscous and inertial moduli were significantly increased from control state ((44.5 +/- 7.7) x 10(4) Pa; (12.3 +/- 4.7) x 10(4) Pa s; (0.048 +/- 0.028) x 10(4) Pa s(2) ) to active state ((85.3 +/- 29.5) x 10(4) Pa, P < 0.001; (22.4 +/- 8.3) x 10(4) Pa s, P < 0.05; (0.148 +/- 0.060) x 10(4) Pa s(2), P < 0.05). These moduli, obtained using the linear model, did not present significant differences compared with those derived using the non-linear model. In control conditions, the magnitude of the normalised complex Young's modulus was found to be similar to that reported in previous animal studies ranging from 1 to 10 Hz. During vascular smooth muscle activation, this modulus was found to be increased with regard to control conditions (P < 0.01) in the frequency range used in this study. The frequency-dependent Young's modulus of the aortic wall was obtained for the first time in conscious, unsedated dogs. The parametric modelling approach allows us to verify that vascular smooth muscle activation increases the elastic, viscous and inertial moduli with the advantage of being able to track their time evolution. Furthermore, under activation, the aortic wall remains stiff in the physiological frequency range, suggesting the impairment of the arterial buffering function. Experimental Physiology (2001) 86.4, 519-528.
Abstract: OBJECTIVES: We sought to investigate wall shear rate (WSR) and brachial artery diameter (BAD) changes simultaneously and to determine whether any gender differences exist in arterial reactivity. BACKGROUND: Wall shear rate/stress and arterial reactivity are rarely assessed at the same time. Furthermore, flow-mediated vasoconstriction has received less attention than flow-mediated vasodilation in humans. METHODS: A new noninvasive evaluation of WSR in the brachial artery, using multigated, pulsed Doppler velocimeter and a double-transducer probe moved and fixed by a robotic system, was developed. RESULTS: The validity of the system was tested in vitro with calibrated tubes and showed a high correlation (r = 0.98, p < 0.001). In 10 men and 10 women of similar age, induction of low and high shear rates by forearm occlusion produced significant vasoconstriction and vasodilation, respectively. The time lag for maximal BAD changes was 3 min for vasoconstriction and 1 min for vasodilation. A greater half-time for vasodilation (96 +/- 6 for men and 86 +/- 12 s for women) than for shear rate (31 +/- 5 s for men and 34 +/- 4 s for women) was observed after discontinuation of occlusion. Relative BAD was correlated with WSR changes, showing a significantly higher slope in women than in men (p < 0.01). Moreover, a larger normalized arterial diameter per shear rate was observed for vasoconstriction (p < 0.01) and vasodilation (p < 0.01) in women than in men. CONCLUSIONS: Shear-mediated arterial vasodilation and vasoconstriction were more pronounced in women than in men, suggesting different gender-related sensitivity in the regulation of large-artery vascular tone.
Abstract: Sterol-regulatory element binding proteins (SREBPs) are ubiquitous transcription factors that regulate the genes encoding key proteins in the control of cholesterol homeostasis. We looked for mutations or polymorphisms within the sequences of the SREBP-1a gene critical for the synthesis and/or activity of the protein in 204 asymptomatic men. A single G deletion at base pair -36 of the translation initiation site (designated G-) was found using single-strand conformation polymorphism (SSCP), in addition to three rare variants. This new marker was then assessed for its influence on the lipid parameters of 812 men at high cardiovascular risk, and on the presence of echographic atherosclerotic plaque in their peripheral arteries. The allelic frequency of the -36delG polymorphism was 0.58. At least one plaque was found in the carotid in 24% of subjects, in the femoral arteries of 48%, and in the aorta of 25%. There were significant associations between the -36delG polymorphism and mean total cholesterol (p=0.02) and LDL-cholesterol (P=0.02). There was a graded relationship between the G- allele and the presence of carotid plaque (r=0.084, P=0.02). In addition, there was a statistically significant interaction between the -36delG genotype and the apoE phenotype for plasma LDL-cholesterol (P=0.04) and apoB (P=0.05), suggesting a gene-gene interaction. Stepwise multiple regression analysis for lipid traits, risk factors, and apoE phenotype showed an independent association between carotid plaque and the -36delG polymorphism (beta=0.311, P=0.03). Thus, we have identified a new polymorphism in the 5' untranslated region of the SREBP-1a gene, and demonstrated its association with an atherogenic lipid profile and echographic plaques.
Abstract: Effects of antihypertensive treatment on large arteries may be influenced by the type of drug and concomitant risk factors such as blood cholesterol. To explore these possibilities we investigated the common carotid artery of 20 subjects with low cholesterol and 19 subjects with high cholesterol, all with essential hypertension, randomly allocated to 3 months of treatment with nitrendipine (20 mg/d) or trandolapril (2 mg/d). Carotid parameters were determined by recording instantaneous pressure (applanation tonometry) and diameter (echotracking device) and by modeling the pressure-diameter loop to obtain the Peterson modulus, stiffness index, measured and isobaric compliances, and wall viscosity. Effects of drugs on carotid parameters did not differ, except on systolic and diastolic diameters (p < 0.01), which increased insignificantly under nitrendipine but decreased (p < 0.01) under trandolapril. Blood cholesterol status did not influence carotid effects of trandolapril, whereas patients with low and high cholesterol treated with nitrendipine exhibited significant differences in drug effects on (a) systolic and pulse pressures (p < 0.05), which decreased in patients with low cholesterol (p < 0.01, p < 0.05) but not in those with high cholesterol; (b) diastolic diameter (p = 0.05), which increased insignificantly in patients with low cholesterol but was unchanged in those with high cholesterol; and (c) wall viscosity (p < 0.01), which decreased in patients with low cholesterol (p < 0.05) but increased insignificantly in those with high cholesterol. Also, wall viscosity change under nitrendipine was positively related to the baseline blood cholesterol ( r = 0.64, p < 0.01). Thus, nitrendipine and trandolapril show noteworthy differences in their effects on the carotid artery, in particular with respect to the status of blood cholesterol, but these differences should be confirmed by larger studies.
Abstract: Plasma viscosity and intima-media thickness (IMT) are frequently associated with cardiovascular disease and its risk factors. We evaluated the association of rheologic and vascular factors in asymptomatic subjects. Plasma viscosity (coaxial cylinder viscometry) and both preintrusive and intrusive atherosclerosis in the carotid arteries (ultrasonography) were investigated in 246 men and 337 women aged 17 to 65 years from the AXA study, a prospective cohort of healthy workers. Plasma viscosity was positively related to age-adjusted mean bifurcation carotid artery IMT (P < .01 for men; P < .04 for women) and maximum carotid artery IMT (P < .01 for men; P < .02 for women), but not to mean common carotid artery IMT. Multivariate adjustment affected these relations to a greater extent in men than in women. The odds ratio (range) of having intrusive atherosclerosis in relation to 1 SD greater plasma viscosity was 2.27 (1.52 -3.38) in men and 1.63 (1.17-2.26) in women. Adjustment of age, waist-to-hip ratio, smoking, hypercholesterolemia, hypertension, diabetes, and fibrinogen had very little effect on the magnitude of these odds ratios. Thus, plasma viscosity was associated with carotid thickening, suggesting that rheologic factors are involved in the subclinical phase of atherosclerosis.
Abstract: The vascular endothelium and circulating blood cells are exposed to a hemodynamic environment related to the pulsatile nature of the pressure and blood flow which influence the morphology, the physical properties and the metabolism of the cells. Among these mechanical forces, shear stresses, related to the speed gradients and to the blood viscosity, control vascular vasomotor tone and thrombogenecity, stimulating the production of the endothelial factors of relaxation or contraction, of the coagulation factors or activating erythrocyte and platelet aggregation or disaggregation phenomena. Low shear stress is considered to be a critical factor in the causation of thickening of the arterial wall and in the formation of atheromatous plaques. These plaques develop predominantly in specific parts of the arterial tree where asymmetries in the velocity profiles occur. A close relationship has been found in a large general population between plasma viscosity and thickening of the carotid bifurcation. The blood cells share the same environment as the endothelial cells. Thus, the shear stresses to which the erythrocytes are submitted is a major determinant of the blood viscosity. Shear is also an important physiological parameter regulating platelet aggregation in flowing suspensions. However, in vivo, the response of platelets depends on the balance between activation of the platelets by shear and the same rheological forces acting on the endothelial cells which produce mediators which inhibit this activation in order to maintain blood fluidity.
Abstract: Despite its potential usefulness for assessing preclinical atherosclerosis and cardiovascular risk, the ankle/arm blood pressure index (AAI) has not yet been the matter of study evaluating its feasibility and reliability by nonspecialist doctors in a general population. This study was planned for two steps. In step 1, the measurement of AAI, (ratio between Doppler systolic pressure at the ankle for each lower limb and the highest value of Doppler systolic pressure of the two upper limbs), should be performed by 50 general practitioners (GPs), 50 social security center physicians, and 50 occupational health physicians in 3,000 male smokers, 40 to 59 years, without clinical cardiovascular disease. In step 2, AAI measurement, coupled with echography-Doppler of iliofemoral arteries, should be repeated by a specialist in all subjects with decreased AAI (<0.90) and the first two subjects with normal AAI recruited in step 1 by each nonspecialist. The number of physicians and subjects participating in step 1 was lower than planned (80 physicians and 962 subjects) with the greatest defect for GPs (six physicians and 35 subjects) and the prevalence of decreased AAI was low (28 subjects). AAI measurement was repeated in step 2 in only 12 subjects with decreased AAI in step 1 and in 124 subjects with normal AAI in step 1. Five of the six subjects with decreased AAI in step 2 also had decreased AAI in step 1 and 123 of the 130 subjects with normal AAI in step 2 also had normal AAI in step 1. As regards echographic stenosis, decreased AAI had a sensitivity of 44% and a specificity of 98%. AAI seems more feasible for occupational health physicians and social security center physicians and AAI is also reliable for nonspecialists previously trained, but its predictive value as regards echographic stenosis is poor in asymptomatic subjects, which may limit its usefulness for detecting preclinical atherosclerosis.
Abstract: BACKGROUND: We hypothesized that arterial wall thickening, an early atherogenic alteration, might be associated with smoking differently according to gender, considering the cardiovascular protection of female sex hormones. METHODS AND RESULTS: We measured ultrasonographically carotid and femoral intima-media thickness (IMT) in 194 men and 330 women without risk factors other than smoking. In men: (i) current smokers had greater carotid and femoral IMT (P<0.01, P<0.001) and former smokers had greater femoral IMT (P<0.01) than never smokers; (ii) in pooled never, current and former smokers carotid and femoral IMT correlated to current daily smoking (P<0.01) and lifelong smoking (P<0.001); and (iii) carotid and femoral IMT correlated to age in never smokers (P<0.001), current smokers (P<0.01, P<0.001) and former smokers (P<0.01), with greater slopes in current than in former smokers at carotid site (P<0.05) and in current than in never smokers at femoral site (P<0.05). In women: (i) IMT did not differ by smoking status; (ii) in pooled smokers and non smokers femoral IMT correlated to current daily smoking (P=0.01) and to lifelong smoking (P<0.01) with a lower slope than in men (P<0.001), while carotid IMT did not; and (iii) carotid and femoral IMT correlated to age in never smokers (P<0.001), current smokers (P<0.001, P<0.05) and former smokers (P<0.001, P<0.01) with no different slopes. CONCLUSION: Smoking-related increase in IMT existed in men but not in women, suggesting a possible protection of female gender from early structural arterial alteration of smoking.
Abstract: Our objective was to provide a description of 'normal' carotid artery dimensions which are increasingly used for detecting early atherosclerosis and predicting clinical complications. Far wall intima-media thickness (IMT), lumen diameter and cross-sectional area intima-media thickness (CSA-IMT) were measured on 1 cm-distal common carotid artery segments on both sides by B-mode ultrasound, using an automated computerized edge-detection program, in 133 men and 216 women aged 17-65 years and free from cardiovascular disease and traditional risk factors. IMT and CSA-IMT increased with age in both sexes and on both sides, while diameter did not, except on the right side in men. Women had lower diameter than men except on the left side at 30 years or below, while IMT did not differ between sexes except on the left side from 31 to 50 years where IMT was higher in men; as a result of their lower diameter, women had lower CSA-IMT than men except on the right side above 50 years. IMT was lower on the right side than on the left side in both sexes, except in 30-year old or younger men and 31- to 40-year old women, while diameter was higher on the right side than on the left side in men and women aged 31-40 years and in women aged 41-50 years; also CSA-IMT was lower on the right side than on the left side in both sexes above 40 years. These data provide reference values of carotid artery dimensions and show that age, sex and side of measurement should be taken into account in the interpretation of 'normal' values of IMT and diameter in clinical practice and trials.
Abstract: We previously showed that hypercholesterolemic asymptomatic men had lower erythrocyte vitamin E content, despite normal plasma concentrations compared to normocholesterolemic men. We hypothesized that the reduced erythrocyte vitamin E concentration could be due to an impairment of transfer of vitamin E from plasma lipoproteins. We first developed a model for testing the ability of erythrocytes to accept vitamin E from high-density lipoproteins (HDL) pre-enriched in vitamin E, which allows to measure a net mass transfer of vitamin E from HDL to erythrocytes. Vitamin E-enriched HDL were obtained in controlled conditions of concentration and incubation time with a good reproducibility (CV </= 10%). The kinetic study of the net mass transfer of vitamin E to erythrocytes of healthy volunteers shows small inter- and intraindividual variations. The application of this model to erythrocytes of hyper- and normocholesterolemic men demonstrates that the reduced erythrocyte vitamin E content observed in hypercholesterolemic men was not due to a reduced ability of these cells to accept vitamin E from HDL. It might rather be due to an impairment of lipoproteins in the delivery of vitamin E to tissues, or to an oxidative stress which consumes antioxidants.
Abstract: Shear forces induce platelet aggregation and stimulate the endothelial production of anti-aggregatory factors. Among them, endothelin-3 (ET-3) has been reported to reduce aggregation and to increase platelet cyclic GMP (cGMP) content. Since hypercholesterolemia modifies both platelet aggregability and endothelial function, we compared in 14 hypercholesterolemic and 15 normocholesterolemic subjects the influences of shear forces (240 and 650 s(-1)) on platelet aggregation and cGMP content, and their modulation by ET-3. Spontaneous maximal aggregation occurred earlier and at a greater extent in hypercholesterolemic than in normocholesterolemic subjects (63+/-2 vs 46+/-6% P < 0.01). Pre-treatment with ET-3 abolished the shear-induced facilitation of maximal aggregation in platelets of normocholesterolemic (from 70+/-2 to 52+2% at 240 s(-1) and from 73+/-1 to 59+/-2S at 650s(-1); P < 0.05) and hypercholesterolemic (from 78+/-3 to 64+/-2 at 240 s(-1) and from 78+/-2 to 66+/-3 at 650 s(-1); P < 0.05) subjects. cGMP content did not significantly differ between normocholesterolemic and hypercholesterolemic subjects (6.1+/-0.5 vs 6.9+/-0.7 pmol/10(9) platelets). It was reduced in platelets submitted to shear forces (P < 0.05). This shear-dependent reduction was suppressed by ET-3 pre-treatment. These results demonstrate that shear forces enhance platelet aggregation and diminish their cGMP content. ET-3 reduces the pro-aggregating effects of shear, suggesting a rise in cGMP content as a dynamic associated mechanism.
Abstract: Several markers of preclinical atherosclerosis are currently available, such as: wall thickening and stiffening and endothelial dysfunction of large peripheral arteries detected by ultrasonography, or coronary calcification detected by ultrafast computed tomography. They reflect the integrated effects over time of multiple risk factors, traditional and emerging, and some of them (wall thickening and coronary calcification) have demonstrated a powerful predictive value as regards subsequent clinical events. Also these markers are invaluable targets for testing the effects of preventive treatments. Their detection should help selecting those asymptomatic subjects at risk for cardiovascular disease in whom prevention is justified.
Abstract: OBJECTIVE: The aim of this study is to evaluate the relationship between carotid intima-media thickness (IMT) and arterial wall inertial behaviour. METHODS: The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. The common carotid artery of eleven normotensive subjects (NTA) and eleven mild-to-moderate essential hypertensive patients (HTA) were measured noninvasively using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure (P) and diameter (D) loops. A linear discrete time model was used to estimate the inertial index (K(M)) using a system modelling-identification approach. RESULTS: In NTA K(M) was 0.333+/-0.256 (mmHg x s2/mm) and IMT 0.643+/-0.061 (mm), whereas in HTA K(M) was 0.798+/-0.590 (P < 0.05) and IMT 0.760+/-0.034 (P < 0.025). When all data of K(M) versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r = 0.61 (P < 0.05) was obtained. CONCLUSION: Wall inertia increase was associated with a higher IMT, suggesting that the intima-media thickening might be partially related to vascular hypertrophy manifested as increase of inertial behaviour.
Abstract: A new automated computerized system (IôTEC) that assesses concomitantly the instantaneous temporal arterial diameter and intimal media thickness (IMT) obtained from B-mode ultrasound (US) images was validated by sonomicrometry in sheep, by an echo-tracking system in humans, and by a Lucite phantom in vitro. Differences between methods for diameter measurements did not vary in any systematic way, with no significant differences in the lower frequency range. Ultrasonic measurements of the true phantom gap sizes showed high correlation (r2 = 0.98,p < 0.001) with no systematic errors. Carotid and femoral arteries in humans were strongly related between IôTEC and echo-tracking device (r2 = 0.94 carotid; R2 = 0.88 femoral, p < 0.001), with a Gaussian distribution of the errors. This new method showed high intra- and interobserver repeatability of arterial diameter and IMT, allowing consistent characterization of arterial dynamics in humans.
Abstract: This study was carried out to examine the relationship between the charge on low density lipoproteins (LDLs) and lipid and clinical parameters in 104 asymptomatic dyslipidemic men and to identify biochemical and genetic factors that could contribute to the charge variability of LDL. LDL charge heterogeneity was evaluated by relative electrophoretic mobility (REM) on preformed 0.5% agarose gels and by chromatographic quantification of a minor electronegative LDL subfraction designated LDL(-). The mean REM value for LDL was 0.147+/-0.016 and the mean LDL(-) subfraction percentage was 5.6+/-2.8%. Both were positively correlated with common atherosclerotic risk factors, especially total cholesterol [for REM, r=0.27, P<0.005; for LDL(-), r=0.28, P=0.008] and LDL cholesterol [for REM, r=0.27, P=0.007; for LDL(-), r=0.26, P=0.01)] levels, and REM was positively correlated with triglycerides (r=0.27, P<0.005) and negatively with apoAI levels (r=-0.30, P<0.002). The variations in LDL charge were not due to oxidation, as measured by the lag phase and binding to the LDL receptor. The results of the 2 methods used to measure LDL charge were significantly correlated and had some identical characteristics (eg, association with LDL apoCIII content and plasma triglyceride levels in borderline and IIb dyslipidemic subjects); these methods reflect different specific features of LDL charge. The percentage of LDL(-) was correlated positively with the LDL sialic acid content (P<0.0001), whereas the REM was related to at least 2 distinct chromosomal loci. Multiple logistic analysis showed that individuals carrying minor alleles of BsrDI (P<0.05), apoCIII/SacI (P<0.01), as well as the frequent allele of XbaI (P<0.05) at the apoB and CIII gene loci had high REMs. This result suggests that LDL charge heterogeneity, which is positively correlated with the atherogenic lipid profile, is influenced by both genetic and biochemical factors.
Abstract: FUNDAMENTAL PRINCIPLES: Therapeutic management of hypercholesterolemia requires information on two fundamental aspects: the patient's lipid profile and his/her risk of coronary artery disease. RISK EVALUATION: The latest therapeutic trials have partially confirmed the LDL-cholesterol levels retained for the different guidelines, including those proposed by the ANDEM. It is clear however, that the assessment of the individual beneficial effect of primary prevention must be based on a multifactorial evaluation of risk. But there is no standardization of methodologies currently used to evaluate risk. Briefly, these methodologies use mathematical equations deducted from statistical models or noninvasive quantification of preclinical atherosclerosis. PERSPECTIVES: In the future, this strategy based on quantification of cardiovascular risk should be evaluated in a prospective study.
Abstract: Increases in arterial wall viscosity and intima-media thickness (IMT) were found in hypertensive patients. Because smooth muscle cells are responsible for the viscous behavior of the arterial wall and they are involved in the process of thickening of the intima-media complex, this study evaluates the relationship between carotid thickness and wall viscosity. The simultaneous and noninvasive assessment of the intima-media complex and arterial diameter waveform was performed using high-resolution ultrasonography. This technique was contrasted against sonomicrometry in sheep, showing that the waveforms obtained by both methods were similar. The common carotid arteries of 11 normotensive subjects (NTA) and 11 patients with mild to moderate essential hypertension (HTA) were measured noninvasively by using tonometry and an automatic densitometric analysis of B-mode images to obtain IMT and instantaneous pressure and diameter loops. A viscoelastic model was used to derive the wall viscosity index (eta) using the hysteresis loop elimination criteria. In NTA, eta was 2.73+/-1.66 (mm Hg x s/mm) and IMT was 0.58+/-0.08 (mm), whereas in HTA, eta was 5.91+/-2.34 (P<.025) and IMT was 0.70+/-0.12 (P<.025), respectively. When all data of eta versus IMT of NTA and HTA were pooled in a linear regression analysis, a correlation coefficient of r=.71 (P<.05) was obtained. Partial correlation between eta and IMT holding constant pressure was r=.59 (P<.05). In conclusion, wall viscosity increase was associated with a higher IMT even maintaining blood pressure fixed, suggesting that the intima-media thickening might be related to smooth muscle alterations manifested as an increase in viscous behavior.
Abstract: The detection of preclinical atherosclerosis may contribute to better identifying hypertensive subjects at high risk of complications. Three alterations can be diagnosed noninvasively: calcification, thickening, and stiffening of the arterial wall. Their prevalence is increased in asymptomatic hypertensives and their presence may have important prognostic significance, especially with respect to coronary artery disease. They are also ideal targets to test the efficacy of hypertensive therapy on the arterial wall. Finally, the detection of early atherosclerosis may help to improve the clinical management of hypertensive patients.
Abstract: Erythrocyte aggregation, which plays an important role in the physiological behavior of blood fluidity, was found to be enhanced in hypertension and hypercholesterolemia. While the role of macromolecule bridging force has been widely described, cellular factors related to membrane sialic acid content, which might contribute to the negative charge of cell surface causing the repulsion of erythrocytes, have been less studied. Cell age-dependent changes in membrane sialic acid content (in micromoles per gram of integral membrane protein) were investigated in 24 normotensive and 24 hypertensive matched subjects, each divided into 2 identical subgroups according to a cutoff of 6.2 mmol/L serum cholesterol. A progressive and significant (P<0.001) decrease in membrane sialic acid content associated with an increase (P<0.001) of disaggregation shear rate threshold (laser reflectometry in the presence of dextran) were observed with increased erythrocyte density (erythrocytes fractionated by density using ultracentrifugation) in both normotensive and hypertensive groups regardless of the cholesterol level. However, disaggregation shear rate threshold was significantly higher and sialic acid content was lower (P<0.001) in both hypertensive and normotensive subjects with hypercholesterolemia compared with either normotensive or hypertensive subjects with low cholesterol, respectively. A high membrane sialic acid content variance, beginning in the younger erythrocytes, was due mainly to triglyceride and LDL cholesterol levels (R2=0.49 for low, R2=0.43 for middle, and R2=0.54 for high densities, ie, young, mean, and senescent erythrocytes, respectively). We conclude that an early decrease in erythrocyte sialic acid content may influence the rheological properties of blood by increasing the adhesive energy of erythrocyte aggregates.
Abstract: BACKGROUND: We aimed to determine whether intima-media thickness (IMT) was increased in the carotid artery of subjects with homocystinuria to better understand the in vivo contribution of homocysteine to early atherogenesis. METHODS AND RESULTS: We investigated ultrasonographically the right common carotid artery in 14 subjects with homozygous homocystinuria aged 3 to 34 years (mean, 13 years) and in 15 of their heterozygous parents aged 32 to 47 years (mean, 41 years) by comparison with 2 control groups of 15 healthy subjects of the same age. Far-wall IMT and lumen diameter were measured with a computerized program, and the cross-sectional area of the intima-media complex (CSA-IMC) was calculated from IMT and diameter. Comparison with their respective controls, adjusted for body surface area or height, showed that homozygotes had greater IMT (P<0.001) and CSA-IMC (P<0.05) and smaller diameter (P<0.05), whereas heterozygotes had values similar to their controls. Multivariate analysis of the arterial parameters with age, body surface area (or height), and plasma total homocysteine in the homozygous and heterozygous groups combined showed that IMT was related to age (P<0.05) and homocysteine (P<0.01), diameter was related to body surface area (P<0.001) or height (P<0.05), and CSA-IMC was related to age (P<0.05), body surface area (P<0.05) (but not height), and homocysteine (P<0.05). CONCLUSIONS: Homozygous homocystinuria was associated with common carotid wall hypertrophy, whereas heterozygous disease was not. Such hypertrophy may reflect a smooth muscle proliferation induced by hyperhomocysteinemia and represent a promising target for testing vascular effects of therapeutic measures to lower homocysteine.
Abstract: BACKGROUND AND AIMS: One-third of acromegalic patients have hypertension. Acromegaly is also associated with intrinsic cardiac abnormalities known collectively as a hyperkinetic heart syndrome, which is characterized by an increased cardiac index and decreased systemic vascular resistance. As a result, blood flow should be increased in the regional vascular beds of acromegalic patients. The aim of the study was to measure, using direct methods, blood flow and vascular resistance at the level of the brachial artery in acromegalic patients with a confirmed hyperkinetic heart syndrome. PATIENTS AND CONTROLS: Twelve patients with active acromegaly (five females, seven males; mean (+/- SD) age, 43 +/- 10 years) were studied. Twelve age- and sex-matched normal subjects served as controls. METHODS: Right heart catheterization was used to measure the cardiac index and stroke volume and to calculate systemic vascular resistance in the acromegalic patients. Brachial haemodynamics were evaluated with a two-dimensional pulsed Doppler system (double transducer probe and range-gated time system of reception). The mean diameter of the brachial artery and mean blood velocity were measured and used to calculate mean blood flow. Vascular resistance was calculated in the brachial artery as the mean arterial pressure/blood flow ratio. RESULTS: Age, body weight, height, body surface area and heart rate were similar in the acromegalic patients and controls, while mean arterial pressure was higher in patients. The cardiac index and stroke volume were increased in the acromegalic patients, at 4.08 +/- 0.47 (mean +/- SD) l/min/m2 body surface area and 116.7 +/- 19.4 ml, respectively, while systemic vascular resistance was low (12.5 +/- 2.1 U). Brachial artery diameter was similar in the patients and controls. Brachial artery mean blood velocity (P < 0.01) and mean blood flow (P < 0.05) were lower in the patients than in the controls (3.35 +/- 1.26 vs. 5.12 +/- 1.74 cm/s, and 16.4 +/- 9.4 vs. 25.6 +/- 11.6 ml/min/m2, respectively). The higher mean arterial pressure and lower mean blood flow resulted in higher forearm vascular resistance in the patients than in the controls (132 +/- 61 vs. 83.8 +/- 47 mmHg/ml/s/m2, respectively, P < 0.01). CONCLUSION: While cardiac output is increased and systemic vascular resistance is decreased in active acromegaly, direct measurement of brachial artery haemodynamics showed lower regional blood flow and increased local resistance relative to healthy controls. These results suggest a heterogeneous distribution of cardiac output in acromegaly.
Abstract: The objective of this study was to test the value of electrocardiogram for predicting left ventricular mass (LVM), assessed echographically in 136 asymptomatic men with at least one major cardiovascular risk factor. We measured the Sokolow-Lyon and Cornell voltages, as well as the ratio of Cornell voltage to QRS voltage in lead II. The prevalence of left ventricular hypertrophy (LVH), defined as LVM of > or = 125 g/m2, was 6%, whereas that of increased LVM, defined as LVM of > or = 99 g/m2, the 90th upper percentile of a control group, was 29%. Receiver operating characteristics curves showed that for predicting LVH at 80% specificity, the Cornell/QRS(II) voltage ratio had a sensitivity of 75%, whereas those of the Cornell and Sokolow-Lyon voltages were 50% and 12.5%, respectively. For predicting increased LVM at 80% specificity, the Cornell/QRS(II) voltage ratio had a sensitivity of 56%, whereas the sensitivities of the Cornell and Sokolow-Lyon voltages were 36% and 22%, respectively. We conclude that, in constrast with the Sokolow-Lyon voltage, the new dimensionless Cornell/QRS(II) voltage shows a sensitivity at a high specificity value at least as acceptable as that of the Cornell voltage for predicting borderline-high LVM in a population with a low prevalence of LVH.
Abstract: BACKGROUND: Carotid artery structure change was associated with coronary artery stenosis by angiography of subjects who were for the most part symptomatic. OBJECTIVE: To determine whether structural changes at multiple extracoronary sites were associated with noninvasively detected coronary calcium for 94 asymptomatic high-risk men. METHODS AND RESULTS: B-mode ultrasonography allowed us to detect plaque at three sites (carotid, femoral, and abdominal aorta) and to measure intima-medial thickness both in common carotid and in femoral arteries. Ultrafast computed tomography determined the presence and amount of coronary calcification. After adjustment for age, plaques at two or three sites were associated with extensive amounts of coronary calcium [odds ratio 4.94 (95% confidence interval 1.08-23)], but not with the presence of coronary calcium; increase in carotid intima-medial thickness was not associated with presence and extent of coronary calcium; and increase in femoral intima-medial thickness was associated with presence of coronary calcium [odds ratio 1.44 (95% confidence interval 1.03-2)] and extensive coronary calcium [odds ratio 1.50 (95% confidence interval 0.97-2.33)]. Adjustment for cardiovascular risk factors attenuated these associations. CONCLUSIONS: Femoral intima-medial thickness predicted presence of coronary calcium whereas femoral intima-medial thickness and overall multiple plaques predicted extensive coronary calcium. Because coronary calcium is a marker of atherosclerosis and a predictor of coronary events, B-mode ultrasonography could be of clinical value for stratifying coronary risk.
Abstract: An imbalance between antioxidant and oxidant-generating systems leading to an oxidative stress has already been proposed in the pathogenesis of atherosclerosis. In the present study we investigated the antioxidant status in 60 asymptomatic hypercholesterolemic (HC) men compared with 48 normocholesterolemic (NC) men. Hypercholesterolemic subjects had a significantly lower red blood cell vitamin E (vit E-RBC) content in spite of their normal total plasma and HDL vitamin E concentrations. Activities of erythrocyte superoxide dismutase and glutathione peroxidase were not significantly different between groups. We also determined the resistance of RBCs to an oxidative stress by determining the extent of hemolysis induced by a water-soluble azo-compound. This resistance was significantly decreased in HC men compared with NC subjects. These results demonstrate an altered antioxidant status of RBC in asymptomatic HC men associated with an increased erythrocyte susceptibility to an oxidative stress. The measure of the vitamin E content in RBC might be the most sensitive parameter for evidencing early oxidative stress which does not need an adaptation of enzymatic protective systems.
Abstract: Stiffness of aortic walls has been shown to be a marker of coronary and cerebrovascular diseases in patients with myocardial infarction or stroke. However, its value for predicting preclinical atherosclerosis has not been demonstrated. Therefore, this study tested the association of aortic wall stiffness and coronary and extracoronary atherosclerosis in the absence of clinical cardiovascular disease. In 190 asymptomatic men at cardiovascular risk, carotid-to-femoral pulse wave velocity (PWV) was measured mechanographically and the compliance of the aorta (C), as well as the intrinsic compliance (Ci), was deduced after correction for the effect of blood pressure. Also determined noninvasively were 1) the degree of coronary calcium deposit coded as grade 0, 1, 2, or 3 using ultrafast computed tomography; 2) the extent of extracoronary plaque detected by B-mode echography at three different sites (carotid, abdominal aorta, and femoral) coded as 0, 1, 2, or 3 diseased sites; and 3) the estimated Framingham coronary risk. The grade of coronary calcium was not associated with any aortic elastic parameter. The number of extracoronary diseased sites was not associated with PWV and C but correlated negatively with Ci before but not after age adjustment. The coronary risk correlated positively with PWV and negatively with C before but not after age adjustment and was not associated with Ci. In symptom-free subjects aortic stiffening does not predict the presence of coronary and extracoronary atheroma and therefore cannot be considered as a useful surrogate marker of early atherosclerosis.
Abstract: Previous reports have investigated associations between carotid intima-media thickness (IMT) and cardiovascular risk factors. Our objective was to investigate this question in greater depth by measuring both femoral and carotid IMT in relation to sex and multifactorial coronary risk. We investigated carotid and femoral artery IMT by using ultrasonography in 326 men and 462 women, 17 to 65 years old. We also evaluated body mass index, blood pressure, blood lipids, glucose, smoking, and Framingham coronary risk. In both vessels, IMT was lower in women than in men. Significant relations between carotid and femoral IMT existed with age and most risk factors in both sexes. After adjustment for age, carotid IMT was related to risk factors in both sexes except for diastolic blood pressure, HDL cholesterol, and smoking in women, whereas femoral IMT was related to triglycerides and smoking in both sexes, systolic blood pressure and blood glucose in men, and total and HDL cholesterol in women. Significant unadjusted and age-adjusted relations of Framingham risk existed with carotid and femoral IMT in both sexes, but slopes of these relations were greater (1) before than after age adjustment, (2) in men than in women at both sites, except the femoral artery after age adjustment, and (3) at the carotid than at the femoral site in both sexes before age adjustment. Carotid IMT in men appears to be a more powerful predictor than it is in women and femoral IMT in both sexes in reflecting multifactorial coronary risk burden, but these differences are partly conditional on age.
Abstract: The present study was designed to assess plasma and erythrocyte vitamin E concentrations in 57 asymptomatic hypercholesterolemic (HC) men compared with 56 normocholesterolemic (NC) men. Vitamin E concentrations were determined by using a reversed-phase HPLC method. Compared with NC subjects, HC men had a significantly lower red blood cell (RBC) vitamin E content in spite of their normal plasma vitamin E concentration. This study demonstrates that total plasma vitamin E concentration is not a suitable predictor of cell vitamin E status and suggests an abnormal transfer of tocopherol between plasma and RBCs in HC men. Moreover, the RBCs of HC men were more susceptible to a peroxidative stress. The strong correlation between RBC susceptibility to oxidation and RBC vitamin E content suggests that the low RBC vitamin E content found in HC men has physiological consequences on the RBC oxidation.
Abstract: The influence of the renin-angiotensin system (RAS) on the aortic wall mechanical properties under angiotensin I converting enzyme inhibition (enalaprilat, 0.3 mg/kg iv) or angiotensin II receptor (AT1) blockade (E-3174, 1 mg/kg iv) was examined in eight normotensive and eight renovascular hypertensive conscious dogs. Aortic diameter (D; sonomicrometry)-pressure (P; microtransducer) hysteresis loops during steady state and during rapid distal aortic occlusion allowed (after hysteresis elimination) calculation of the aortic wall viscosity index, the purely elastic P-D relationship, and derivation into compliance-pressure curves. At the early stage ofrenovascular hypertension when activation of RAS is more pronounced, aortic wall stiffness and wall viscosity were increased as compared with normotensive states. Blood pressure remained unchanged in normotensive animals and was reduced during hypertension after antihypertensive treatments. In hypertensive animals, enalaprilat and E-3174 decreased viscosity index and shifted the compliance-pressure curve upward with respect to pretreatment conditions. In normotensive dogs, whereas E-3174 did not change the compliance-pressure curve and viscosity index, enalaprilat increased compliance and reduced viscosity index. We concluded that in normotensive dogs converting enzyme inhibition modifies arterial viscoelastic parameters by angiotensin-independent mechanisms that contribute to the modulation of the buffering function of large arteries.
Abstract: BACKGROUND: Evidence-based treatment of hypercholesterolemia currently recommended for rationalizing drug prescription requires justification of treatment by randomized trials, such as the West of Scotland Coronary Prevention Study (WOSCOPS) or the Scandinavian Simvastatin Survival Study (4S), and evaluation of its benefit from the estimation of the coronary risk of each patient. METHODS AND RESULTS: The latest European guidelines and Sheffield tables apply these principles and justify the decision to treat hypercholesterolemia if the Framingham coronary multivariate risk estimate is high enough, ie, >20% risk of coronary event at 10 years in the former and >1.5% risk of coronary death per year in the latter. Nevertheless, the practice of these two recent guidelines results in discrepancies in the decision to treat, because coronary morbidity was considered in one but mortality was considered in the other, and the risk required for treating may be extrapolated from different trials (4S or WOSCOPS). CONCLUSIONS: Although the principle of targeting lipid-lowering treatment to high-risk subjects is unquestioned, further studies are needed to demonstrate that the Framingham risk profile is useful in selecting persons who are likely to benefit and to determine the place of newer risk factors and that of early noninvasive detection of atheroma in the risk estimation-based treatment.
Abstract: To determine whether or not the lower rate of coronary disease in France, in comparison with Sweden, might be explained by different cardiovascular risk profiles, a cross-sectional analysis (first step of a longitudinal study) of comparable samples of automotive workers was carried out in corporate occupational health clinics of Renault and Volvo. Traditional cardiovascular risk factors were evaluated and the Framingham coronary risk was estimated for 1000 randomly selected 45-50 years old Caucasian males from each company. Compared with the Frenchmen, the Swedish men consisted of more white collar workers and were slightly older. After adjustment for age and blue/white collar status, the Swedish men showed lower body mass indexes, waist to hip rations and heart rates, lower frequency of treatment of hypercholesterolemia and diabetes than the Frenchmen. The Swedish males also exhibited higher averages of blood cholesterol, low density lipoprotein (LDL) cholesterol and glucose, but lower frequencies of hypercholestrolemia and diabetes, and a higher frequency of family histories of cardiovascular disease. Blood pressure, hypertension prevalence, triglycerides level, and high density lipoprotein (HDL) did not differ between the groups. The average number of traditional risk factors was 1.1/person for the Frenchmen and 0.8/person for the Swedes. However, the coronary risk as estimated using the Framingham index was not different between the groups. This, together with the more frequent family history of cardiovascular disease in Swedish men, suggests a lower susceptibility to risk factors as a possible explanation for the lower cardiovascular disease prevalence reported in France, and/or the possibility that factors not measured were involved.
Abstract: Because of the limited ability of blood pressure elevation to predict risk, the mass drug treatment of hypertension above an arbitrary threshold may result in many subjects being overtreated. One potential way to overcome this problem is to noninvasively detect preclinical atherosclerosis. Hypertension has been shown to be associated with 1) increased intima-media thickness and more frequent plaques in extracoronary arteries, 2) more frequent calcifications in coronary arteries, 3) increased wall rigidity in the aorta and peripheral arteries, and 4) impaired endothelium dependent vasodilation and abnormal blood rheology, which are capable of promoting the conversion of atherosclerosis into atherothrombosis. The prognostic significance of these markers of preclinical atherosclerosis is supported by evidence of their association with numerous risk factors, and prevalence and incidence of cardiovascular damages. Preclinical arterial lesions also constitute ideal targets to test whether antihypertensive treatment can reverse or slow down arterial disease, and whether such a reversal produces better prevention than simply lowering blood pressure. Finally, the detection of atherosclerosis applied to large populations of mildly hypertensive subjects safely and at relatively low cost could help to better target the pharmacological treatment, given that a substantial proportion of subjects without evidence of preclinical disease may be suitable for nondrug treatment.
Abstract: Ultrasonography of the arterial wall allows detection of structural (thickening, plaque) and/or functional (rigidity, reactivity) changes associated with preclinical atherosclerosis. Thickening of the arterial wall may be observed by measuring the intima-media thickness of the posterior wall of the common carotid or superficial femoral arteries. Hypertension, hypercholesterolaemia, diabetes and cigarette smoking induce carotid (and femoral) intima-medial thickening, the atherogenic nature of which however has not been clearly demonstrated. An atheromatous plaque results in a localised echogenic thickening which intrudes into the lumen and which may be assessed qualitatively by its presence or absence in peripheral arteries at risk of atherosclerosis (carotids, abdominal aorta, femorals). The number of these peripheral sites involved increases in parallel with the number of traditional risk factors in a given individual. The elasticity of the arterial walls may be evaluated at carotid or femoral levels by measuring systolo-diastolic distension by a technique known as "echotracking". The increased rigidity of the arterial wall observed in hypertension or diabetes is a marker of the sclerotic component of atherosclerosis. Arterial reactivity, dependent on changes in blood flow, is assessed by pulsed Doppler at the humeral and femoral arteries by changes in diameter induced by ischaemia/hyperameia. Changes in arterial reactivity are observed in hypercholesterolaemia even in the absence of atherosclerosis. Structural and functional changes detected by arterial ultrasonography and associated with atherosclerosis have a prognostic value which may contribute to a more accurate assessment of global vascular risk and may be useful in evaluating the efficacy of antihypertensive or lipid lowering therapy.
Abstract: The association between plasma fibrinogen and the presence of carotid, femoral, and aortic plaque (high-resolution B-mode ultrasonography) and coronary calcium deposit (ultrafast computed tomography scanner) was determined in 693 hypercholesterolemic, never-treated men free of previous or current clinical symptoms of cardiovascular disease. The number of subjects with extracoronary disease sites and coronary calcification deposits was significantly higher in the upper than in the lower tertile of fibrinogen. Plasma fibrinogen increased according to the number of diseased sites. The odds ratio of the upper to lower fibrinogen tertile for the presence of arterial lesions was 2.6 (1.7 to 4) for carotid, 2.2 (1.5 to 3.2) for aorta, 2.2 (1.5 to 3.1) for femoral, 1.8 (1.3 to 2.6) for coronary, and 3.6 (2.3 to 6.1) for one of four diseased sites. Adjustment for age, total cholesterol, HDL cholesterol, triglycerides, current smoking, and systolic pressure slightly reduced the association between fibrinogen and atherosclerosis. A synergistic effect between fibrinogen and total cholesterol/ HDL cholesterol (TC/HDL) ratio seemed to be operating on atherosclerosis, because nearly all of the individuals (98%) had a diseased site when fibrinogen and TC/HDL tertiles were the highest. This result suggests that fibrinogen is involved in the subclinical phase of extracoronary and coronary atherosclerosis and may potentiate the atherogenic effect of hyperlipidemia.
Abstract: The detection of early atherosclerosis, accelerated by the presence of diabetes mellitus, is of major importance for improving the prediction and the prevention of subsequent clinical events. Three markers of atherosclerosis can be detected non invasively: arterial wall thickening, coronary calcification and arterial wall stiffening. Intima-media thickness can be measured by B-mode ultrasonography in common carotid and femoral arteries. Increased intima-media thickness has been found to be associated with both insulin-dependent and non insulin-dependent diabetes. Such thickening might be partly of atherogenic nature but may also be due to a non-atherogenic process such as medial hypertrophy possibly related to insulin effects. Coronary calcification, an anatomic marker of coronary atheroma, is detected radiographically by fluoroscopy or ultrafast computed tomography. Cross-sectional studies of asymptomatic high-risk populations have found independent associations between diabetes and the presence and amount of coronary calcium deposit. The mechanisms by which diabetes promotes coronary calcium deposit are unknown, but mineralization proteins, such as osteopontin and its genetic expression, might be implicated in the calcinosis process. Arterial wall stiffening, a marker of sclerosis, detected by pulse wave velocity measurement or by determination of arterial wall motion using an echotracking device, has been found to be associated with diabetes in several case-control and transverse studies. The mechanisms of such association may involve the effect of glycoregulation of bioelastomers in the arterial wall. The detection of early atherosclerosis in diabetic patients may be clinically relevant by helping to improve the prediction of vascular risk, the justification to treat, and the evaluation of the efficacy of antidiabetic treatment on the vessels.
Abstract: 1. We tested whether lipid lowering treatment with HMG CoA reductase inhibitor modified the flow mediated large artery reactivity in primary pure hypercholesterolaemia. 2. Abnormalities in arterial reactivity have been described in the presence of high blood cholesterol, in particular an enhanced constriction of the brachial artery in response to acute induction of a low flow state. 3. Using pulsed-Doppler, we measured brachial artery diameter and flow velocity at rest and their changes induced by wrist occlusion before and after 3 months of double-blind treatment by pravastatin (40 mg orally) in 13 subjects and placebo in 15 others. 4. The significant decrease (P < 0.01) in diameter induced by wrist occlusion before (0.34 +/- 0.08 mm) placebo and pravastatin (0.39 +/- 0.10 mm) persisted after placebo (0.26 +/- 0.07 mm) but was abolished after pravastatin (0.07 +/- 0.05 mm). The absolute change in diameter induced by wrist occlusion was lower after than before pravastatin (P < 0.01) and lower after pravastin than after placebo (P < 0.05). Diameter during the wrist occlusion was higher after pravastatin than after placebo (4.35 +/- 0.16 vs 3.89 +/- 0.09 mm); P < 0.01). 5. These findings indicate that the lipid changes induced by pravastatin and/or some unknown but direct mechanism of the drug itself inhibit low-flow-mediated vasoconstriction associated with hypercholesterolaemia. Such effects may have important implications for the treatment of vasospasm often seen in the presence of high blood cholesterol.
Abstract: To determine whether a relationship between echographically assessed carotid artery and left ventricular (LV) structures existed in asymptomatic men at risk for cardiovascular disease, we evaluated carotid and LV parameters in 69 subjects (23-62 years) without LV hypertrophy. The right common carotid far wall intima-media thickness (IMT) was measured using an automated technique and the cross-sectional intima-media complex area (IMC-CSA) was calculated, assuming a circular profile of carotid wall layers, as (IMC-CSA = pi x IMT x (IMT + D)), D being the lumen diameter. LV mass was evaluated using the M-mode echocardiography. Among study subjects 30% were hypertensive, 67% hypercholesterolemic, 21% current smokers and 52% had a positive smoking history. In the study population LV mass correlated both with IMT (r = 0.54, P < 0.001) and IMC-CSA (r = 0.62, P < 0.001). In multivariate analysis LV mass was associated with IMC-CSA (P < 0.001), body mass index (P < 0.01), lifelong smoking dose (P < 0.01) and systolic blood pressure (P < 0.05), r2 = 0.58, P < 0.001. Therefore, IMC-CSA may be a clinically relevant independent indicator of LV mass even within its normal ranges.
Abstract: The respective role of adhesive forces induced by fibrinogen and repulsive forces induced by erythrocyte sialic acid content on erythrocyte aggregation, was investigated in hypercholesterolemic and control subjects. Aggregation index (AI) and disaggregation shear rate threshold (gamma t) were determined in the presence of either autologous plasma or dextran. Compared with controls, fibrinogen (p < 0.001) and aggregation parameters (AI p < 0.01; gamma t p < 0.01) were higher in hypercholesterolemics while erythrocyte sialic acid content (p < 0.001) was lower; in addition total serum sialic acid was increased (p < 0.01). The aggregation properties of erythrocytes, independent of plasma environment using dextran as a bridging macromolecule, showed an enhanced disaggregation shear rate threshold and an inverse relationship with erythrocyte sialic acid content. We conclude that decreased erythrocyte sialic acid content may intensify the effect of fibrinogen on aggregation and disaggregation of erythrocytes and participate in the development of atherothrombotic complications.
Abstract: Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations and possibly reduced cell deformability. Since decreased erythrocyte deformability is known to disturb blood flow in capillaries and may promote ischaemic diseases, this study was designed to investigate erythrocyte deformability using a new filtration system, the Cell Transit Analyser (CTA), and to examine lipid compounds in the blood of 23 patients affected with GSD, aged from 1 to 20 years and 18 controls aged from 1 to 17 years. The patients showed a mixed hyperlipidaemia with predominant hypertriglyceridaemia and an increase in erythrocytes mean transit times (TT) due to the presence of more rigid erythrocytes subpopulations when compared to controls. Thus the erythrocyte rigidity, in addition to the lipid abnormalities must be taken into account for long-term evolution of GSD patients. Moreover this cellular alteration may contribute to shortened erythrocyte survival.
Abstract: Despite its important role in coronary disease, coronary atherosclerosis has been poorly investigated in uncomplicated hypertension. Therefore, we evaluated the presence and amount (score) of coronary calcium with ultrafast computed tomography in 73 pairs of age-matched asymptomatic hypertensive or normotensive men. We also estimated the extent of peripheral atherosclerosis as the number of arterial sites (carotid, aortic, femoral) with echographic plaque. Compared with normotensive men, hypertensive men had more frequent coronary calcium (63% versus 47%), a higher calcium score (57 +/- 111 versus 18 +/- 38), and an odds ratio of calcium deposit of 1.95 (with confidence intervals [CI] 95%, 1.01 to 3.79) for any score and of 2.38 (95% CI, 1.02 to 5.52) or 4.84 (95% CI, 1.53 to 15.3) for scores above 50 or 100, respectively. Hypertensive men showed correlations of calcium score with age and hypertension duration but not with the height of blood pressure, and the odds ratio of calcium deposit between extensive and minor peripheral atherosclerosis was 4.67 (95% CI, 1.41 to 15.45) for any score and 8.63 (95% CI, 2.10 to 35.5) or 8.13 (95% CI, 1.64 to 40.3) for scores above 50 or 100. Thus, high blood pressure and in particular its duration rather than its value promotes the presence and overall extent of coronary calcium, a potential predictor of sudden coronary death, in parallel with the extent of peripheral atherosclerosis. The mechanisms of the interaction of hypertension and coronary calcification may be multifactorial and not specific to hypertension.
Abstract: OBJECTIVES: Hyperlipidemia is a feature of liver glycogen storage disease (GSD). Recent studies have suggested that rheological mechanisms such as elevated erythrocyte aggregation may be involved in the pathogenesis of ischemic syndromes associated with hyperlipidemia. DESIGN AND METHODS: We investigated erythrocyte aggregation, lipids, and circulatory proteins in the blood of 24 patients affected with GSD, aged from 1 to 23 years (mean = 8) and 26 controls aged from 1 to 28 years (mean = 9). RESULTS: The aggregation results were much higher in patients than controls. The lipid data showed a mixed hyperlipidemia with predominant hypertriglyceridemia, low HDL-C, apoA-I and LpA-I/A-II, and high apoB as compared with controls. However, the LpA-I was not significantly different from controls. CONCLUSIONS: In conclusion, patients with GSD presented hyperlipidemia and elevated erythrocyte aggregation such that they are at long-term risk of ischemic complications.
Abstract: Extracoronary in vivo structural arterial changes were studied in asymptomatic essential hypertension. Carotid and femoral arteries were examined with B-mode echography for the presence or absence of plaque (the whole vascular segments of each vessel in the both sides) and for automated measurement of the far wall intima-media thickness (the vascular segment of each vessel proximal to the bifurcation in the right side) in 53 never treated hypertensive men and 133 normotensive men similar with regard to age, serum cholesterol levels, and smoking history. In the hypertensive group carotid plaque was more frequent (P < .05) and carotid and femoral intima-media thicknesses were greater (P < .001) than in the normotensive group. In the overall normotensive and hypertensive population intima-media thickness was independently associated with age and systolic pressure in both arteries (P < .001) and with cholesterol in the femoral artery (P < .05) while plaque was associated with systolic pressure (P < .01), and cholesterol (P < .01) in the carotid arteries and with age (P < .01), cholesterol (P < .05), and smoking (P < .001) in the femoral arteries. No significant difference in intima-media thickness in both arteries existed between hypertensive subjects with plaque and those without. Wall thickening and plaque were more frequent in hypertensive patients. Thickening was distributed homogeneously to both arteries, while plaque affected preferentially the femoral bed. The influence of age and pressure was more marked on intima-media thickness than on plaque. The lack of association between wall thickening and plaque suggested that vascular hypertrophy and early atherosis might be two different structural changes.
Abstract: To evaluate changes in distal cutaneous arteries during hypertension, we used a noninvasive method to assess the compliance and vascular resistance of the hand radial arteries, mainly distributed to the skin, in 10 normotensive and 10 hypertensive (HT) men. Radial artery diameter and blood velocity were measured by means of pulsed Doppler concomitantly with measurements of finger arterial pressure by photoplethysmography. Hand radial vascular resistance was calculated as the ratio of mean arterial pressure to mean radial blood flow. A simple resistive-capacitive model of large and small arteries of the hand allowed us to evaluate arterial compliance from the exponential slope of finger diastolic pressure decay and vascular resistance. Measurements were made at baseline and during reactive hyperemia after 5 min of complete occlusion of the brachial artery with a pneumatic cuff. Except for pressure, there were no baseline differences between the groups. In normotensive and HT subjects, hyperemia increased radial artery diameter and blood velocity (P < 0.001) and compliance (P < 0.01 and P < 0.05, respectively) and decreased mean pressure (P < 0.01 and P < 0.001, respectively) and resistance (P < 0.001). During hyperemia, the only difference between the groups, except for pressure, was lower compliance in HT subjects (P < 0.01). Moreover, compliance during hyperemia negatively correlated with baseline mean pressure (P = 0.001). Thus hyperemia unmasked reduced compliance in the HT patients but did not show abnormal resistance, suggesting that the elastic properties of the hand skin radial arteries might be more sensitive than their resistive properties to high blood pressure.
Abstract: We compared the properties of common carotid and femoral arteries of 16 normotensive and 14 hypertensive men. Arterial pressure and diameter were recorded noninvasively in each vessel by tonometric and echotracking devices. The x-y composition of pressure and diameter waves provided the diameter-pressure hysteresis loop. The elastic diameter-pressure curve and wall viscosity index were deduced after hysteresis elimination. The compliance-pressure and distensibility-pressure curves were derived from the diameter-pressure curve, allowing the calculation of effective compliance and distensibility at the prevailing pressure of each subject and isobaric compliance and distensibility at the same standard pressure in all subjects. Systolic, diastolic, mean, and pulse pressures and diameters in each vessel were higher in the hypertensive than the normotensive group, except carotid pulse diameter, which did not differ. The carotid diameter-pressure, compliance-pressure, and distensibility-pressure curves did not differ between groups. In the carotid artery hypertensive patients had isobaric compliance and distensibility values similar to those of normotensive subjects, despite lower effective compliance (P < .05) and distensibility (P < .01). The femoral diameter-pressure curve was higher (P < .05) and the femoral compliance-pressure and distensibility-pressure curves were lower (P < .01) in the hypertensive than the normotensive group. Hypertensive patients had effective and isobaric femoral compliance and distensibility values lower than to those of normotensive subjects (P < .001). In both arteries, viscosity index was higher in the hypertensive than the normotensive group (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: This study was designed to evaluate the relationships between platelet cytosolic Ca2+ concentration ([Ca2+]i) and plasma lipids in patients with primary hypercholesterolemia. In a double-blind, placebo-controlled trial, we determined platelet [Ca2+]i in the presence and virtual absence of extracellular Ca2+ and the effects of prolonged treatment with pravastatin, a selective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase. Platelet [Ca2+]i and membrane microviscosity were determined in 22 normotensive hypercholesterolemic men. Platelet [Ca2+]i was observed to vary with in vivo plasma lipid characteristics: in untreated patients, [Ca2+]i determined at low extracellular Ca2+ concentration was significantly associated with plasma triacylglycerols (P = .008) and with the total cholesterol to HDL cholesterol ratio (P = .044). Triacylglycerol levels also correlated inversely with the external Ca(2+)-dependent [Ca2+]i rise. Pravastatin treatment reduced plasma total cholesterol (-20 +/- 3%), LDL cholesterol (-30 +/- 3%), triacylglycerols (-17 +/- 6%), and apoB levels (-25 +/- 4%) and simultaneously decreased platelet [Ca2+]i measured in a low-Ca2+ medium by 14 +/- 6% (P = .03). However, [Ca2+]i values remained positively correlated with the total cholesterol to HDL cholesterol ratio (P = .04). Prvastatin treatment did not induce marked changes in membrane microviscosity, although the changes in trimethylaminodiphenylhexatriene anisotropy were inversely correlated with those of HDL cholesterol. These results indicate that plasma lipids can modulate cytosolic Ca2+ in platelets by affecting Ca2+ transport pathways that are dependent and independent of Ca2+ influx.
Abstract: 1. The objectives of this study were to study the flow-dependent arterial reactivity and pressure-independent arterial compliance of the calcium antagonist amlodipine in hypertensive men. 2. Twenty-one hypertensive patients were randomized to receive 2 months treatment with placebo (n = 10) or 5-10 mg amlodipine (n = 11) once a day. Non-invasive measurement of brachial artery mean blood pressure, diameter and flow (pulsed Doppler) and compliance (arterial mechanography and logarithmic elastic model) were obtained before and after drug administration. Vasoreactivity was studied by means of response of the brachial artery during exclusion of the hand and hyperaemia post-ischaemia. 3. Compared with placebo, amlodipine reduced mean blood pressure (% change +/- s.e. mean 11 +/- 1% vs 4 +/- 3%, P < 0.05), and increased arterial compliance at prevailing pressure (44 +/- 13%, vs 1 +/- 8%, P < 0.05) and at isobaric pressure (26 +/- 10% vs -3 +/- 6%, P < 0.05). A significant % change increase from baseline in brachial artery diameter between placebo and amlodipine was observed at rest (-2 +/- 3 vs 8 +/- 3%; P < 0.05), after wrist occlusion (-3 +/- 3 vs 6 +/- 2%; P < 0.05) and during reactive hyperaemia (-5 +/- 3 vs 18 +/- 5%; P < 0.05). No significant differences between amlodipine and placebo groups were observed in blood velocity after forearm manoeuvres before and after treatment. 4. No differences were observed between groups in brachial flow-dependent vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Elevated concentration of plasma homocyst(e)ine is an independent risk factor for clinical atherosclerosis. In this study, the concentration of plasma homocyst(e)ine in men who lacked a history of atherosclerotic disease was correlated with hemodynamic, rheological and biochemical parameters. Hypertensive subjects had higher concentrations of plasma homocyst(e)ine than normotensive subjects. Positive correlations were found between concentrations of plasma homocyst(e)ine and several risk factors, but some of these correlations disappeared when they were adjusted for other variables. However, multivariate analyses demonstrated that systolic blood pressure, plasma uric acid, and hematocrit were predictors of concentrations of plasma homocyst(e)ine, after adjusting for certain risk factors. The possible significance of these interrelationships in atherogenesis require further study.
Abstract: Many techniques were proposed to assess erythrocyte aggregation in clinical and experimental investigations in view of in vitro determination. However no methodology until now is available to measure erythrocyte aggregation in flowing blood in vivo. High resolution ultrasonography provides an original way to quantify erythrocyte aggregation using the echogenicity of blood. We have developed and A-mode ultrasound scanner coupled with an oscilloscope and a computer allowing the analysis of ultrasonic signals produced by erythrocytes. A closed measurement chamber connected to a calibrated roller-type blood pump where blood was perfused was used. The echogenicity of blood was determined at different shear rates. Dextran, fibrinogen and other high molecular weight substances were added to increase erythrocyte aggregation. Changes in red blood concentration was also tested. An increase in blood echogenicity rate was observed at low shear. At a given shear rate blood echogenicity increased when fibrinogen or dextran were added. Such determination of the echogenicity of flowing blood in vitro will provide an approach to the quantification of erythrocyte aggregation in vivo circulation, especially in the veins where low shear rates are observed.
Abstract: Fibrinogen may play an active role in the development and progression of atherosclerotic plaques. We assessed the association between fibrinogen levels and atherosclerotic plaques over three different arterial sites in an asymptomatic never-treated male population with increased cardiovascular risk. We included 652 men aged 40 to 60 years old with at least one of the following cardiovascular risk factors: cholesterol > 6.2 mmol/L and/or systolic blood pressure > or = 160 mm Hg and/or diastolic blood pressure > or = 95 mm Hg, and/or because they smoked. Carotid and femoral arteries and the abdominal aorta were assessed by using ultrasonographic methods for the presence of plaque, and subjects were categorized according to the presence (or absence) and extent (one versus two or three sites) of plaque. Plasma fibrinogen was measured according to the thrombin-time method of Clauss. While the presence of atherosclerosis was significantly related to age, current smoking, systolic pressure, LDL cholesterol, and fibrinogen levels, the extent of atherosclerosis was related to age and triglyceride and fibrinogen levels. Multiple regression analysis indicated independent associations between fibrinogen and the presence and extent of atherosclerosis. Plaque prevalence was significantly more pronounced with increasing tertile of fibrinogen levels. The odds ratio of the upper to lower fibrinogen tertiles for the presence of plaque was 1.6 (95% confidence interval, 1.4 to 1.8) and 1.4 (95% confidence interval, 1.2 to 1.7) for its extent. Adjustment for other risk factors slightly reduced the association between fibrinogen and atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: OBJECTIVE: To study the relationship between high blood pressure and hyperlipidaemia and the cytosolic calcium concentration in unstimulated platelets, focusing on the effects of an alteration in membrane dynamics. MATERIALS AND METHODS: Basal cytosolic calcium concentrations were determined in the presence and the absence of a significant calcium influx in platelets of 47 untreated hypertensive patients and 26 normotensive subjects. Membrane microviscosity was investigated by fluorescence depolarization of diphenylhexatriene and trimethylaminodiphenylhexatriene. To study the influence of plasma factors, unstimulated platelets were loaded in the presence of plasma with Quin-2, which forms a relatively strong intracellular calcium buffer. The cytosolic calcium concentration was then determined at two extracellular calcium concentrations (1 mmol/l and in the absence of a Ca2+ influx). RESULTS: Irrespective of the external calcium concentration, the cytosolic calcium concentration increased significantly with diastolic blood pressure (P = 0.026 in the presence and P = 0.003 in the absence of Ca2+ influx) and with plasma triacylglycerols (P = 0.03 and 0.001, respectively). Multiple regression analysis indicated that the cytosolic Ca+ concentration was independently related to these two factors [Ca2+ = 35 + (18.6 +/- 4.6). In triacylglycerols (mmol/l) + (0.45 +/- 0.15) mmHg diastolic blood pressure; P < 0.001]. The relationship between the cytosolic calcium concentration and diphenylhexatriene or trimethylaminodiphenylhexatriene anisotropies was not independent of blood pressure and plasma triacylglycerol levels. CONCLUSIONS: The present results confirm the link between blood pressure and the platelet cytosolic calcium concentration and indicate that plasma triacylglycerols directly or indirectly modulate the ex vivo efficacy of platelet calcium storage and/or extrusion mechanisms. They could facilitate cell stimulation.
Abstract: Hypertension is a major risk factor for cardiovascular disease and atherosclerosis is the cause of most hypertensive complications. Therefore the detection of preclinical atherosclerosis may contribute to the better identification of hypertensive subjects at high risk of complications. Three main alterations are currently able to be diagnosed noninvasively: calcification, thickening, and stiffening of the arterial walls. Calcification of epicardial coronary arteries can be seen noninvasively by ultrafast computed tomography thanks to its rapid acquisition of image. Coronary calcification of epicardial coronary arteries can be seen noninvasively by ultrafast computed tomography thanks to its rapid acquisition of image. Coronary calcification is typical of atherosclerosis but not of stenosis. Conversely, the absence of calcification eliminates, practically, coronary artery disease as a diagnosis. Coronary calcification is present in only 63% of asymptomatic hypertensive men, suggesting that the degree of coronary atherosclerosis associated with high blood pressure varies among individuals. Wall thickening can be quantified in vivo by automated computerized analysis of ultrasonic images of the far wall intima-media complex of extracoronary vessels. Carotid and femoral wall thickening was observed in hypertensive subjects who had never been treated for hypertension compared to normotensive controls of similar age. Such vascular hypertrophy was not found in all patients, attesting to the disparity of the structural arterial changes within hypertensive subjects. Recent evidence from studies of essential hypertension suggests the lack of association between diffuse wall thickening of carotid or femoral arteries and the presence of atherosclerotic plaque (focal echogenic encroachment) in the same vessel. However, other studies in at-risk subjects suggest that extracoronary wall thickening could be related to the presence of coronary atherosclerosis, and to the incidence of coronary events. Wall stiffening is the third arterial alteration related to the sclerotic component of atherosclerosis. Its evaluation is based on the velocity of pulse wave propagation within the arterial tree or on the ultrasonic (echotracking) assessment of arterial wall distension during the cardiac cycle. Arterial stiffening is increased in the presence of hypertension, and such an increase is potentiated by the presence of other risk factors, such as smoking or hypercholesterolemia. Finally, the detection of early atherosclerosis with the above techniques optimizes the stratification of atherosclerotic risk, and may provide relevant information on comparative effectiveness of various classes of antihypertensive agents.
Abstract: BACKGROUND: Recent studies have suggested that knowledge of the extent of subclinical atherosclerosis may improve prognostic information in subjects at risk of cardiovascular disease. Therefore, we tested the value of extracoronary plaque detected with echography at multiple sites and that of total coronary calcification deposit evaluated with ultrafast computed tomography for predicting the risk of coronary events estimated on the basis of traditional risk factors. METHODS AND RESULTS: We analyzed in 618 asymptomatic at-risk men the extent of extracoronary atherosclerosis, as assessed with ultrasound imaging of carotid, aortic, and femoral sites and coded as number of disease sites (none, one, two, or three) on the basis of the presence of plaque at each site, and the amount of total coronary calcification deposit, as evaluated with ultrafast computed tomography and coded as grade 0, 1, 2, or 3 on the basis of the determination of a total coronary calcium score. Concomitantly, age, systolic pressure, total and HDL cholesterol levels, current smoking, presence of diabetes, and presence of ECG left ventricular hypertrophy (ECG-LVH) were evaluated with the goal of estimating coronary risk with the use of the Framingham Study risk algorithm. The prevalence rates of at least one extracoronary disease site and coronary calcification (any grade) were high (72% and 63%). There was a strong association between the number of extracoronary disease sites and the grade of coronary calcification (P < .001). As the number of extracoronary disease sites increased, age, systolic pressure, smoking frequency, and number of risk factors increased (P < .001). As the grade of coronary calcification increased, age and systolic pressure increased (P < .001), as did the number of risk factors (P < .01). The estimated coronary risk increased with the number of extracoronary disease sites and the grade of coronary calcification (P < .001). The odds ratio of coronary risk between three and no extracoronary disease site was 2.37 (95% confidence interval [CI], 1.08 to 5.21), whereas that between grade 3 and grade 0 of coronary calcification was 1.79 (95% CI, 0.94 to 3.40). CONCLUSIONS: In an apparently healthy population, the extracoronary atherosclerotic burden as measured with multiple-site echography appears to be more powerful than the ultrafast computed tomography-detected coronary calcium burden in reflecting the multifactorial coronary risk profile. However, only men were included in the present study, and the present findings cannot be extrapolated to women.
Abstract: To evaluate arterial physiopathology, complete arterial wall mechanical characterization is necessary. This study presents a model for determining the elastic response of elastin (sigma E, where sigma is stress), collagen (sigma C), and smooth muscle (sigma SM) fibers and viscous (sigma eta) and inertial (sigma M) aortic wall behaviors. Our work assumes that the total stress developed by the wall to resist stretching is governed by the elastic modulus of elastin fibers (EE), the elastic modulus of collagen (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the maximally contracted vascular smooth muscle (ESM) affected by an activation function (fA). We constructed the constitutive equation of the aortic wall on the basis of three different hookean materials and two nonlinear functions, fA and fC: sigma = sigma E + sigma C + sigma SM + sigma eta + sigma M = EE. (epsilon - epsilon 0E) + EC.fC.epsilon + ESM.fA.epsilon + eta. [equation: see text] + M.[equation: see text] where epsilon is strain and epsilon 0E is strain at zero stress. Stress-strain relations in the control state and during activation of smooth muscle (phenylephrine, 5 micrograms.kg-1.min-1 IV) were obtained by transient occlusions of the descending aorta and the inferior vena cava in 15 conscious dogs by using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. The fC was not linear with strain, and at the onset of significant collagen participation in the elastic response (break point of the stress-strain relation), 6.02 +/- 2.6% collagen fibers were recruited at 23% of stretching of the unstressed diameter. The fA exhibited a skewed unimodal curve with a maximum level of activation at 28.3 +/- 7.9% of stretching. The aortic wall dynamic behavior was modified by activation increasing viscous (eta) and inertial (M) moduli from the control to active state (viscous, 3.8 +/- 1.3 x 10(4) to 7.8 +/- 1.1 x 10(4) dyne.s.cm-2, P < .0005; inertial, 61 +/- 42 to 91 +/- 23 dyne.s2.cm-2, P < .05). Finally, the purely elastic stress-strain relation was assessed by subtracting the viscous and inertial behaviors.
Abstract: Recent studies have shown that the sialic acid content of LDL isolated from patients with angiographically demonstrated advanced coronary atherosclerosis is lower than that of LDL isolated from healthy subjects. These observations raise the question as to whether LDL sialic acid content could be used as an early marker of atherosclerosis. We screened for carotid, aortic, and femoral plaques by ultrasonography and for coronary calcifications by ultrafast computed tomography in 160 hypercholesterolemic subjects free of cardiovascular disease to investigate the relation between LDL sialic acid content and the prevalence of these early atherosclerotic lesions. LDL sialic acid values varied from 19.6 to 46.6 nmol/mg LDL protein (33.9 +/- 4.4, mean +/- SD) in the whole population, but the distribution was very similar: (1) in subjects with no plaque (34.1 +/- 4.9) relative to those with one or several plaques at one (34.2 +/- 4.4), two (33.0 +/- 3.6), or three (34.8 +/- 3.4) different arterial sites; (2) in subjects with (33.9 +/- 3.7) and without (34.1 +/- 4.8) coronary calcification; and (3) in subjects with both extracoronary and coronary lesions (33.8 +/- 3.9) relative to those with no arterial lesions (34.2 +/- 4.5). LDL sialic acid content was not related to sex, age, body mass index, smoking, blood pressure, or serum total cholesterol and lipoprotein(a) levels but correlated negatively with serum triglyceride levels (P < .001). These results suggest that LDL sialic acid content is not a discriminant marker of early atherosclerosis in asymptomatic hypercholesterolemic subjects.
Abstract: Several non-pharmacological interventions such as weight reduction in obese subjects or diet alteration in subjects having hypercholesterolemia have been shown to be effective in therapeutic trials. Our aim was to test the value of two different ways of teaching patients about their diet. From March 1, 1993, to May 30, 1994, 300 consecutive patients seen in a one-day care hospital were randomised into two groups. The 2 inclusion criteria were: 1) body mass index > 27 kg/m2 in men and > to 25 kg/m2 in women and/or 2) presence of a hypercholesterolemia defined by a total cholesterol > 6.5 mmol/l. Patients in the first group (C) were educated in a 20 to 50 minutes consultation tailored to their needs. Patients in the second group (CC) were given in addition a one-hour course about diet. The goal of the diet was to loss at least 3 kg of body weight and/or to have a cholesterol value below 6.5 mmol/l without treatment. All Patients were followed-up by the same 3 dietician nurses. An out-patient visit was planned at 3 months, and a recall letter was sent to the patients who missed their appointments. Among the 300 patients, 169 (55%) were seen at the 3-month outpatient visit. This proportion did not differ between the 2 groups. Knowledge on diet was assessed by the same 33-item self-administered questionnaire. At baseline scores were comparable between groups (16 vs 17). Scores improved more in the CC than in the C group both at the end of the teaching question (27 vs 23 in the CC and C group respectively, p < 0.001), and at 3 months (25 vs 23 in the CC and C group respectively; p < 0.001). Total cholesterol decreased below 6.5 mmol/l in 28% of the patients with dyslipidemia and a weight loss > 3 kg was observed in 32% of the obese subjects, but improvement did not differ between the 2 groups. We conclude that a specific one-hour course on diet is able to improve knowledge of patients more than a consultation alone, but that better knowledge did not result in improved alteration of risk factors at 3 months.
Abstract: Although the inverse relation between high-density lipoprotein (HDL) cholesterol concentration and the risk of ischemic heart disease is well established, little is known about the relation of HDL subfractions HDL2 and HDL3 or lipoprotein A-I and A-I-A-II to extracoronary disease, particularly at its silent phase before the appearance of clinical lesions. We investigated the potential influence of HDL subfractions as risk markers, among the other main lipid and nonlipid risk factors, by assessing early atherosclerotic plaques detected by 3 ultrasound imaging sites in 181 hypercholesterolemic symptom-free men. No plaques were found in 36% of the patients, but plaques were found at carotid, aortic, and femoral sites in 24%, 40%, and 46% of subjects, respectively. Data were analyzed using univariate comparisons and multiple logistic regression. According to the logistic analysis, plaques were associated (1) with blood pressure (p = 0.008) and low-density lipoprotein (LDL) cholesterol (p = 0.02) in the carotid arteries; (2) with age (p = 0.0005), triglycerides (p = 0.002), and cigarette smoking (p = 0.02) at the aortic site; and (3) inversely with HDL3 cholesterol (p = 0.0008) and positively with cigarette smoking (p = 0.004), and age (p = 0.04) in the femoral site. The number of arterial sites affected (0, 1, 2, and 3) by plaques was inversely associated with HDL3 cholesterol (p = 0.001), and positively associated with smoking (p = 0.002), blood pressure (p = 0.002), LDL cholesterol (p = 0.003), and age (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: This study was performed to determine whether hypercholesterolemic men had increased large artery intima-media thickness (IMT), a potential surrogate measure of atherosclerosis, compared to normocholesterolemic controls. The measurements were performed in the far walls of common carotid and femoral arteries with non-invasive automatic computerized ultrasonic technique in 101 asymptomatic men (28-60 years) of whom 40 were normocholesterolemic (total cholesterol < 5.2 mmol/l, controls), 25 had borderline hypercholesterolemia (5.2 < or = total cholesterol < 6.2 mmol/l, group 1) and 36 had hypercholesterolemia (total cholesterol > or = 6.2 mmol/l, group 2). All the subjects had no other traditional risk factors, except smoking. Carotid and femoral IMT were significantly increased in group 2 (P < 0.01) but not in group 1 compared to controls. When all subjects were pooled for analysis, carotid and femoral IMT were correlated (r = 0.47, P < 0.001) and increased with total cholesterol (r = 0.35, P < 0.001) and LDL cholesterol (r = 0.33, r = 0.34, respectively; P < 0.001). Carotid and femoral IMT increased with age in each group: controls, r = 0.46, P < 0.01 and r = 0.50, P < 0.001, respectively; group 1, r = 0.42, P < 0.05; group 2, r = 0.48, P < 0.01, and r = 0.59, P < 0.001, respectively. At the carotid and femoral sites, the regression slopes between age and IMT were steeper in group 2 than in controls (P < 0.01). Thus, hypercholesterolemia was associated with diffuse large artery wall thickening, whose presence might be useful in the identification of those hypercholesterolemic individuals most prone to developing atheromatous changes, in the decision to treat, and in the monitoring of lipid-lowering treatment.
Abstract: Haemodynamic shear forces have been reported to exert direct and indirect effects on platelet reactivity. In vitro, they activate platelets leading to spontaneous or facilitated aggregation. In vivo, they stimulate the production of endothelium-derived anti-aggregatory agents. This study was designed to evaluate in hypertensive patients, before and after antihypertensive treatment, the possible role of these haemodynamic forces, determined at the brachial artery level on the ex vivo platelet aggregatory response to ADP and collagen. Platelet reactivity, evaluated by EC50 for ADP and collagen, was found to be related to blood velocity, shear rate and shear stress (p < 0.01 for each). These inverse correlations of platelet aggregation with stress levels did not depend on age, body mass index, mean blood pressure, serum cholesterol and triglycerides or haematocrit. They were also independent of platelet cytosolic Ca2+ and cyclic AMP. The changes in shear forces and in aggregatory responses to ADP and collagen induced by nitrendipine treatment for 6 months remained negatively correlated, confirming the relationships existing between haemodynamic shear forces and platelet reactivity. These results indicate that the shear antiaggregant effects, likely mediated by flow-dependent endothelium-derived factors, prevail over its direct platelet aggregating effects.
Abstract: A description of the arterial wall elastic properties comprehends both collagen and elastin, clearly shown in a biphasic stress-strain relationship. From chronically instrumented conscious dogs, aortic pressure-diameter curves can be obtained in a single beat, which is impossible to perform in human beings. In control conditions, the collagen fibers are almost not distended and the resistance to stretch is mainly supported by the elastin fibers. Therefore, the mechanical properties of the aorta are almost purely elastic in the basal beat to beat conditions. In this study we propose and test five indexes, which include as variables: systolic, diastolic and mean arterial pressure and diameter; besides, arterial compliance and pressure-strain elastic modulus as suggested to evaluate the elastic behaviour of the elastic fibers. This data can be easily obtained by non-invasive methods, such as Doppler-ultrasound techniques and auscultative esphygmomanometrical measurements, while the indexes evaluated can be retrieved from a single beat evaluation. Of three measurements performed in chronically instrumented conscious dogs on different days, one of these indexes, the ME5 = [formula: see text] x Rdias proved to be an accurate and reliable parameter to evaluate the mechanical behaviour of arteries. This kind of parameter may be useful for research and evaluation of several diseases that markedly alter the arterial wall compliance.
Abstract: The effects of isradipine (Lomir, CAS 75695-93-1) and metoprolol (CAS 37350-58-6) on geometry and arterial compliance of the arteria brachialis of 14 patients each with essential hypertension were compared acutely and after three months of therapy by means of pulsed Doppler sonography and the determination of pulse wave velocity. A calculation model was used that allowed to determine the drug-specific effects on arterial diameter and compliance under isobaric conditions. Isradipine increased measured and isobaric diameter during short-term (p < 0.05) and long-term administration (p < 0.05) whereas metoprolol did not change it. Isradipine increased measured and isobaric compliance during short-term (p < 0.05) and long-term administration (p < 0.05). Metoprolol reduced measured compliance acutely (p < 0.01) and isobaric compliance acutely (p < 0.05) and long-term (p < 0.05). Drug-specific effects on compliance were different during short-term and long-term administration (p < 0.01); the diameter was influenced differently only during short-term administration (p < 0.05). These opposite drug effects on the A. brachialis are probably due to a vasoselective relaxation of smooth muscle in large arteries by isradipine and-in the case of metoprolol-arterial constriction. The increase of arterial compliance by isradipine reduces very effectively the load on the heart and could form the basis for the improvement in the prognosis of the hypertensive patient.
Abstract: OBJECTIVE: We set out to evaluate the relationship between aortic stiffness and serum lipids and lipoprotein fractions, including high-density-lipoprotein (HDL) cholesterol subfractions. METHODS: One hundred and five asymptomatic, normotensive, untreated, hypercholesterolaemic men underwent measurement of aortic pulse-wave velocity (PWV) by mecanography and assay of total cholesterol, triglycerides, HDL cholesterol and its subfractions (HDL2 cholesterol and HDL3 cholesterol), determined by electrophoresis. RESULTS: PWV was related to HDL cholesterol (r = 0.21, p = 0.05) and more specifically to HDL3 cholesterol subfraction (r = 0.29, p < 0.01). The latter association remained significant after adjustment for systolic blood pressure and age. Multivariate analysis demonstrated an independent association of PWV (r2 = 0.27, P < 0.001) with age, systolic blood pressure and HDL3 cholesterol. CONCLUSION: Although hypercholesterolaemia was not accompanied by increased aortic rigidity, there was a positive relationship between PWV and HDL cholesterol and between PWV and HDL3 cholesterol independently of the influence of age and systolic blood pressure on PWV. These results suggest that, in hypercholesterolaemic men, HDL3 could, in addition to its anti-atherogenic property, have a prosclerotic stiffening effect. This duality could explain why, in clinical studies, although the level of the HDL2 subfraction is frequently associated with a lower incidence of coronary artery disease, results for the HDL3 subfraction are less convincing and remain equivocal.
Abstract: Coronary calcifications (CC) are the witness of atheromatous disease because they lies in intima. This is a best stamp of coronary atheromatosis than all the well know risk factors. CC scores is perfectly estimated by EBT. The reproductibility expressed in logarithm data is 7.2% in inter-examination, 1.3% in inter-observers, 2% in intra-observers [4]. CC detection is more specific in young population than in old population because CC appear and increase with age in asymptomatic patients [12]. But the score curve raised higher in symptomatic than in asymptomatic subjects. A patient with an abnormal score for his age will have 5 to 10% of ischemic cardiac disease during the following 6 months [11].
Abstract: Recent studies have suggested that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. We investigated the association between erythrocyte aggregation and components of lipoproteins in the blood of 60 normotensive, hypercholesterolemic men aged 45 +/- 8 years. The rheological parameters assessed were aggregation index (AI) and disaggregation shear rate threshold (gamma t) as determined by laser reflectometry, plasma fibrinogen, total serum protein, and hematocrit. The lipoprotein variables included total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol and its subfractions HDL2 cholesterol and HDL3 cholesterol, apolipoprotein (apo) B, apoA-I, HDL particles containing apoA-I without apoA-II (LpA-I), and HDL particles containing both apoA-I and apoA-II (LpA-I/A-II). Covariables considered for possible confounding effects were age, body mass index, and smoking behavior. Fibrinogen, total serum protein, and both aggregation parameters (AI and gamma t) were elevated in this hypercholesterolemic population. Univariate analysis showed that both AI and gamma t correlated positively with fibrinogen (P < .001) and total serum protein (P < .01) and negatively with HDL2 cholesterol (P < .01) and LpA-I (P < .01); gamma t also provided a positive correlation with LpA-I/A-II (P < .05). A multivariate model analysis demonstrated that HDL2 cholesterol, LpA-I, and LpA-I/A-II also emerged as significant factors influencing erythrocyte aggregation; 60% to 68% of the variance of AI and 47% to 64% of the variance of gamma t could be explained by these factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Little is known of the in vivo structural changes of large arteries in uncomplicated hypertension. Therefore, we measured the intima-media thickness and lumen diameter of common carotid and femoral arteries by a computerized ultrasonographic technique in 25 normotensive and 25 never treated hypertensive men of similar age (from 25 to 72 years). The intraobserver variability of carotid and femoral wall thicknesses was 4.3% and 5.6%, respectively. Moreover, an in vitro study of 13 human arterial segments removed at autopsy demonstrated a strong correlation (r = .989, P < .001) between computerized ultrasonic and histological intima-media thickness measurements. Compared with control subjects, hypertensive patients had similar arterial diameters but higher carotid and femoral intima-media thicknesses (P < .001) as well as higher ratios of carotid and femoral intima-media thickness to lumen (P < .001, P < .01). The carotid thickness was correlated with age in control subjects (r = .48, P < .05) but not in hypertensive patients. The femoral thickness was correlated with age both in control subjects (r = .55, P < .01) and in hypertensive patients (r = .46, P < .05). Thus, carotid and femoral arterial walls of hypertensive patients were thickened. This thickening was not due to age, although aging also thickened both vessels in control subjects and the femoral artery only in hypertensive patients. Such a wall thickening associated with a normal diameter provides direct evidence of vascular growth and represents a new target to monitor noninvasively in vivo for large artery changes in human hypertension.
Abstract: Early investigators found contradictory evidence that vascular smooth muscle activation reduces the elastic modulus of the arterial wall under isotonic conditions but increases it under isometric conditions, concomitant with increased pulse-wave velocity. We examined the individual contributions of aortic constituents to the elastic modulus of the aortic wall to determine if isobaric analysis produces an accurate assessment of vascular smooth muscle activation. We used a modified Maxwell model assuming an incremental elastic modulus (Einc) composed of the elastic modulus of elastin fibers (EE), the elastic modulus of collagen fibers (EC) affected by the fraction of collagen fibers (fC) recruited to support wall stress, and the elastic modulus of the vascular smooth muscle (ESM) according to the following formula: Einc = EE+EC x fC+ESM.Einc was assessed in eight conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometry) measurements. Stress-strain relations in the control state and during activation of smooth muscle by continuous administration of phenylephrine (5 micrograms.kg-1 x min-1) were obtained by transient occlusions of the descending aorta and inferior vena cava. Results were as follows: EE was 4.99 +/- 1.58 x 10(6) dynes/cm2 (mean +/- SD), and EC was 965.8 +/- 399.8 x 10(6) dynes/cm2, assessed during the control state. Phenylephrine administration increased the theoretical pulse-wave velocity (Moens-Korteweg equation) from 5.25 +/- 1.03 m/s during the control state to 7.57 +/- 2.53 m/s (P < .005). Active muscle exhibited a unimodal stress-strain curve with a maximum stress of 0.949 +/- 0.57 x 10(6) dynes/cm2 at a corresponding strain value of 1.299 +/- 0.083. The maximum value observed corresponded, on the pressure-diameter curve of the active artery, to a pressure of 234.28 +/- 46.6 mm Hg and a diameter of 17.94 +/- 1.6 mm. The maximum ESM derived from the stress-strain relation of the active muscle was 8.345 +/- 7.56 x 10(6) dynes/cm2 at a strain value of 1.283 +/- 0.079. This point was located at 208.01 +/- 40.8 mm Hg and 17.73 +/- 1.41 mm on the active pressure-diameter curve. During activation of vascular smooth muscle, Einc decreased (P < .05) when plotted against internal pressure but increased (P < .05) when plotted against strain, over the operative range.(ABSTRACT TRUNCATED AT 400 WORDS)
Abstract: To determine the effects of female hormones on peripheral vasculature we studied the brachial artery circulation. Nine young women (27-37 yrs) having inactive ovaries received transdermal estradiol (E2) (0.1-0.4 mg/d) and vaginal progesterone (P) (300 mg/d) to duplicate the menstrual cycle levels of E2 and P. Brachial artery diameter, blood velocity and flow were measured by bidimensional pulsed Doppler in basal conditions, and during hand exclusion by a cuff inflated at suprasystolic pressure. Vascular resistance was calculated by the ratio of mean blood pressure over mean flow. Measurements were obtained before hormonotherapy (d0), on day 14 (d14, after E2), and on day 28 (d28, after E2 and P). The increase of brachial artery diameter began at d14 (3.73 +/- 0.12 mm, vs 3.66 +/- 0.11 mm; NS) to become significant at d28 (3.91 +/- 0.10 mm, p < 0.05). Blood velocity and flow increased at d28 (4.78 +/- 0.55 cm/s, vs 3.55 +/- 0.65 cm/s; P < 0.05 and 35.2 +/- 5.2 ml/mn vs 22.2 +/- 3.6 ml/mn, P < 0.05 respectively). No change was noted in mean blood pressure. The decrease of resistance began at d14, in order to be significant at d28 (158 +/- 17 mmHg/ml/s at d0 vs 263 +/- 31 mmHg/ml/s at d28; P < 0.05). Brachial vasoconstriction during hand exclusion, in response to low flow state disappeared at d14 with estradiol. In conclusion, in women deprived of ovarian function, physiological E2 and P replacement vasodilates small and large arteries, whereas E2 alone attenuates the large artery vasoconstriction in acute response to low flow state.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Cross-sectional associations between aortic elasticity assessed by carotid to femoral pulse wave velocity (PWV) and cardiovascular risk factors were examined in 429 apparently healthy middle-aged women. PWV was strongly and positively related to blood pressure and hypertension. Weak but significant positive associations were also found between PWV and age, heart rate, some lipids and lipoproteins, blood glucose (either as a continuous or dichotomous variable), body mass index, haematocrit, leucocyte count and family history of diabetes. No associations were observed between PWV and high density lipoprotein cholesterol, apolipoprotein A1, fibrinogen, cigarette smoking, menopausal status and a family history of hypertension or myocardial infarction. After adjustment for systolic blood pressure, PWV remained significantly related to heart rate, leucocyte count, blood glucose (as a dichotomous variable) and a family history of diabetes. Multiple regression analysis showed that systolic blood pressure and, to a lesser extent, heart rate, leucocyte count and a family history of diabetes were all independent determinants of PWV. This pattern of associations suggests that arterial stiffness measured by PWV reflects the sclerotic rather than the atherotic component of atherosclerosis. The potential influence of a family history of diabetes on the elastic properties of the aorta needs to be ascertained in further studies.
Abstract: 1. To evaluate the response of red blood cells subjected to the shear flow in hypertension, the relationships between wall shear phenomena determined in vivo in the brachial artery of hypertensive patients and the modifications of the membrane dynamics measured in vitro in erythrocyte ghosts of 32 patients were investigated. 2. Two fluorescent probes, diphenylhexatriene (DPH) and its trimethylamino-derivative (TMA-DPH), localized respectively in the lipid membrane core and at the lipid-water interface, were used. 3. Shear rate, shear stress and blood velocity were positively correlated with TMA-DPH anisotropy (P = 0.015, 0.005 and 0.026, respectively), but not with that of DPH. This indicates that wall shear forces were associated with the microviscosity of the outer part of the cell membrane. 4. The changes in wall shear forces and erythrocyte membrane microviscosity probed by TMA-DPH or DPH were observed to vary in parallel under nitrendipine therapy. 5. These results suggest that in vivo shear forces participate in the control of erythrocyte membrane fluidity or that erythrocytes adapt their membrane properties to blood flow conditions.
Abstract: Subclinical atherosclerosis can be non-invasively detected via calcifications, thickening and stiffening of arteries. Coronary calcifications seen with ultrafast computed tomography are frequent in hypertension or hypercholesterolemia and synonymous of coronary atherosis but not of coronary stenosis. Wall thickening detectable by extracoronary ultrasonography may be characterized by an intimamedia thickening shown in hypertension or by a focalized plaque whose the presence in the aortic or femoral level seem influenced by systolic pressure. Extracoronary wall thickening may be an aid in the diagnosis of coronary atherosclerosis, a predictor of coronary event, and a therapeutic target. Wall stiffening, which reflects sclerosis, is detected by pulse wave velocity. Its increase in hypertension may be an indicator of atherosclerosis and can be reversed by certain antihypertensive agents. Clinical care of at risk individuals might profit from subclinical atherosclerosis which adds objectivity and sensitivity in the individualization of risk and the decision to treat.
Abstract: OBJECTIVE: The aim was to assess the influence of the renin-angiotensin system on the geometrical and elastic properties of the aorta in conscious dogs, using a model of renovascular hypertension, and to examine the effects of inhibition of the system by the angiotensin converting enzyme inhibitor spirapril. METHODS: The aortic elastic behaviour in response to renovascular hypertension was studied in 15 conscious dogs instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. Renovascular hypertension was induced by surgical occlusion of one renal artery and stenosis of the other. One day after renal surgery, dogs were randomly assigned to two groups receiving for two months either the new angiotensin converting enzyme inhibitor spirapril (n = 8) or a placebo capsule (n = 7). The two groups of dogs were compared to a control group of normotensive dogs (n = 7). After two months of treatment the elastic properties of the aorta were studied by computation of the beat to beat pressure-diameter hysteresis loops obtained during transient increase of pressure induced by bolus doses of angiotensin. The aortic pressure-diameter (P-D) relationship, obtained over a wide range, was fitted by an exponential fit (P = alpha.e beta D), where beta is the stiffness index. A decomposition of the P-D curve according to a biphasic model of the parallel arrangement of elastin and collagen enabled two pressure-diameter elastic moduli to be obtained, one representing the resistance to stretch at low pressure levels (elastic fibres and smooth muscle), and the other representing the resistance to stretch at the highest pressures (collagen fibres). RESULTS: The pressure-diameter curve of the placebo group was shifted to the left compared to the curves of the control and spirapril groups, showing that renovascular hypertension was associated with isobaric reduction of aortic diameter. The stiffness index beta was higher (p < 0.05) in the placebo group [0.605(SD 0.304) mm-1] than in either the control group [0.362(0.126) mm-1] or the spirapril group [0.348(0.083) mm-1], suggesting that renovascular hypertension was associated with aortic stiffening. The biphasic analysis showed that the collagen pressure-diameter elastic modulus was unaffected by spirapril, whereas the elastin pressure-diameter elastic modulus was significantly reduced by converting enzyme inhibitor with respect to the placebo (p < 0.05). CONCLUSIONS: Chronic converting enzyme inhibition by spirapril prevents the isobaric aortic diameter reduction induced by renovascular hypertension in conscious dogs and decreases aortic stiffness, in particular by changing the elastic behaviour of the elastin fibres rather than of the collagen fibres.
Abstract: The authors present a new strategy for cardiovascular disease prevention based on risk factor detection in occupational medicine and silent atherosclerosis detection in a specialized investigation centre. Employees from several firms in the Paris region were searched, in their working place, for cardiovascular risk factors, including blood cholesterol measurement. The subjects at risk thus selected underwent non-invasive explorations aimed at an early detection of silent atherosclerosis. Extracoronary plaques in the carotid, aorta and femoral arteries were detected by high-resolution ultrasonography, and coronary calcifications by ultrafast CT. The prevalence of arterial lesions and their relationship with risk factors were analysed in a subgroup of 208 untreated male subjects with high blood cholesterol level: 74 percent of these subjects had extracoronary plaques and 65 percent had coronary calcifications. This high prevalence of silent arterial lesions suggested that hypercholesterolaemia, even when moderate, has an early but inconsistent atherogenic effect. Moreover, extracoronary plaques and coronary calcifications were related to risk factors other than blood lipids, and among these factors age was predominant. The simultaneous detection of extracoronary and coronary lesions has demonstrated that extracoronary ultrasonography of several arteries is a good diagnostic test predicting the presence of coronary calcifications in the absence of coronary symptoms. Detection of silent atherosclerosis in subjects at risk therefore is an original and helpful complement to risk factor detection. It should better refine and individualize the diagnosis of risk and evaluate the effects of preventive cardiovascular treatments on atherosclerosis.
Abstract: The effects of isradipine and metoprolol were studied on the brachial arteries of two groups of 14 patients with hypertension, 90 minutes after the first dose and after 3 months of treatment. Diameter (pulsed Doppler) and compliance (pulse-wave velocity) were measured and calculated in isobaric conditions by way of a model that allowed discrimination of the active intrinsic drug action. Isradipine increased measured and isobaric diameter during short-term (p < 0.05) and long-term administration (p < 0.05), whereas metoprolol did not change it. Active diameter effects were different between drugs during short-term administration (p < 0.05). Isaradipine increased measured and isobaric compliance during short-term (p < 0.05) and long-term administration (p < 0.05). Short-term administration of metoprolol decreased measured compliance (p < 0.01). Metoprolol decreased isobaric compliance during short-term (p < 0.01) and long-term (p < 0.05) administration. Active compliance effects were different between drugs during short- and long-term administration (p < 0.01). These arterial intrinsic drug effects, independent of the pressure-lowering influence, suggested different mechanisms, consisting of a large artery smooth muscle relaxation for isradipine and an isometric arterial constriction for metoprolol.
Abstract: The effects of antihypertensive drugs on the large arteries consist of two parts: the passive effect due to the change in pressure and the active effect, the drug action per se. This study proposes a method of dissociating the passive effect from the active effect. The diameter of the arterial artery was determined by the pulsed Doppler method and the pulse wave velocity of the brachioradial artery by mecanography. Arterial compliance was calculated by the Bramwell-Hill formula. Active and passive effects were determined by a logarithmic pressure-diameter model. This model was supported by in situ direct measurements of blood pressure and diameter in a segment of the femoral artery in dogs. Six drugs, cadralazine, ketanserin, medroxalol, nitrendipine, captopril, and isosorbide dinitrate, administered orally, were tested in 70 essential hypertensive patients. For all drugs, the pressure reduction induced a passive decrease in arterial diameter (p less than 0.02 to p less than 0.01). Cadralazine actively decreased arterial diameter (p less than 0.01), ketanserin had no active effect on diameter, and medroxalol, nitrendipine, captopril, and isosorbide dinitrate actively increased arterial diameter (p less than 0.05, p less than 0.01, p less than 0.01, and p less than 0.01, respectively). For all drugs, the pressure reduction also induced a passive increase in arterial compliance (p less than 0.05 to p less than 0.01). However, only nitrendipine, captopril, and isosorbide dinitrate actively increased arterial compliance (p less than 0.01, p less than 0.05, and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Hypercholesterolemia and hypertension are two of the major risk factors associated with increased atherosclerotic vascular disease. An abnormal platelet function is one of the mechanisms proposed to participate in atherogenesis. This study was undertaken to find out whether hypercholesterolemia in hypertensive patients can change platelet lipid composition and reactivity. Twenty-nine untreated hypertensive patients were distributed into 3 age, body mass index and blood pressure-matched groups according to their plasma cholesterol levels (normal, borderline or elevated, group NC, BC and HC respectively). Their platelet lipid composition, cytosolic Ca2+ concentration, cyclic AMP content and aggregating response to ADP and collagen were determined. Platelet from group HC patients were characterized by reduced cyclic AMP content (evaluated in the presence and absence of a platelet phosphodiesterase inhibitor) and aggregating responses to ADP and collagen, increased palmitic acid content and decreased arachidonic, eicosapentaenoic and docosatetraenoic and pentaenoic acid content, resulting in a lowered polyunsaturated to saturated fatty acid ratio (P less than 0.001). In contrast, platelet cytosolic Ca2+ concentration, DPH steady-state anisotropy and cholesterol to phospholipid molar ratio were not significantly changed. This indicates that hypercholesterolemia is accompanied in hypertensive patients by marked changes in platelet fatty acid composition, cyclic AMP content and response to aggregating agents. These changes, which clearly differ from those induced by in vitro cholesterol loading, could reflect not only the balance between LDL and HDL stimulation but also an adaptation to hemodynamic perturbations.
Abstract: Arterial compliance in humans is generally measured by modeling analysis of pulse tracing or of pulse wave propagation in the arterial tree. It is decreased in hypertension in part because elevation of blood pressure stiffens the arteries by stretching the rigid collagen fibres of their walls. Using a modeling evaluation of the compliance-pressure relationship in large arteries, it is possible to correct compliance from the mechanical effect (passive effect) due to pressure elevation. This makes it possible to show that, at the same pressure as in normal controls, hypertensive patients maintain decreased arterial compliance. This finding suggests that functional and/or structural changes other than pressure-mediated stretching of arteries (active effect) contribute toward reducing arterial compliance. Thus, the response of compliance to antihypertensive drugs must be studied by differentiating between passive and active effects. The diameter and compliance-pressure relationship in arteries allow differentiation of a passive arterial effect due to the pressure-lowering action of the drug, and an active pharmacological effect calculated at the same pressure before and after drug administration. Four drugs--ketanserin, urapidil, nitrendipine, and nicardipine (acute administration)--are given as examples. No active or passive compliance changes are observed with urapidil and ketanserin. In contrast, an active increase in compliance is observed in isobaric conditions with calcium antagonists, together with large-artery dilation due to a potent smooth muscle-relaxing effect. This active increase in compliance is potentiated by a passive increase due to the pressure-lowering effect that reduces the mechanical stretch exerted by blood pressure on arterial bioelastomers. Finally, an optimum increase in arterial compliance is achieved by drugs that vasodilate large arteries by smooth muscle relaxation and concomitantly decrease blood pressure. This may be of importance because low compliance has adverse effects on the cardiovascular system by contributing to the pathogenesis of systolic hypertension and left ventricular hypertrophy. Loss of arterial compliance may also be an early marker of atherosclerosis.
Abstract: Since Ca2+ ions seem to directly participate in the control of erythrocyte membrane structure and deformability and because cell Ca2+ metabolism has been repeatedly proposed to be modified in hypertension, the intracellular calcium ion concentration ([Ca2+]i) was investigated in red blood cells from hypertensive and normotensive subjects. [Ca2+]i was measured by using the fluorescent Ca2+ chelator fura-2. Red blood cell [Ca2+]i was increased in hypertensive compared with normotensive subjects in the whole population and further increased when hypertensive were compared with age-matched normotensive subjects. An inverse relation between age and [Ca2+]i was observed when calculated with blood pressure adjusted. In hypertensive patients, high [Ca2+]i values were associated with a reduced erythrocyte deformability. The initial rate of 45Ca2+ uptake did not differ between the two blood pressure groups. Similarly, when the extracellular Ca2+ concentration was elevated from 1 to 2 mmol/l, [Ca2+]i increased by 16 +/- 4% (p less than 0.03) in red blood cells from both groups, thus maintaining a significant difference between hypertensive and normotensive subjects. Under these conditions, the addition of 10(-7) mol/l nicardipine, a dihydropyridine Ca2+ antagonist, decreased [Ca2+]i by 15 +/- 4% (p less than 0.05) and 7 +/- 5% in erythrocytes from hypertensive and normotensive subjects, respectively, thereby reducing the difference in [Ca2+]i observed between these two groups. This nicardipine effect was positively correlated to the initial [Ca2+]i. In the presence of 5 mumol/l W7, a calmodulin antagonist, [Ca2+]i increased significantly only in erythrocytes from hypertensive patients (26 +/- 6%, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: We have already reported that erythrocyte aggregation (EA) is increased in hypertensive subjects. To study the influence of other risk factors in EA, we have measured aggregation index IA and disaggregation shear rate threshold (gamma c) by a laser technique and the biochemical parameters in 16 normotensive normocholesterolemic subjects (NT/NCT) and 45 hypertensive subjects where 17 were normocholesterolemic (HT/NCT), 18 were pure hypercholesterolemic (HT/HCTIIa) and 10 were hypercholesterolemic hypertriglyceridemic (HT/HCTIIb). The results show that IA and gamma c are more important in HT/NCT than NT/NCT patients and much more in patients with hypercholesterolemia and hypertriglyceridemia. The cumulative effects of hypertension and hyperlipidemia merit take into consideration in pathophysiology of cardiovascular complications and could help to new strategy therapeutic developments for treatment of these complications.
Abstract: Since calcium in coronary artery walls is considered as an indicator for atherosclerosis, we used ultrafast computed tomography to quantify it non invasively in 111 hypercholesterolemic men. They were selected at worksite by a cholesterol screening program, had total cholesterol (TC) above 5.2 (6.88 +/- 0.82, SD) mmol/l, were aged from 30 to 63 (46 +/- 5 years), had never been treated with lipid lowering or antihypertensive drug, and had no clinical coronary heart disease. Body mass index, blood pressure, smoking and other serum lipids as HDL cholesterol, triglyceride (TG) were evaluated. Calcium score of proximal coronary arteries was calculated on 30 contiguous 3 mm slices from areas and peak density of calcium lesions. The mean score was 30 +/- 69 and ranged from 0 to 440. A zero score was found in 39 subjects who differed from the 72 others only by TG levels (1.44 +/- 0.60 vs 1.85 +/- 0.80; p < 0.05). A multiple regression analysis showed that elevated calcium score was associated independently to age (F = 6.6; p < 0.05) and TG (F = 6; p < 0.05) but not to blood. Thus 65% of these asymptomatic subjects had a non-zero calcium score in coronary arteries. Elevated calcium score was influenced independently by age and triglyceride level, but not by other risk factors, such as blood pressure. This potential adverse effect of moderate triglyceride elevation on large coronary arteries merits attention in the assessment of the risk of coronary heart disease.
Abstract: To evaluate the influence of hypercholesterolaemia on arterial and blood factors related to cardiovascular disease in hypertension, 20 normocholesterolaemic and 31 hypercholesterolaemic hypertensive patients underwent determinations of whole blood filterability (WBF), plasma fibrinogen concentration (PF) and aortic pulse wave velocity (PWV). Both of the groups had similar age, body mass index, cumulative smoking dose and blood pressure. Hypercholesterolaemics had lower WBF (P less than 0.02), higher PF (P less than 0.02) and higher PWV (P less than 0.01) than normocholesterolaemics. In the whole population WBF correlated with age (P less than 0.005), mean blood pressure (P less than 0.01), total cholesterol (P less than 0.05) and plasma fibrinogen (P less than 0.01). However, in a multivariate analysis where age and pressure were controlled as variables, only the association between WBF and PF remained significant (P less than 0.001). Thus, the higher fibrinogen affects whole blood filterability in hypercholesterolaemic hypertensive patients. In the whole population PWV correlated positively with HDL cholesterol (P less than 0.01) and age (P less than 0.001) and the association with HDL cholesterol remained significant in a multivariate analysis (P less than 0.001) where age was controlled. The effect of ageing on arterial rigidity seems to be similar in both hypertensive groups as deduced from the identical regression slopes relating pulse wave velocity to age. So in hypertension with high cholesterol, arterial rigidity was increased without changes in arterial stiffening with age.
Abstract: The aggregation and disaggregation behaviors of red blood cells were investigated in 17 normotensive and 21 hypertensive subjects with a laser reflectometry technique, and simultaneous measurements were taken of blood viscosity with a coaxial viscometer. Increased red blood cell aggregation (26%, p less than 0.001) and disaggregation shear rate (20%, p less than 0.01) and shear stress (18%, p less than 0.01) were observed in hypertensive subjects when compared with normotensive subjects. Similar elevations in hypertensive subjects were found when the hematocrit was adjusted to 40%. Variation of red blood cell concentration caused the red blood cell disaggregation shear rate to change in an opposite direction but did not modify red blood cell aggregability and disaggregation shear stress. The increase of the reversible aggregation of red blood cells was associated with higher fibrinogen and plasma protein concentrations in hypertension. An increase in red blood cell aggregability and in the shear resistance of red blood cell aggregates may play a role in the development of the cardiovascular complication in hypertension. The quantification of red blood cell disaggregation shear stress, which represents the hydrodynamic force required to disperse the aggregates, may provide a useful parameter for clinical investigations.
Abstract: To investigate the role of lipoprotein (a) (Lp[a]) as an atherogenic condition related to hypercholesterolemia, we studied the serum concentration of Lp(a) as measured by immunonephelometry in relation to the presence of asymptomatic echographic plaques in the peripheral arteries of 103 untreated hypercholesterolemic, normotensive, middle-aged men. Plaque was found at carotid, aortic, and femoral sites in 36%, 51%, and 53% of subjects, respectively. The Lp(a) level was higher in the group with carotid plaques than in the group without (0.29 +/- 0.20 versus 0.17 +/- 0.14 g/l, p < 0.01), not significantly higher in the group with aortics plaque than in the group without (0.24 +/- 0.19 versus 0.19 +/- 0.16 g/l), and not different between groups with and without femoral plaques (0.21 +/- 0.18 versus 0.22 +/- 0.17 g/l). A logistic regression analysis confirmed that Lp(a) was associated with carotid plaques (p = 0.004), independent of other risk factors. However, in patients with low density lipoprotein cholesterol values above the group median value (4.7 mmol/l), Lp(a) was associated not only with carotid plaques (p < 0.01) but also with aortic plaques (p < 0.05), as well as with the number of diseased sites (p = 0.02). In contrast, in patients with low density lipoprotein cholesterol levels below or equal to 4.7 mmol/l, Lp(a) only remained associated with carotid plaques (p < 0.05). Thus, in symptom-free, hypercholesterolemic men, early atherosclerosis was influenced by serum Lp(a), particularly in the carotid arteries, as well as by the presence of a higher level of low density lipoprotein cholesterol.
Abstract: BACKGROUND. The prevalence of coronary calcifications and extracoronary plaques was studied in patients with asymptomatic hypercholesterolemia. METHODS AND RESULTS. Ultrafast computed tomography for coronary calcification (presence or absence: calcium score) and echographic assessment of carotid, aortic, and femoral plaques were performed in 111 hypercholesterolemic men: 65% had coronary calcification, 72% had extracoronary plaque. The two lesions were associated as: 1) compared with subjects without coronary calcification, those with calcification had a higher prevalence of aortic (p less than 0.05) and femoral (p less than 0.01) plaque and of two diseased sites (p less than 0.05); 2) the prevalence of coronary calcification was higher in the presence than in the absence of aortic (p less than 0.05) or femoral (p less than 0.01) plaque and higher in two (p less than 0.01) and three diseased (p less than 0.05) sites than in no diseased site; 3) the calcium score was higher in the presence than in the absence of carotid (p less than 0.05), aortic (p less than 0.05), or femoral (p less than 0.001) plaque, higher in two (p less than 0.001) and three diseased (p less than 0.05) sites than in no diseased sites, and higher in two (p less than 0.01) than in one diseased site; and 4) the calcium score correlated with femoral plaque (p less than 0.001). Overall, the presence of two or three diseased extracoronary sites versus no or one diseased site showed a power of 78% for predicting coronary calcification. Coronary calcium score correlated with age (p less than 0.01) and triglycerides (p less than 0.05). CONCLUSIONS. The close relation between coronary calcium and extracoronary plaques suggests that echography of extracoronary vessels could aid in the screening of coronary atherosclerosis in high-risk, asymptomatic individuals.
Abstract: OBJECTIVES. The effects of hypertension and diabetes on the physical properties of large arteries were compared in men. BACKGROUND. Although these two diseases are linked to vascular stiffening, no study has analyzed whether the arterial rigidity in diabetes is as substantial as in hypertension. METHODS. Noninvasive measurements of brachial artery mean pressure, diameter (pulsed Doppler study) and compliance (pulse wave velocity) were obtained in 29 men: 11 control subjects, 9 hypertensive nondiabetic patients and 9 diabetic normotensive patients. Individual diameter- and compliance-pressure curves extrapolated from the measured diameter and mean pressure point with a logarithmic elastic model permitted calculation of isobaric diameter and compliance at the same pressure in each subject. RESULTS. Compared with control subjects, hypertensive patients had a larger brachial artery measured diameter and isobaric diameter (p < 0.01) and lower measured and isobaric compliance (p < 0.001, p < 0.01). Compared with control subjects, diabetic patients had lower measured and isobaric compliance (p < 0.01). Comparison of diabetic and hypertensive patients showed that measured diameter and isobaric diameter were decreased in the former (p < 0.01). In the control and hypertensive groups, mean pressure correlated positively with measured diameter and isobaric diameter (p < 0.01) and negatively with measured and isobaric compliance (p < 0.001 and p < 0.01, respectively). In the control and diabetic groups, fasting glucose correlated negatively with measured and isobaric compliance (p < 0.01, p < 0.05). CONCLUSIONS. Intrinsic alterations of the large artery independent of a stretching pressure effect reduce arterial elasticity similarly in those with hypertension or diabetes. The loss of compliance is related to the chronic elevation of blood pressure in hypertension and to that of glycemia in diabetes and is associated with a relative large artery vasoconstriction in diabetic patients as compared with patients with hypertension.
Abstract: Differences exist between short- and long-term haemodynamic effects of diuretics. In the short term, plasma volume depletion is accompanied by increased peripheral vascular resistance and decreased cardiac output. In the long term cardiac output returns toward normal, peripheral resistance falls to below pretreatment values and blood volume remains lower than before therapy. This long-term decrease in volume may contribute to the chronic antihypertensive effects of diuretics. Many studies have reported that arterial compliance is increased after antihypertensive drug administration. However, it is important to known whether such action is a primary pharmacological effect or mediated by the reduction in blood pressure. Two different methods using pulse wave velocity measurements have been applied to determine the pressure-dependence of compliance before and after thiazide administration. In the first method, blood pressure was controlled as a variable by changing transmural pressure of the forearm encased in a rigid plastic tube. In the other method arterial compliance in the brachial artery was evaluated using a simple non-linear arterial model. Both methods demonstrated that the decrease in blood pressure with thiazide therapy was associated with increased arterial compliance. However, by measuring arterial compliance at the same pressure, its isobaric values were found to be unchanged. The implication is that the increase in compliance of the peripheral artery observed with diuretics is due to the decline in blood pressure rather than to a change in the intrinsic properties of the arterial wall.
Abstract: Systolic time intervals and brachial circulation, evaluated by pulsed Doppler in terms of arterial diameter, blood velocity and flow, and vascular resistance, were studied in 12 hyperthyroid patients and in 12 normal controls. In patients, arterial circulation was studied before and during mechanical exclusion of the hand, and hemodynamic measurements were repeated after beta-blocker treatment and after obtainment of euthyroid state. Compared with controls, patients had higher heart rate (P < 0.001), lower systolic time intervals (P < 0.05, P < 0.01), and higher blood velocity (P < 0.05). Beta blockade decreased heart rate (P < 0.05, P < 0.001) but did not change systolic time intervals and arterial circulation. Euthyroid state decreased heart rate (P < 0.01), preejection period (P < 0.01), and blood velocity (P < 0.01) and flow (P < 0.05). The decreases in velocity and flow before hand exclusion when euthyroid state was obtained were correlated with hyperthyroid values of velocity and flow respectively (r = 0.85, r = 0.90, P < 0.01, P < 0.001). Vascular resistance during hand exclusion was correlated negatively with serum T3 level during hyperthyroid and euthyroid states. Thus, thyroid hormones but not beta-adrenoreceptors participate in the peripheral hyperkinesia of hyperthyroidism.
Abstract: The diameter, blood velocity, and blood flow of the brachial artery were evaluated with a pulsed-Doppler apparatus before and after wrist occlusion in 16 normocholesterolemic and 27 hypercholesterolemic male subjects of similar age and body mass index. Before occlusion, no hemodynamic differences were observed between the two groups. Occlusion significantly reduced blood velocity and blood flow in the two groups (p less than 0.001), but such reductions were not different between hypercholesterolemic and normocholesterolemic groups. Occlusion decreased the arterial diameter in the hypercholesterolemic group only (p less than 0.001), and absolute diameter changes after occlusion were significantly different between the two groups (p less than 0.001). No correlation was found between the change in arterial diameter after occlusion and the baseline diameter before occlusion in the normocholesterolemic and hypercholesterolemic population overall. Absolute and percent diameter changes after occlusion were correlated with total cholesterol (r = -0.73, r = -0.72; p less than 0.001) and with low density lipoprotein (LDL) cholesterol (r = -0.68, r = -0.69; p less than 0.001) in the normocholesterolemic and hypercholesterolemic population overall, respectively. These findings indicate that the low-flow state induces a reduction in large-artery diameter in the hypercholesterolemic but not in the normocholesterolemic state and is closely related to the degree of elevation of blood cholesterol and of its LDL fraction.
Abstract: Both marked hypercholesterolemia and severe hypertension have been reported to be associated with an enhanced sensitivity of blood platelets to activating agents. To investigate a possible mutual synergistic effect of moderate hypercholesterolemia and mild hypertension on platelet reactivity, we studied in 29 patients the response to aggregating agents, ADP and collagen, and the intracellular cyclic AMP content and cytosolic Ca2+ concentration that participate, respectively, as inhibitory and stimulatory mediators in platelet responses. When compared to age- and blood pressure-matched patients with normal or slightly elevated plasma cholesterol, the patients with total platelet cholesterol higher than 6.4 mM were characterized by a decreased response to collagen and ADP (14.5 +/- 3.0 vs. 23.8 +/- 2.0 a.u. and 17.7 +/- 4.5 vs. 26.9 +/- 2.7 a.u., respectively), a tendency to a reduced cAMP content both in the basal state and after phosphodiesterase inhibition by Ro-15 2041 (2.83 +/- 0.18 vs. 3.26 +/- 0.22 mumol/10(8) cells and 4.57 +/- 0.29 vs. 5.38 +/- 0.36 mumol/10(8) cells, respectively), and no change in cytosolic Ca2+ concentration (190 +/- 11 vs. 203 +/- 13 nM). After a chronic treatment with nitrendipine (20 mg/day for 6 months), blood pressure, platelet [Ca2+]i and cAMP content decreased in the patients with normal or moderately elevated hypercholesterolemia (p less than 0.001, less than 0.001, and less than 0.05, respectively), but these effects were attenuated or absent in the patients with higher hypercholesterolemia. Plasma lipids and the platelet-aggregating response to ADP and collagen were unchanged by this long-term nitrendipine treatment in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Arterial compliance describes a change in the volume of arteries following a change in blood pressure. The physical basis of the compliance concept and experimental procedures in animals both indicate that the relation between arterial compliance and blood pressure pattern is often unclear. Compliance is pressure-dependent because of the biphasic elastin and collagen composition of arteries and, hence, decreases when blood pressure increases. Compliance also determines the pulsatile amplitude of the pressure wave by regulating the buffering function of an artery's face to the cardiac pump and, accordingly, its reduction induces a selective increase in systolic level. The questions are whether these theoretical and experimental phenomena can be extrapolated to human hypertension and whether they can be assessed from indirect measurement of arterial compliance by means of a time-domain analysis of arterial pressure and flow waves via various models of the arterial tree. Whatever the method and site of measurement, arterial compliance was found to be decreased in different forms of hypertension. This low compliance can be considered to have a causal role in elderly patients with isolated systolic hypertension. In contrast, in patients with systolo-diastolic hypertension physiologic and pharmacologic arguments exist against the fact that low arterial compliance may be the pure consequence of mean blood pressure elevation. Moreover, it is suggested that aging acts in concurrence with pressure elevation to decrease arterial compliance, and that in certain hypertensive patients additional factors, perhaps atherosclerotic in nature, contribute to impair the elastic properties of arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The purpose of this study was to estimate the effect of hypertension on the visco-elastic properties of the brachial artery in man. Seventy-five subjects including 23 with normal blood pressure (group N, PN = 95 +/- 7 mmHg, P designates the arterial mean pressure, P = DBP + (SBP-DBP)/3) and 52 with essential hypertension (group H, PH = 122 +/- 12 mmHg) participated to this study. We measured the diameter of the brachial artery (D) by the pulsed Doppler method, the brachial-radial pulse wave velocity (PWV) by the mecanographic method, and calculated the arterial compliance (C) by the Bramwell-Hill formula. A nonlinear model was used to calculate compliance and pression at any given pressure, in particular at PN or PH. We obtained the following results: [table; see text] Passive (pressure-induced) effect was obtained by comparing D(PH) to D(PN) and C(PH) to C(PN). Isobaric effect of hypertension was estimated by comparing D(PH) and C(PN) between the N and H groups. We concluded that hypertension actually induces a decrease in compliance. However, arterial diameter is increased in hypertension. The increase in diameter appears as a compensatory effect, without which the reduction in compliance would be more nocive to the circulatory system.
Abstract: Aggregation index and critical disaggregation shear rate (which represent the minimum shear rate necessary to break up the aggregates) have been measured for 21 hypertensive and 17 normotensive subjects by a laser technique (erythro-aggregameter SEFAM). A simultaneous measurement of blood viscosity by a Couette viscometer with coaxial cylinders at different shear rate allowed the calculation of critical disaggregation shear stress by the product of critical disaggregation shear rate and blood viscosity. The comparison of the results of normotensive and hypertensive subjects showed a higher aggregation index (22%, p less than 0.0001), critical disaggregation shear rate (19%, p less than 0.002) and critical disaggregation shear stress (29%, p less than 0.004) in hypertensive patients. These alterations might play an important role on development of cardiovascular complication in hypertensive subjects.
Abstract: Hypertensive and diabetic mellitus diseases are known to increase stiffness of the arterial wall. However these alterations probably involve different mechanisms. To this end, we compared the effect of hypertension and diabetes on large artery caliber and elasticity at real pressure conditions and at the same level of pressure. Nine poorly controlled non insulino-dependent diabetic men without hypertension and 9 non-diabetic essential hypertensive men underwent measures of lumen diameter (pulsed Doppler) and segmental compliance (Bramwell and Hill formula; pulse wave velocity) at the brachial artery. Isobaric diameter and compliance were deduced from a non linear model, comparing diameter and pressure on one part, and compliance and pressure on the other. Pulse wave velocity was similarly increased in both diseases (11.5 +/- 1 vs 12.8 +/- 1 m/s; NS; respectively in diabetes and hypertension). Both measured and isobaric diameters were smaller in diabetic patients (4.05 +/- 0.2 vs 5.03 +/- 0.2 mm, p less than 0.1% for the measured diameters respectively in diabetes and hypertension and 4.06 +/- 0.2 vs 5.01 +/- 0.2 mm, p less than 1% for isobaric diameters). The measured and isobaric compliances were not significantly different (2.38 +/- 0.4 vs 2.08 +/- 0.2 cm/mmHg10(-4), NS, for the measured compliance respectively in diabetes and hypertension; 2.28 +/- 0.4 vs 2.4 +/- 0.2, NS for the isobaric compliance). After correction of the effect of mechanical arterial stretch induced by the different blood pressure level of the two groups, significant reduction of diameter in diabetic subjects persisted and isobaric and measured compliances remained unchanged between groups.
Abstract: Brachial artery diameter and compliance were measured in 23 normotensive control subjects and 49 hypertensive patients. The results were compared in isobaric conditions by a modeling analysis extrapolating from the measured data a short segment of the pressure-diameter and pressure-compliance curves in the artery. A logarithmic diameter-pressure function was used as well as measurements of brachial artery blood pressure and lumen diameter (by pulsed Doppler), and of brachial-to-radial pulse wave velocity (by mechanography). The measured values of diameter and compliance in the hypertensive patients were 109% and 63%, respectively, of the control group values. By extrapolating the data via the model at the same pressure level in all subjects (the average level of mean blood pressure of the two groups), the isobaric values of diameter and compliance in the hypertensive patients were 107% and 81%, respectively, of the control group values. Overall, measured isobaric diameters and measured compliance correlated with systolic, diastolic, and mean blood pressure values (p less than 0.001), whereas isobaric compliance correlated only with systolic (p less than 0.05) and pulse (p less than 0.01) pressure values. Thus, the increased diameter and reduced compliance of the brachial artery observed in hypertensive humans cannot be attributed solely to the stretching effect of elevated blood pressure, but also to intrinsic alteration of the arterial walls. These could represent either adaptative structural or functional changes secondary to the chronic increase in arterial pressure, or primary abnormalities of the vessel wall.
Abstract: The effects of short-term administration of indomethacin and propranolol were studied in two groups of patients with borderline hypertension and both central and peripheral hyperkinesia. Indomethacin and propranolol both significantly increased total peripheral resistance (respectively +32 +/- 3%, +59 +/- 7%, p less than 0.001). The increase in blood pressure after administrating propranolol was not significant (+3 +/- 2%), as opposed to what was obtained with indomethacin, (+5 +/- 2%, p less than 0.02). On the brachial artery, Indomethacin had no effect on blood flow and local resistance, on the other hand propranolol induced a decrease in blood flow in the brachial artery (-43 +/- 3%, p less than 0.001) and an elevation of local resistance (+105 +/- 18%, p less than 0.01). While central hyperkinesia depends on both prostaglandins and on the beta-adrenergic system, high muscle blood flow seems to be regulated by the beta-adrenergic system alone, without participation of prostaglandins.
Abstract: Hypertension may influence the atherosclerotic process of large arteries via pressure and shear forces. The pressure force dilates and stiffens arteries because of the non-linear elastic behaviour of arterial walls. This partly explains the increased diameter and decreased compliance of the brachial artery in hypertensive subjects compared with normotensive controls. However, pressure lowering by antihypertensive drugs does not always reverse large artery alterations indicating that other mechanisms are involved. Reversal of low compliance obtained with certain antihypertensive drugs is generally concomitant with large artery vasodilation, suggesting that smooth muscle relaxation plays a major role in the compliance response to drugs. Atherosclerosis associated with hypertension also causes additional loss of compliance and creates a vicious circle of sclerosis development by accelerating the biophysical fatigue of bioelastomers. Hypertension may contribute to atherogenesis by means of wall shear stress which is the frictional force exerted by the circulating blood column on the intima of arteries. Since it is likely that atherosis lesions may develop preferentially in low shear conditions, hypertension may promote the haemodynamic conditions of atherogenesis at the blood-wall interface. The response of wall shear to antihypertensive treatment is not unequivocal. For example, the beta-blocker, atenolol, does not change shear whereas carteolol increases shear rate and stress and these effects are closely related to change in platelet-free calcium concentration. This finding is consistent with the effect of shear forces on cell permeability to calcium demonstrated in vitro and points to the crucial role of wall shear as a biophysical signal capable of modifying the endothelial structure and function of arteries.
Abstract: Ultrasonic detection of atherosclerotic plaque of carotid abdominal aortic and femoral arteries and evaluation of risk factors were performed in 208 hypercholesterolemic men without cardiovascular disease. Twenty-six percent of them had no plaque. Plaque at the carotid, aortic, and femoral sites was found in 37%, 48%, and 53% of subjects, respectively. Plaque was associated (1) in carotid arteries with increased total and low-density lipoprotein cholesterol; (2) in the aorta with increased age, pressure, glycemia, and smoking; and (3) in femoral arteries with increased age, systolic pressure, low-density lipoprotein cholesterol, and smoking. Multiple regression analysis showed correlations between carotid plaque and low-density lipoprotein cholesterol; aortic plaque and age, smoking, glycemia, and pressure; femoral plaque and age, smoking, and pressure. This suggests that multiple risk factors influence lesions, and risk profile differs according to atherosis site.
Abstract: We studied the aortic elastic behavior in response to vitamin D3-induced accelerated calcinosis in conscious dogs chronically instrumented with a pressure microtransducer and a pair of ultrasonic diameter dimension gauges in the upper descending thoracic aorta. The two functional phases of the elastic segmental properties of the aorta in vivo were discriminated by computation on a beat-by-beat basis from the phasic pressure-diameter (P-D) hysteresis loops in basal conditions and during the transient state of a wide range of pressures obtained mechanically (aortic occlusion) or pharmacologically (angiotensin bolus). The overall P-D curve formed by all P-D hysteresis loops was comprised of two linear relations according to a model that assumes that only elastin is stretched at lower pressures, whereas both elastin and collagen are stretched at higher pressures. The slope of the first linear portion of the P-D curve was considered as the elastin P-D elastic modulus, and the slope of the curve obtained by subtraction between the P-D curve and the extrapolation of the elastin straight line was assumed to be the collagen P-D elastic modulus. After vitamin D3-induced calcinosis, the elastin elastic modulus was unaffected, whereas the collagen elastic modulus decreased significantly during occlusion maneuvers (58.6%, p less than 0.01) and during bolus injections of angiotensin (37.2%, p less than 0.05). The collagen elastic modulus correlated with the serum calcium concentration (r = -0.65, p less than 0.001) and with the aortic pulse pressure (r = 0.51, p less than 0.01), and this relation persisted at constant heart rate. Histopathologic analysis evidenced calcium-depositing elastic lamina, focal disappearance of collagen, and rupture of elastic fibers. The present study shows that accelerated, severe, experimental calcinosis-inducing calcium deposition inside the large artery walls is accompanied by a clear-cut paradoxical reduction in arterial rigidity that is mainly due to functional and structural modification of collagen elasticity.
Abstract: The elastic behavior of total elastin (EE) and collagen (EC) and the recruitment of collagen fibers (FC) supporting wall stress at a given transmural pressure level were assessed in seven conscious dogs using descending thoracic aortic pressure (microtransducer) and diameter (sonomicrometer) measurements. Stress-strain relationships values calculated at control and during bolus administration of angiotensin and nitroglycerin enabled quantification of angiotensin and nitroglycerin enabled quantification of elastic moduli of elastin (EE = 4.868 +/- 1.753 x 10(6) dyn/cm2; means +/- SD) and collagen (EC = 1,306 +/- 637 x 10(6) dyn/cm2) according to a biphasic model of elastin and collagen parallel arrangement. The FC was found to be 6.1 +/- 2.6% at a pressure level of 118 +/- 16 mmHg. Values for EE and EC were similar to those reported in in vitro studies and showed scarce variability. This approach provides a quantitative evaluation of elastin and collagen moduli in conscious animals and also permits the evaluation of FC, which may be of interest in studies of connective tissue diseases involving the aortic wall.
Abstract: Brachial artery wall shear phenomena were studied in 20 untreated essential hypertensive patients and in 11 normotensive controls of similar age. A pulsed-Doppler velocimeter was used to measure brachial artery internal diameter and mean cross-sectional and systolic centreline blood velocities. A coaxial-cylinder viscometer was used to measure blood viscosity at a shear rate of 96 s-1. A Poiseuille model of velocity distribution across the arterial lumen was used to determine wall shear rate and stress from, respectively, the ratio of blood velocity to arterial diameter and the product of shear rate and blood viscosity. Mean and systolic shear rates and stresses were calculated using, respectively, mean cross-sectional and systolic centreline blood velocities. Hypertensive patients had larger brachial artery diameters (P less than 0.001), lower systolic centreline and mean cross-sectional blood velocities (P less than 0.001, P less than 0.05), higher blood viscosity (P less than 0.001), lower mean and systolic wall shear rates (P less than 0.01, P less than 0.001) and lower systolic wall shear stress (P less than 0.05) than normotensive controls. In all subjects, mean blood pressure was negatively correlated both with mean and systolic shear rates (r = -0.38, P less than 0.05;r = -0.45, P less than 0.01). Thus the hypertensive state was associated with decreases in both mean and systolic wall shear rates, and in systolic wall shear stress. These shear abnormalities merit attention because of the atherogenic effect of low-shear conditions.
Abstract: A new geometric procedure determination of velocity profiles inside large human arteries, such as the brachial and femoral, has been developed. The procedure requires the use of two crystal element Doppler probes and a highly precise micromanipulator with three degrees of freedom. Precise positioning is needed to obtain the required high degree of parallelism between the vessel axis and the plane containing the two crystal elements. Once the appropriate degree of parallelism is achieved, a controlled translation of the probe, perpendicular to the ultrasonic beam plane, allows velocity waveforms to be recorded at sequential radial positions across the measured artery. Velocity profiles obtained with this geometric procedure depended on the type of artery investigated. The profiles measured with the geometric procedure were more symmetrical than those found using the electronic range-gated time system of reception. While the geometric and electronic methods were almost identical in determining the diameter values of the three arteries measured, the geometric procedure enabled greater accuracy for detailed analysis of velocity profiles in the peripheral large arteries in humans. Although the present methodology is not applicable in clinical practice due to prolonged data acquisition time (approximately 45 s) it is expected that future equipment improvements will reduce this time significantly.
Abstract: STUDY OBJECTIVE - The aim of the study was to examine oscillating arterial wall shear stress in hypertension. DESIGN - Pulsatile flow and oscillating wall shear stress were measured in brachial artery in hypertensive v normotensive subjects using pulsed Doppler apparatus. Methods were tested in four subjects using a micrometric procedure of Doppler probe displacement providing instantaneous real time velocity profiles. SUBJECTS - 19 ambulatory male patients with mild to moderate hypertension (diastolic blood pressure 95-114 mm Hg) and 11 normotensive male controls of similar age were studied. All were non-smokers. MEASUREMENTS and RESULTS - Arterial diameter and pulsatile centreline blood velocity were determined with pulsed Doppler, and blood viscosity was measured with a coaxial cylinder viscometer. Shear rates corresponding to maximum (gamma Vmax), minimum (gamma Vmin), and pulse (gamma Vpulse) velocities were evaluated with a simplified method of computation of Womersley equations. Corresponding shear stresses (tau Vmax, tau Vmin, tau Vpulse) were calculated as the product between shear rate and viscosity. The differences in wall shear rates obtained with the Womersley method and with the micrometric procedure were less than 10%. Compared to normotensives, hypertensives had greater arterial diameter [0.508(SEM0.006) v 0.446(0.014), p less than 0.001], lower maximum velocity [36.2(1.5) v 46.3(2.4) cm.s-1, p less than 0.001], lower absolute value of minimum velocity [-8.3(1.2) v -14.3(2.3) cm.s-1, p less than 0.01], lower pulse velocity [44.5(2.2) v 61.2(3.9) cm.s-1, p less than 0.001], and higher blood viscosity [4.77(0.08) v 4.28(0.09) mPa.s, p less than 0.001]. gamma and tau Vmax, Vmin and Vpulse were all lower in absolute value in hypertensives. Overall mean blood pressure in all subjects was negatively correlated to gamma Vmax (r = -0.65), tau Vmax (r = -0.46), gamma Vmin (r = -0.45), tau Vmin (r = -0.37), gamma Vpulse (r = -0.63), and tau Vpulse (r = -0.48). In hypertensives, age was correlated negatively to gamma Vmax (r = -0.44), tau Vmax (r = -0.46), gamma Vmin (r = -0.57), tau Vmin (r = -0.57), gamma Vpulse (r = -0.58), and tau Vpulse (r = -0.58). In normotensives, age was not correlated with shear parameters, except for tau Vmax (r = -0.60) and tau Vpulse (r = -0.66). CONCLUSIONS - The hypertensive state is associated with a reduction in oscillating wall shear in large arteries despite an increase in blood viscosity. Age in combination with hypertension also decreases wall shear conditions.
Abstract: STUDY OBJECTIVE--The aim of the study was to evaluate in hypertensive subjects the longitudinal pressure drop and segmental resistance in a large artery in relation to shearing forces of the circulating blood column at the arterial wall. DESIGN--Arterial diameter, blood velocity, and flow were measured in the brachial artery using pulsed Doppler apparatus. Blood viscosity was measured at 96 s-1 with a low shear viscometer. Segmental resistance per unit arterial length was calculated using the basic Poiseuille resistance expression from the ratio between blood viscosity and the fourth power of arterial diameter. Longitudinal pressure drop was deduced as the product between segmental resistance and blood flow. The Poiseuille model of velocity distribution also enabled wall shear rate and stress to be calculated from the ratio between blood velocity and arterial diameter and from the product between shear rate and blood viscosity respectively. PATIENTS--19 ambulatory male patients with mild to moderate hypertension and 11 normotensive male controls of similar age were studied. RESULTS--Compared to controls, hypertensive patients had higher arterial diameter (p less than 0.001) lower blood velocity (p less than 0.05), higher blood viscosity (p less than 0.01), lower segmental resistance and pressure drop (p less than 0.001, p less than 0.01) and lower shear rate and stress (p less than 0.01, p less than 0.05). A negative correlation existed in the overall normotensive and hypertensive population between pressure drop and mean blood pressure (r = -0.55, p less than 0.01). CONCLUSION--The hypertensive state is associated with a clear reduction in large artery segmental resistance and longitudinal pressure drop concomitantly with a decrease in shear conditions at the arterial wall. The mechanisms of reduced resistance and pressure drop are related to decreased wall shear and increased diameter of the artery, both of which reduce the frictional forces at the blood-arterial wall interface.
Abstract: Hypertension may induce early alterations in large arteries by 2 mechanical stresses: one related to intravascular pressure, the other to blood flow dynamics. Distending pressure force acts in a circumferential direction, inducing decreased arterial distensibility. Arterial distensibility can be evaluated in humans by measurement of arterial compliance and pulse-wave velocity. It is well established that in chronic hypertension age and elevated pressure act together to increase arterial rigidity. Blood flow dynamics induce frictional forces in the endothelial surfaces of arteries. These forces, expressed by shear stress, are proportional to the viscosity of the blood and to the velocity gradient at the arterial wall. Measurement of blood viscosity and evaluation of velocity profile in the brachial arteries of hypertensive subjects have shown a reduction in wall shear rate and stress despite the elevation in blood viscosity. Several studies have shown that drug therapy that successfully reduces blood pressure does not necessarily improve arterial compliance. In contrast, few data are available on the effects of antihypertensive medication on arterial wall shear in humans. Arterial compliance and wall shear stress are 2 main therapeutic targets of potential importance in the physiopharmacologic approach to the effects of hypertension on atherogenesis.
Abstract: A new non-invasive methodology of measurement of pulsatile wall shear in superficial large arteries in man is presented from simple determinations of internal diameter of large artery and centerline instantaneous blood velocity (pulsed Doppler apparatus) and asymptotic blood viscosity (coaxial cylinder viscometer). Pulsatile distribution of velocity across the arterial lumen has been represented by a Womersley model enabling to define and calculate wall shear rate as the slope at the wall to the velocity profile at each cardiac time. These complex mathematical calculations have been performed on micro-computer by means of appropriate programmation according to the following steps (1) Digitization and processing of instantaneous centerline blood velocity (2) Decomposition of velocity signal into Fourier series as a sum of elementary velocity sinusoids of increasing frequency (3) computation of velocity profile and slope at the wall to the profile for each harmonic (4) Resynthetization of instantaneous wall shear rate as function in time (5) calculation of wall shear stress by multiplying wall shear rate by blood viscosity. Taking the brachial artery as model of peripheral large artery, pulsatile wall shear rate and stress curves were determined in individual subjects and analysed by means of several characteristic indices including: maximum, minimum and mean values; time of systolic increase and time of systolic relaxation; and oscillating index defined from the positive and negative surfaces of the shear curve. This original methodology open new way for studying hemodynamical conditions at the interface between blood and endothelium surface of large arteries and might be applied to the physiopharmacological approach of vascular disease such as hypertension.
Abstract: Since resistance to flow is theoretically determined by arteriolar geometry and blood viscosity, we studied these two factors in 44 normal and 106 hypertensive subjects. Brachial bed vascular resistance was calculated as the ratio between mean pressure and brachial artery flow. Systemic blood viscosity in vitro was determined at 96 per s, while microvessel blood viscosity in vivo was estimated from the haematocrit-viscosity relationship at 240 per s. A resistive radius index was calculated which was only related to the microvessel viscosity: resistance ratio. Compared to normal subjects, hypertensive subjects had higher systemic in vitro blood viscosity (4.75 +/- 0.47 versus 4.50 +/- 0.43 mPa.s; P less than 0.005) and microvessel blood viscosity (2.60 +/- 0.21 versus 2.43 +/- 0.16 mPa.s; P less than 0.001). Hypertensive subjects also had a higher brachial vascular resistance (161 +/- 89 versus 124 +/- 58 mmHg/ml per s; P less than 0.01), but showed a similar resistive radius index (2.47 +/- 0.36 versus 2.57 +/- 0.35) compared to normal subjects. There was a positive correlation between systemic viscosity and brachial artery diameter and a negative correlation between microvessel viscosity and vascular resistance in the normotensive (P less than 0.05 and P less than 0.001, respectively) and hypertensive groups (P less than 0.001 and P less than 0.005, respectively). The resistive radius index was positively related to viscosity in normal and in hypertensive groups (P less than 0.001) but these relationships were significantly different (P less than 0.001), showing that, at the highest viscosities, arterial radius increased less in hypertensive than in normal subjects. Thus, the level of blood viscosity might influence arterial diameter.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The relations between carotid arteries and/or abdominal aortic plaque and cardiovascular risk factors were investigated by ultrasonography in 161 untreated hypercholesterolemic normotensive men. Of them, 58 had no plaque (NP group), 34 had carotid but not aortic plaque (CP group), 34 had aortic but not carotid plaque (AP group) and 35 had both carotid and aortic plaques (CAP group). Groups significantly differed for age, smoking, blood pressure, and the ratio of total to HDL cholesterol. Age was higher in CAP group than in NP and CP groups and in AP and CP groups than in NP group. Life long smoking dose was higher in CAP group than in CP, AP, and NP groups. Systolic and diastolic pressures were higher in CAP group than in NP group, systolic pressure was higher in CAP group than in CP group, and diastolic pressure was higher in AP group than in CP and NP groups. The ratio of total to HDL cholesterol was higher in CAP group than in AP, CP, and NP groups. Multiple regression analysis showed that carotid plaque was only related to age, while aortic plaque and the number of sites affected by plaque were correlated to age, smoking and diastolic pressure. These findings suggest that in hypercholesterolemia risk factors other than lipids seem to influence arterial plaque and that risk profile differs according to the plaque location.
Abstract: 1. Blood cells and vascular endothelial cells are subjected to a wide range of haemodynamically generated shear stress forces. In vitro, membrane stretching or shear stress have been observed to activate ion channels and cell metabolism and to facilitate erythrocyte and platelet aggregation. 2. The present study was designed to evaluate the participation of shear stresses in the control of apparent platelet cytosolic free Ca2+ concentration in hypertensive patients. 3. Shear conditions and platelet cytosolic free Ca2+ concentration in vitro were studied after a dynamic perturbation induced by 3 months of double-blind treatment with one of two beta-antagonists, carteolol and atenolol. Brachial artery wall shear rate and stress were estimated by means of a pulsed Doppler velocimeter, and blood viscosity was measured by a co-axial viscometer at a shear rate of 96 s-1. Platelet cytosolic free Ca2+ concentration was simultaneously measured by using the Quin-2 fluorescent chelator. The direct effect of atenolol and carteolol on platelet cytosolic free Ca2+ concentration in vitro was also measured after addition of the beta-blockers to platelet-rich plasma. 4. Atenolol and carteolol decreased blood pressure similarly but their effects on shear rate (P less than 0.02), shear stress (P less than 0.01) and platelet cytosolic free Ca2+ concentration (P less than 0.05) differed after 3 months of therapy. In contrast, neither of the drugs significantly altered platelet cytosolic free Ca2+ concentration, in vitro per se. 5. In the overall population, strong positive correlations existed not only between changes in platelet cytosolic free Ca2+ concentration and those in shear rate (r = 0.81, P less than 0.001) and shear stress (r = 0.83, P less than 0.001), but also between their absolute values, suggesting a possible haemodynamic shear-dependent modulation of transmembrane Ca2+ transport.
Abstract: Brachial artery flow patterns were studied in 10 hyperthyroid and 10 normal subjects. Mean blood velocity and flow were evaluated by pulsed Doppler, and peak systolic acceleration was calculated by computer-assisted digitization of the instantaneous velocity curve. Compared to control subjects, hyperthyroid patients had higher velocity and flow (p less than 0.01, p less than 0.02) and higher peak systolic acceleration (p less than 0.01). In hyperthyroid patients, measurements were repeated after (1) mechanical exclusion of the hand from brachial circulation, (2) short-term beta-blocker treatment and (3) inducement of the euthyroid state. Exclusion of the hand reduced velocity and flow (p less than 0.001) but did not change peak systolic acceleration. Beta blockade induced disparate changes of velocity and flow but reduced peak systolic acceleration (p less than 0.05). In the euthyroid state, decreased blood velocity (p less than 0.01), flow (p less than 0.02) and acceleration (p less than 0.02) were observed. A hyperkinetic arterial circulation consisting of an increase in both velocity and acceleration is thus observable in hyperthyroidism. Hand exclusion showed that velocity seems to be influenced by peripheral factors while beta blockade suggests that acceleration is dependent of beta 1 adrenoceptors. Comparison between euthyroidism and hyperthyroidism indicates that both mean blood velocity and peak systolic acceleration are influenced by thyroid hormones.
Abstract: Systolic wall shear conditions were studied in the brachial artery of 4 groups of subjects including 11 non-smokers normotensives (NSNT), 25 non smokers hypertensives (NSHT), 21 smokers normotensives (SNT) and 10 smokers hypertensives (SHT). Brachial artery diameter (D) and systolic centerline blood velocity (VCLS) were measured with a pulsed Doppler device and blood viscosity at 96 sec-1 was measured with a coaxial cylinder viscometer. The wall shear rate (gamma S) corresponding to systolic velocity was calculated using a Womersley model of pulsatile flow according to the formula: alpha = (D/2) (omega/mu) 1/2, omega being the angular pulse frequency and mu the kinematic viscosity. The wall shear stress was then calculated as the product between wall shear rate and viscosity. The analysis of results in the 4 groups showed that both hypertension and smoking increased blood viscosity bu their effects on wall shear were opposite since hypertension decreased shear and stress while smoking did not change it. However, in hypertensive patients, smoking induced a clear elevation in wall shear rate and stress, whereas in smokers hypertension did not change shear conditions. Thus, opposite and interactive effects of hypertension and smokers exist on large artery wall shear phenomena which could induce differences in response of functional and structural endothelial cells to these two vascular risk factors.
Abstract: To determine the effects of parasympathetic blockade and beta-blockade on the elastic response of aortic stiffness to vasopressive interventions, we studied 5 unanesthetised adult mongrel dogs by means of a pressure microtransducer and two ultrasonic crystals positioned at opposing sites in the proximal descending thoracic aorta which were used for diameter measurements. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced using infusions of epinephrine during the control period and later propranolol (1.5 mg/kg) plus atropine (0.2 mg/kg). Percent variations of mean aortic diameter were correlated to percent variations in mean aortic pressure in the control period and after autonomic blockade (P less than .001). The slopes of these correlations in the control group were higher than after autonomic blockade (P less than .05). Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control group and after autonomic blockade (P less than .001). The slopes of the correlations of incremental elastic modulus and Peterson's modulus versus mean aortic pressure were lower in the control group than after blockade (P less than .001). We conclude that in conscious dogs, autonomic blockade with propranolol and atropine decreased the distension and increased the stiffness of the aortic wall in response to acute hypertension mediated by epinephrine.
Abstract: Brachial and carotid artery diameters, blood velocities and blood flows were determined by a pulsed-Doppler flowmeter in 22 normotensive and 74 mild to moderate essential hypertensive subjects, aged 46 +/- 8 years. The product age x MAP/1000 (where MAP is mean arterial blood pressure), called 'arterial age' (expressed in years x mmHg/1000), was used to assess the progress of age and blood pressure. The moving-mean method was first used to explore the chronic hemodynamic changes in the two circulations with a progressive increase in arterial age. The method indicated that an arterial age of about 4-4.5 units a noticeable decrease in both brachial and carotid blood velocities occurred, and at an arterial age of about 5 units an important increase in brachial artery diameter occurred. In order to test these findings, the total sample (n = 96) was divided into three groups of equal size with low, median and high arterial ages. Brachial blood velocity decreased significantly in groups 2 (P less than 0.05) and 3 (P less than 0.05) compared with group 1, and carotid blood velocity decreased significantly from group 1 to group 2 (P less than 0.02) and from group 2 to group 3 (P less than 0.05). Brachial artery diameter did not change from group 1 to group 2, but increased significantly from group 2 to group 3 (P less than 0.05). Over the whole arterial age range, the carotid artery diameter remained identical.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Segmental pressure drop and longitudinal resistance of brachial artery were evaluated in 11 normotensive (NT) and 19 hypertensive (HT) subjects of similar age by measuring arterial diameter (D), blood velocity (V) and flow (Q) with pulsed Doppler and blood viscosity (mu) at 96 sec-1 with a coaxial cylinder viscometer. Mean pressure drop (delta P) per unit of length of artery was calculated according to the relation delta P = 4 tau/D, where tau is the mean wall shear stress evaluated on the basis of a Poiseuille velocity profile by the formula: r = vV/D. Brachial artery resistance per unit of length was deduced as the (delta P/Q) ratio. (table; see text) In the overall normotensive and hypertensive group, (n = 30), pressure drop (delta P) was negatively correlated with mean blood pressure (r = -0.55, P less than 0.01). Despite increased viscosity hypertensive patients have a decreased resistance of large arteries whose mechanisms include a reduction in shear stress close to the endothelium and a dilation of the conduit artery; these two abnormalities contribute to decrease the viscous force of the circulating blood column against the arterial wall.
Abstract: Arteriolar geometry and blood viscosity, the two main factors determining vascular resistance were studied in 44 normotensive subjects and 106 hypertensive patients at the brachial circulation level. Vascular resistance was calculated as the ratio between mean blood pressure and mean arterial flow determined by pulsed Doppler. Blood viscosity at 240 sec-1 was measured with a coaxial cylinder viscometer: Compared to controls, hypertensive patients had higher vascular resistance (161 + 8 vs 124 + 9 mmHg.ml-1.sec, P less than 0.05) and higher viscosity (4.75 + 0.05 vs 4.50 + 0.07 mPasec, P less than 0.01). Vascular resistance was negatively correlated to blood viscosity both in control (r = 0.48; P less than 0.001) and in hypertensive (r - 0.39, P less than 0.001) groups. Arteriolar equivalent radius (a) calculated from Poiseuille's equation from the relation a = (8 mu/pi R) 1/4 was positively correlated to viscosity in the two regressions were statistically different (P less than 0.001) indicating that at higher viscosity levels, arteriolar equivalent radius had lesser increase in normotensive than in hypertensive groups. Thus chronic increase in blood viscosity is accompanied by a small vessels vasodilatory phenomenon which seems less efficient in normotensive than in hypertensive subjects and might contribute in part to the mechanisms of vascular resistance elevation observed in hypertension.
Abstract: Pulsatile wall shear conditions close to the brachial artery were evaluated in 11 normotensive and in 19 hypertensive patients of similar age by determining arterial diameter and centerline blood velocity with a pulsed Doppler and blood viscosity at 96 sec-1 with a coaxial cylinder viscometer. A Womersley model of intraluminal distribution of blood velocities enabled to determine from unsteadiness parameter alpha of Womersley, arterial diameter and maximal minimal and pulse (maximal-minimal) values of centerline velocity, the maximal minimal and pulse shear rate and shear stress (product between shear rate and viscosity) close to the endothelium. Compared to normotensives hypertenvises had higher arterial diameter (p less than 0.001), lower maximal minimal and pulse centerline velocities (p less than 0.001, p less than 0.01, p less than 0.001) higher blood viscosity (p less than 0.001), lower maximal, minimal and pulse wall shear rate (p less than 0.001, p less than 0.05, p less than 0.001) and lower maximal minimal and pulse shear stress (p less than 0.01). In the overall normotensive and hypertensive group, mean blood pressure negatively correlated to maximal minimal and pulse shear rates (r = -0.65; r = -0.45, r = -0.63) and to maximal, minimal and pulse shear stress (r = -0.46; r = -0.37, r = -0.48). Thus, hypertension is associated with a reduction of oscillating shear conditions in the viscosity of the brachial artery wall which might in long term influence structural and/or functional response to the endothelium.
Abstract: Aortic compliance is a major determinant of systolic blood pressure and of impedance to left ventricular ejection. However, little is known about its regulating factors. To assess the effects of preload and adrenergic activity on aortic compliance, we studied 10 normal subjects and nine untreated hypertensive patients at rest and during lower body negative pressure. Aortic compliance was measured invasively from the diastolic decay of the aortic pressure tracing and systemic vascular resistance. Preload was decreased stepwise by lower body negative pressure (-5 to -40 mm Hg) while adrenergic activity was assessed by the change in plasma norepinephrine at a maximum level of negative pressure suction. At rest, aortic compliance was lower in hypertensive subjects compared with its value in normal individuals (0.048 +/- 0.012 [SD] versus 0.071 +/- 0.009 units, p less than 0.001) but correlated inversely with systolic blood pressure in both groups (r = -0.64 in normotensive individuals, r = -0.83 in hypertensive subjects, r = -0.88 for the whole group, p less than 0.001 for all). Whereas resting pulmonary wedge pressure was higher in hypertensive subjects compared with normal individuals (16 +/- 4 [SD] versus 11 +/- 3 mm Hg, p less than 0.05), resting plasma norepinephrine levels were not different between the two groups (261 +/- 139 versus 251 +/- 103 pg/ml). Neither of these two resting indices correlated with baseline aortic compliance in both normotensive individuals and hypertensive patients. During lower body negative pressure (LBNP), cardiac filling pressure (right atrial pressure and pulmonary wedge pressure) as well as cardiac output decreased in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The long-term effects of selective (atenolol) and nonselective (carteolol) beta-blockers on brachial artery diameter velocity and flow and on vascular resistance (pulsed Doppler) were compared in two groups of 10 hypertensive patients at respective daily doses of 100 and 20 mg. The drugs decreased mean blood pressure (p less than 0.01) with similar magnitude, although systolic blood pressure was decreased more by atenolol than by carteolol (p less than 0.05). Heart rate was decreased by atenolol (p less than 0.01) but was unchanged by carteolol. The drugs did not change brachial circulation when the hand circulation was present. During hand exclusion (wrist occlusion) comparison from baseline showed that atenolol decreased velocity and flow (p less than 0.01, p less than 0.05) and increased resistance (p less than 0.05), whereas carteolol decreased resistance (p less than 0.05); after 3 months of treatment, velocity and flow were higher (p less than 0.01, p less than 0.001) and resistance was lower (p less than 0.01) with carteolol than with atenolol. Thus, hand exclusion demonstrated opposite drug effects on arterioles--dilation for carteolol and constriction for atenolol.
Abstract: Essential hypertension is associated with various cell abnormalities, including alterations in the metabolism of intracellular messengers, such as cytosolic free Ca2+ and cyclic AMP or IP3. Intracellular pH is implicated in the regulation of number vital functions, including cell metabolism, division and response to various stimuli. We have measured cytosolic H+ concentration ([H+]i) in human platelets and investigated a possible relationship with free Ca2+ concentrations ([Ca2+]i) in hypertensive patients. [H+]i was determined with the pH sensitive fluorescent probe BCECF in platelets from 15 normotensive subjects and 15 patients with mild to moderate essential hypertension, free from medication, il any, for at least two weeks. Donor characteristics are indicated in the table. (table; see text) [H+] cytosolic from hypertensive patients was significantly lowered by 21 p. 100 compared to normotensive values (table). Cytosolic free Ca2+ concentrations, measured with the Ca2+ fluorescent probe Fura2, were significantly increased by 19 p. 100 in platelets from hypertensive patients when compared to those of normotensive donors. Taken all together, [H+]i and [Ca2+]i varied inversely (r = -0.421, p = 0.02) in these thirty donors and tends to be correlated in the essential hypertensive patients (r = 0.490, p = 0.06). This correlation remained significant at constant age systolic and diastolic blood pressures. The simultaneous rise in [H+]i and [Ca2+]i in platelets from essential hypertensive patients are compatible with their observed enhanced sensitivity to several aggregating agents. This alkalinisation, if present in the vascular smooth muscle cells, may also reflect facilitated cell proliferation and increased sensitivity to stimulating agents, two parameters implicated in the rise of arterial blood pressure.
Abstract: Effects of experimental calcinosis induced by daily overdose of 500.000 IU Vit D3 during 10 days were studied in 6 mongrel conscious dogs chronically instrumented with intra-aortic Konigsberg microtransducer and two ultrasonic piezo-electric crystals diametrically opposed in the adventitia of the descending thoracic aorta. Simultaneous recording of instantaneous aortic pressure and diameter waves in basal state and during transient acute hypertension induced by intravenous angiotensin bolus (0.1 microgram/kg) allowed to obtain the pressure (y) diameter (x) relationship of the aorta according to an exponential regression: P = expo (beta D + A), with a highly significant correlation coefficient in all animals (r greater than 0.99). (table; see text) Anatomopathological studies of aortas revealed abnormal calcium deposition, ruptures of elastic fibers and disorganization of collagen. Thus, a striking decrease in aortic rigidity is observed after calcinosis in relation with structural changes of elastic materials and responsible in part for a reduction in pulsatile pressure; moreover this unexpected phenomena might represent an initiative process of development of aortic aneurysms.
Abstract: The effects of ketanserin (40 mg p.o.) on blood pressure and brachial haemodynamics (brachial artery diameter, brachial blood velocity and blood flow) have been compared in a double-blind study with those of ritanserin (10 mg p.o.) and placebo. Haemodynamic parameters were measured before and 1 h after treatment. Patients with mild to moderate essential hypertension participated in this study, 6 each on ketanserin, ritanserin and placebo. Placebo significantly reduced heart rate and did not modify the other parameters. Compared to placebo, ketanserin significantly reduced systolic and diastolic blood pressure, increased brachial blood velocity and flow, and decreased forearm vascular resistance. Compared to placebo, ritanserin slightly decreased blood pressure and slightly increased blood flow, but neither effect was significant. When blood circulation to the hand was excluded, neither ketanserin nor ritanserin modified the proximal arterial resistance or blood flow. It is concluded that the actions of ketanserin and ritanserin essentially occurred in the distal part of the upper limb, and alpha 1-receptor blockade is probably involved.
Abstract: Alterations in the metabolism of intracellular messengers, such as calcium and cyclic adenosine 5'-phosphate (cAMP), have been reported in essential hypertension. Since intracellular pH (pHi) participates in the control of fundamental cell functions, we looked for changes in platelet cytosolic H+ concentration [( H+]i) in hypertension and investigated whether or not its impaired metabolism is linked to the calcium handling abnormalities. The fluorescent pH indicator BCECF has been used to evaluate intracellular H+ concentration in platelets, unstimulated ex vivo, from normotensive (n = 20) and hypertensive patients (n = 20). Cytosolic [H+] was 20% lower in hypertensive than in normotensive subjects (49.5 +/- 3.4 and 61.8 +/- 2.2 nmol/l cells, respectively, P less than 0.005; mean pHi values were 7.21 and 7.33, respectively). Platelet cytosolic H+ and free Ca2+ concentrations ([Ca2+]i) were determined in parallel in 15 normotensive and 15 hypertensive patients. [Ca2+]i was found to be 19% higher (P less than 0.01), and [H+]i 22% lower (P less than 0.02), in the hypertensive patients compared with the normotensive subjects. Platelet pHi and [Ca2+]i were increased simultaneously in some hypertensive patients. These results are compatible with the hypothesis of an in vivo activation of platelets in hypertension. If a similar alkalinization exists in smooth muscle cells, it may participate in cell proliferation and in an enhanced sensitivity to agonists, two parameters thought to be involved in blood pressure elevation.
Abstract: The effects of a single oral dose of 20 mg of nicorandil were evaluated in 12 untreated patients with mild to moderate essential hypertension. Serial measurements of arterial pressures were obtained by means of an automatic device (Dynamap) up to 120 minutes after drug administration. Forearm hemodynamics were determined with a pulsed Doppler velocimeter, or strain gauge mecanography and plethysmography enabling measurement of the diameter, velocity and flow of the brachial artery as well as the arterial pulse wave velocity and forearm venous tone. In addition, local vascular resistance, compliance and impedance were deduced. Nicorandil administration produced a significant decrease in systolic and diastolic blood pressure, from 18 minutes after dosing which lasted up to the end of the study (i.e., 120 minutes after drug administration) (p less than 0.01). This decrease in blood pressure was not associated with reflex tachycardia. The brachial artery diameter increased significantly (p less than 0.01) with no change in brachial artery blood flow. A decrease in brachial-radial pulse wave velocity and arterial impedance (p less than 0.01) and an increase in arterial compliance were observed. Thus, this study demonstrated an antihypertensive activity of a single oral administration of nicorandil without baroreflex activation. This decrease in blood pressure was associated with a dilation of peripheral large arteries leading to an increase in arterial compliance. Thus, clinical testing to evaluate the antianginal activity of nicorandil, especially in hypertensive patients with coronary heart disease, should be encouraged.
Abstract: Wall shear phenomena were studied in the brachial artery in non-smoking and smoking normotensive and hypertensive subjects of similar age. Pulsed Doppler investigation revealed brachial artery diameter, and mean and systolic blood velocities (at the centerline of the vessel). A Poiseuillean blood velocity distribution was used to determine the wall shear rate and stress from velocity, diameter and viscosity. This was expressed in terms of mean and systolic values. Although hypertension and smoking both increased blood viscosity, hypertension reduced mean and systolic shear rates and stresses in non-smokers but not in smokers, and smoking increased mean and systolic shear rates and stresses in hypertensives but not in normotensives. Thus, the decreasing shear effect of hypertension was blunted by smoking, while the increasing shear effect of smoking was elicited by hypertension, suggesting an interaction of these factors on wall shear conditions.
Abstract: Right brachial artery and common carotid artery haemodynamic parameters were studied using pulsed Doppler velocimetry enabling non invasive measurements of their internal diameters and blood velocities in 74 untreated essential hypertensive patients subdivided in two groups of younger than (33 patients) and older than 45 years (41 patients). There were no significant differences in the haemodynamic parameters of brachial artery (i.e. diameter and blood velocity) between the two groups of patients. In the patients older than 45, there were no changes in the diameter of common carotid artery, but there was a decrease in carotid artery blood velocity as compared with patients younger than 45 (p less than 0.001). In the patients younger than 45, there were no correlations between the haemodynamic parameters of both circulations; in contrast, in patient older than 45 significant relationship were found between the common carotid artery diameter and the brachial artery diameter (r = 0.45, p less than 0.01) and between the blood velocity in the common carotid artery and in the brachial artery (r = 0.55, p less than 0.001). Thus, in these hypertensive patients, brachial artery circulation was not affected by age; but age older than 45 was associated with a decrease in common carotid blood flow, with no change in common carotid artery diameter. However, the existence of strong correlations between brachial and carotid artery diameters and blood velocities in patients older than 45, suggests that age might interfere, in hypertensive patients, with the specific regulatory adjustments of the brachial and carotid circulations.
Abstract: Brachial artery wall shear rate and stress were studied in 20 untreated hypertensive patients and 11 normotensive controls of similar age. A pulsed Doppler velocimeter enabled to determine the internal diameter, the mean cross-sectional blood velocity and the systolic centerline blood velocity of the brachial artery. A coaxial cylinder viscosimeter provided blood viscosity at a shear rate of 96 s-1. A Poiseuille model of arterial flow was used for evaluating wall shear rate from the ratio between blood velocity and arterial diameter and wall shear stress from the product between shear rate and blood viscosity. Shear rate and stress were expressed in terms of systolic and mean values by using respectively systolic centerline and mean cross-sectional blood velocities. Comparatively to normal controls, hypertensive patients had higher blood viscosity (4.80 +/- 0.08 vs 4.28 +/- 0.09 cpoise, p less than 0.001) lower systolic wall shear rate (303 +/- 18 vs 413 +/- 20 s-1, p less than 0.001), lower mean wall shear rate (70 +/- 6 vs 109 +/- 16 s-1, p less than 0.01) and lower systolic wall shear stress (13.86 +/- 0.81 vs 17.02 +/- 1.26, p less than 0.001) but mean wall shear stress was not statistically different between patients and controls. Such wall shear abnormalities are described for the first time in large artery of hypertensive patients and merit attention because of the experimental critical role of low shear conditions on the atherogenic process.
Abstract: The aortic elastic behavior has been studied in conscious dogs chronically instrumented with a pressure microtransducer and two ultrasonic crystals. Pressure and diameter measurements were analyzed in terms of their mean values and systolic-diastolic variations, enabling calculation of Peterson elastic modulus, and were displayed in the x-y form to obtain pressure diameter hysteresis loops. After recovery from surgery and under autonomic blockade, intravenous perfusions of angiotensin, norepinephrine, and epinephrine were made at incremental steps of doses until steady-state pressure-diameter changes were achieved. The slopes of the positive pressure-diameter correlations obtained at each dose of the same vasoactive substance were higher for angiotensin than norepinephrine (p less than 0.01) and epinephrine (p less than 0.001) and were higher for norepinephrine than epinephrine (p less than 0.05). Similarly, the slopes of the elastic modulus to mean pressure relation were significantly lower for angiotensin than for norepinephrine (p less than 0.05) and epinephrine (p less than 0.001) and were significantly lower for norepinephrine than epinephrine (p less than 0.001). Thus, at the same transmural pressure, the distension and stiffness of the aorta were lower and higher with epinephrine than with norepinephrine, respectively, and with norepinephrine than with angiotensin suggesting different potencies of these drugs in terms of smooth muscle activation in the aorta.
Abstract: The elastic response of the thoracic aorta to increasing steps of angiotensin was studied in chronic instrumented conscious dogs with and without parasympathetic blockade by atropine. A pressure microtransducer and two ultrasonic crystals diametrically opposed and fixed in the adventitia enabled to determine the mean and systolic-diastolic changes of pressure (P) and diameter (D). By computing these measurements two representative indexes of dynamic elastic modulus in vivo were calculated; the elastic modulus of Peterson (Ep) Ep = delta P/D.D and the incremental elastic modulus (Ei) Ei = 0.75 EP/gamma, gamma being the ratio of the thickness to the external radius. A positive correlation (p less than 0.01) was obtained between pressure and diameter variations in the presence or absence of atropine but the slope of these relationship were lower with atropine than in controls. The slope of the positive correlations observed between Peterson and incremental elastic modulus and the increase in mean arterial pressure in response to angiotensin (p less than 0.01) was higher in the presence of atropine (p less than 0.05). These observations indicate that in response to angiotensin mediated high blood pressure, the cholinergic blockade of muscarinic receptors with atropine induce a contraction and increasing rigidity of the aorta.
Abstract: The simultaneous acute effects of converting enzyme inhibition by intravenous enalaprilat on the circulating renin-angiotensin system and on the brachial artery were studied in 12 hypertensive patients by a double-blind comparison with saline effects in 14 hypertensive patients. The brachial artery was investigated in terms of arterial section (measured by pulsed Doppler technique) and wall rigidity (assessed by pulse wave velocity). Arterial and biochemical parameters were measured in baseline before injection and at 20 to 40 minutes (t1) and 80 to 100 minutes (t2) after saline and drug injections. Compared with the saline vehicle, enalaprilat significantly decreased angiotensin enzyme converting activity (p less than 0.001), increased plasma renin activity (p less than 0.01) and decreased plasma aldosterone concentrations (p less than 0.01). The drug reduced blood pressure (p less than 0.01) and increased the brachial artery section (p less than 0.01), but did not change pulse wave velocity. In the enalaprilat group, significant postinjection relations were observed between: (1) enalaprilat concentration and plasma angiotensin converting enzyme activity (r = -0.72, p less than 0.001); (2) plasma renin activity and mean blood pressure (r = -0.46, p less than 0.02); (3) plasma enalaprilat concentration and pulse wave velocity (r = -0.50, p less than 0.01) and (4) pulse wave velocity and brachial artery section (r = 0.42, p less than 0.05). Thus, the brachial artery effects of enalaprilat were not directly related to the blockade of the renin-angiotensin system in plasma.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The effects of sex, hypertension, morphologic status, and heart rate were assessed on the large arteries of 46 normotensive subjects (23 men and 23 women) and 50 hypertensive patients (25 men and 25 women) by means of pulsed Doppler determination of diameter and blood velocity of the brachial artery. Compared to men, women had lower height, weight, and forearm volume (P less than 0.001), higher heart rate (P less than 0.001), and lower brachial artery diameter (P less than 0.001) both in the normotensive and hypertensive groups. Compared to normotensives, hypertensives of the same sex showed an increase in brachial artery diameter, only significant in men (P less than 0.001), and an increase in heart rate, only significant in women (P less than 0.001). The multiple regression analysis of brachial artery diameter showed significant coefficients for sex and hypertension (P less than 0.001), and for age and heart rate (P less than 0.05); the multiple regression analysis of blood velocity showed that only the coefficient of hypertension was significant (P less than 0.05). The study of first-order interactions between the independent variables revealed that effect of sex on arterial diameter did not depend on the other variables. In contrast the effects of age and heart rate were influenced by the presence or the absence of hypertension, and arterial caliber was positively related to age in normotensive subjects (P less than 0.05) but not in hypertensive patients, and negatively related to heart rate in hypertensive patients (P less than 0.001) but not in normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: The elasticity of the thoracic aorta was studied in nine dogs instrumented with a pressure microtransducer and two ultrasonic crystals diametrically fixed in the adventitia. Systolic and diastolic changes in pressure and diameter were used to calculate Peterson and incremental elastic moduli. Acute hypertension was induced by infusions of angiotensin performed 1) during the control period, 2) after propranolol (1.5 mg/kg), 3) after atropine (0.2 mg/kg), and 4) after propranolol plus atropine. Absolute and percent variations of mean diameter were correlated to pressure in the control period and after autonomic blockade (p less than 0.01). The slopes of these correlations were not different between propranolol and control groups, but were lower with atropine (p less than 0.01) and with atropine plus propranolol (p less than 0.001) than in the control period. Correlations were also found between Peterson and incremental elastic moduli and mean pressure in the control period and after blockade (p less than 0.001). No differences of slopes existed between propranolol and control groups, but the slope of the correlation relative to the incremental elastic modulus was higher with atropine than in the control period (p less than 0.05), and the slopes of the correlations relative to the Peterson and the incremental elastic moduli were respectively higher with atropine plus propranolol than in the control period (p less than 0.05, p less than 0.05). Thus, atropine decreased the distention and increased the stiffness of the aorta in response to acute angiotensin-mediated hypertension.
Abstract: To assess the vascular involvement of renin-angiotensin system inhibition in human hypertension, acute effects of intravenous enalaprilat on brachial artery diameter, blood flow, and blood velocity were investigated in hypertensive patients by pulsed Doppler technique and compared with effects of saline vehicle. Compared with saline vehicle, enalaprilat reduced blood pressure (P less than 0.001) and increased brachial arterial diameter (P less than 0.01) and brachial blood flow (P less than 0.01). Enalaprilat effect on arterial pulse pressure was dependent on preinjection pulse pressure (r = -0.76; P less than 0.001), but its effect on mean blood pressure was not dependent on preinjection mean blood pressure. On the other hand, enalaprilat effect on arterial blood flow was negatively correlated with preinjection blood pressure (r = -0.64; P less than 0.02). The findings point to different responses of large and small arteries to intravenous enalaprilat.
Abstract: The vascular impact of different antihypertensive drugs was assessed in patients with mild to moderate essential hypertension by the use of the forearm circulation as a simple model to characterise the geometrical and distensible properties of the arterial system. The acute and chronic responses of the forearm arteries, expressed in terms of geometry (vasodilatation or vasoconstriction) and distensibility (arterial compliance, pulse-wave velocity), were not solely dependent on blood pressure levels. For similar blood pressure decreases, the dilatation of the forearm resistive vessels was associated either with an increase (calcium antagonists, angiotensin-converting enzyme inhibitors) or with a reduction (hydralazine-like drugs) or with no change (alpha- and beta-blocking drugs) in the calibre of the large forearm vessel. These non-homogeneous geometrical responses to antihypertensive drugs had important haemodynamic effects on the conduit, the buffering and the baroreflex functions of the arterial tree.
Abstract: The relationship between cardiac hypertrophy, ventricular function, and aortic volume distensibility was studied in men with sustained essential hypertension by echocardiography and determination of pulse-wave velocity. The more reduced the aortic distensibility, the higher was the blood pressure response to exercise and the greater were the degree of cardiac hypertrophy and the modifications in systolic time intervals. Changes in cardiac performance as determined by vasodilators equipotent in relation to blood pressure reduction were found to have markedly different effects on aortic distensibility; volume distensibility was unchanged by cadralazine but was improved by calcium entry blockers and isosorbide dinitrate. Our findings suggest that alterations in the buffering function of the large arteries, as indicated by decreased volume distensibility, participate in the increased afterload in patients with essential hypertension and thus influence the degree of cardiac hypertrophy and changes in cardiac function and selective use of antihypertensive drugs may influence cardiovascular morbidity and mortality by their differential effect on large-vessel distensibility.
Abstract: 1. Hypertension is associated with a distension of the large arteries and consequently a marked reduction in arterial compliance, which does not result merely from the mechanical effects of elevated arterial pressure but also from early functional and/or structural changes in the arterial walls. This suggests that one of the aims of antihypertensive therapy should be to reverse these arterial abnormalities in the hope of protecting the patient from the atherosclerotic complications of hypertension. 2. Studies have been carried out to compare the effects of equieffective antihypertensive doses of pindolol and propranolol on the arterial circulation in patients suffering from essential hypertension. After 3 months therapy pindolol produced a dilatation of the brachial artery with an increase in arterial compliance and blood flow. In contrast, propranolol, despite comparable antihypertensive effects, did not influence brachial artery circulation. 3. These different effects on the arterial circulation presumably reflect the differing pharmacological properties of the two beta-adrenoceptor antagonists and suggest that the intrinsic sympathomimetic activity of pindolol may be responsible for the qualitative differences in the arterial responses to the two drugs. 4. The results reviewed here reveal that even when two drugs of the same class are used to treat patients with essential hypertension the effects of these agents on arterial haemodynamics can vary greatly and are unrelated to the degree of blood pressure lowering. Thus, pindolol, in contrast to propranolol, not only lowers blood pressure but also reverses some of the changes in arterial haemodynamics which are characteristic of hypertensive disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: We have studied the efficacy of clonidine hydrochloride administered transdermally once a week for 9 to 15 weeks in 12 patients with mild to moderate hypertension. Clonidine reduced both supine and standing blood pressures on average, but only 8 subjects were responders, i.e. had a decrease in supine diastolic blood pressure to below 90 mm Hg or more than 10% from baseline. Supine heart rate was unchanged, but in the responders the orthostatic increase in heart rate was reduced by clonidine from baseline (p less than 0.05). Moreover, in all the patients the change in the orthostatic increase in heart rate was correlated with the change in supine diastolic pressure (p less than 0.05). Brachial artery blood flow, forearm arterial compliance, vascular resistance, and venous tone were not affected by clonidine. Thus, transdermal clonidine reduced blood pressure, probably by a baroreflex-mediated effect, but did not affect the vasculature of the forearm.
Abstract: The brachial artery diameter and blood flow rate were measured by pulsed Doppler velocimetry in 9 healthy subjects and 24 patients of the same age group with borderline hypertension. To evaluate the results, the patients were divided into two groups according to their cardiac output: high cardiac output group (i.e. patients whose cardiac output was superior to the mean +/- 2 S.D. value in the control population), and normal cardiac output group (i.e. cardiac output lower than that value). Patients in both groups were of the same age and had the same level of blood pressure. The brachial artery diameter and blood flow rate values were the same in the normal cardiac output group and in the control population. However, these values were significantly higher in patients with high cardiac output than in controls (P less than 0.05 and P less than 0.001) and in patients with normal cardiac output (P less than 0.01). These results suggest that the haemodynamic profile in the brachial artery is not the same in all patients with borderline hypertension: there was a tendency to vasoconstriction in patients with normal cardiac output, whereas the brachial artery was clearly dilated in patients with high cardiac output.
Abstract: Studies in humans have shown that chronic elevation of blood pressure induces early alterations in the large arteries, consisting mainly of increased diameter, increased pulse wave velocity, and decreased arterial compliance. Acute reduction of blood pressure, per se, does not necessarily correct these alterations homogeneously. For instance, cadralazine reduced brachial artery diameter and urapidil decreased pulse wave velocity, without accompanying changes in forearm arterial compliance. In contrast, acebutolol, isosorbide dinitrate, nicardipine, and nitrendipine, for the same acute decrease in blood pressure, improved forearm arterial compliance by a concomitant decrease in pulse wave velocity and increase in arterial diameter. To determine whether or not these vascular effects persist with long-term acebutolol therapy, nine hypertensive patients were treated for a period of 3 months. Forearm hemodynamic and cytosolic free calcium concentrations in platelets were simultaneously assessed before and after treatment. Compared with placebo baseline values, chronic acebutolol therapy significantly decreased mean arterial pressure (p less than 0.01), pulse wave velocity (p less than 0.01), and platelet free calcium concentration (p less than 0.05); forearm arterial compliance was increased (p less than 0.01), but brachial artery diameter did not change. Platelet calcium concentration correlated closely with pulse wave velocity even at constant mean arterial pressure. These findings suggest a relaxant effect of acebutolol on the smooth musculature of large arteries, which is independent of changes in blood pressure and arterial diameter, and possibly mediated by changes in cytosolic calcium levels.
Abstract: The effects of cigarette smoking and hypertension on hemorheological variables (blood viscosity over a wide range of shear rates, plasma viscosity, microhematocrit, and plasma protein concentration) and on arterial stiffness (pulse wave velocity) were investigated in 33 normotensive men and 81 mild to moderately hypertensive men. Of these, 22 normotensive and 24 hypertensive subjects were cigarette smokers. Cigarette smoking and hypertension were independently associated with higher blood viscosity at all studied shear rates (from 0.2 to 241 sec-1) as well as with higher plasma viscosity, hematocrit, and pulse wave velocity. At constant hematocrit levels, hypertension remained associated with a higher blood viscosity, while the association with cigarette smoking disappeared. Normotensive smokers had the same increase of blood and plasma viscosity and pulse wave velocity as hypertensive nonsmokers. No interactive effects of hypertension or cigarette smoking on blood or arterial variables were observed, suggesting that the effect of these two factors on blood and vascular rheology are cumulative. Smoking and hypertension may change the flow properties of the blood and the behavior of the arterial wall and this may explain the arterial damage observed in cigarette smokers and hypertensive patients.
Abstract: The effects of sex, hypertension, morphological status, and heart rate were assessed on the large arteries of 46 normotensive subjects (23 men and 23 women) and 50 hypertensive patients (25 men and 25 women) by means of pulsed Doppler determination of diameter and blood velocity of the brachial artery. Compared with men, women had lower height, weight, and forearm volume (p less than 0.001), higher heart rate (p less than 0.001), and lower brachial artery diameter (p less than 0.001), both in the normotensive and hypertensive groups. Compared with normotensive subjects, hypertensive patients of the same sex showed an increase in brachial artery diameter (only significant in men [p less than 0.001]) and an increase in heart rate (only significant in women [p less than 0.001]). The multiple regression analysis of brachial artery diameter showed significant coefficients for sex and hypertension (p less than 0.001) and for age and heart rate (p less than 0.05); the multiple regression analysis of blood velocity showed that only coefficient of hypertension was significant (p less than 0.05). The study of first-order interactions between the independent variables revealed that effect of sex on arterial diameter did not depend on the other variables. In contrast, the effects of age and heart rate were influenced by the presence or the absence of hypertension, and arterial caliber was positively related to age in normotensive subjects (p less than 0.05) but not in hypertensive patients and negatively related to heart rate in hypertensive patients (p less than 0.01) but not in normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: It has been proposed that plasma cholesterol, a major risk factor for atherosclerosis, may modify cellular Ca2+. In particular, higher membrane cholesterol contents induce higher Ca2+ influx and decrease the activity of the Ca2+ pumps. Cellular Ca2+ may also control the number of accessible low density lipoprotein receptors. We investigated the question of whether plasma cholesterol influences cellular Ca2+ metabolism, by analysing the cytosolic free Ca2+ concentration [( Ca2+]i) in unstimulated platelets from 61 untreated hypertensive patients [systolic and diastolic arterial pressure: 157 +/- 3/95 +/- 2 mmHg (mean +/- s.e.m.), respectively, age 41.8 +/- 1.7 years, body mass index 24.7 +/- 0.6 kg/m2]. The subjects' plasma total cholesterol (5.5 +/- 0.5 mmol/l) and platelet [Ca2+]i concentration (228 +/- 7 nmol/l) were positively correlated (r = 0.375, P less than 0.003). This correlation persisted at constant age, arterial pressure or body mass index. Platelet [Ca2+]i tended to increase with plasma low-density lipoprotein concentration (n = 21, P = 0.01), and to decrease with the ratio of high-density lipoprotein cholesterol to total cholesterol (n = 21, P = 0.08). The observation that in normocholesterolaemic hypertensive patients [Ca2+]i concentration in unstimulated platelets was correlated with plasma cholesterol suggests that cell activation may be modulated by membrane fluidity or that cholesterol metabolism is influenced by cell Ca2+.
Abstract: A cross-sectional study of 85 patients with poorly controlled treated hypertension was performed to detect, by means of aortic pulse wave velocity measurement and ultrasonic examinations, subclinical alterations of arteries. Pulse wave velocity was related to the product of age and diastolic blood pressure (BP) according to a nomogram obtained from normotensive subjects, and was found inside the nomogram in 37 patients (group I) and outside in 48 (group II). Group II had higher systolic and pulse BP (p less than 0.01), lower diastolic BP (p less than 0.01), higher proportion of cigarette smokers (p less than 0.05) and higher blood glucose levels (p less than 0.02) than group I. In group II a positive correlation existed between blood glucose and pulse wave velocity (p less than 0.01). Group II had a higher frequency of carotid artery stenosis (p less than 0.05) and a trend toward increased frequency of aortic and lower limb atherosclerotic lesions. The results indicate a heterogeneous pattern of arterial alterations in which systolic BP, cigarette smoking and blood glucose level are implicated.
Abstract: Diameter, blood velocity, and flow of the brachial artery and vascular resistance of the brachial circulation were evaluated with a pulsed Doppler velocimeter before and after wrist occlusion in 8 younger and 8 older normotensive subjects and in 11 younger and 11 older hypertensive patients. Before occlusion, no differences existed between younger and older normotensives. However, in hypertensives, systolic peak velocity was higher in younger than in older hypertensives (P less than 0.001) and correlated to age in the overall patients (r = -0.57, P less than 0.01). Occlusion decreased velocity and flow and increased vascular resistance in all groups, but the change in resistance was not correlated with the base-line resistance. During occlusion, no differences existed between younger and older normotensives. However, in hypertensives mean and systolic peak velocity was higher (P less than 0.01), and vascular resistance was lower (P less than 0.01) in younger than in older patients. In hypertensive patients, during occlusion mean and systolic peak velocity were negatively correlated to age (r = -0.72, P less than 0.001; r = -0.59, P less than 0.01), and vascular resistance was positively related to age (r = +0.66, P less than 0.001). Thus wrist occlusion modified the brachial circulation in normotensive and hypertensive populations but revealed age-related differences only in hypertensive patients, suggesting a combined effect of age and hypertension on the muscle vascular bed.
Abstract: Quantitative evaluation of brachial artery diameter, blood velocity and flow (pulsed Doppler velocimetry) and of forearm arterial compliance (FAC)--mathematical analysis of the simultaneous diastolic pressure and flow according to a first-order arterial model--was carried out in 10 normotensive controls, and in 23 borderline hypertensive patients, of the same age. Using a value of 2 standard deviations above the average cardiac index of 20 normotensive subjects, enabled us to classify 12 patients as having a normal cardiac output and 11 patients as having a high cardiac output. Each group was of similar age and pressure. FAC was lower in patients with a normal cardiac output than in normal controls (P less than 0.01) and also lower than in patients with high output (P less than 0.01). Brachial artery diameter and flow were higher in patients with high output than in normal controls (P less than 0.01, P less than 0.001) and also higher than in patients with a normal output (P less than 0.001). A positive correlation (r = 0.55; P less than 0.01) was found between heart rate and brachial artery diameter in the 23 patients. These results demonstrate a non-homogenous pattern of brachial artery characteristics of patients with borderline hypertension. Patients with normal cardiac output exhibited a clear reduction of the distensibility of the forearm arteries while patients with high cardiac output had strong dilation of the brachial artery.
Abstract: Hypertension in older atherosclerotic patients is characterised by a disproportionate elevation of systolic and pulse pressure contrasting with a subnormal diastolic level. Increased systolic pressure is strongly related to the excess of cerebrovascular complications and congestive heart failure observed in these patients. The physiopathological pattern is marked by a strong reduction in compliance of large arteries directly responsible for the predominant high systolic pressure because of the impairment of the buffering function of the arteries on the cardiac pulse wave. Clinical management is directed to the elevation of athero-arteriosclerotic changes of large arteries by means of appropriate non-invasive ultrasonic techniques and specific lowering in systolic pressure. Antihypertensive treatment must specifically decrease systolic pressure without superimposing adverse effects on the generalized and focalized atherosclerotic process. In this respect, new pharmacological agents capable of direct actions on large arteries might be suitable.
Abstract: The purpose of the study was to assess whether cigarettes smoking could induce blood hyperviscosity and arterial rigidity in 30 normotensive and 70 hypertensive men aged from 24 to 65 years. Of those, 20 normotensive and 20 hypertensive were cigarettes smokers, while the remaining subjects were non smokers. Age and weight were similar in the 4 groups of subjects. A couette viscometer with coaxial cylinders allowed the measurements of blood viscosity over a wide range of shear rates (0.033 to 241 sec-1) mimicking the flow condition of the circulation, and two strain gauge transducers permitted the measurements of the brachial to radial pulse wave velocity as an index of arterial wall distensibility. In normotensive subjects cigarettes smoking increased pulse wave velocity from 7.1 + 1 to 9.2 + 0.6 m/sec. (P less than 0.05) as well as blood viscosity, which increased both at higher shear rates (+10% from 52 to 241 sec-1, P less than 0.05) and lower shear rates (+20% from 11.2 to 0.2 sec-1, P less than 0.02). In hypertensives, cigarettes smoking increased pulse wave velocity (9.8 + 0.3 to 11.3 + 0.4; P less than 0.05) and blood viscosity (4% at higher shear rate P less than 0.05 and 10% at lower shear rates P less than 0.02). Although hypertensive patients had increased pulse wave velocity and blood viscosity compared to normotensive controls, these variables were not significantly different when hypertensive non smokers were compared to normotensive. The present study demonstrated that cigarettes smoking produced in normotensive and hypertensive men significant rheological disturbances of flow and wall arteries.2
Abstract: The viscoelastic behaviour of the aorta has been studied in 7 adult non-anesthesized mongrel dogs, chronically instrumented with a microtransducer pressure (Konigsberg P7) implanted inside the aortic lumen, and 2 ultrasonic crystals diametrically opposed and fixed in the adventitia of the thoracic aorta. Pressure and diameter were analysed in terms of mean values and of systolic diastolic variations, enabling to calculate the elastic modulus of Peterson. After recovery from surgery, and under autonomic blockade by atropine and propranolol, perfusions of angiotensin and norepinephrine were performed at incremental steps of doses. In individual dogs, instantaneous pressure-diameter relationships were formed by the different pressure diameter hysteris loops obtained at each dose of the same drug; the relationships obtained with the two drugs were curvilinear and were mixed at lower pressure ranges, but at highest levels of pressures it was found, that comparatively to angiotensin curve, that of norepinephrine had shifted toward lower diameter. The percent increase in mean diameter from baseline obtained at each dose of the same drug, was positively correlated to the corresponding per cent increase in mean pressure, with angiotensin (r = 0.83 P less than 0.001), and for norepinephrine (r = 0.82 P less than 0.001), but the slope of the relation was lower with angiotensin (22.3 +/- 3.2) than with norepinephrine (12.8 +/- 1.9) (P less than 0.001); likewise, the elastic modulus, for each dose of a same drug, was positively correlated to the corresponding mean pressure for angiotensin (r = 0.53 P less than 0.01), norepinephrine (r = 0.69 P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Fluid volumes and cardiac and renal hemodynamics were investigated in 44 obese men, 22 with normal blood pressure and 22 with sustained essential hypertension. For the same degree of obesity hypertensive patients had a higher value in extracellular (p less than 0.05) and interstitial fluid (p less than 0.01) volumes than normotensive subjects, while plasma volume, total body water, body cellular water, cardiac output, renal blood flow and glomerular filtration rate were similar. For the same level of blood pressure, the expansion of extracellular and interstitial fluid volume paralleled the degree of obesity. Thus, obese patients with hypertension have an absolute increase in extracellular and interstitial fluid volumes. The increase was related both to the degree of overweight and to the mechanisms of hypertension.
Abstract: The haemodynamic pattern of the common carotid artery was studied before and after administration of captopril isosorbide dinitrate and nitrendipine, in men with sustained essential hypertension. Pulsed Doppler methods were used. Captopril produced both a fall in vascular resistance and an increase in the arterial diameter of the common carotid artery. Thus, in the common carotid artery circulation of patients with essential hypertension only captopril dilated both small and large arteries.
Abstract: The buffering function of arteries consists of damping down cardiac pulsatility. This function can be evaluated by measuring arterial compliance using pulsed Doppler and pulse wave velocity measurements and analysis of pressure and flow waves in arteries. In human hypertension, the reduction of arterial compliance is well-documented; it is not only due to increased stretching of the arteries consecutive to the rise in blood pressure, but also to the fact that structural and/or functional changes in these vessels, as suggested by the fact that compliance is reduced in patients with borderline and mild hypertension and does not necessarily vary in parallel to drug-induced changes in blood pressure. Furthermore, arterial compliance is heterogeneously altered in borderline hypertension according to the level of cardiac output and in sustained hypertension according to the degree of arterial aging. Finally, reduced arterial compliance, by impairing the buffering function of arteries, increases arterial pulsatility and its adverse effects on cardiac load and on cyclic stress of arteries.
Abstract: The effects of pindolol were studied on the large arteries, arterioles, and veins of the forearm in 13 patients with essential hypertension after 12 weeks of dosing. The methods used were pulsed Doppler velocimetry of the brachial artery and strain gauge mercury-in-silicone rubber plethysmography of the forearm. Compared with placebo baseline values, chronic pindolol significantly decreased systolic and diastolic blood pressure (P less than 0.001), pulse pressure (P less than 0.001), and pulse rate (P less than 0.05). A significant increase was observed in brachial artery diameter (P less than 0.01), brachial artery blood flow and velocity (P less than 0.001), and forearm arterial flow (P less than 0.001). Forearm vascular resistance and venous tone were decreased (P less than 0.001 and P less than 0.05, respectively), whereas forearm arterial compliance was increased (P less than 0.001). These results demonstrate a dilatory effect on large and small peripheral arteries and on veins of pindolol after chronic dosing, which leads to improvement in the conduction and buffering arterial function of the forearm.
Abstract: The effects of medroxalol, a new beta-blocking drug, were simultaneously studied on the brachial artery, the arterioles and the veins of the forearm in 15 patients with mild to moderate essential hypertension after administration of a single oral dose of 200 mg, by means of pulsed Doppler velocimetry of the brachial artery and strain gauge mercury-in silastic plethysmography of the forearm. In addition the systolic time intervals including preejection period (PEP) and left ventricular time (LVET) were also measured after drug administration. Acute oral medroxalol produced a rapid and significant decrease in systolic and diastolic blood pressure and in heart rate. Concomitantly a significant increase was observed in brachial artery diameter (p less than 0.05), blood velocity and flow (p less than 0.01); forearm vascular resistance decreased (p less than 0.001) but forearm venous tone was unchanged. Lastly medroxalol prolonged PEP but shortened LVET corrected for heart rate. These results demonstrate a rapid antihypertensive action of a single dose of medroxalol with a dilation of the arteries but not of the veins of the forearm and a discrepant effect on the systolic time intervals.
Abstract: Pharmacokinetics of isosorbide dinitrate (ISDN) and brachial arterial hemodynamics have been studied in 15 patients with sustained essential hypertension. The hemodynamic study was performed by using a pulsed Doppler device enabling evaluation of the diameter of the brachial artery with an error of less than 10%. After intravenous administration until plateau concentrations were reached, the ISDN infusion was stopped in order to study the disappearance curve of the drug and the pharmacokinetic parameters. ISDN caused a significant decrease in systolic pressure, a significant increase in arterial diameter, and no change in heart rate. Brachial hemodynamics were not correlated with the plasma concentration in the steady state or the area under the disappearance curve. In contrast, the changes in arterial diameter during perfusion were significantly correlated with the apparent distribution volume, a finding that might indirectly reflect the affinity of ISDN for vascular tissues.
Abstract: The effect of a sustained-release oral isosorbide dinitrate (ISDN) preparation on cerebral and forearm circulation was determined in 16 patients with mild to moderate essential hypertension. Measurements were made by pulsed Doppler velocimetry in the common carotid and the brachial arteries. Pulse wave velocity of the forearm was simultaneously recorded by means of strain gauge arterial mechanography allowing non-invasive evaluation of compliance and characteristic impedance of the brachial artery. Four hours after ISDN ingestion, the patients exhibited a significant decrease in blood pressure without a change in heart rate. An increase in carotid and brachial artery diameter was shown whereas blood flow increased only in the forearm. Resistance decreased significantly in both carotid and brachial vascular beds but only in the brachial vascular bed was the baseline resistance directly correlated with the change in brachial bed resistance. Concerning pulsatile large artery parameters, pulse wave velocity and characteristic impedance diminished, and brachial artery compliance increased significantly. The tangential tension of carotid and brachial arteries did not change. An increase in plasma renin activity was observed and related to the vasodilating effect on small arteries of the brachial vascular bed. This study showed that the antihypertensive effects of ISDN were accompanied by a strong vasodilatory action on small and large arteries and by an improvement in the pulsatile behaviour of large arteries.
Abstract: The haemodynamic pattern of the common carotid artery was studied in men with sustained essential hypertension using pulsed Doppler methods before and after administration of vasodilating drugs. Captopril produced both a fall in vascular resistance and an increase in arterial diameter of the common carotid artery. Isosorbide dinitrate increased markedly the arterial diameter but did not change vascular resistance. Nitrendipine decreased vascular resistance with no change in the arterial diameter. In the common carotid circulation of patients with essential hypertension, vasodilating drugs may either dilate small arteries (nitrendipine), large arteries (isosorbide dinitrate), or both (captopril).
Abstract: Forearm venous tone and brachial artery hemodynamics, including determinations of the arterial diameter and compliance by the use of pulsed Doppler systems, were measured in 16 patients with sustained essential hypertension before and after acute oral cadralazine dosing. Systolic and diastolic blood pressures significantly decreased, whereas heart rate increased. Brachial artery diameter and vascular resistance decreased, respectively, from 0.501 +/- 0.015 to 0.485 +/- 0.015 cm (P less than 0.001) and from 124.8 +/- 13.8 to 99.3 +/- 11.9 mm Hg/ml . sec (P less than 0.01). Blood flow velocity increased (P less than 0.05) but volumic flow, pulse wave velocity, and brachial artery compliance did not change. Forearm venous tone increased but the increase was inversely related to the degree of arteriolar vasodilatation. Our results indicate that, with cadralazine, forearm vascular resistance decreased while forearm blood flow was unchanged, the dilatation of small arteries contrasted with a significant reduction in the diameter of the large brachial artery, and the decrease in blood pressure was associated with a lack of increase in arterial compliance and changes in venous tone. This suggests an overriding influence of the activation of the autonomic nervous system on the action of cadralazine on large arteries and veins.
Abstract: Brachial artery diameter (pulsed Doppler method), forearm vascular resistance, and venous tone (plethysmographic method) were studied in 18 patients with sustained essential hypertension. Hemodynamic parameters were reevaluated after 3 months of treatment by propranolol (9 patients) or pindolol (9 patients). For the same decrease in pressure, propranolol decreased heart rate significantly while pindolol did not, indicating the role of intrinsic sympathomimetic activity. After pindolol, forearm vascular resistance and venous tone significantly decreased while brachial artery cross-sectional area significantly increased. After propranolol, forearm vascular resistance and brachial artery cross-sectional area did not change significantly, while forearm venous tone increased markedly. The study shows that, in the long term, pindolol dilates small and large arteries and veins of the forearm circulation whereas Propranolol apparently does not.
Abstract: The effect of beta-blockade was studied in 3 different kinds of human hypertension: borderline, sustained and isolated systolic hypertension. Young patients with borderline hypertension had a similar decrease in cardiac output with both nonselective and selective beta-blockade. Only nonselective beta-blockade decreased brachial artery blood flow and increased forearm vascular resistance. In patients with sustained essential hypertension, chronic administration of 2 nonselective beta-blockers, propranolol and pindolol, caused a similar significant decrease in blood pressure with different effects on forearm circulation. Pindolol produced a significant vasodilation of both large and small arteries of the forearm while propranolol did not. In patients with isolated systolic hypertension, short-term beta-adrenergic blockade with propranolol had different effects according to age. In younger patients, propranolol significantly decreased systolic pressure with a concomitant increase in rapid ventricular ejection. In older patients, a lack of systolic pressure reduction was observed with an increase in total peripheral resistance and a decrease in systemic arterial compliance. The results suggested that beta-adrenergic blockade in hypertension may affect blood vessels with different effects, according to age, to the characteristics of hypertension and to the specific properties of the beta-blocking agent. The vascular effects involve not only resistive vessels but also large arteries.
Abstract: Quantitative evaluation of brachial artery diameter and blood flow (pulsed Doppler velocimetry) was carried out in nine normal subjects and 24 borderline hypertensive patients of the same age. The analysis of patients according to their value of cardiac index compared with the normal mean value plus 2 SD (standard deviation) enabled us to subdivide the patients into those with normal cardiac output and those with high cardiac output of similar age and pressure. Brachial artery diameter and flow were not different in patients with normal output and in normal controls, but were higher in patients with high output than in normal controls (p less than 0.05; p less than 0.01) and lower in patients with normal output than those with high output (p less than 0.01). These results demonstrate a nonhomogeneous pattern of the brachial artery of patients with borderline hypertension. Patients with normal cardiac output exhibited a trend to vasoconstriction, while patients with high cardiac output had a strong dilatation of the brachial artery.
Abstract: In patients with essential hypertension, vasodilating antihypertensive drugs act differently on small and large arteries. For similar blood pressure reductions, the diameter of the brachial artery may be unchanged (alpha- and beta-blocking drugs), decreased (dihydralazine), or increased (nitrates, renin-angiotensin and calcium-entry inhibitors). Increase in blood flow is due preferentially to an increase in blood flow velocity and is caused additionally by an increase in the diameter of the large artery. Increase in arterial compliance is observed only with nitrates, calcium-entry, and renin-angiotensin inhibitors. It is concluded that blood pressure reduction due to arteriolar vasodilatation may have various effects on the conducting function and the buffering function of large arteries, a point of importance in the prognosis of hypertensive cardiovascular disease.
Abstract: Determinations of central venous pressure, cardiac haemodynamics and rapid volume expansion using iso-oncotic dextran were made in 49 men with sustained, uncomplicated essential hypertension and compared with those in 27 normotensive subjects of the same age and sex. In the hypertensives, central venous pressure was significantly increased in basal conditions while the cardiac index was normal and total blood volume was reduced. There was a positive and significant correlation of central venous pressure with age, arterial pressure and pulmonary wedge pressure. After rapid volume expansion, the slope of the curve relating cardiac output to central venous pressure was within the normal range, while the slope of the curve relating blood volume to central venous pressure was significantly reduced. The study provided evidence that in hypertensives: central venous pressure as well as arterial pressure is increased, the elevated central venous pressure is not due to an alteration in the cardiac 'pump function' or to hypervolaemia but rather to a decrease in the compliance of the venous bed or the left ventricle or both, and the strong correlation with age of the venous disturbances is similar to that found for the arterial side of the circulation.
Abstract: Echocardiographic determinations, left ventricular mass-volume ratio (M/V), left ventricular end-systolic stress (ESS), carotidofemoral pulse wave velocity (PWV), and brachial artery compliance (BAC), deduced from pulsed Doppler measurements and from the Bramwell-Hill equation, were evaluated in 20 patients with sustained essential hypertension in comparison with 20 control subjects of the same age and sex. In hypertensive patients, M/V ratio, ESS, and PWV were significantly increased while BAC was reduced. In the overall population, ESS was directly correlated with PWV (r = 0.73), and M/V ratio was significantly correlated with PWV (r = 0.60), BAC (r = -0.70), and systolic arterial pressure (r = 0.71). No comparable results were observed with diastolic arterial pressure. PWV was unchanged after cadralazine, a dihydralazine-like substance, and was decreased with the same blood pressure reduction following nitrendipine, a new calcium-blocking agent. These results suggest that: (1) the distensibility of large arteries plays an important role in the maintenance of cardiac hypertrophy in hypertension, and (2) antihypertensive drugs may act differently on arterial distensibility with possible consequences on ESS and reversion of left ventricular hypertrophy.
Abstract: The large arteries are impaired in uncomplicated, permanent, essential arterial hypertension. The peripheral arteries such as the humeral artery or the common carotid artery have a normal or increased diameter, reduced blood flow and, especially, reduced compliance. Reduction of the arterial compliance reflects an impairment peculiar to the large blood vessels, independent of the pressure. Antihypertensive medicines, for a given drop in pressure, may increase, diminish or not change arterial compliance. This is an important point to be taken into account in relation to cardiovascular morbidity and mortality of treated hypertensives. It has been particularly well studied in the context of inhibitors of the renin-angiotensin system.
Abstract: The forearm arterial effects of enalapril and propranolol were compared by means of pulsed Doppler velocimetry in 28 patients with hypertension after treatment for 3-6 months. Enalapril decreased blood pressure, increased both brachial artery diameter and blood flow, decreased vascular resistance, and increased the arterial compliance of the forearm. Propranolol also decreased blood pressure but did not produce any other changes. It may be concluded that the treatment of hypertension with enalapril, but not propranolol, is associated with dilatation effects on the arterial circulation of the forearm.
Abstract: Arterial diameter, blood velocity and blood flow of both common carotid arteries were studied in 24 patients with isolated unilateral internal carotid artery stenosis, without any other significant lesion of the carotid system. The methodology used a pulsed Doppler system with two original characteristics: an adjustable range-gated system and a double transducer probe enabling both the arterial diameter and blood velocity to be evaluated. On the involved side, the diameter, the blood velocity and the blood flow were significantly reduced (p less than 0.001) in comparison with the opposite side. The degree of the internal carotid artery stenosis judged on arteriography was negatively correlated with (i) the blood flow of the common carotid artery homolateral to the stenosis (r = -0.78, p less than 0.001); and (ii) the ratio of the common carotid artery blood flow between the involved and the opposite side (r = -0.80, p less than 0.001). The proposed quantitative evaluation can be suitable for the detection and for the follow up of patients with stenosis of the internal carotid artery who do not have any other lesion of the carotid system.
Abstract: Noninvasive evaluation of brachial artery diameter (pulsed Doppler velocimetry) and pulse wave velocity (strain gauge mechanography) was performed in 23 normal subjects and 49 patients with uncomplicated essential hypertension. Pulsatile arterial function was described in terms of derived characteristic impedance and arterial compliance. Compared with normal controls, hypertensive patients had greater arterial diameter (p less than 0.01) and pulse wave velocity (p less than 0.001). Two nomograms obtained from normal subjects relating the product of age and diastolic pressure to diameter and pulse wave velocity were used for analysis of the hypertensive group; 35 patients were inside the 95% confidence limits of the diameter and pulse wave velocity nomograms (Group 1), while 14 patients were outside the pulse wave velocity nomogram (Group 2). Age and mean pressure were similar, but pulse wave velocity was higher (p less than 0.001), arterial compliance lower (p less than 0.001), and characteristic impedance higher (p less than 0.001) in Group 2 than in Group 1. The amplitude of pulse pressure was higher in Group 2 than in Group 1 (p less than 0.001), and a negative correlation was found between pulse pressure and arterial compliance in Group 2, but not in Group 1. Thus, in the majority of hypertensive patients, arterial modifications could be related to the normal influence of age and pressure. In contrast, other patients exhibited features suggesting excessive arterial stiffness, manifested by abnormally high pulse wave velocity, decreased arterial compliance, and increased characteristic impedance.
Abstract: The non invasive investigation of the brachial artery was performed in 51 mild to moderate essential hypertensive patients and 23 normal subjects of similar age. It included quantitative evaluation of arterial diameter (pulsed Doppler velocimetry), pulse wave velocity (strain gauge mechanography) and arterial compliance deduced from the former indices. Hypertensive patients exhibited higher pulse wave velocity (Pw 0.001) and arterial diameter (p less than 0.01) than normal controls. The strong correlation found in normal subjects between pulse wave velocity and the product of age and diastolic pressure (r = 0.88, p less than 0.001) was used as a nomogram for the analysis of those hypertensive arterial changes. Accordingly the projection of patients on this nomogram enables to distinguish two groups according to that pulse wave velocity was inside (Group 1) (37 patients) or above (Group II) (34 patients) the upper limit of the nomogram. The comparison of these two groups of hypertensive patients showed that despite a similar level of age and pressure, arterial compliance was lower and pulse pressure higher in Group II than in Group I. These results demonstrate that early alterations of brachial artery occur in hypertension: these arterial changes can be attributed in most of the patient to the exclusive effect of aging and pressure elevation; however, in some patients additional degenerative process, perhaps atherosclerotic in nature, is responsible for profound decrease in arterial compliance and increase in pulse pressure so that such patients may appear as especially predisposed to systolic hypertension and degenerative arterial complications.
Abstract: By using simultaneous recording curves obtained with pulsed Doppler velocimetry and strain gauge mechanography, forearm arterial haemodynamics were studied in 26 patients with mild to moderate essential hypertension. Fifteen patients received a single oral dose of nicardipine 40 mg, and 11 patients were treated with nicardipine 30 mg three times daily for 3 months. In both groups of patients there was a similar and significant (P less than 0.001) reduction in mean, systolic, and diastolic pressures. There was a slight increase in heart rate (P less than 0.05) after the single dose, but no change after 3 months of treatment. The diameter, blood velocity, and blood flow of the brachial artery increased significantly in both treatment groups. The decrease in forearm vascular resistance was significant for both treatment groups. Brachial artery compliance increased (P less than 0.01) and characteristic impedance decreased (P less than 0.01) after both single-dose and long-term therapy with nicardipine. In patients who received nicardipine for 3 months, there were close correlations between the baseline serum calcium level and the percent change in vascular resistance (r = -0.73, P less than 0.01), blood flow (r = 0.89, P less than 0.001), and blood velocity (r = 0.91. P less than 0.001) of the forearm. No correlation was found between the baseline serum calcium and the change in arterial pressure. This study provided evidence that the blood-pressure-lowering effect of nicardipine was accompanied by a direct vasodilatory action in the small and large arteries of the forearm. An increase in peripheral blood flow with concomitant improvement of arterial compliance are the consequences of these arterial actions.
Abstract: Simultaneous determinations of cardiac output and brachial arterial blood flow were performed in patients with hypertension and high cardiac output in comparison with normal subjects of the same age. Brachial arterial blood flow was measured with a previously described pulsed Doppler apparatus that permitted the noninvasive determination of arterial diameter and blood flow velocity. In patients with borderline hypertension, brachial blood flow was significantly increased (136 +/- 11 vs 72 +/- 8 ml/min; p less than .001). After short-term administration of indomethacin, cardiac output decreased while brachial blood flow remained constant. After short-term administration of a selective beta 1-receptor antagonist (primidolol) and nonselective blocker (propranolol), cardiac output decreased significantly in both cases but the decrease in brachial blood flow was significant only after the administration of the nonselective beta-blocking agent. The study strongly suggested that in patients with borderline hypertension, the increased cardiac output is related to a prostaglandin and beta 1-adrenergic mechanisms whereas the increased brachial blood flow depends mainly on beta 2-adrenergic mechanisms.
Abstract: The central and peripheral haemodynamic effects of the administration of 10 mg nifedipine sublingually in 6 patients with essential hypertension were compared with those observed after the administration of one 20 mg slow release tablet of nifedipine in 7 other hypertensive patients of the same age. The circulatory effects in the forearm were studied by pulsed Doppler velocimetry which allowed simultaneous measurement of the diameter of the brachial artery and of the velocity of blood flow. Both forms of administration significantly reduced the blood pressure by a significant reduction in total peripheral resistance. This reduction in total peripheral resistance was more significant (p less than 0.001 vs p less than 0.01) and more rapid with sublingual administration and was associated with a greater increase in heart rate and cardiac output. Both forms of administration induced an increase in brachial arterial blood flow due to a simultaneous increase in vessel calibre and velocity of blood flow. The results of this study show that both forms of administration act directly on the vessel wall of the arterioles and great arteries leading to a fall in blood pressure associated with an increase in peripheral blood flow. Sublingual nifedipine would seem to be the drug of choice for the treatment of hypertensive crises, whilst the slow release preparation with its lesser baroreflex stimulation would appear better suited for the long-germ treatment of essential hypertension.
Abstract: Simultaneous brachial artery pressure and blood flow measurements were made in 15 patients with arteriosclerosis of the lower limbs (AOLL) and in controls of the same age and sex. Blood flow was evaluated by a pulsed Doppler device with a double-transducer probe. From analysis of the pressure-flow curves during diastole, regional arterial compliance (RAC) was determined by using as a model of the forearm arterial tree a system of tubes, each with a storage capacity, in series with the arteriolar resistance vessels. In AOLL patients, RAC was significantly reduced (102 +/- 13 vs 173 +/- 14.10(-4) ml/mm Hg, p less than 0.01), and systolic pressure was significantly increased. After saline infusion, systolic pressure continued to increase and arterial compliance, to decrease; brachial blood flow did not change. Study of the baroreflex sensitivity in AOLL patients under basal conditions indicated that a higher pulse pressure was required to obtain the same heart rate as in the controls. The study provided evidence that in AOLL patients: 1) compliance was reduced in the brachial artery (a regional circulation with no clinical evidence of arterial occlusion); 2) an increase in systolic pressure resulted from the decreased arterial compliance; and 3) saline infusion exaggerated the observed reduction in arterial compliance and increase in systolic pressure.
Abstract: Using noninvasive measurements of arterial diameter, compliance, and distensibility permits the mechanisms of increased systolic pressure in hypertensive humans to be better understood. Reduced arterial compliance causing a disproportionate increase in systolic pressure is a characteristic feature not only of pure systolic hypertension in the elderly but also of sustained essential systolodiastolic hypertension, mainly in persons aged over 50 years. Antihypertensive drugs should improve the status of large vessels through an active effect on the tone of the vascular smooth muscle of large arteries, a field as yet poorly investigated in hypertensive humans.
Abstract: The effects of angiotensin-converting enzyme inhibition on large arteries have been examined in uncomplicated essential hypertensive patients (grade 1-2 WHO). These effects were determined from (a) changes in arterial compliance as measured from the slope of the decline in arterial pressure during diastole and (b) alterations in diameter of the brachial artery and blood flow velocity within its lumen, as assessed by pulsed Doppler velocimetry. Both acute and chronic ACE inhibition were accompanied by a significant increase in arterial compliance and a dilation of the brachial artery. This response might be related to changes in plasma and/or intraarterial angiotensin and/or to changes in plasma potassium. Whatever their mechanism, the arterial dilatation and increase in compliance would improve the buffering and the conducting functions of the large arteries, and these in turn may, if persistent, prove beneficial in possibly preventing arterial complications of hypertension.
Abstract: Diameter, blood flow velocity, and volumic flow of the common carotid artery were measured in 38 patients with sustained essential hypertension and compared with those of 38 age-matched normal subjects. Both hypertensive and control subjects were classified according to age into those younger and those older than 45 years. For the determinations, a pulsed Doppler velocimeter with an adjustable range-gated time system and a double transducer probe was used. In the younger group, the diameter of the common carotid artery had a similar value in hypertensive patients (0.639 +/- 0.014 cm) and in controls (0.651 +/- 0.015). The same level of blood flow velocity in hypertensive patients (19.7 +/- 0.9 cm/s) and in controls (21.2 +/- 0.9 cm/s) was observed. Therefore, the volumic flow was equal in the common carotid artery of the hypertensive patients (385 +/- 20 ml/min) and of the normotensive subjects (410 +/- 23 ml/min). In the older group, blood flow velocity was reduced in the common carotid artery of the hypertensive patients (19.4 +/- 1.0 cm/s vs. 15.6 +/- 0.6 cm/s; p less than 0.01), but the diameter was unchanged (0.653 +/- 0.018 cm in hypertensive patients and 0.665 +/- 0.018 cm in controls). Thus, there was a significant reduction of volumic blood flow in common carotid artery of the hypertensive patients over 45 years (321 +/- 14 ml/min). A negative relationship was observed between common carotid artery blood flow and age in elderly hypertensive patients (r = -0.42; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Arterial compliance was determined in eight normal subjects and 23 patients with hypertension and vascular disease by two independent techniques: (a) with a plethysmographic strain gauge (to measure pulsatile forearm volume changes as representing intra-arterial volume changes) and an automated sphygmomanometric system (to measure pulse pressure) and (b) calculation from the local pulse wave velocity and dimension of the brachial artery measured by pulsed wave Doppler ultrasound. Arterial compliance measured both by the plethysmographic technique and calculated from the pulse wave velocity was reduced in subjects with hypertension and vascular disease as compared with normal subjects. The regression equation between the compliance determined by the plethysmographic technique (x) and that calculated (y) from the pulse wave velocity and brachial arterial diameter was y = 3. 35x + 1.53, r = 0.77, P less than 0.001. The good correlation appears to validate the plethysmographic technique as a method of determining arterial compliance.
Abstract: The physical properties of intact superficial arteries can be studied in humans by using original pulsed Doppler systems. Measurements of the diameter, blood flow velocity, volumic flow, and compliance of the brachial artery can be obtained in hypertensive humans in comparison with controls of the same age. In sustained essential hypertension, arterial compliance is decreased, in a manner that is not related exclusively to age and to the level of blood pressure. On the basis of pharmacological studies, the predominant role of activation of the autonomic nervous system can be excluded. As observed in isolated systolic hypertension and in arteriosclerosis obliterans of the lower limbs, the reduction in arterial compliance is probably due to structural alterations of the arterial wall, which produce a disproportionate increase in systolic pressure. Nitroglycerine is able to reverse both the decreased compliance and the increased systolic pressure. The conclusion follows that adaptive changes of large arteries participate in the structural autoregulation of blood flow in hypertension and lead to a predominant elevation of systolic pressure in older subjects.
Abstract: Acute effects of a new calcium entry blocker, nitrendipine, on large arteries of the forearm were studied by using arterial pulse strain gauge mecanography and pulsed Doppler velocimetry of the brachial artery in 13 mild to moderate essential hypertensive patients. Ninety minutes after nitrendipine ingestion, patients exhibited significant decreases in blood pressure without changes in heart rate; increases in brachial artery diameter and decreases in brachial to radial pulse wave velocity; increases in arterial compliance and decreases in characteristic impedance; and increases in brachial artery blood velocity and flow and decreases in forearm vascular resistance. Lastly, amplitude of pulse pressure was decreased by nitrendipine and negatively correlated to the level of arterial compliance. These results suggest that nitrendipine exerts a direct benefit effect on the hypertensive large arteries whose two main consequences are a decrease in pulsatility of arterial pressure and an increase in arterial flow.
Abstract: Cardiac output (CO), renal blood flow (RBF), calf blood flow (CBF), and hepatic blood flow (HBF), glomerular filtration rate (GFR), and dopamine beta hydroxylase (D beta H) activity were studied in 198 men (67 normotensive controls and 131 hypertensive patients) of the same age with sustained uncomplicated essential hypertension. In the hypertensive men, the RBF and the RBF/CO ratio were significantly decreased (p less than 0.001). The RBF and RBF/CO ratio were negatively correlated with age (p less than 0.01), blood pressure (p less than 0.01), and D beta H activity (p less than 0.01). None of these relationships were observed with CBF and HBF. The observed decreases in RBF and the RBF/CO ratio in hypertensive men were reversed after administration of clonidine and alpha-methyldopa (p less than 0.01), but not after administration of propranolol. The study provides evidence that the reduction of renal perfusion in essential hypertension is partly reversible and related to an abnormality in the adrenergic system control.
Abstract: Extracellular fluid volume (ECF), plasma volume (PV), glomerular filtration rate (GFR), renal plasma flow (RPF), efferent arteriolar oncotic pressure (pi E), sodium output (UNaV), and sodium clearance (CNa) were determined in 150 men including 50 normal controls (NC) and 100 sustained essential hypertensive patients (EH). Total effective vascular compliance (TEVC) and central venous pressure (CVP) were measured in 17 normotensives and 24 EH. EH had a decreased RPF and TEVC (P less than 0.001), while CVP and pi E were higher than in NC (P less than 0.001). ECF, GFR, UNaV, and CNa were identical in EH and NC. A positive correlation between RPF and CNa (P less than 0.01) and a negative correlation between pi E and CNa existed in both groups with a significant reset of the curve in EH: For any given RPF or pi E the CNa was higher in EH. In the overall population TEVC was negatively correlated with CVP (P less than 0.01) and pi E (P less than 0.01); CVP was positively correlated with pi E (P less than 0.01). The results suggest that physical properties of the low pressure system could participate in the natriuretic adaptation of the kidney in EH man.
Abstract: The effect on large arteries of the converting enzyme inhibitor captopril was studied in men with sustained essential hypertension with two different hemodynamic parameters: (1) systemic arterial compliance and (2) brachial artery diameter. After captopril administration, a 20 percent increase in arterial compliance was observed. The same increase was obtained with a 5 percent (acute experiment) and a 15 percent (short-term experiment) decrease in blood pressure, indicating that the decrease in pressure could not explain exclusively the increase in compliance. This assumption was studied with determinations of brachial artery diameter using original pulsed Doppler systems. After captopril administration, brachial artery diameter increased markedly despite the decrease in blood pressure. In addition to its effect on small arteries, the converting enzyme inhibitor captopril also has a special effect on the large arteries of patients with essential hypertension.
Abstract: Central (six patients) and brachial (12 patients) haemodynamics were studied in men with sustained essential hypertension before and after intravenous administration of an alpha post-synaptic adrenergic blocking drug, urapidil. Brachial arterial compliance was evaluated non-invasively from the simultaneous measurement of pulse wave velocity and arterial diameter. In basal conditions, arterial compliance was reduced in hypertensives. Urapidil caused a significant drop in blood pressure, due to a significant decrease in total peripheral resistance with no change in cardiac output and heart rate. Brachial arterial diameter and compliance did not change significantly. The results show that the decreased arterial compliance in hypertensive patients was not due exclusively to the elevation of blood pressure or to a predominant activation of the autonomic nervous system, or both. Such observations suggest that, in men with sustained essential hypertension, the decreased compliance was probably related to structural alterations of large arteries.
Abstract: The efficacy of MK 421 and propranolol was compared in 48 patients with mild to moderate hypertension. Each patient was randomly assigned to receive 1 of the drugs for 12 weeks. Additionally, a subgroup of 28 patients underwent studies of forearm arterial and venous circulation by means of pulsed Doppler and mercury-in-silastic plethysmography. Both drugs reduced supine and standing blood pressure (BP) (p less than 0.001). Propranolol reduced heart rate (p less than 0.001), while MK 421 did not change it. Brachial artery diameter, blood velocity and flow increased after MK 421 (p less than 0.001), but were not changed after propranolol therapy. Forearm vascular resistance decreased after MK 421 (p less than 0.001) and after propranolol (p less than 0.05). Forearm venous tone was unaffected on MK 421, but increased after propranolol (p less than 0.01). Thus, in moderate hypertension, 3 months of treatment with MK 421 or propranolol similarly decrease BP, but affect the forearm circulation differently: MK 421 dilates both the brachial artery and the arterioles of the forearm, but does not affect the venous vessels, and propranolol causes little arterial change but increases the forearm venous tone.
Abstract: Brachial artery haemodynamics, including arterial diameter, blood flow velocity, blood flow and compliance of the brachial artery may be evaluated non-invasively in man, using pulsed Doppler methods. In patients with sustained untreated essential hypertension, brachial artery diameter is increased, blood flow is normal and arterial compliance is reduced independently of the level of blood pressure. Converting enzyme inhibition may reverse the large artery abnormalities, causing an increase in arterial diameter, blood flow and arterial compliance both in acute and long-term investigations. These changes in large arteries may contribute towards improved cardiovascular morbidity and less mortality in treated hypertensive patients.
Abstract: A study of forearm arterial and venous hemodynamics by pulsed Doppler velocimetry and plethysmography was performed in 21 patients with essential hypertension, aged 16 to 54 years, before and after short-term nadolol administration at a dose of 0.05 mg/kg. Because of a large intersubject variability in the responses of the hemodynamic parameters to nadolol, an unconventional statistic approach was used to divide the overall population of patients into two homogeneous groups. The first included nine patients (group 1) and the second 12 patients (group 2). In patients of group 1, nadolol significantly decreased the systolic blood pressure (p less than 0.001), venous tone (p less than 0.01), and brachial artery flow (p less than 0.05). In patients of group 2, nadolol did not affect any forearm parameters. Each group of patients was compared to an age- and pressure-matched group of patients receiving propranolol at equiblocking doses. Contrary to nadolol, propranolol was found to increase significantly the forearm vascular resistance in patients of groups 1 and 2 (90 +/- 19%, p less than 0.001; 63 +/- 10%, p less than 0.001, respectively). Thus the hemodynamic beta-blocking effects of nadolol in the forearm were less marked than those of propranolol, suggesting that the effects of acute beta blockade by nadolol could be offset by other effects, such as a peripheral partial-agonist effect.
Abstract: Thromboxane B2 (TxB2) was measured in the venous and arterial plasma and in the urine of 15 borderline and 15 sustained essential hypertensive patients, and in the plasma and urine of 12 control normotensive age-matched subjects. Plasma and urine thromboxane B2 were significantly higher in both the borderline and sustained hypertensives than in the control normotensives. There was a significant positive correlation between urinary (i.e. renal)TxB2 excretion and the glomerular filtration rate, and between urinary TxB2 excretion and sodium excretion in the hypertensive but not in the normotensive subjects. Thromboxane A2 participates in pressure natriuresis.
Abstract: Systemic and arterial hemodynamic effects of the new 20 mg tablet of nifedipine were studied in seven patients with mild-to-moderate essential hypertension. Hemodynamics of the forearm arterial circulation were investigated using a new pulsed Doppler system, enabling the simultaneous determination of the brachial artery diameter and the arterial blood flow velocity. After nifedipine administration, blood pressure decreased significantly, due to a fall in total peripheral resistance. Simultaneously, brachial blood flow increased significantly, due both to an increase in arterial diameter and blood flow velocity. The study provided evidence that, with nifedipine, there is both 1) a dilation of small arteries, causing a decrease in blood pressure; and 2) a dilation of peripheral large arteries, leading to an increase in peripheral blood flow.
Abstract: Blood pressure, heart rate, and arterial diameter of the brachial artery were studied in patients with sustained essential hypertension before and after administration of three vasodilating drugs: dihydralazine, diltiazem, and dinitrate isosorbide (ISDN). The diameter of the brachial artery was measured using a pulsed Doppler device, enabling the angle between the ultrasound beam and the vessel axis to be evaluated with a precision inferior to 2 percent. The three drugs had similar effects in decreasing the blood pressure and the forearm vascular resistance. Dihydralazine reduced the arterial diameter (p less than 0.001) and increased heart rate. Diltiazem and ISDN increased markedly the arterial diameter (p less than 0.001) but did not change heart rate. Dihydralazine decreased the tangential tension of the arterial wall, while diltiazem and ISDN did not. The study provided evidence that, with vasodilating drugs, the changes in the caliber of peripheral large arteries, which are a determinant of wall arterial tension, can influence the baroreflex-mediated tachycardia caused by use of the drugs.
Abstract: Cardiac hemodynamics, diameter, blood flow velocity, and volumic flow of the brachial artery were studied before and after diltiazem administration in 11 patients with sustained essential hypertension. The study was compared with the hemodynamic effects of dihydralazine. The caliber of the brachial artery was evaluated with a pulsed Doppler velocimeter enabling the determination of the angle between the ultrasound beam and the vessel axis with a precision of 2%. After bolus administration of diltiazem, blood pressure and total peripheral resistance significantly decreased (P less than 0.001) while cardiac index and heart rate significantly increased (P less than 0.01). After 25 minutes of perfusion, cardiac output and heart rate returned toward control values, while blood pressure and total peripheral resistance remained decreased. The results contrasted with those observed after dihydralazine, which induced a sustained increase in cardiac index and heart rate. The caliber of the brachial artery decreased significantly (P less than 0.001) after dihydralazine and increased significantly after diltiazem (P less than 0.01). The study provided evidence that the antihypertensive effect of diltiazem was due to a fall in total peripheral resistance, associated with a transient baroreflex mediated tachycardia, and that--in addition to their effects on small arteries--vasodilating drugs may either increase (diltiazem) or decrease (dihydralazine) the caliber of peripheral large arteries.
Abstract: The efficacy of MK-421 was compared with that of propranolol in patients with mild to moderate essential hypertension, using a placebo-controlled double-blind randomized protocol. The two drugs reduced supine and standing blood pressures, but propranolol, unlike MK-421, reduced heart rate. Using a pulsed Doppler method, brachial artery diameter, blood velocity and blood flow were measured during the study. These indices increased after MK-421 but were not modified after propranolol. Forearm vascular resistance decreased both after MK-421 and propranolol. Thus, chronic treatment with MK-421 or propranolol in hypertension lowers blood pressure but acts differently on forearm circulation. MK-421 dilates both the brachial artery and the arterioles of the forearm while propranolol has no effect on these arterial indices.
Abstract: Hemodynamic variables were measured in 34 patients with isolated systolic hypertension before and after acute administration of propranolol. The patients were separated into two groups, those younger than and those older than 45 years of age, respectively. After drug administration, systolic pressure decreased significantly (P less than 0.001) in younger subjects with a concomitant increase in rapid ejection time (P less than 0.001). In the older patients, cardiac and peripheral factors determining systolic pressure were each altered after beta-adrenergic blockade. The most striking result was the reduction in systemic arterial compliance (P less than 0.01) probably due to unmasked alpha-adrenergic vasoconstriction. This arterial effect explains the lack of systolic pressure reduction despite a decrease in cardiac performance.
Abstract: Arteriovenous fistula (AVF) blood flow was evaluated in 32 dialysis patients using a pulsed Doppler velocimeter with two dominant features: a range-gated time system and a double transducer probe. With the proposed apparatus, the observation angle between the ultrasound beam and the vessel axis was known. In radial AVF, blood flow was 728 +/- 53 ml/min and was negatively correlated with the age of the AVF (r = -0.62; p less than 0.01). In brachial AVF, blood flow was 778 +/- 152 ml/min. In bovine heterograft AVF, blood flow was 1,225 +/- 125 ml/min. In the overall population, a negative relationship was observed between the diameter of the fistula and the blood flow velocity (r = -0.57; p less than 0.01). The study describes an accurate noninvasive method for the determination of fistula blood flow in dialysis patients, which may be helpful in the follow-up of the regional hemodynamics of this vascular access.
Abstract: Since systolic pressure is governed by the rate of ventricular ejection and the rigidity of the aortic wall, antihypertensive agents may have different effects on systolic and diastolic pressure. Despite an adequate decrease in diastolic pressure, systolic pressure may remain elevated due to structural alterations of large arteries. In the present study, a procedure is described to distinguish the dilation of small and large arteries. The former is evaluated from the calculation of forearm resistance and the latter from the determination of the arterial diameter of the brachial artery, using a bidimensional pulsed Doppler system. Nitroglycerin dilates the brachial artery, with no change in forearm resistance. Dihydralazine reduces the diameter of the brachial artery but decreases forearm resistance. Only calcium and converting-enzyme inhibitors dilate both small and large arteries and cause an increase in brachial blood flow.
Abstract: Central and forearm arterial and venous hemodynamics, arterial baroreflex sensitivity, plasma renin activity, and catecholamines were studied in supine position and after -10 degrees head-down tilt in 29 patients with sustained essential hypertension and in 29 normotensive controls of the same age and sex. In both populations, blood pressure, heart rate, and arterial baroreflex sensitivity did not change during the maneuver. Head-down tilt induced a similar increase in cardiopulmonary blood volume in controls and hypertensives, whereas the increase in central venous pressure, cardiac output, and forearm blood flow was higher in hypertensives. Forearm venous tone decreased in controls (from 16.6 +/- 0.8 to 13.8 +/- 0.9 mmHg X ml-1 X 100 g-1; P less than 0.01) but did not change in hypertensive patients (24.9 +/- 1.6 vs. 25.1 +/- 1.9. The magnitude of forearm vascular resistance changes induced by head-down tilt were significantly related to the basal venous tone in the overall population (P less than 0.01). The decrease in plasma renin activity and plasma catecholamines was similar in the two groups. The study provides the evidence that the higher increase in cardiac output and local flow observed in head-down tilt in hypertensive patients is probably due to a higher change in central venous pressure related to a decrease in venous distensibility.
Abstract: Simultaneous brachial artery pressure and blood flow measurements were made in 45 men. Blood flow was evaluated by means of a pulsed Doppler device with a double transducer probe. From analysis of the pressure-flow curves during diastole, forearm arterial compliance (FAC) was determined by using the model of the forearm arterial tree as a system of tubes, each with a storage capacitance, in series with the arteriolar resistances vessels. The value of FAC for seven normal subjects, aged 44 +/- 3 (mean +/- SEM) years, was between 0.78 and 1.73 X 10(-10) m5 . N-1. By comparison, a 30% reduction in FAC was observed in 38 men of the same age with essential hypertension, which was similar whether the intra-arterial diastolic pressure was above or below 90 mmHg. In the more severe group (Intra arterial diastolic pressure greater than 90 mmHg), the reduced FAC was associated with a significant increase in brachial artery diameter; after administration of dihydralazine, blood pressure and arterial diameter returned to normal but FAC remained diminished. The study is the first to evaluate FAC in intact men. The reduced FAC in hypertension is independent of blood pressure "per se" but may reflect adaptive change in the walls of the large arteries. In the more severe hypertension, arterial calibre was increased; this could be a mechanism which could prevent FAC from decreasing further with chronic elevation of blood pressure.
Abstract: We studied blood pressure, arterial diameter, and blood flow of the brachial artery in patients with sustained essential hypertension before and after administration of the vasodilating drugs nitroglycerin, captopril, dihydralazine, diltiazem, and isosorbide dinitrate (ISDN). The diameter and the blood flow of the brachial artery were measured with a pulsed Doppler device which allowed the angle between the ultrasound beam and the vessel axis to be determined with a precision better than 2%. Nitroglycerin and captopril decreased blood pressure slightly but increased arterial diameter markedly. Dihydralazine, diltiazem, and ISDN decreased blood pressure similarly and significantly and also reduced forearm vascular resistance. Dihydralazine reduced arterial diameter (p less than 0.001), but did not change brachial blood flow. Diltiazem and ISDN increased the arterial diameter markedly (p less than 0.001 and p less than 0.01, respectively), but only the former increased brachial blood flow. We conclude that antihypertensive drugs that dilate small arteries can either reduce (dihydralazine) or increase (nitroglycerin, captopril, diltiazem, ISDN) the caliber of large peripheral arteries and thus have different effects on peripheral blood flow.
Abstract: 1 Blood pressure, systemic arterial compliance, and diameter, blood flow velocity, volumic flow and impedance of the brachial artery were measured before and after intravenous administration of nitroglycerin (15 micrograms/min during 15 min) in 11 patients with sustained essential hypertension. 2 For the evaluation of the diameter of the brachial artery, a bidimensional pulsed Doppler was used, enabling the angle of the ultrasound beam relative to the flowing stream of blood to be measured with an error of less than 2%. 3 After nitroglycerin, systolic pressure significantly decreased (P less than 0.01) without significant change in diastolic and mean arterial pressures, cardiac index, stroke index and total peripheral resistance. 4 Systemic arterial compliance and brachial artery diameter significantly increased (P less than 0.001; P less than 0.01) while velocity and blood flow of the brachial artery were unchanged. 5 The pattern of the input impedance of the brachial artery was consistent with a predominant effect of nitroglycerin on the viscoelastic properties of peripheral large arteries. 6 The study provided evidence that, in hypertensive patients, nitroglycerin has a direct effect on peripheral large arteries, causing an increase in arterial diameter and compliance, thus leading to a predominant decrease in systolic pressure.
Abstract: Plasma aldosterone (PA), plasma renin activity (PRA), extracellular fluid volume (EFV) and hepatic blood flow were measured in forty-four patients with sustained essential hypertension and compared with forty-two normotensive controls of same age and sex. All patient had inulin clearances within the normal range and balanced sodium intake and urinary output. In hypertensives, PA, PRA, EFV and hepatic blood flow were within normal ranges; the log-ratio PA:PRA was significantly elevated (P less than 0.001). In normotensives, a negative relationship was observed between PA and EFV (r=-0.55; P less than 0.001) while a positive relationship was observed between PA and PRA (=+0.70; P less than 0.001). In hypertensives, the two relationships were disrupted or less significant: for a given value of EFV, PA was more elevated in hypertensives than in normotensives; for a given value of PRA, PA was more evaluated in hypertensives than in normotensives. The results could not be explained on the basis of a disturbance in hepatic blood flow and/or in the metabolic clearance rate of aldosterone. The study provided evidence that, in patients with sustained essential hypertension and equilibrated sodium balance, there is an excess of plasma aldosterone relative to the levels of extracellular fluid volume and plasma renin activity. The excess of probably related to an abnormality in the adrenal secretion.
Abstract: The antihypertensive, renal and hormonal effects of captopril were studied in 10 patients with essential hypertension. Captopril significantly decreased arterial blood pressure with a concomitant increase in glomerular filtration rate, natriuresis and kaliuresis and a significant selective increase in urinary (renal) prostaglandin E2; other plasma and urinary prostaglandin (F2 alpha, 6-keto-prostaglandin F1 alpha; thromboxane B2) were not significantly changed. The urinary prostaglandin E2 increase was observed even in patients with pretreatment subnormal prostaglandin E2 excretion. Increases in urinary prostaglandin E2 were significantly positively correlated with increases in urinary sodium concentration. It is concluded that the antihypertensive effect of captopril is mediated, at least partially, by prostaglandin E2 release from renal and extrarenal tissues. Captopril enhances natriuresis at a lower perfusion pressure.
Abstract: Hemodynamic parameters were measured in 24 patients with arteriosclerosis obliterans of the lower limbs, in comparison with 16 normal subjects of same age. Systemic arterial compliance was estimated from a simple visco-elastic model. In patients with arteriosclerosis obliterans, systolic pressure was significantly increased (P less than 0.001) while diastolic pressure remained within normal ranges. Arterial compliance was reduced (P less than 0.01) and was negatively correlated with systolic pressure (r = -0.72). Intravenous administration of nitroglycerin significantly decreased systolic pressure (P less than 0.05) and increased arterial compliance (P less than 0.01) without any change in mean arterial pressure. This study provided evidence that, in patients with arteriosclerosis obliterans of the lower limbs, the reduced systemic arterial compliance contributes in the increase in systolic pressure.
Abstract: Plasma prostaglandins PGE2 and PGF2 alpha, cardiac hemodynamics, total effective vascular compliance, plasma (PV), interstitial (IFV) and extracellular fluid volumes, and renal indices were determined in 13 men with either borderline or sustained essential hypertension. PGE2 measured in the central venous blood was increased in borderline and in sustained hypertensives (p less than 0.01), while PGF2 alpha remained within normal ranges. Pulmonary degradation of both prostaglandins was decreased. In the overall population, the PGE2/PGF2 alpha ratio was: (i) negatively correlated with central venous pressure (r = -0.68; p less than 0.01), and (ii) positively correlated with total effective vascular compliance (r = 0.76; p less than 0.001), the PV/IFV ratio (r = 0.63; p less than 0.02) and the renal plasma flow (r = 0.79; p less than 0.001). The study suggests that, in hypertensive patients, prostaglandins PGE2 and PGF2 alpha play an important role on the compliance of the venous system and on the control of renal blood flow, contributing to the autoregulatory mechanisms of the hypertensive vascular disease.
Abstract: Hemodynamic parameters and systemic arterial compliance were measured in patients with arteriosclerosis obliterans of the lower limbs before and after acute administration of propranolol. Arterial compliance was evaluated from a simple viscoelastic model, enabling the calculation of diastolic drainage and diastolic blood flow as indices of the reservoir role of the larger arteries in overall circulation. In comparing basal conditions with normal subjects of the same age, patients with arteriosclerosis obliterans exhibited a significant decrease in arterial compliance (p less than 0.01) and heart rate (p less than 0.02) with a significant increase in systolic pressure (p less than 0.001). Diastolic drainage was increased (p less than 0.01) and was positively correlated with diastolic time (r = 0.73, p less than 0.001). Diastolic blood flow remained within normal ranges (52 +/- 2 vs 49 +/- 3 ml/m2/sec). After acute propranolol intravenous administration, heart rate and stroke volume decreased (p less than 0.001), while total peripheral resistance increased (p less than 0.001). Systemic arterial compliance and diastolic blood flow significantly decreased (p less than 0.01). The study provided evidence that in patients with arteriosclerosis obliterans, the diastolic blood flow was maintained in basal conditions despite the observed reduction in arterial compliance, and that intravenous propranolol administration decreased systemic arterial compliance and diastolic blood flow.
Abstract: Cardiac hemodynamic and diameter, blood flow velocity, volumic flow of the brachial artery measured by pulsed Doppler, were studied before and after diltiazem administration in comparison with dihydralazine in hypertensive patients. After diltiazem administration, blood pressure and total peripheral resistance significantly decreased (P less than 0.001) while cardiac index and heart rate increased (P less than 0.01). After 25 minutes perfusion cardiac output and heart rate returned toward control values, while blood pressure and total peripheral resistance remained decreased. The result contrasted with those observed after dihydralazine, which induced an increase in cardiac index and heart rate. The caliber of the brachial artery decreased significantly (P less than 0.001) after dihydralazine and increased after diltiazem (P less than 0.01). This study shows that 1). The antihypertensive effect of diltiazem was due to a fall in total peripheral resistance associated with a transient baroreflex mediated tachycardia, and 2) diltiazem dilated also large arteries.
Abstract: The pharmacokinetics of intravenous isosorbide dinitrate was investigated in 11 patients with labile hypertension and with normal renal and hepatic functions. The mode of administration (constant rate infusion without loading dose) was chosen in order to minimize side-effects and to approximate clinical conditions. Isosorbide dinitrate levels were measured by electron-capture gas chromatography. The volume of distribution during steady state (Vd beta = 318 +/- 117 I) and the elimination half-life (t1/2 beta = 64.8 +/- 30.5 min) were similar to those found after perlingual and oral administration. Systemic clearance (Cls = 3.80 +/- 1.48 I/min) was high for a drug given intravenously, presumably because of active hepatic extraction, intensive pre-systemic degradation and very active extra-hepatic metabolism. These findings should be compared with the considerable inter-individual variations observed in theoretical plasma concentrations during steady state and with the presence of two pharmacokinetic models (one -- and two -- compartments) in the patients under study. Comparison of the results obtained by the intravenous route with previously published results after perlingual and oral administration indicates the following bioavailability ratios: perlingual/i.v. = 31%, oral/i.v. = 20%, and oral/perlingual = 63%.
Abstract: Thromboxane A2 (TxA2) is a vasoconstrictor synthetized by the kidney. Its role in hypertension is unknown. We measured urinary TxB2 (the metabolite of renal TxA2) by radioimmunoassay and studied renal functions in 15 borderline, 15 sustained essential hypertensive patients and 12 age-matched normotensive subjects (6 young and 6 older adults). Results were as follows: Normotensive subjects: Mean arterial blood pressure (MBP) 97 +/- 2 mmHg, urinary TxB2 (UTxB2V) 159 +/- 12 pg/min, glomerular filtration rate (GFR) 120 +/- 8 ml/min, sodium excretion (UNaV) 73 +/- 9 mueq/min. Hypertensive patients: MBP 115 +/- 2 mmHg (p less than 0,001 vs controls), UTxB2V 298 +/- 24 pg/min (p less than 0,005), GFR 128 +/- 6 ml/min, UNaV 51 +/- 4 mueq/min (p less than 0.02). There was a positive significant correlation between UTxB2V and GFR (p less than 0,005) and between UTxB2V and UNaV (p less than 0,005) in hypertensive but not in normotensive subjects. There was no correlation between GFR and UNaV in either group. Conclusion: 1. Urinary (i.e. renal) TxB2 is significantly elevated in hypertensive patients; 2. TxA2 may be a mediator of pressure natriuresis.
Abstract: Systemic arterial compliance was estimated in 31 men, including 15 patients with sustained essential hypertension and 16 normal subjects of the same age. Values were derived from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple viscoelastic model. In normal subjects, baseline arterial compliance was 2.56 +/- 0.18 ml/mm Hg. A significant decrease (1.88 +/- 0.13 ml/mm Hg; P less than 0.001) was observed in hypertensives. Administration of vasoactive substances (angiotensin and sodium nitroprusside) showed that, for the same blood pressure levels, normal subjects and hypertensives had similar values for compliance. However, the correlation between the basal values of diastolic pressure and compliance was significant in normal subjects (r = --0.76) but not in hypertensives (r = --0.33); these results suggested differences between acute and long-term conditions in patients and controls. Calculated diastolic runoff was similar in both groups, approximating 58 and 55% of the stroke volume respectively. This study provides evidence that, in sustained essential hypertension, (1) the reduced arterial compliance cannot be related exclusively to the level of blood pressure, but also requires some abnormality of the volume of large arteries, and (2) the reservoir role of the large arteries is maintained.
Abstract: 1. Cardiac output, lower-limb blood flow, hepatic and renal blood flows were studied in 16 patients with borderline and 16 patients with sustained essential hypertension and compared with 16 age-matched control subjects. 2. In borderline hypertension cardiac output and lower-limb blood flow were significantly elevated, while hepatic and renal blood flows were within the normal range. Cardiac output and lower-limb blood flow were positively correlated. 3. In sustained hypertension cardiac output, lower-limb blood flow and hepatic blood flow were within the normal range. Renal blood flow was significantly reduced. Lower-limb blood flow was negatively correlated with mean arterial pressure. 4. If borderline hypertension is an early stage of fixed hypertension, the present study suggests that the changes in cardiac output observed in hypertension are mainly related to lower-limb (and muscle) blood flow.
Abstract: A pulsed Doppler velocimeter suitable for the determination of blood flow velocity and volumic flow in peripheral arteries is described. The apparatus has two main characteristics: an adjustable range-gated time system and a double transducer probe. The error in the determination of the angle between the ultrasound beam and flow of blood with this apparatus was less than 2%, and overestimation of the arterial diameter due to the sample volume size did not exceed 0.035 +/- 0.015 cm. The apparatus was used to determine diameter, blood flow velocity and volumic flow of the brachial artery of 22 healthy men. The values were respectively 0.440 +/- 0.010 cm, 9.15 +/- 1.01 cm.s-1 and 85 +/- 10 cm3.min-1. Administration of intravenous nitroglycerin significantly increased the arterial diameter (p less than 0.001) without any significant change in volumic flow. The described pulsed Doppler velocimeter provides an accurate noninvasive method for determining volumic flow in peripheral arteries in clinical investigation and cardiovascular pharmacology.
Abstract: 1. In basal conditions, plasma arterial prostaglandin (PG) E2 was significantly increased in borderline hypertensive patients (BH) (28.5 +/- 6.7 pg/ml) in comparison with sustained essential hypertensive patients (EH) (11.6 +/- 3.2 pg/ml) and in comparison with control normotensive subjects (NTS) (5.8 +/- 1.4 pg/ml). 2. Plasma arterial PGE2 was positively significantly correlated with cardiac index and negatively significantly correlated with total peripheral resistance in basal conditions. 3. Indomethacin induced more pronounced haemodynamic changes in borderline than in sustained hypertensive patients, with a significant increase in arterial blood pressure and total peripheral resistance and a significant decrease in stroke volume and cardiac index. 4. Indomethacin significantly decreased arterial PGE2 in borderline hypertensive patients. The decrease was less important in sustained hypertensive patients. 5. In the overall population, a significant positive correlation between arterial PGE2 concentration and cardiac index was observed before and after indomethacin treatment. 6. The study suggests an important role of PGE2 in the regulation of cardiac output (positive inotropic effect) and blood pressure of essential hypertensive patients.
Abstract: Extracellular fluid volume, hemodynamic parameters, total effective compliance, and renal indices were measured in 58 patients with sustained essential hypertensive in comparison with 56 normotensive subjects of the same age and sex. All subjects had a balanced sodium intake and urinary output with inulin clearance and extracellular fluid volume within normal ranges. In patients with hypertension, the ratio between plasma volume (PV) and interstitial fluid volume (IFV) was decreased (P less than 0.01) and was negatively correlated with the filtration fraction (FF) (r = -0.43; P less than 0.001). Total effective compliance was significantly reduced (P less than 0.001) and was positively correlated with the PV/IFV ratio (r = 0.73; P less than 0.001) and negatively correlated with FF (r = -0.56; P less than 0.001. The study provides evidence that the relationships between PV/IFV, FF, and vascular compliance reflect an alteration of the postcapillary segment of the circulation in hypertension.
Abstract: Hemodynamic parameters were studied before and after administration of SQ 14 225, an orally active converting enzyme inhibitor, in 6 sustained essential hypertensive patients. Blood pressure and total peripheral resistance significantly decreased while cardiac output and heart rate remained unchanged. Systolic time intervals and plasma volume were not modified. No correlation was observed between the basal value of plasma renin activity and the decrease in blood pressure. The study demonstrated the vasodilatator effect of SQ 14 225 and questionned the role of the renin-angiotensin system in the mechanism of the pressure decrease.
Abstract: 1. Cardiac haemodynamics were studied in 14 male patients with phaeochromocytoma, in comparison with 33 normal male subjects and 65 males with essential hypertension. 2. At the time of investigation, seven patients with phaeochromocytoma were hypertensive and seven were normotensive. Cardiac output was within normal limits. Total peripheral resistance was elevated in the hypertensive patients. Heart rate was elevated both in the normotensive and in the hypertensive patients, but decreased after surgical treatment. 3. The relationships between blood volume and blood pressure and between blood volume and cardiac output were the same as those observed in the control groups. 4. During tilt, a predominant systolic orthostatic hypotension was observed and was associated with decreased stroke volume and impaired adaptation of total peripheral resistance during tilt, indicating inadequate arteriolar and venous reflexes. 5. The study suggested that, except for tachycardia, the haemodynamic pattern of patients with phaeochromocytoma and with essential hypertension was nearly the same.
Abstract: A methodology for the determination of arterial compliance in men was developped. Arterial compliance was estimated from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple visco-elastic model. Arterial compliance and indices of ventricular ejection were measured in patients with systolic hypertension. In the younger patients, arterial compliance and stroke volume were within normal ranges. Rapid ejection time was significantly reduced, indicating an increased velocity in the first part of ventricular ejection. Systolic pressure decreased significantly after administration of propranolol, which also caused prolongation of rapid ejection time. In the older patients, indices of ventricular ejection were within normal values. Arterial compliance significantly reduced. Systolic pressure decreased significantly after administration of sodium nitroprusside, which caused an increase in arterial compliance. These findings provide evidence that the hemodynamic mechanisms of systolic hypertension differ in younger and older patients, and could influence the choice of drugs to decrease systolic pressure.
Abstract: Plasma renin activity and extracellular fluid volume were determined in 34 normotensive and in 35 sustained essential hypertensive patients with normal renal function, balanced sodium intake and urinary output. In normotensives, plasma renin activity was negatively correlated to extracellular fluid volume (r = 0.54; p = 0.001). The 95% confidence limits of the normotensive curve was used as nomogram to classify the hypertensive patients into two groups: those (23 cases) that fell within the limits of the normal curve (group I) and those (12 cases) that were below these limits (group II). In comparison with group I, group II was characterized by: (i) similar values for age, blood pressure, inulin clearance and extracellular fluid volume and (ii) significantly but lower values (p less than 0.001) for plasma renin activity with maintenance of the relationship between extracellular fluid volume and renin. The study strongly suggests that (i) the hypertensives of group I had no abnormal regulation of the renin-angiotensin system in comparison with the control subjects and (ii) the hypertensives of group II had an extracellular fluid volume-renin relationship set for lower values of renin.
Abstract: Cardiac output, blood pressure, and the characteristics of diastolic pressure decay were studied in 12 normal subjects and 23 sustained hypertensive patients of the same age. In normal subjects and in hypertensives, analysis of the diastolic decay showed that i) the form of the decay approximated a simple monoexponential curve during the last two-thirds of the diastolic segment, and ii) the time constant (t) of the curve was positively correlated with the total peripheral resistance (TPR), with an intercept of nearly zero. The validity of the relationship t = K x TPR was demonstrated both in groups of patients and also in individuals. Using a simple model for the vascular system, the K value was identified as the large arteries compliance and could thus be calculated in each individual. The values of arterial compliance was 1.26 +/- 0.04 ml.mmHg-1.m-2 in normal subjects and was significantly reduced in hypertensive patients (0.88 +/- 0.02 ml.mmHg=1.m-2,. P less than 0.001).
Abstract: Hemodynamic parameters were studied before and after rapid dextran infusion in 34 men including 17 patients with sustained essential hypertension and 17 normotensive controls. In both groups of patients, dextran infusion induced a significant increase (p less than 0.001) in central venous pressure (CVP), cardiac output (CO), and stroke volume. The percent change in stroke volume was significantly higher in hypertensives (p less than 0.001) than in controls. Three indices of volume expansion were calculated: 1) the ratio between the change in CO and the change in volume, which was significantly higher in hypertensives (p less than 0.025), 2) the ratio between the change in CO and the change in CVP, which was similar in both groups, and 3) the ratio between the change in volume and the change in CVP, which was significantly reduced in hypertensives (p less than 0.001). In the overall population, the latter ratio was negatively correlated with the change in CO (or in stroke volume) induced by expansion ( r = -0.75). The results provided evidence that: 1) the slope of the relationship between CO and blood volume was steeper in hypertensives than in normotensives, and 2) the steeper slope was due to a reduction in the effective compliance of the vascular bed, causing a greater elevation in CO per unit rise in volume.
Abstract: Guanfacine kinetics were studied in 19 patients with hypertension after single and repeated oral doses. The single-dose study was performed in two homogeneous groups who received 2 mg (n = 9) and 4 mg (n = 10). The plasma concentrations were fitted in a two-compartment open model with first-order absorption. After a lag time of 0.8 hr, the absorption occurred rapidly (t 1/2 congruent to 0.53 hr). The fast and slow elimination phases occurred with t 1/2s of 2 and 19 hr. At therapeutic levels the percent of drug in red blood cells (55%) was independent of total drug concentration. Peak plasma levels had small interindividual variations. Comparison of kinetic parameters and AUC at the two doses studied demonstrated that their bioavailability was equal and the kinetics were linear. In a multiple-dosing study, performed in the same subjects, the plasma levels at steady state were in good agreement with the predicted values (p less than 0.001) and proportional to daily dosage. A single method based on four blood samples collected after 24, 28, 32, and 36 hr allows a reasonable prediction of the effective steady-state plasma levels during chronic dosing with guanfacine.
Abstract: Systolic time intervals, echocardiographic dimensions and hemodynamic parameters were determined in 42 borderline hypertensive patients with high cardiac output and 33 normal subjects. In borderline hypertensive patients, the preejection period was significantly reduced (P less than 0.001) and was negatively correlated to cardiac index (P less than 0.001). The interventricular septum thickness (IVS) was significantly increased (P less than 0.001) while the posterior wall thickness (PW) was within normal values. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). These findings suggest that (i) myocardial hypertrophy and increased left ventricular performance exist in borderline hypertension, (ii) myocardial contractility is reduced as myocardial hypertrophy increases.
Abstract: Arterial compliance and indexes of ventricular ejection were measured in 27 men with systolic hypertension. The patients were separated into two age groups, younger or older than age 35 years, and matched with normotensive control subjects. Arterial compliance was estimated from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple viscoelastic model. In the younger patients, arterial compliance and stroke volume were within normal ranges. Rapid ejection time was significantly reduced (P less than 0.001), indicating an increased venlocity in the first part of ventricular ejection. Systolic pressure decreased significantly after administration of propranolol, which also caused prolongation of rapid ejection time. In the older patients, indexes of ventricular ejection were within normal limits. arterial compliance was significantly reduced (P less than 0.01) and was negatively correlated with the level of systolic pressure (P less than 0.001). Systolic pressure decreased significantly after administration of sodium nitroprusside, which caused an increase in arterial compliance. These findings provide evidence that: (1) the hemodynamic mechanisms of systolic hypertension differ in younger and older patients, and (2) these hemodynamic differences should be taken into account when choosing drugs to decrease systolic pressure.
Abstract: Echocardiographic dimensions and hemodynamic indexes were determined in 42 patients with borderline hypertension and in 22 with sustained hypertension and the results were compared with findings in 33 normal subjects. In patients with borderline hypertension the thickness of the interventricular septum (IVS) was significantly increased (P less than 0.001), whereas the posterior wall PW) thickness remained within normal range. The IVS/PW ratio was significantly elevated (P less than 0.001) and was correlated negatively with the cardiac index (P less than 0.01) and positively with the preejection period (P less than 0.01). In patients with sustained hypertension a symmetric cardiac hypertrophy was observed, and there was a significant positive correlation between the IVS/PW ratio and diastolic pressure (P less than 0.05). The study suggested that (1) in sustained hypertension the symmetric cardiac hypertrophy was secondary to a progressive increase in pressure load, whereas (2) in borderline hypertension the asymmetric cardiac hypertrophy could not be directly related to the level of blood pressure and was probably associated with abnormalities of the sympathetic nervous system.
Abstract: Electrocardiographic finding were studied in 34 severe hypertensions submitted to antihypertensive therapy. The duration of the survey was between 2 and 6 years. No significant correlation was observed between the changes in pressure and the changes in electrocardiogramm: normalisation of blood pressure could be associated with abnormalities in the electrocardiogramm, concerning especially ST segments and T waves. In the latter case, a high frequency of coronary insufficiency was observed. The results suggested that cardiac factors, independent of the pressure level, could determine the electrocardiographic changes during antihypertensive therapy.
Abstract: Extracellular fluid volume (EFV), total blood volume (TBV), and renal indices were determined in 53 permanent essential hypertensive patients with normal renal function and balanced sodium intake and urinary output. In comparison with normal subjects, hypertensives had normal EFV values while TBV and the TBV/EFV ratio were significantly reduced (p less than 0.001). In hypertensives, a significant negative relationship (r = -0.40; p less than 0.005) was observed between the TBV/EFV ratio and diastolic arterial pressure. No correlation existed between TBV and diastolic pressure, whereas EFV (and also interstitial fluid volume) was positively related to diastolic arterial pressure (r = +0.41; p less than 0.005). Extracellular fluid volume and interstitial fluid volume were both directly correlated to the renal filtration fraction (r = +0.45; p less than 0.005). The study suggests that, in the disturbed partition of the extracellular fluid of hypertensives, changes in the interstitial space are involved and are related to variations in the renal indices.
Abstract: Hemodynamic and blood volume changes, systolic time intervals, and baroreflex mechanisms were studied in 20 patients with hypertension after methyldopa (12 +/- 0.9 mg/kg/day). The drug was administered orally during 7 days' hospitalization on a normal sodium diet (110 mEq/day). There was a fall in blood pressure and in total peripheral resistance, without significant change in cardiac index, heart rate, and stroke index. There were increases in plasma and blood volume (p less than 0.05) but no change in cardiopulmonary blood volume or systolic time intervals. The unchanged heart rate was associated with an increased sensitivity ( less than 0.05) of the baroreflex mechanisms. The study supports the view that the unchanged cardiac output after methyldopa is related to important changes in control of cardiac output, including redistribution of blood volume and modifications in baroreflex mechanisms.
Abstract: Hepatic blood flow and peripheral plasma renin activity were determined in 15 true renovascular hypertensive patients and in 13 patients with essential hypertension. In the renovascular hypertensives, plasma renin activity and hepatic blood flow were negatively correlated ( p less than 0.01). In contrast, no relationship was observed in the essential hypertensives. The study suggests that hyperactivity of the renin-angiotensin system could induce splanchnic arteriolar constriction in patients with renovascular hypertension.
Abstract: 1 Hepatic blood flow was determined before and during (+)- and (+/-)-propranolol plasma concentration plateaus in 19 patients with suspected renal hypertension and normal liver function. 2 Hepatic blood flow significantly decreased (P less than 0.001) during (+/-)-propranolol administration and remained unchanged during (+)-propranolol administration. 3 Hepatic extraction ratio was 74 +/- 1% (+/-)-propranolol and 79 +/- 2% for (+)-propranolol. 4 Total propranolol clearances were determined during the steady-state achieved by a constant infusion. A highly significant positive relationship was observed (r = +0.86; P less than 0.01) between hepatic blood flow and (+)-propranolol clearance. The slope of the curve was 1.05 +/- 0.27. 5 The result implies that the total clearance of (+)-propranolol constitutes an accurate estimation of basal hepatic blood flow in subjects with normal liver function.
Abstract: Cardiac output (isotopic dilution method) and systolic time intervals were studied in 11 sustained and 8 borderline essential hypertensive patients, before and after intravenous administration of atenolol, a potent beta-blocking agent. Atenolol decreased significantly (p less than 0.01) cardiac output and heart rate. In borderline hypertensives, the preejection periods were significantly reduced. Atenolol prolonged the preejection periods more significantly (p less than 0.01) in borderline than in permanent hypertensives. Non invasive hemodynamic technics enabled the cardiac performance to be evaluated in hypertensives and the contribution of neurogenic factors in borderline hypertension to be estimated.
Abstract: Systemic arterial compliance was measured in 22 patients with permanent essential hypertension and compared with 11 sex- and age-matched normal normal subjects. Determinations were made from analysis of the monoexponential blood pressure-time curve during diastole, according to a simple visco-elastic model. Arterial compliance was significantly decreased (P less than 0.001) in hypertensives. In the overall population, arterial compliance was negatively correlated to age (P less than 0.005) and blood pressure (P less than 0.001), suggesting that the changes in compliance could be attributable to the level of blood pressure per se and/or to the rigidity of the arterial wall. Administration of vasoactive substances (angiotensin and sodium nitroprusside) enabled a strong negative relationship (P less than 0.01) between arterial compliance and diastolic blood pressure to be demonstrated in each individual. The slope of the curve was not dependent on age and represented the ability to decrease compliance per unit rise in pressure. The slope was steeper in hypertensives, suggesting a change reactivity of the arterial wall in these patients.
Abstract: 1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function. 2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow. 3. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged transfer rate constants and distribution volumes, (ii) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance. 4. Analysis of data obtained after oral administration of the drug by the Loo-Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) a significantly decreased fraction of dose effectively absorbed, (ii) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance. 5. The study provided evidence that in patients with renal insufficiency, (i) no increase in the metabolism of the drug accompanied the decrease in renal function, and (ii) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.
Abstract: Total effective compliance, hemodynamic parameters, extracellular fluid volume, cardiopulmonary (CPBV) and total blood (TBV) volumes were determined in 32 men, including 14 normotensive controls and 18 sustained essential hypertensive patients. The effective compliance was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume obtained after a rapid Dextran infusion. In normotensive controls, compliance was 2.08 +/- 0.09 ml/mm Hg/kg and was positively correlated with plasma (r = 0.79) and extracellular fluid (r = 0.84) volumes. In hypertensives, compliance was significantly reduced (1.49 +/- 0.06 ml/mm Hg/kg; P is less than 0.001) and was correlated negatively with the CPBV/TBV ratio (r = -0.75) and positively with the plasma volume/interstitial fluid volume ratio (r = 0.84). These results suggest that in normotensives, there is a regulatory mechanism between volume and compliance and that this contributes to maintaining filling pressure and cardiac output within normal ranges. In hypertensives, the reduced compliance could participate in the maintenance of normal values of cardiac output and extracellular fluid volume by influencing the partition of intravascular and extracellular fluid volumes.
Abstract: Repeat hemodynamic determinations were performed in 37 young men with borderline hypertension. The duration of the follow up study was 47 +/- three months. At each determination, those with borderline hypertension were compared to a group of matched normal subjects. Blood pressure increased from the first to the second determination, but the increase was significant only for systolic (P less than 0.001) and mean (P less than 0.01) arterial presssures. Cardiac index and heart rate, which were initially increased, decreased significantly (P less than 0.02; P less than 0.01, respectively) and decreased to normal values; total peripheral resistance increased (P less than 0.01); blood and plasma volumes decreased (P less than 0.01). At the first determination, the cardiac index-heart rate correlation was significant (P less than 0.01) and the cardiac index-blood volume correlation was not. At the second determination, on the contrary, the cardiac index-total blood volume correlation was significant (P less than 0.001) whereas the cardiac index-heart rate correlation was not. The study provides evidence that patients with borderline hypertension, over a short-term period, show (1) a greater increase in systolic than in diastolic pressure, (2) a return of cardiac output toward normal values through a decrease both in heart rate and blood volume, and (3) an increased importance of volume factors in the cardiac output control.
Abstract: The long terme hemodynamic effect of cyclothiazide 3 mg-triamterene 150 mg was studied in 10 patients with permanent essential hypertension. Diuretic therapy induced a significant fall in blood pressure (p less than 0.001) and total peripheral resistance (p less than 0.01), without significant change in cardiac index or blood volume. The result suggests that adaptative mechanisms of the circulatory system determine the decrease of blood pressure, independently of the pharmacological effect of the drug.
Abstract: Total effective vascular compliance, hemodynamic parameters, cardiopulmonary (CPBV) and total blood volumes (TBV) were determined in 31 men, including nine normotensive controls and 22 permanent essential hypertensive patients. The effective compliance was calculated from the changes in central venous pressure recorded simultaneously with the changes in blood volume obtained after a rapid dextran infusion. In hypertensives, compliance was significantly reduced (1.55 +/- 0.6 vs 2.25 +/- 0.11 ml./mm. Hg/Kg. in controls) (P less than 0.001) and negatively correlated with blood pressure (P less than 0.01), cardiac index (P less than 0.01), and the CPBV/TBV ratio (P less than 0.01). These results suggest that venous compliance contributes to the control of cardiac output in essential hypertension.
Abstract: Role of the clinical and experimental data suggesting the role of the sympathetic nervous system in some essential hypertension are reviewed: increase in heart rate and diastolic blood pressure during orthostatism, increase in cardiac output resulting from increase in cardiopulmonary blood volume and/or in myocardial contractility, increase in peripheral resistances, elevated plasma catecholamines and dopamine-bêta-hydroxylase, disturbances in arterial baroreceptor sensitivity and in vascular response to adrenergic stimuli, elevated plasma renin activity. It appears that the role of a sympathetic overactivity is mainly important in labile hypertension with hyperkinetic syndrome and elevated plasma renin activity.
Abstract: The decrease of sympathetic activity by the beta-blocking drug, as demonstrated by the decreased electric activity of the splanchnic nerve and by the decreased urinary catecholamine reponse to tilt as well as by the decreased levels of plasma dopamine beta-hydroxylase exists not only in hypertension with elevated PRA but also in hypertension with normal or low PRA. In these latter cases the antihypertensive effect is better explained by the decrease in the sympathetic nervous system activity than by the decrease of PRA. This effect seems to be indirect and probably, as suggested by Lewis, as a result of damping sensory input to the central nervous system from the heart, whose capacity to respond to exercice and stress is blunted by beta-adreno-receptor blockade.
Abstract: Correlates of plasma renin activity and plasma aldosterone levels with hemodynamic functions were studied in 47 male patients with untreated, permanent essential hypertension. All subjects had a normal creatinine clearance and received a diet of 110 mEq/day of sodium. Supine plasma renin activity was directly correlated with cardiac index (P less than.01) and cardiopulmonary blood volume (P=.01).Percentage changes in plasma renin activity and total peripheral resistance in response to upright position were positively correlated (P less than.001). Supine plasma aldosterone level was directly correlated with stroke index (P less than .001) and negatively correlated with hear rate (P less than .05). No significant correlation of aldosterone level was observed with the other measurements, including plasma renin activity. The study points to the neural sympathetic control of plasma renin activity in essential hypertension and suggests the existence of some interrelationships between aldosterone level and cardiac performance.
Abstract: Central hemodynamics were determined in 202 men including 101 normotensive and 101 permanent essential hypertensive patients of the same age. Cardiac output was identical in the two groups while blood pressure and total peripheral resistance were significantly different. Strong differences between the two groups are revealed by a systematic correlation study: (i) correlations of blood pressure (with respectively heart rate and total blood volume) were significant in the normotensive group but not in the hypertensive group; (ii) correlations of cardiac output (with respectively heart rate and total blood volume) were significant in both groups; (iii) correlations of renal blood flow (with respectively cardiac output and blood pressure) were significant in the hypertensive group but not in the normo tensive group. This study provided evidence that the volume and neural pressure controls are impaired in hypertensive patients while the cardiac output control is maintained and, suggested the existence of adaptive mechanisms involving the kidney in the maintenance of normal cardiac output in permanent essential hypertensive patients.
Abstract: Blood pressure, renal blood flow, total blood volume (TBV), plasma renin activity, and vascular reactivities to angiotensin and norepinephrine were studied in 48 normotensive subjects and 106 essential, sustained, hypertensive patients with normal renal function, balanced sodium intake, and urinary output. A significant negative pressure-volume relationship was observed in normal subjects. Among the hypertensive patients, some were inside the 95% confidence limits of the normal curve and the others were above, indicating a disturbance in the pressure-volume relationship. A quantitative evaluation of the pressure-volume disturbance was proposed and discussed. The blood pressure of each hypertensive patient corresponded to two different blood volume values: the renal valve and the theoretical value extrapolated from the normal curve. The difference between the two values was called deltaTBV and was positive in hypertensive patients. The deltaTBV value was negatively correlated with the renal blood flow, the creatinine clearance, the plasma renin activity, and the vascular reactivities to angiotensin and norepinephrine (P less than 0.0001). The parameters were not correlated with the real blood volume. This study demonstrates quantitatively a pressure-volume disturbance in essential hypertension. This disturbance is strongly correlated with the renal function and the renin-angiotensin system changes.
Abstract: A study of 100 men with arterial hypertension showed that: 1) hypertension was predominantly moderate with 14% index of placebo reactivity; 2) only 3 patients had a surgically curable etiologic factor; 3) frequent associated findings were hereditary factors (60%), overweight and metabolic disorders (30 to 40%). Such results suggest that: a) hypertension could be treated, in the majority of patients, without preliminary etiologic investigations and, b) non invasive hemodynamics techniques are required to evaluate arterial and cardiac lesions which are the dominant factors in the prognosis.
Abstract: Baroreflex sensitivity and cardiopulmonary blood volume were determined in 95 men, including normotensive and hypertensive subjects with normal renal function and balanced sodium intake and urinary output. Baroreflex sensitivity was estimated by determining the slope of the regression line relating the increase of systolic pressure to the cardiac slowing after transient rises of arterial pressure. A technique of gradual atropinisation was used to evaluate the parasympathetic mediated component of the reflex. With this method, it was possible to calculate the exact atropine dose abolishing the reflex sensitivity. This index was not dependent on age. It was negatively correlated to the diastolic pressure in normotensive patients but not in hypertensive patients. The ratio between the cardiopulmonary and the total blood volume was considered as an index of sympathetic venous tone. This ratio was positively correlated to the diastolic pressure in normotensive patients, but not in hypertensive patients. This study strongly suggests that a precise sympathetic-parasympathetic balance existed in the normotensive patients. This balance was disrupted in the hypertensive patients pointing to abnormalities in the autonomic nervous system of permanently hypertensive patients.
Abstract: Cardiac output, cardiopulmonary (CPBV) and total (TBV) blood volumes, vascular reactivity to norepinephrine and dopamine B hydroxylase (DBH) were determined in 41 borderline hypertensives patients in comparison with 28 normal subjects. Cardiac output (P less than 0.001) and CPBV/TBV ratio (P less than 0.01) were significantly increased. The ratio was directly correlated to the pressor-response to norepinephrine (P less than 0.01) and the DBH level (P less than 0.005). The results suggest that sympathetic overactivity plays a dominant role in the cardiac output elevation of borderline hypertensive patients.
Abstract: 1. Blood pressure, blood volume and renal blood flow were determined in 101 men; forty-three were normal subjects and fifty-eight were untreated permanent essential hypertensive patients with normal renal function and equilibrated sodium balance. 2. A significant negative pressure-volume relationship was observed overall. The relationship could be expressed as a hyperbola whose slope expressed the reduction in blood volume per unit rise in pressure: the higher the blood pressure, the lower the slope. Thus essential hypertensive subjects have a smaller decrement in blood volume per unit rise in pressure than normal subjects. 3. The relation between change in blood volume and change in pressure was confirmed in each individual by defining for each a ration deltaV/deltaP, statistically identical with the hyperbolic slope dV/dP. The deltaV/deltaP ratio was found to be well correlated with the renal blood flow and the creatinine clearance. No correlation existed between the total blood volume and these two renal parameters. 4. It is concluded that the present study demonstrates a blood volume regulation disturbance in essential hypertension and provides evidence from human studies that a renal defect accompanies high blood pressure.
Abstract: In borderline and permanent hypertensives after rapid i.v. injection of dl-propranolol 0.2 mg/kg plasma levels were measured and were fitted to a two-compartment open-model. In borderline patients, characterized by a high basal cardiac output (CO), plasma levels were always lower than in permanent hypertensives. The biological half-life was reduced and the central volume of distribution, volume of distribution at pseudo-equilibrium and total clearance (TC) were markedly increased. In the overall population, there was a significant positive correlation between CO and TC. Rapid achievement of a predetermined plateau in each group constituted experimental proof of the validity of the two-compartment open-model for kinetic analysis of propranolol i.v. If kinetic parameters from permanent hypertensive were applied to borderline hypertensives a lower plateau was obtained. Thus, in so far as beta-blockade is related to plasma level of propranolol, an increased intravenous dose may be required in patients with high CO.
Abstract: The pressor-response to norepinephrine was determined in the whole body circulation of 15 normal subjects and 86 untreated essential hypertensive patients. The slope, the threshold-dose and the critical-dose were calculated from the log dose-response curve. In the overall population (101 subjects) a slight correlation (r = +0.20 less than 0.05) was observed between the basal diastolic arterial pressure and the threshold-dose. In contrast, highly significant parabolic correlations (r = +0.46 less than 0.00001) were observed between the diastolic arterial pressure and the slope or the critical dose. When diastolic arterial pressure was above 100 mmHg, the slope increased while the blood pressure increased. This result suggests either a decreased sympathetic tone or an adaptative structural change of the arterial wall. When diastolic arterial pressure was under 100 mmHg, the slope decreased while the blood pressure increased. This observation points to an enhanced sympathetic activity in mild blood pressure.
Abstract: Antihypertensive therapy was performed in 47 patients having severe or malignant hypertension. The duration of the survey was two years. A highly significant decrease in blood pressure was observed. The decrease was not dependent on the type of antihypertensive treatment. Renal function was reduced at the beginning of the treatment. The renal insufficiency partly or totally diminished in course of time. Coronary insufficiency was noted in 5 patients. Coronarography showed thrombotic atherosclerosis in only one patient. A significant increase in lipids, cholesterol and triglycerids was nearly constant. The meaning of such facts is discussed.
Abstract: The anti-hypertensive effect of propranolol is studied in 35 essential permanent hypertensive patients. The decrease in blood pressure in higher in the presence (p is less than 0.01) than in the absence of diuretic therapy. The anti-hypertensive effect is higher in severe than in moderate hypertension. No side effect was observed except the decrease in heart rate (p is less than 0.001). Dihydralazine was added in 4 severe hypertensive patients and induced in 2 of them anginal attacks.
