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: 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: 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: 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. Copyright (c) 2007 S. Karger AG, Basel.
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: 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: 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: 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: 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: 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: 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: 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: 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: Homocystinuria is a genetically determined inborn error of the methionine amino acid pathway characterized by increased plasma homocysteine. In its major form, homocystinuria, is due to cystathionine beta synthase deficiency. Treatment of these adulthood patients lead physicians to call up on the skilled advices of pediatricians. But prevention and treatment of age related vascular and osteoporotic complications are still to be evaluated.
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: We have developed a robotic system to assist doctors when they are moving ultrasonic probes on a patient's skin while exerting a given effort. The probes are used to monitor arteries for cardiovascular disease prevention, namely to reconstruct the three-dimensional profile of arteries. A preliminary feasibility study making use of an industrial robot has been made to validate the force control scheme. It has proven the interest of the robotized approach for such medical applications where force control is needed. In order to comply with safety constraints, a dedicated robotic system 'Hippocrate' has been designed. This paper describes the arm and the controller architectures, with emphasis on design strategies selected to meet safety requirements. Preliminary in vivo results are presented as well as a possible new application of Hippocrate as a tool for reconstructive surgery.
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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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 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: 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: 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: 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: 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: 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: 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: 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: 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: 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: 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.
