Publications in PubMed: http://www.ncbi.nlm.nih.gov/pubmed?term=Angeli+Fabio
Research Profile on BiomedExperts: http://www.biomedexperts.com/Profile.bme/1638434/Fabio_Angeli
fangeli@cardionet.it
Fabio Angeli is a cardiologist and a biomedical researcher.
Research Interests â– Cardiovascular risk assessment in patients with hypertension, diabetes, heart failure and coronary artery disease. â– Evaluation of cardiovascular treatment. â– Diagnosis and treatment of acute myocardial infarction.
Scientific Activity â– Author of scientific works on cardiovascular disease, diabetes and hypertension (including original articles, meta-analyses, reviews and commentaries) published in leading journals. â– Reviewer for several leading medical journals. â– Investigator and co-responsible for planning and management of mono-centre and multi-centre Clinical Studies on Cardiovascular Drugs (in connection with Hospitals and Universities). â– Member of the Editorial Board of several international Journals.
Abstract: Blood pressure (BP) targets in diabetic patients stills represent the object of a major debate, fueled by the recent publication of post hoc observational analyses of the INVEST and the ONTARGET trials, suggesting an increased risk of cardiovascular events with tighter control, the J-curve effect, and by the results of the ACCORD trial, showing no improvements in the composite primary outcome of nonfatal myocardial infarction, stroke, or cardiovascular death in the intensive BP-lowering arm (<120/80Â mmHg). In the present review, we focus on existing evidence about different BP targets in diabetic subjects and we present the results of our recent meta-analysis, showing that tight BP control may significantly reduce the risk of stroke in these patients without increasing the risk of myocardial infarction. Therapeutic inertia (leaving diabetic patients with BP values of 140/90Â mmHg or higher) should be avoided at all costs, as this would lead to an unacceptable toll in terms of human lives, suffering, and socioeconomic costs.
Abstract: Aliskiren, a drug which inhibits the initial and rate-limiting step of the renin angiotensin aldosterone system (RAAS), recently approved for the treatment of hypertension, may become a reasonable therapeutic choice in a broad number of clinical conditions sharing an increased cardiovascular risk, where the inhibition of the RAAS has been shown to be beneficial.
Abstract: Traditional risk factors for premature cardiovascular disease such as systemic hypertension and hypercholesterolemia, all described more than half a century ago, are relatively few in number. Efforts to expand the epidemiological canon have met with limited success due to the high hurdle of causality. Fortunately, another solution to current deficiencies in risk assessment - in particular, the underestimation of risk both before and after initiation of pharmacotherapy - may exist. Parallel to the investigation of novel biomarkers, such as high-sensitivity C-reactive protein, ongoing research has yielded improved metrics of known causative conditions. This evolution of traditional risk factors, heralded by measures such as ambulatory blood pressure, central hemodynamics, low density lipoprotein particle concentration, genetic testing, and "vascular age," may better address the detection gap in cardiovascular disease.
Abstract: Cardiovascular disease (CVD) poses a significant healthcare and economic burden on societies and individuals. Angiotensin II is a key component of the renin-angiotensin system that plays a central role in atherosclerotic mechanisms that contribute to CVD. Renin-angiotensin system blockers are widely used to reduce cardiovascular (CV) risk owing to their potential both to lower blood pressure, a CV risk factor, and to attenuate the atherosclerotic disease process directly. Telmisartan has a number of pharmacological properties that distinguish it from other angiotensin II receptor blockers (ARBs) - the longest plasma half-life, highest lipophilicity and strongest receptor binding affinity in class. The ONTARGET(®) trial showed that telmisartan is as effective as ramipril in reducing CV morbidity (including myocardial infarction and stroke) and mortality in a broad range of patients at increased CV risk. Evidence from other ARBs remains largely restricted to patients with heart failure, diabetic nephropathy or specific subsets of hypertensive patients. Telmisartan is, therefore, the only ARB with a broad indication for CV risk reduction in patients with atherothrombotic disease or diabetes with end-organ damage.
Abstract: Myocardial ischemia is a relatively frequent complication in patients undergoing non-cardiac surgery and β-blockers may have a protective effect. β-Blockers reduce the oxygen supply:demand ratio, and exert anti-inflammatory and anti-arrhythmic effects. However, randomized trials, specifically conducted to test this hypothesis, yielded conflicting results. The absolute risk for cardiac mortality and morbidity during and after non-cardiac surgery varies between patient groups defined by surgical risk categories, making it difficult to establish a risk:benefit ratio. We discuss the hypothesis that the protective effect of β-blockers on cardiovascular outcome differs across the different risk classes of surgical procedures, thereby explaining the conflicting evidence across studies. In particular, we examine the results of a recent meta-analysis that suggests that β-blockers may reduce mortality in patients under going high-risk non-cardiac surgery.
Abstract: Diabetes and its micro- and macrovascular complications represent a worldwide epidemic that will place an enormous financial burden on poorer countries in the years to come. In patients with diabetes and hypertension, the main determinant of the cardiovascular and renal benefits of antihypertensive drugs is the blood pressure (BP) level achieved under treatment. Quite recently, the paradigm of a BP target <  130/80 mm Hg in these patients has been questioned by a number of trials, including data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure-lowering arm and from the diabetic cohort of International Verapamil SR-Trandolapril Study (INVEST). At the same time, even if the key role of BP control is unquestionable, a growing number of published trials suggest that different antihypertensive combinations may offer specific cardio-, vasculo-, and renoprotective advantages that go beyond BP reduction per se. The present review focuses on the most recent and important literature that explored the "optimal" antihypertensive therapy in patients with type 2 diabetes and concomitant hypertension, and it discusses in detail the various areas of uncertainty, including the specific renoprotective effects of renin-angiotensin system blocking agents and the long-term effects of angiotensin-converting enzyme/angiotensin receptor blocker combinations on the progression of diabetic nephropathy.
Abstract: Guidelines generally recommend intensive lowering of blood pressure (BP) in patients with type 2 diabetes. There is uncertainty about the impact of this strategy on case-specific events. Thus, we generated estimates of the effects of BP reduction on the risk of myocardial infarction (MI) and stroke in diabetic patients.
Abstract: Elevated neutrophil count, a marker of systemic inflammation, has been suggested as a prognostic marker of cardiovascular disease in postmenopausal women with hypertension. We tested the hypothesis that an association exists between elevated neutrophil count and increased arterial stiffness, as reflected by a wide pulse pressure (PP), in this population of women. We also tested PP as predictor of cardiovascular adverse events in this population.
Abstract: Indications for angiotensin-converting enzyme (ACE) inhibitors include heart failure, postmyocardial infarction, diabetes mellitus and proteinuric chronic renal disease. ACE inhibitors provided life-saving benefits in patients with heart failure or left ventricular systolic dysfunction. On the other hand, there are conflicting data regarding the ability of ACE inhibitors to reduce the incidence of cardiovascular events in patients with vascular disease and preserved left ventricular systolic function. Results of the main randomized clinical trials that evaluated the benefit of ACE inhibitors in patients with vascular disease are discussed in this editorial. In particular, the different prognostic impact of ACE inhibitors in high-risk patients with and without heart failure or preserved left ventricular systolic function is examined in detail. The possible impact of lipids and statins on the effect of ACE inhibitors is also discussed. In our opinion, the available data indicate that ACE inhibitors should continue to be used in all patients with documented coronary artery disease or different phenotypes of high vascular risk, even in a context of modern and aggressive preventive strategies.
Abstract: Prediction of hypertensive complications during pregnancy remains limited, especially in healthy and initially normotensive women. We conducted a prospective screening study for hypertensive complications in pregnant women. We studied 221 nulliparous healthy and normotensive women with singleton pregnancies whose first routine visit was carried out before the twelfth week of gestation. We tested several demographic, clinical and laboratory variables as predictors of a composite pool of prespecified events, including gestational hypertension, preeclampsia or eclampsia. We analyzed the potential additive role of ECG in the identification of women at increased risk of hypertensive disorders. Mean age at entry was 30 years. During pregnancy, there were 28 prespecified events (22 women with gestational hypertension, 5 with preeclampsia and 1 with eclampsia). In univariate analyses, blood pressure (BP), weight, body mass index (BMI) and left atrial (LA) abnormality detected by ECG in lead V(1) showed an association with the risk of hypertensive disorders (all P<0.05). In a multivariable analysis, only mean BP (OR: 3.08, 95% confidence interval (CI): 1.61-5.92; P=0.001 for each 10 mm Hg increase) and LA abnormality in lead V(1) (OR: 4.35, 95% CI: 1.84-10.31; P=0.001) were independent predictors of hypertensive disorders. The final model discriminated well between women who developed hypertensive disorders and women who remained normotensive (AUC=0.75; 95% CI: 0.67-0.84; P<0.0001). This study suggests that standard ECG is valuable to refine risk stratification for hypertensive disorders in initially normotensive pregnant women. LA abnormality, easily detected by simple visual inspection of the traditional ECG, and mean arterial pressure (MAP), allows a rapid and effective risk stratification for hypertensive disorders.
Abstract: The use of a composite cardiovascular endpoint (CCEP) is frequent in clinical trials. However, the relation between the reduction in blood pressure (BP) and the risk of CCEP is poorly known.
Abstract: Aliskiren is an orally active direct renin inhibitor which inhibits the synthesis of angiotensin I by linking to active renin on a deep cleft of its molecular structure, the site of hydrolysis of the Leu10-Val11 bond of angiotensinogen. At variance with angiotensin-converting enzyme (ACE) inhibitors, aliskiren eliminates the main substrate for the 'escape' phenomenon (synthesis of angiotensin II from angiotensin I through alternative enzymatic pathways). The possibility that the antihypertensive effect of aliskiren differs from that of ACE inhibitors needs to be proved in specifically designed clinical trials. Over the past 2 years, three studies have been published which directly compared aliskiren with ramipril, in patients with hypertension. We made a pooled analysis of these studies. In order to avoid interference with additional drugs, analysis was restricted to trial periods when the two drugs were given as monotherapy. In each individual study, systolic blood pressure (BP) was slightly lower with aliskiren. Overall, systolic BP was lower with aliskiren than with ramipril (weighted mean difference between the treatments 1.84 mmHg; fixed effect model; p < 0.0001; and 1.87 mmHg; random effect model; p = 0.0055). The standardized mean difference between the treatments was 2.58 (fixed effect model; p < 0.0001) and 2.92 (random effect model; p = 0.0017) in favor of aliskiren. Compared with ramipril, aliskiren may have induced a more complete 'upstream' inhibition of the renin-angiotensin-aldosterone system, with consequent greater suppression of angiotensin II. Another potential explanation may be the longer terminal elimination halflife of aliskiren (about 40 hours) compared with ramiprilat (13-17 hours). These data provide further evidence that aliskiren monotherapy provides a sustained BP reduction over the 24 hours.
Abstract: Angiotensin II receptor blockers (ARBs) are widely used in the treatment of patients with hypertension, heart failure, diabetic nephropathy and other clinical conditions. Several intervention trials and systematic overviews showed that both angiotensin-converting enzyme inhibitors and ARBs effectively reduce the risk of stroke, myocardial infarction and congestive heart failure in hypertensive patients. Two recent intervention trials conducted in Japan (JIKEI and Kyoto studies) suggested that the protective effect of ARBs on major cardiovascular events might be partly independent from the degree of blood pressure (BP) reduction. Both studies used a prospective randomized open blinded end point (PROBE) design. No significant differences emerged in both studies between the ARB group (valsartan) and the control group in the achieved BP. We made a pooled analysis of the JIKEI and Kyoto studies. Overall, valsartan significantly reduced the risk of the primary composite outcome (by 42%; P<0.0001), angina pectoris (by 38%; P<0.0001), heart failure requiring hospitalization (by 43%; P=0.013) and cerebrovascular events (by 42%; P=0.002). The protective effect on the dissecting aneurysm of aorta bordered statistical significance. These data reinforce the notion that the protective effect of angiotensin II inhibition is partly independent of BP reduction.
Abstract: ß-Adrenergic receptor antagonists (beta-blockers) are frequently used with the aim of reducing perioperative myocardial ischemia and infarction. However, randomized clinical trials specifically designed to evaluate the effects of beta-blockers on mortality in patients undergoing non-cardiac surgery have yielded conflicting results.
Abstract: High white blood cell and neutrophil counts identify patients at increased cardiovascular risk in various clinical settings. However, the prognostic value of white blood cell and neutrophil counts in hypertensive postmenopausal women is unknown. We tested the independent prognostic value of total white blood cell and neutrophil counts for cardiovascular events in hypertensive postmenopausal women.
Abstract: Myocardial ischemia is a frequent complication in patients undergoing non-cardiac surgery and beta-blockers may exert a protective effect. The main benefit of beta-blockers in perioperative cardiovascular morbidity and mortality is believed to be linked to specific effects on myocardial oxygen supply and demand. beta-blockers may exert anti-inflammatory and anti-arrhythmic effects. Randomized clinical trials which evaluated the effects of beta-blockers on all-cause mortality in patients undergoing non-cardiac surgery have yielded conflicting results. In 9 trials, 10,544 patients with non-cardiac surgery were randomized to beta-blockers (n = 5274) or placebo (n = 5270) and there were a total of 304 deaths. Patients randomized to beta-blockers group showed a 19% increased risk of all-cause mortality (odds ratio [OR] 1.19, 95% confidence interval (CI) 0.95-1.50; p = 0.135). However, trials included in the meta-analysis differed in several aspects, and a significant degree of heterogeneity (I( 2) = 46.5%) was noted. A recent analysis showed that the surgical risk category had a substantial influence on the overall estimate of the effect of beta-blockers. Compared with patients in the intermediate-high-surgical-risk category, those in the high-risk category showed a 73% reduction in the risk of total mortality with beta-blockers compared with placebo (OR 0.27, 95% CI 0.10-0.71, p = 0.016). These data suggest that perioperative beta-blockers confer a benefit which is mostly limited to patients undergoing high-risk surgery.
Abstract: The combined use of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) poses a dilemma to clinicians. On the one hand, indirect evidence from compelling, but still surrogate outcome measures such as blood pressure and proteinuria suggest some merits of this combination. On the other hand, the outcome benefits of the ACEIs+ARBs combination in morbidity/mortality trials remain confined to patients with severe congestive heart failure (CHF) and reduced ejection fraction. Incidentally, most of the benefit offered by the ACEIs+ARBs combination in these patients was not driven by mortality, but by fewer rehospitalizations for CHF. Even in patients with renal disease and proteinuria, the combined use of ACEIs and ARBs, although highly effective in reducing urinary protein excretion, has not yet been proven to significantly delay end-stage renal disease and the need for dialysis. In the Ongoing Telmisartan Alone and In Combination With Ramipril Global Endpoint Trial (ONTARGET), the dual blockade of the renin angiotensin system did not produce additional outcome benefit over that afforded by ACE inhibition alone. Notably, however, patients with BP >160/100 mmHg at entry were excluded from ONTARGET, thus limiting the applicability of these results to the treatment of hypertension. The European Society of Hypertension guidelines do not suggest large-scale use of the ACEIs+ARBs combination in patients with hypertension. However, patients with resistant hypertension, particularly if proteinuria coexists, could benefit from this combination, which however requires close monitoring for adverse events, including hyperkalemia and worsening renal function.
Abstract: Patients without a history of diabetes often develop hyperglycemia during an acute coronary syndrome (ACS). New onset of hyperglycemia (NH) is associated with higher mortality both in the short and long-term.
Abstract: Although repolarization abnormalities on ECG are frequent in post-menopausal hypertensive women, their prognostic value in these women is uncertain.
Abstract: Blood pressure (BP) may be high during usual daily life in one out of 7-8 individuals with normal BP in the clinic or doctor's office. This condition is usually defined as masked hypertension (MH). Prevalence of MH varied across different studies depending on patient characteristics, populations studied, and different definitions of MH. Self-measured BP and ambulatory BP (ABP) have been widely used to identify subjects with MH. Various factors have been identified as possible determinants of MH. Cigarette smoking, alcohol, physical activity, job, and psychological stress may increase BP out of the clinical environment in otherwise normotensive individuals, leading to MH. In most studies, target organ damage was comparable in subjects with MH and those with sustained hypertension, and greater than in those with true normotension. Subjects with MH showed a 1.5- to 3-fold higher risk of major cardiovascular (CV) disease than those with normotension, and their risk was not different from that of patients with sustained hypertension. In an overview of literature, we found that the risk of major CV disease was higher in subjects with MH than in the normotensive subjects regardless of the definition of MH based on self-measured BP (hazard ratio (HR) 2.13; 95% confidence interval (CI): 1.35-3.35; P = 0.001) or 24-h ABP (HR 2.00; 95% CI: 1.54-2.60; P < 0.001). MH is an insidious and prognostically adverse condition that can be reliably diagnosed by self-measured BP and ABP. MH should be searched for in subjects who appear to be more likely to have this condition. Antihypertensive treatment is envisaged in these subjects, although the associated outcome benefits are still undetermined.
Abstract: None of the available outcome-based studies was primarily designed to compare different blood pressure (BP) goals in patients with coronary artery disease (CAD). Consequently, there is uncertainty about the most appropriate BP treatment goal in these patients. Although US guidelines recommend a target less than 130/80 mm Hg, recent European guidelines state that such aggressive target is not consistently supported, therefore making the case for a less aggressive target (<140/90 mm Hg) in all hypertensive patients including those with CAD. A low systolic BP may be beneficial to limit myocardial workload, but an excessive lowering of diastolic BP might impair coronary perfusion, with potentially adverse effects (J-curve phenomenon). The optimal BP target for patients with CAD remains undefined. A reasonable target appears to be in the range of 130-140/80-90 mm Hg. Any further reduction may be safe, but not much productive from a prognostic standpoint.
Abstract: In the last few years, advances have been made in the diagnosis and management of ST-segment elevation myocardial infarction (STEMI). Recent guidelines have been developed to improve outcome of STEMI patients by implementation of the recommendations into clinical practice. In order to assess the disease burden, the treatment modalities and the mid-term outcome of STEMI in the Umbria region, Italy, we performed a prospective observational study of all patients hospitalized with a diagnosis of STEMI from October 14, 2006 to April 14, 2008 (Umbria-STEMI registry).
Abstract: We tested the hypothesis that the voltages of QRS on ECG improve risk stratification in hypertensive patients without left ventricular hypertrophy on ECG.
Abstract: It is unclear whether prevention of congestive heart failure (CHF) by drugs that inhibit the renin-angiotensin system (RAS) occurs over and beyond the reduction in blood pressure (BP) achieved by these drugs.
Abstract: The diabetes epidemic continues to grow unabated, with a staggering toll in micro- and macrovascular complications, disability, and death. Diabetes causes a two- to fourfold increase in the risk of cardiovascular disease, and represents the first cause of dialysis treatment both in the UK and the US. Concomitant hypertension doubles total mortality and stroke risk, triples the risk of coronary heart disease and significantly hastens the progression of microvascular complications, including diabetic nephropathy. Therefore, blood pressure reduction is of particular importance in preventing cardiovascular and renal outcomes. Successful antihypertensive treatment will often require a combination therapy, either with separate drugs or with fixed-dose combinations. Angiotensin converting enzyme (ACE) inhibitor plus diuretic combination therapy improves blood pressure control, counterbalances renin-angiotensin system activation due to diuretic therapy and reduces the risk of electrolyte alterations, obtaining at the same time synergistic antiproteinuric effects. ACE inhibitor plus calcium channel blocker provides a significant additive effect on blood pressure reduction, may have favorable metabolic effects and synergistically reduce proteinuria and the rate of decline in glomerular filtration rate, as evidenced by the GUARD trial. Finally, the recently published ACCOMPLISH trial showed that an ACE inhibitor/calcium channel blocker combination may be particularly useful in reducing cardiovascular outcomes in high-risk patients. The present review will focus on different ACE inhibitor combinations in the treatment of patients with type 2 diabetes mellitus and hypertension, in the light of recent clinical trials, including GUARD and ACCOMPLISH.
Abstract: Cardiovascular and renal disease can be regarded as progressing along a sort of continuum which starts with cardiovascular risk factors (hypertension, diabetes, dyslipidemia, smoking, etc), evolves with progression of atherosclerotic lesions and organ damage, and then becomes clinically manifest with the major clinical syndromes (myocardial infarction, stroke, heart failure, end-stage renal disease). The blood pressure control remains a fundamental mechanism for prevention of cardiovascular disease. The renin-angiotensin system is believed to play an important role along different steps of the cardiovascular disease continuum. Convincing evidence accumulated over the last decade that therapeutic intervention with angiotensin receptor blockers (ARBs) is effective to slow down or block the progression of cardiovascular disease at different steps of the continuum, with measurable clinical benefits. However, despite the shared mechanism of action, each ARB is characterized by specific pharmacological properties that may influence its clinical efficacy. Indeed, important differences among available ARBs emerged from clinical studies. Therefore, generalization of results obtained with a specific ARB to all available ARBs may be misleading. The present review provides a comparative assessment of the different ARBs in their efficacy on major clinical endpoints along the different steps of the cardiovascular disease continuum.
Abstract: Diabetes causes approximately 2.9 million deaths yearly, mainly through an increased risk of cardiovascular disease. In hypertensive diabetics, blood pressure reduction determines a significantly lower rate of cardiovascular and renal events. Conversely, reaching the generally recommended target of lower than 130/80 mmHg is a difficult challenge and, in most cases, two or more antihypertensive drugs are required. Until recently, there was a general consensus that combination treatment should include a diuretic as one of the two fundamental agents. However, recently published trials using calcium channel blockers plus renin-angiotensin system-blocking agents showed that such a combination reduces the risk of major cardiovascular events, provides greater renoprotection, and improves metabolic outcomes as compared with diuretic-based combinations. The present review explores the potential for an 'optimal' combination therapy in patients with diabetes mellitus and hypertension, in view of recent experimental and clinical evidence.
Abstract: The level to which systolic blood pressure should be controlled in hypertensive patients without diabetes remains unknown. We tested the hypothesis that tight control compared with usual control of systolic blood pressure would be beneficial in such patients.
Abstract: Guidelines for the management of hypertension almost invariably include sections where the evidence for or against treatment or for certain types of treatment in certain types of patients is inconclusive. This is especially the case of older patients with hypertension. As a consequence, although a large number of randomized trials including hypertensive patients aged > or = 60 years showed that antihypertensive drugs reduce cardiovascular morbidity and mortality, health care professionals who take care of older adults have been often reluctant to provide adequate antihypertensive therapy. In a recent meta-analysis, the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) compared the effects of different drugs for reducing blood pressure (BP) in older and younger adults; the reduction in BP levels and the relative risk reduction of a cardiovascular event with various antihypertensive drugs occurred independently of the patients' ages, and the benefits of antihypertensive regimens based on different drug classes were widely comparable across age groups. The BPLTTC analysis strongly suggests an early and aggressive management of hypertension irrespectively of age; more myocardial infarctions, strokes, heart failures and deaths will be prevented by treating hypertensive patients aged > or = 65 years than by treating patients < or = 50 years with the same BP levels. Antihypertensive treatment should be embedded within the management of global cardiovascular risk, with the use of charts for stratifying risk based on additional risk factors, target organ damage or additional clinical conditions.
Abstract: An association has been shown between plasma renin activity (PRA) and the risk of cardiovascular disease. There is also evidence that angiotensin II exerts detrimental effects on progression and instabilization of atherosclerotic plaque. The renin-angiotensin system (RAS) can be inhibited through inhibition of angiotensin I (Ang I) generation from angiotensinogen by direct renin inhibitors, inhibition of angiotensin II (Ang II) generation from angiotensin I by angiotensin-converting enzyme inhibitors and finally by direct inhibition of the action of Ang II receptor level. Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis. Because of its long pharmacological half-life, aliskiren is suitable for once-daily administration. Its through-to-peak ratio approximates 98% for the 300 mg/day dose. Because of its mechanism of action, aliskiren might offer the additional opportunity to inhibit progression of atherosclerosis at tissue level. Hypertension is an approved indication for this drug, which is also promising for the treatment of heart failure. The efficacy of this drug in reducing major clinical events is being tested in large ongoing clinical trials.
Abstract: Traditionally, diagnosis and management of arterial hypertension are based on blood pressure (BP) measurements taken in the physician's office. However, 24-h noninvasive ambulatory BP monitoring is increasingly used in patients with essential hypertension. Several prospective studies provided unequivocal evidence of an independent association between ambulatory BP and risk of cardiovascular disease in the general population and hypertensive patients. Ambulatory BP is a better predictor of cardiovascular morbidity and mortality than office BP after adjustment for traditional cardiovascular risk factors such as age, sex, smoking status, baseline office BP, and use of antihypertensive drugs. The more accurate prognostic value of ambulatory BP may be related to the closer association with hypertension-related organ damage such as left ventricular mass, intima-media thickness, and microalbuminuria. The superiority of ambulatory over clinic BP in predicting clinical outcome and the most appropriate way of interpreting results of ambulatory BP monitoring will be discussed in this review.
Abstract: To compare the effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on the risk of myocardial infarction, stroke, cardiovascular mortality and total mortality.
Abstract: Although the prognostic value of the day-night blood pressure (BP) changes is established, the most appropriate method for defining day and night is undefined. We assessed the prognostic value of the day-night BP changes by using three definitions of day and night in 2,934 initially untreated hypertensive subjects who underwent 24-hour ambulatory BP monitoring. Over a median follow-up period of 7 years, there were 356 cardiovascular events and 176 deaths. Total cardiovascular events and all-cause mortality were similarly higher in non-dippers (night/day ratio of systolic BP >10% or >0%) than in dippers regardless of the definition of day and night. In a receiver-operated characteristic (ROC) curve analysis of the night/day ratio of systolic BP on the occurrence of events, the area under the ROC curve did not differ among the different definitions of day and night (large fixed-clock intervals, narrow fixed-clock intervals, diary) for both total cardiovascular events (0.61 [95% confidence interval (CI): 0.58 to 0.64], 0.61 [95% CI: 0.57 to 0.63], 0.62 [95% CI: 0.58 to 0.65], respectively; P = 0.20) and all-cause mortality (0.65 [95% CI: 0.61 to 0.70], 0.64 [95% CI: 0.60 to 0.69], 0.65 [95% CI: 0.61 to 0.70], respectively; P = 0.78). The prognostic value of the diurnal BP changes is comparable when using different clock-dependent or independent definitions of day and night.
Abstract: Although the prognostic value of the day-night blood pressure (BP) changes is well established, the most appropriate method for definition of daytime and nighttime BP is still undefined. In a recent guidelines document of the European Society of Hypertension, there is no clear position in favor of one definition over other.
Abstract: Blood pressure (BP) measured in the office is usually higher than the average ambulatory BP, a difference generally taken as an estimate of the white-coat effect. This study was designed to assess whether such a difference is associated with impairment of the conduit arterial system.
Abstract: The independent prognostic value of daytime and night-time blood pressure (BP) variability estimated by noninvasive 24-h BP monitoring is unclear.
Abstract: Sleep deprivation induced by cuff inflations during overnight blood pressure (BP) monitoring might interfere with the prognostic significance of nighttime BP. In 2934 initially untreated hypertensive subjects, we assessed the perceived quantity of sleep during overnight BP monitoring. Overall, 58.7%, 27.7%, 9.7%, and 4.0% of subjects reported a sleep duration perceived as usual (group A), <2 hours less than usual (group B), 2 to 4 hours less than usual (group C), and >4 hours less than usual (group D). Daytime BP did not differ across the groups (all Ps not significant). Nighttime BP increased from group A to D (124/75, 126/76, 128/77, and 129/79 mm Hg, respectively; all Ps for trend <0.01). Over a median follow-up period of 7 years there were 356 major cardiovascular events and 176 all-cause deaths. Incidence of total cardiovascular events and deaths was higher in the subjects with a night/day ratio in systolic BP >10% compared with those with a greater day-night BP drop in the group with perceived sleep duration as usual or <2 hours less than usual (both P<0.01), not in the group with duration of sleep >or=2 hours less than usual (all Ps not significant). In a Cox model, the independent prognostic value of nighttime BP for total cardiovascular end points and all-cause mortality disappeared in the subjects with perceived sleep deprivation >or=2 hours. In conclusion, nighttime BP rises and loses its prognostic significance in the hypertensive subjects who perceive a sleep deprivation by >or=2 hours during overnight monitoring.
Abstract: Angiotensin II receptor blockers (ARBs) are widely used in patients with hypertension, heart failure, diabetic nephropathy, and other conditions. Over-stimulation of AT2 receptor as a result of AT1 blockade may contribute to the beneficial effects of ARBs through vasodilation and inhibition of cardiac and vascular hypertrophy and fibrosis. Some experimental studies, however, suggested that AT, receptor overstimulation, in addition to beneficial effects, might trigger inhibition of angiogenesis and apoptosis. In a review, some authors suggested that ARBs may increase the risk of myocardial infarction. This position triggered a hot scientific debate and further analyses of existing data. We completed a meta-analysis of randomized clinical trials comparing ARBs with either placebo or active drugs different from ARBs. ARBs were not associated with an excess risk of myocardial infarction (odds ratio 1.03 in a random-effect model and 1.02 in a fixed-effect model). Cardiovascular mortality did not differ between ARBs and drugs different from ARBs (odds ratio 1.00 in a random-effect model and 0.99 in a fixed-effect model) and it was slightly lesser with ARBs than with placebo (odds ratio 0.91; 95% confidence interval 0.83-0.99; p = 0.042) in a prespecified subgroup analysis. Other meta-analyses confirmed these data. In conclusion, evidence from randomized trials does not support the hypothesis that AT2 receptor over-stimulation produces harmful clinical effects. Current indications and contraindications to the use of ARBs in patients with hypertension, heart failure, and diabetic nephropathy should be maintained and probably extended to the entire class of these drugs.
Abstract: Self-measured blood pressure (BP) and 24-hour ambulatory blood pressure (ABP) monitoring are used to define the arbitrary clinical categories of masked hypertension (MH) and white-coat hypertension (WCH). Severity of target organ damage and incidence of major cardiovascular events are greater in patients with MH than in patients whose BP is normal both inside and outside the doctor's office.
Abstract: For more than 30 years, beta-blockers have widely been used in the treatment of patients with myocardial infarction, angina pectoris, heart failure, certain cardiac arrhythmias and hypertension. Quite recently, however, beta-blockers have been put under trial by results of some controlled studies and meta-analyses conducted in patients with essential hypertension. In summary, beta-blockers proved not better, or even worse, than alternative treatments and only marginally better than placebo. However, some arguments of caveat must be remarked. First, most of these studies have been conducted in hypertensive subjects of old age or complicated by several concomitant risk factors. A considerable portion of hypertensive patients most frequently examined in the usual practice would have not meet inclusion criteria for the above trials. In addition, several methodological issues of meta-analyses raised concern. Results were mainly driven from two major trials (LIFE and ASCOT). Unexpectedly, recent hypertension guidelines issued by the British Hypertension Society fully endorsed these results and recommended beta-blockers as fourth-line drugs in hypertensive patients with blood pressure not adequately controlled by angiotensin-converting enzyme inhibitors, calcium channel blockers and diuretics in combination. Because most of the above trials used atenolol, several lines of evidence warn against extending limitations to beta-blockers to the entire class of these drugs. Some new-generation beta-blockers, although not yet widely tested in outcome-based studies, induce peripheral vasodilatation and do not exert the detrimental effect of atenolol on central blood pressure and arterial distensibility. The present review addresses facts and theories related to the actual concern on the role of beta-blockers in the modern management of hypertensive patients.
Abstract: The interpretation of serial electrocardiographic (ECG) changes in hypertensive subjects is uncertain. We tested the hypothesis that serial changes in repolarization and voltage are independent determinants of outcome.
Abstract: Brachial pulse pressure (PP) is an established risk marker for cardiovascular disease. PP is largely determined by the stroke volume in young subjects, although the progressive amplification of pulse wave from central to peripheral arteries could make brachial PP not representative of the central PP in the young. With advancing age, brachial PP better reflects the progressive stiffening of aorta and the large elastic arteries. PP correlates with vascular and cardiac hypertrophy, although the association with cardiac hypertrophy seems more closely attributable to systolic blood pressure (BP). An association has been noted in several longitudinal studies between PP and the incidence of major cardiovascular events. However, some longitudinal studies carried out in subjects with predominantly systolic and diastolic hypertension showed that PP is the dominant predictor of coronary events, while mean BP is the major predictor of cerebrovascular events. Such an assumption may not be held in subjects with isolated systolic hypertension, where a wide PP seems to predict coronary and cerebrovascular events to a similar extent. From a pathophysiological standpoint, a wide PP might reflect diffuse atherosclerotic processes potentially involving also the large coronary arteries. Some data suggest that a wide PP could also represent a direct and independent stimulus for progression of atherosclerosis.
Abstract: Left ventricular hypertrophy (LVH) is a risk marker for stroke and its regression confers protection from stroke. The relationship between serial LVH changes and risk of stroke has never been investigated in a mixed population of hypertensive subjects with and without LVH.
Abstract: Although electrocardiography (ECG) is recommended in all subjects with hypertension, no information is available on the influence exerted by random changes in the placement of electrodes on the day-to-day variability of ECG criteria for diagnosis of left ventricular hypertrophy (LVH).
Abstract: To determine the accuracy of the A&D UB-511 (UB-512) oscillometric wrist-cuff device for self-measurement of blood pressure, the only difference between the two devices being the size of storage memory.
Abstract: Some questions about new-onset diabetes (NOD) must still be completely addressed: 1) its incidence; 2) the possible association between NOD and some classes of antihypertensive drugs; and 3) its prognostic impact. It is well known that diuretics and beta blockers can increase plasma glucose and, in available hypertension trials, diuretics and beta blockers caused a higher incidence of NOD than new antihypertensive drugs. NOD heralds a high risk of major cardiovascular events, but the absolute difference between old and new drugs was too small to significantly drive the differences in cardiovascular event rates between the two groups of treatment. This evidence suggests a judicious use of drugs more frequently associated with NOD in subjects at high risk of diabetes (impaired fasting glucose, overweight, family history of diabetes, low high-density lipoprotein cholesterol levels). The lowest effective dose of these drugs should be used, plasma glucose should be checked periodically, and concomitant lifestyle measures to prevent diabetes should be implemented with resolution.
Abstract: The uncertainty surrounding safety of angiotensin receptor blockers (ARBs) increased after publication of experimental and clinical studies which suggested an excess risk of myocardial infarction (MI) in people treated with ARBs.
Abstract: We investigated whether protection from coronary heart disease (CHD) and stroke conferred by angiotensin-converting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs) in hypertensive or high-risk patients may be explained by the specific drug regimen. We extracted summary statistics regarding CHD and stroke from 28 outcome trials that compared either ACEIs or CCBs with diuretics, beta-blockers, or placebo for a total of 179,122 patients, 9509 incident cases of CHD, and 5971 cases of stroke. CHD included myocardial infarction and coronary death. In placebo-controlled trials, ACEIs decreased the risk of CHD (P<0.001), and CCBs reduced stroke incidence (P<0.001). There were no significant differences in CHD risk between regimens based on diuretics/beta-blockers and regimens based on ACEIs (P=0.46) or CCBs (P=0.52). The risk of stroke was reduced by CCBs (P=0.041) but not by ACEIs (P=0.15) compared with diuretics/beta-blockers. Because heterogeneity between trials was significant, we investigated potential sources of heterogeneity by metaregression. Examined covariates were the reduction in systolic blood pressure (BP), drug treatment (ACEIs versus CCBs), their interaction term, sex, age at randomization, year of publication, and duration of treatment. Prevention of CHD was explained by systolic BP reduction (P<0.001) and use of ACEIs (P=0.028), whereas prevention of stroke was explained by systolic BP reduction (P=0.001) and use of CCBs (P=0.042). These findings confirm that BP lowering is fundamental for prevention of CHD and stroke. However, over and beyond BP reduction, ACEIs appear superior to CCBs for prevention of CHD, whereas CCBs appear superior to ACEIs for prevention of stroke.
Abstract: An elevated urinary albumin excretion (UAE) below the proteinuric level, i.e. microalbuminuria (MAU), has long been recognized as a marker of kidney disease and increased cardiovascular risk in both types of diabetes mellitus. Subsequent clinical evidence documented an association between MAU and other cardiovascular risk factors, target organ damage and risk of cardiovascular disease in the general population and in specific clinical contexts including essential hypertension. This article reviews the available evidence on the clinical value of MAU in subjects with essential hypertension. In these subjects, the reported prevalence of MAU ranges from about 4% to 46% across different studies and these differences may be explained by the huge intraindividual variability in UAE, age and ethnicity, discrepancies in the technique of measurement and different definitions of MAU. A direct and continuous association between UAE and blood pressure (BP) and left ventricular mass has been found in most studies. In contrast, it is not yet clear whether the association between UAE and other factors including age, gender, smoking, ethnicity, insulin resistance, lipids and obesity is independent or due to confounders, particularly BP. Several prospective studies disclosed an association between MAU and the risk of future cardiovascular disease. Of particular note, in some of these studies the incidence of major cardiovascular events progressively increased with UAE starting below the conventional MAU thresholds. Thus, besides being a direct risk factor for progressive renal damage, MAU can be considered a marker which integrates and reflects the long-term level of activity of several other detrimental factors on cardiovascular system. Antihypertensive treatment reduces UAE and such effect may be detected after just a few days of treatment. Among available antihypertensive drugs, angiotensin converting enzyme (ACE) inhibitors and the angiotensin II receptor antagonists seem to be superior to other antihypertensive drugs in reducing UAE. The dual blockade of the renin angiotensin system with an ACE inhibitor and an angiotensin II receptor antagonist is a new and promising approach to control UAE in hypertensive patients. Determination of MAU is recommended in the initial work-up of subjects with essential hypertension as suggested in the most recent European hypertension guidelines, even though, as upcoming evidence suggest, the periodic evaluation of this simple, inexpensive and predictive marker might be valuable and cost-effective.
Abstract: White-coat hypertension is defined by the coexistence of persistently high office blood pressure (BP) with normal self-measured or ambulatory blood pressure. The prognostic impact of white-coat hypertension is a subject of debate. Cardiovascular morbidity seems to be lower in white-coat hypertension than in ambulatory hypertension, and, according to some but not all studies, is not dissimilar between white-coat hypertension and clinical normotension. In a large collaborative study including individual data from four prospective cohort studies, the incidence of stroke tended to increase in the white-coat hypertension group in the long run, crossing the hazard curve of the ambulatory hypertension by the ninth year of follow-up. These data raise the hypothesis, to be tested in future studies, that white-coat hypertension might not be a benign condition for stroke in the long term. Further studies are needed in order to: (1) test whether white-coat hypertension is really a benign condition for stroke in the long term; (2) compare, in patients with white-coat hypertension, a regimen based on life-style measures without drugs and a standard regimen consisting of life-style measures with the possible addition of drugs. On the basis of current evidence, it is reasonable to suggest a treatment based on life-style measures in the low-risk stratum of patients with white-coat hypertension under the conditions of correct definition, absence of comorbid conditions and target-organ damage, and adequate follow-up
Abstract: Interpretation of some recent trials in hypertension opened a debate on the clinical value of new-onset diabetes in treated hypertensive patients. It is not completely clear whether certain antihypertensive drug classes are associated with a higher risk for developing type 2 diabetes when compared with other classes. Some longitudinal studies suggest that new-onset diabetes in treated hypertensive subjects carries a risk for subsequent cardiovascular disease similar to that of previously known diabetes. In a study, plasma glucose before treatment and diuretic treatment were independent predictors of new-onset diabetes in hypertensive patients, independent of confounding factors. We estimated that one cardiovascular event associated with new-onset diabetes might be prevented for every 385 to 449 patients treated with "new," rather than "old," antihypertensive drugs for approximately 4 years. These observations suggest that concern about the risk for new-onset diabetes should prompt a more judicious use of diuretics and beta-blockers in the treatment of hypertension. These drugs should be given cautiously in subjects who are at increased risk for new-onset diabetes, owing to impaired fasting glucose or obesity. The lowest effective dose should be used, and plasma glucose should be carefully monitored.
Abstract: Prevalence, determinants, and prognostic value of asymptomatic left ventricular systolic dysfunction (LVSD) in uncomplicated subjects with essential hypertension are still incompletely known. We studied 2384 initially untreated subjects with hypertension, no previous cardiovascular disease, and no symptoms or physical signs of congestive heart failure (CHF). These subjects were studied at entry and followed for up to 17 years (mean 6.0). Asymptomatic LVSD (ALVSD), defined by an echocardiographic ejection fraction <50%, was found in 3.6% of subjects. Cigarette smoking (P=0.013), increased left ventricular (LV) mass (P=0.001), and higher 24-hour heart rate (P=0.014) were independent correlates of ALVSD. During follow-up, a first cardiovascular event occurred in 227 subjects, and 24 of these events were hospitalizations for symptomatic CHF. Incidence of CHF per 100 persons per year was 0.12 in patients without and 1.48 in patients with ALVSD (log-rank test P=0.0001). In a Cox model, after adjustment for age (P=0.0001), LV mass (P=0.0001), and cigarette smoking (P=0.039), LVSD conferred a markedly increased risk for CHF (odds ratio, 9.99; 95% confidence interval, 3.67 to 27.2). Incidence of coronary (0.84 versus 0.62x100 person years) and cerebrovascular (0.80 versus 0.62x100 person years) events did not differ (all P=NS) between subjects with and without ALVSD. ALVSD is a potent and early marker of evolution toward severe CHF requiring hospitalization in subjects with essential hypertension.
Abstract: White-coat hypertension (WCH) has been associated with a low risk for stroke, but long-term data are scanty. We analyzed individual data from 4 prospective cohort studies from the United States, Italy, and Japan that used comparable methodology for 24-hour noninvasive ambulatory blood pressure monitoring (ABPM). Overall, 4406 subjects with essential hypertension and 1549 healthy normotensive controls who were untreated at the time of initial ABPM were followed for a median of 5.4 years up to censoring or occurrence of a first stroke. At entry, mean age of subjects was 56 years (range 18 to 97). Prevalence of WCH was 9%. During follow-up, there were 213 new cases of stroke. Stroke rate (x100 person years) was 0.35 in the normotensive group, 0.59 in the WCH group, and 0.65 in the group with ambulatory hypertension. In a multivariate analysis, the adjusted hazard ratio for stroke was 1.15 (95% confidence interval [CI], 0.61 to 2.16) in the WCH group (P=0.66) and 2.01 (95% CI, 1.31 to 3.08) in the ambulatory hypertension group (P=0.001) compared with the normotensive group. After the sixth year of follow-up, the incidence of stroke tended to increase in the WCH group, and the corresponding hazard curve crossed that of the ambulatory hypertension group by the ninth year of follow-up. In conclusion, WCH was not associated with a definitely increased risk of stroke during the total follow-up period. However, WCH might not be a benign condition for stroke in the long term.
Abstract: Recent data suggest that use of relatively high doses of angiotensin II-receptor blockers (ARBs) in hypertensive patients at high cardiovascular risk may reduce the incidence of clinical complications to a greater extent than would be predicted based on blood-pressure (BP) lowering alone. There is also evidence that a sustained reduction in BP, however small, may be important in reducing the risk of cardiovascular disease. Therefore, it is necessary to determine the ARB dosages that optimize the efficacy/tolerability ratio.
Abstract: Diabetes may develop in nondiabetic hypertensive subjects during treatment, but the long-term cardiovascular implications of this phenomenon are not clear. We determined the prognostic value of new diabetes in hypertensive subjects. In a long-term cohort study, 795 initially untreated hypertensive subjects, 6.5% of whom with type 2 diabetes, underwent diagnostic procedures including 24-hour ambulatory blood pressure (BP) monitoring and electrocardiography (ECG). Procedures were repeated after a median of 3.1 years in the absence of cardiovascular events. Follow-up duration was 1 to 16 years (median 6.0). New diabetes occurred in 5.8% of subjects initially without diabetes. Antihypertensive treatment included a diuretic in 53.5% of these subjects, versus 30.4% of those in whom diabetes did not develop (P=0.002). Plasma glucose at entry (P=0.0001) and diuretic treatment on follow-up (P=0.004) were independent predictors of new diabetes. Subsequent to the follow-up visit, a first cardiovascular event occurred in 63 subjects. Event rate in nondiabetic subjects at both visits, new diabetes, and diabetes at entry were 0.97, 3.90, and 4.70x100 person-years, respectively (P=0.0001). After adjustment for several confounders, including 24-hour ambulatory BP, the relative risk of events was 2.92 (95% CI: 1.33 to 6.41; P=0.007) in the group with new diabetes and 3.57 (95% CI: 1.65 to 7.73; P=0.001) in the group with previous diabetes, when compared with the group persistently free of diabetes. In treated hypertensive subjects, occurrence of new diabetes portends a risk for subsequent cardiovascular disease that is not dissimilar from that of previously known diabetes.
Abstract: The possibility that specific antihypertensive treatments may prevent the occurrence of stroke more effectively than other treatments remains unproved. We undertook a meta-analysis to assess whether calcium channel blockers (CCBs) are associated with a lesser risk of stroke as compared with other antihypertensive drugs.
Abstract: Hypertensive left ventricular hypertrophy (LVH) may be detected in about one third of people with hypertension. When an individual with elevated blood pressure develops LVH, the risk of adverse cardiovascular events in the ensuing years almost doubles even in the absence of symptoms. Because of this high added risk, hypertension and other modifiable risk factors should be managed aggressively with lifestyle measures and drugs. LVH can be considered a biological assay which reflects and integrates the long-term exposure not only to pressure overload, but also to several hemodynamic and non-hemodynamic factors which may promote progression and instabilization of atherosclerotic lesions and, ultimately, lead to adverse clinical events. LVH can partially or totally regress following antihypertensive treatment and lifestyle changes including losing excessive weight and decreasing salt intake. Angiotensin II antagonists and ACE-inhibitors seem to be the most effective drugs for reversing LVH. Evidence is accumulating that regression of LVH is associated with a significant reduction in the subsequent risk of cardiovascular disease. According to a recent meta-analysis, effective reversal of LVH is associated with a 59% lesser risk of subsequent adverse events as compared with the persistence or new development of LVH.
Abstract: Systolic blood pressure (SBP) is an important determinant of the development and regression of left ventricular hypertrophy (LVH) in hypertensive humans. However, comparative assessments with other BP components are scarce and generally limited in size. As part of the Progetto Ipertensione Umbria Monitoraggio Ambulatoriale (PIUMA), 743 hypertensive subjects underwent echocardiography and 24-h ambulatory BP monitoring before and after an average of 3.9 years of treatment. The changes in left ventricular mass showed a significant direct association with the changes in 24-h SBP (r=0.40), diastolic blood pressure (DBP) (r=0.33) and pulse pressure (PP) (r=0.35). Weaker associations were found with the changes in clinic BP (r=0.32, 0.31 and 0.16, respectively). In a multivariate linear regression analysis, the changes in 24-h SBP were the sole independent determinants of the changes in left ventricular mass (LVM) according to the following equation: percentage changes in LVM=0.73 x (percentage changes in 24-h SBP) -0.48 (P<0.0001). For any given reduction in 24-h SBP, the reduction in LVM did not show any association with the changes in DBP and PP, either clinic or ambulatory. These data indicate that SBP is the principal determinant of LVH regression in hypertensive humans.
Abstract: Regression of left ventricular hypertrophy (LVH) is an important intermediate target for antihypertensive therapy. Thus, several trials and meta-analyses have attempted to compare the effects of different antihypertensive agents on LVH, but flawed study designs and methodologic problems have limited the utility of these studies. PRESERVE (Prospective Randomized Enalapril Study Evaluating Regression of Ventricular Enlargement), LIVE (LVH: Indapamide Sustained Release Versus Enalapril) and LIFE (Losartan Intervention For Endpoint reduction in hypertension) represent a new generation of large well designed trials with the power to compare different antihypertensive drugs. These studies have shown that treatment regimens based on enalapril and a nifedipine gastrointestinal therapeutic system are of similar efficacy (PRESERVE), that indapamide sustained release (SR) is superior to enalapril (LIVE), and that a regimen based on losartan is superior to a regimen based on atenolol (LIFE) in reversing hypertensive LVH. LIVE incorporated on-treatment echocardiographic quality control, with centralized readers blinded for both treatment and sequence of recording. The findings of these rigorous studies, to some extent in disagreement with results of previous meta-analyses, support the notion that antihypertensive drugs need to be judged on their individual effects on important intermediate endpoints such as LVH in well designed and adequately sized studies. However, extrapolation of the results of these studies in terms of class effects could be misleading and should be made with caution.
Abstract: We undertook a meta-analysis of large, randomized controlled trials in hypertensive subjects that compared angiotensin-converting enzyme (ACE) inhibitors with different classes of antihypertensive drugs. Compared with subjects randomized to drugs different from ACE inhibitors, those treated with ACE inhibitors did not show a different risk of congestive heart failure (CHF) (odds ratio 1.03, 95% confidence interval 0.96 to 1.12, p = 0.407). The degree of protection from CHF associated with the use of ACE inhibitors showed a nonsignificant trend to increase with age and the degree of blood pressure control. Thus, the hypothesis that ACE inhibitors are superior to other antihypertensive drugs for prevention of CHF in hypertension remains unproven.
Abstract: During the past decade, several prospective studies showed that ambulatory BP (ABP) measurements provide a better prediction of major cardiovascular events when compared with clinic BP measurements. This review summarizes the available evidence supporting the use of ABP monitoring to refine prognostic stratification in hypertension. On the basis of available evidence, an operational flowchart is suggested to interpret results of ABP for better treatment of patients with elevated BP.
Abstract: The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) has recently came to light in a short version. A complete version will soon be available. JNC 7 is the last attempt to bridge the big gap between the current availability of potent and well tolerated antihypertensive strategies and their poor implementation in the clinical practice. Some new and important features characterize the JNC 7 document. The aim of the new and challenging definition of pre-hypertension (BP 120-139/80-89 mmHg) is to sensitize the general population and health professionals to implement effective strategies for a healthier life in order to prevent hypertension and related cardiovascular disease as early as possible. Stage 3 hypertension has been deleted and merged with stage 2 (systolic > or = 160 or diastolic > or = 100 mmHg). BP levels to achieve with treatment (goals) are < 140/90 mmHg (< 130/80 mmHg in diabetics). To reach the goal, diuretics are recommended for initial treatment in most subjects with stage I hypertension. However, combination of at least 2 drugs is recommended if initial BP is 20/10 mmHg higher than goal BP. Apart from the definition of pre-hypertension and the advice to begin therapy with diuretics in most patients with stage 1 hypertension, JNC 7 shares several positions with the hypertension guidelines recently released by the European Society of Cardiology and European Society of Hypertension. JNC 7 seems to dedicate limited space to stratify the level of cardiovascular risk in the individual subjects on the basis of the different combinations between BP levels and concomitant risk factors. In summary, JNC 7 is an updated and well equipped arsenal of formidable weapons against hypertension and its complications. The stage is now set for an hard task: their effective implementation in the clinical practice with the aim to decrease cardiovascular morbidity and mortality.
Abstract: We studied atrial activation during sinus rhythm by combining 12-lead ECG and multipolar esophageal recordings in 30 patients after electrical cardioversion of persistent atrial fibrillation. The primary endpoint was to establish a correlation between atrial activation evaluated by the two methods. Total P wave duration and morphology in inferior leads identified three patterns: normal P wave, late-positive P wave, and late-negative P wave. Proximal and distal esophageal recording characterized the longitudinal direction of activation of the posterior left atrium. We distinguished three activation patterns: normal activation when the interatrial conduction time is normal and depolarizes in craniocaudal direction, delayed activation when the interatrial conduction time is prolonged and the craniocaudal activation is maintained, and finally reversed activation when the posterior left atrium depolarizes in a reversed caudocranial direction. Four patients showed a normal P wave and also had a normal esophageal activation. Twelve patients showed a prolonged P wave (associated with delayed esophageal activation in 10 patients and reversed activation in 2 patients); 14 patients had a late-negative P wave (all associated with a reversed esophageal activation). A high correlation existed between each pattern obtained by surface ECG and esophageal recording (P < 0.001) and between surface P wave duration and interatrial conduction time (R2 = 0.64, P < 0.001). Much information concerning atrial activation can be obtained by meticulous analysis of the P wave, particularly its terminal part. Multipolar esophageal recording can be used when surface ECG appears unclear.
Abstract: Chronic periodontitis has been associated with an increased risk for cardiovascular disease. Left ventricular mass is an established independent predictor of cardiovascular disease. In the present cross-sectional study, we tested the association between periodontitis and left ventricular mass in subjects with essential hypertension. One hundred four untreated subjects with essential hypertension underwent clinical examinations, including echocardiographic study, laboratory tests, and assessment of periodontal status according to the community periodontal index of treatment needs (CPITN). With increasing severity of periodontitis, there was a progressive increase in left ventricle mass. Mean values (g/height2.7) were 39.0 (+/-2.7) in CPITN 0 (periodontal health), 40.2 (+/-6.4) in CPITN 1 (gingival bleeding), 42.7 (+/-6.8) in CPITN 2 (calculus), 51.4 (+/-11.7) in CPITN 3 (pockets 4 to 5 mm), and 76.7 (+/-11.3) in CPITN 4 (pockets > or =6 mm) (overall F 51.2; P<0.0001). Body surface area (P=0.04), systolic (P<0.0001) and diastolic (P<0.01) blood pressure, and left ventricular mass (P<0.0001) were determinants of a composite of CPITN 3 and 4. In a multivariate logistic analysis, left ventricular mass was the sole determinant (P<0.0001) of CPITN stages 3 and 4. Our findings suggest a direct association between severity of periodontitis and left ventricular mass in subjects with essential hypertension. Periodontal evaluation might contribute to refine cardiovascular risk assessment in hypertensive subjects.
Abstract: Incidence, determinants, and outcome of atrial fibrillation in hypertensive subjects are incompletely known. We followed for up to 16 years 2482 initially untreated subjects with essential hypertension. At entry, all subjects were in sinus rhythm. Subjects with valvular heart disease, coronary artery disease, preexcitation syndrome, thyroid disorders, or lung disease were excluded. During follow-up, a first episode of atrial fibrillation occurred in 61 subjects at a rate of 0.46 per 100 person-years. At entry, subjects with future atrial fibrillation differed (all P<0.05) from those without by age (59 versus 51 years), office, and 24-hour systolic blood pressure (165 and 144 versus 157 and 137 mm Hg, respectively), left ventricular mass (58 versus 49 g/height[m](2.7)), and left atrial diameter (3.89 versus 3.56 cm). Age and left ventricular mass (both P<0.001) were the sole independent predictors of atrial fibrillation. For every 1 standard deviation increase in left ventricular mass, the risk of atrial fibrillation was increased 1.20 times (95% CI, 1.07 to 1.34). Atrial fibrillation became chronic in 33% of subjects. Age, left ventricular mass, and left atrial diameter (all P<0.01) were independent predictors of chronic atrial fibrillation. Ischemic stroke occurred at a rate of 2.7% and 4.6% per year, respectively, among subjects with paroxysmal and chronic atrial fibrillation. These data indicate that in hypertensive subjects with sinus rhythm and no other major predisposing conditions, risk of atrial fibrillation increases with age and left ventricular mass. Increased left atrial size predisposes to chronicization of atrial fibrillation.
Abstract: We determined the prognostic value of the Cornell/strain [C/S] index, a simple electrocardiographic (ECG) index for left ventricular hypertrophy (LVH) defined by the presence of either a classic strain pattern or a Cornell voltage (sum of R in aVL + S in V(3)) >2.0 mV in women or 2.4 mV in men, or both.
Abstract: Patients with peripheral arterial disease (PAD) are characterized by a high mortality for cardiovascular events. An impairment of endothelial function, expressed as brachial-artery flow-mediated vasodilation (FMV), has been described in PAD patients. Aim of this study was to investigate the association between FMV and cardiovascular events in patients with PAD.
Abstract: Some studies have suggested that serial changes in left ventricular (LV) mass in hypertensive subjects predict the subsequent risk of cardiovascular disease. The aim of this meta-analysis was to evaluate the prognostic impact of LV hypertrophy regression in hypertension.
Abstract: Over the past decade, several prospective outcome studies have demonstrated that ambulatory blood pressure measurements provide a better prediction of major cardiovascular events compared with clinic blood pressure measurements. This review summarizes the advantages of ambulatory blood pressure over clinic blood pressure to predict outcome in untreated and treated hypertensive subjects. Based on available evidence, an operational flow-chart in order to interpret results of ambulatory blood pressure for a better management of these subjects is suggested.
Abstract: Left ventricular hypertrophy (LVH) detected at electrocardiography (ECG) is a predictor of an increased cardiovascular risk in essential hypertension. However, uncertainty remains concerning the reproducibility of ECG LVH and the prognostic relevance of its regression over time in hypertension. The aim of this study was to determine the prognostic value of baseline ECG LVH and its serial changes in a large cohort of hypertensive patients.
