Gregory P. Vyssoulis

Effects of menopause on aortic root function in hypertensive women

OBJECTIVES This study sought to determine whether the natural decrease in sex hormones that occurs during menopause in hypertensive women plays a role in aortic root stiffness. BACKGROUND The effect of menopause-induced sex hormone deprivation on aortic root function is not known; however, it is of special interest in hypertensive subjects, whose aortic elastic properties are already compromized. METHODS Eighteen women with essential hypertension were followed-up for 3 years, during which time they went through menopause (group A) and were compared with 22 age-matched hypertensive women with normal menses (group B) and 20 hypertensive men (group C). Blind echocardiographic tracings and simultaneous blood pressure measurements were obtained after at least 30 medication-free days, both at baseline and 3.5 years later. RESULTS Aortic root function tended to be aggravated in both groups B and C, but not significantly so, with no between-group differences (p = NS), whereas it deteriorated in group A. Thus, in menopausal hypertensive subjects, aortic root systolodiastolic percent change decreased (from 6.7% to 4.9%, p < 0.0001 [p = 0.002 vs. group B; p = 0.006 vs. group C]); cross-sectional compliance decreased (from 18 to 13 cm2/mm Hg, p < 0.0001 [p = 0.002 vs. group B; p = 0.03 vs. group C]); Petersons elastic modulus increased (from 1.2 to 1.9 dynes/cm2, p = 0.0006 [p = 0.003 vs. group B; p = 0.005 vs. group C]); aortic stiffiness index increased (from 7.0 to 10.8, p = 0.0008 [p = 0.004 vs. group B; p = 0.007 vs. group C]); and aortic root distensibility decreased (from 1.8 to 1.2 dynes/cm2, p < 0.0001 [p = 0.0003 vs. group B; p = 0.007 vs. group C]). Serum lipids did not change significantly in any group (p = NS). CONCLUSIONS In hypertensive women, the effect of menopause on the elastic properties of the aortic root is abrupt and devastating.

Effect of a number of coronary arteries significantly narrowed and status of intraventricular conduction on exercise-induced QRS prolongation in coronary artery disease

Abstract Previous studies have shown that myocardial ischemia decreases conduction velocity at Purkinje fibers, Purkinje muscle junctions and ventricular muscle fibers. 1,8 Thus, exercise-induced ischemia in patients with coronary artery disease may produce QRS prolongation. Although the effects of exercise-induced ischemia on the ST-segment changes, myocardial perfusion defects and segmental contraction abnormalities have been extensively studied in patients with coronary artery disease, the effect of exercise-induced ischemia on QRS duration has not been well evaluated. The present study was undertaken to investigate the effect of exercise on QRS duration in patients with coronary artery disease.

Beneficial Effect of Angiotensin II Type 1 Receptor Blocker Antihypertensive Treatment on Arterial Stiffness: The Role of Smoking

The purpose of the present study was to assess angiotensin receptor blocker (ARB) treatment on arterial stiffness in select hypertensive patients and define possible differences between smokers and nonsmokers. The authors evaluated 81 consecutive, nondiabetic patients (mean age, 52 years; 47 men) with uncomplicated essential hypertension with high plasma renin activity who were administered monotherapy with irbesartan, an ARB, at maximal dose. Patients were divided into smokers (n=24) and nonsmokers (n=57). Carotid‐radial pulse wave velocity (PWVc‐r), carotid‐femoral pulse wave velocity (PWVc‐f), and augmentation index (AIx) were measured before and 6 months after ARB antihypertensive treatment. All mean values of elastic effect indices were decreased after irbesartan monotherapy (AIx, from 26.3%to 21.2% [P<.01]; PWVc‐f, from 7.7 m/s to 7.3 m/s [P<.05], and PWVc‐r, from 8.9 m/s to 8.3 m/s [P<.001]). When comparing smokers vs nonsmokers, no difference was noted in AIx and PWVc‐f change (P=not significant), while PWVc‐r change was greater in smokers compared with nonsmokers (P<.05). Chronic ARB treatment may favorably affect arterial stiffness and wave reflections in hypertensive chronic smokers with elevated plasma renin levels.

Effect of beta-blockade on exercise capacity in hypertensive subjects: A one-year double-blind study of celiprolol and metoprolol

SummaryTo assess the effect of beta-blocker antihypertensive therapy on exercise capacity, 40 patients randomized to celiprolol 200 mg and metoprolol 100 mg daily in a double-blind fashion were studied after a month of placebo and a year of active treatment. Both drugs normalized office blood pressure and produced echocardiographic and electrocardiographic left ventricular hypertrophy regression. In symptomlimited maximal stress tests before and after treatment, exercise duration increased with (p<0.0001) celiprolol (513–700 seconds) and metoprolol (520–634 seconds), although more with the former (p=0.02). Resting heart rate was reduced with both, more with metoprolol (p<0.001), while heart rate at peak exercise was reduced similarly with both medications (p<0.005). Blood pressure at peak exercise was reduced with both celiprolol (217–184 mmHg; p=0.0002) and metoprolol (218–185 mmHg, p<0.0001) to a similar degree (p=NS). Exercise parameters were not related to patient age or the degree of left ventricular hypertrophy regression (p=NS). It is concluded that beta-blocker antihypertensive therapy improves exercise capacity, decreasing heart rate and blood pressure responses to stress, irrespective of left ventricular structural changes.

Regression of left ventricular hypertrophy in systemic hypertension with beta blockers (propranolol, atenolol, metoprolol, pindolol and celiprolol)

Abstract Left ventricular (LV) hypertrophy is frequently associated with systemic arterial hypertension and is a recognized, independent risk factor for coronary artery disease.1,2 Reduction of LV hypertrophy is thus a desirable goal in the treatment of high blood pressure (BP), but not all antihypertensive drugs accomplish this.3 Betaadrenergic blocking agents have not been shown to reverse LV hypertrophy in patients with essential hypertension, but few comparative and quantitative studies with differentβ blockers have been reported.4 This report concerns a study of the effects on echocardiographic LV hypertrophy indexes in 145 hypertensive patients treated with 5 different β-blocking drugs.

The Interplay of Exercise Heart Rate and Blood Pressure as a Predictor of Coronary Artery Disease and Arterial Hypertension

J Clin Hypertens (Greenwich). 2012;00:00–00. ©2012 Wiley Periodicals, Inc.

Correlation of 24-Hour Blood Pressure and Heart Rate Variability to Renal Function Parameters in Hypertensive Patients. The Effect of Smoking

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross‐sectional study sought to determine the association of 24‐hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never‐treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3±13.4 years, 55.3% males). The 24‐hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (CV=standard deviation×100/mean value) derived from ambulatory recording. The CVSBP‐to‐CVHR ratio (CVR) was used as a marker of the interplay between 24‐hour SBP and HR variability. Renal function was estimated via 24‐hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin‐to‐creatinine ratio (ACR), and 24‐hour urine α1‐microglobulin. After adjustment for age, sex, and smoking, CVSBP was found to be weakly correlated to eGFR (r=−0.017, P=.1) and somewhat more strongly to CrCl, ACR, and α1‐microglobulin (r=−0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CVHR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and α1‐microglobulin (r=0.185, 0.134, −0.306, −0.247; all P<.001, respectively). CVR also showed equally good adjusted correlations (r=−0.175, −0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CVHR and CVR were even better in smokers (r=0.213, 0.158, −0.332, −0.272 and −0.183, −0.118, 0.351, 0.275, respectively; all P<.001). CVHR and CVR emerge as better related to kidney function than CVSBP, especially in smokers. The correlation of CVHR and CVSBP to renal function is inverse to each other. ACR and α1‐microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved.

Dyslipidemic effects of cigarette smoking on beta-blocker-induced serum lipid changes in systemic hypertension

To assess the effects of beta blockers on lipids and apolipoproteins in cigarette smokers and nonsmokers, 330 patients with systemic hypertension received 1 month of placebo and 6 months of beta-blocker monotherapy. Serum total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoproteins A1 and B were measured. Total cholesterol increased with propranolol (smokers vs nonsmokers, 8 vs 2%); increased for smokers and decreased for nonsmokers with atenolol (8 vs -3%), metoprolol (6 vs -1%) and pindolol (7 vs -6%); and decreased for both groups with celiprolol (-3 vs -10%). HDL cholesterol decreased with propranolol (smokers vs nonsmokers, -8 vs -18%), atenolol (-7 vs -2%) and metoprolol (-12 vs -1%); increased for smokers and decreased for nonsmokers with pindolol (11 vs -2%); and increased for both groups with celiprolol (5 vs 6%). Similar trends were observed with LDL cholesterol and the total/HDL cholesterol ratio. It is concluded that early noncardioselective beta blockers such as propranolol have significant dyslipidemic effects in both smokers and nonsmokers. Cardioselective drugs such as atenolol and metoprolol, or drugs with partial agonist activity such as pindolol, have variable effects. Celiprolol, a new, highly cardioselective beta 1 blocker with partial beta 2 agonist activity and vasodilatory properties, has favorable effects on lipids and minimizes the dyslipidemic effects associated with smoking.

Disparate Serum Lipid Changes Between Normotensive and Hypertensive Women During the Menstrual Cycle

The homeostasis of serum lipids is dependent on a number of regulatory mechanisms, and in women, sex hormones have a major role.1 The effect of the hormonal control of lipid metabolism in fertile normotensive women has been reported in a small number of studies.2 Hypertensive women are at high risk for coronary artery disease, because of elevated blood pressure.3 However, lipid changes occurring during the menstrual cycle in hypertensive women have not been studied. In the present study, serum lipids and lipoproteins were measured in the 3 phases of the menstrual cycle in hypertensive women and were compared with similar lipid profiles obtained in normotensive control subjects, in relation to hormonal changes.

Comparison of ketanserin and celiprolol on regression of left ventricular hypertrophy in older hypertensive patients

SummaryThe effects of ketanserin, a specific serotonin2-receptor agonist, and celiprolol, a new, highly cardioselective % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaeqOSdi2aaS% baaSqaaiaaigdaaeqaaaaa!3874!\[\beta _1 \] blocker with partial % MathType!MTEF!2!1!+-% feaafeart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXatLxBI9gBaerbd9wDYLwzYbItLDharqqtubsr% 4rNCHbGeaGqiVu0Je9sqqrpepC0xbbL8F4rqqrFfpeea0xe9Lq-Jc9% vqaqpepm0xbba9pwe9Q8fs0-yqaqpepae9pg0FirpepeKkFr0xfr-x% fr-xb9adbaqaaeGaciGaaiaabeqaamaabaabaaGcbaGaeqOSdi2aaS% baaSqaaiaaikdaaeqaaaaa!3875!\[\beta _2 \] agonist activity and peripheral vasodilating properties, on left ventricular (LV) structure and function were assessed in 60 older hypertensive patients (>55 years) with clinical LV hypertrophy (LV mass indes >130 g/m2). The patients were studied using echocardiography after 1 month of placebo treatment, and 6 and 18 months of monotherapy with active drug. Ketanserin and celiprolol lowered blood pressure to normal levels. Heart rate did not change with ketanserin and fell moderately (-5%) with celiprolol (p<.001). Regression of LV hypertrophy was achieved with the use of either medication (p<.0001), although the magnitude of reduction in LV mass was greater with celiprolol at both 6 months (-10% vs-5%, p=.001) and 18 months (-13% vs-7%, p=.002). While LV volume did not change with either drug, celiprolol tended to decrease it, resulting in a 5% reduction in cardiac index (p=.01), which was associated with mild bradycardia. Ketanserin did not change LV ejection fraction, whereas celiprolol caused a slight (1.5%) long-term improvement (p=.003). Systolic wall stress and total peripheral resistance decreased with both agents (p<.01), with no between-group differences. In conclusion, antihypertensive treatment of older persons with ketanserin or celiprolol achieves regression of LV hypertrophy without associated deleterious effects on LV function.