Puneet Narayan

Effects of regular exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension

BACKGROUND The prevalence of hypertension and its cardiovascular complications is higher in African Americans than in whites. Interventions to control blood pressure in this population are particularly important. Regular exercise lowers blood pressure in patients with mild-to-moderate hypertension, but its effects in patients with severe hypertension have not been studied. We examined the effects of moderately intense exercise on blood pressure and left ventricular hypertrophy in African-American men with severe hypertension. METHODS We randomly assigned 46 men 35 to 76 years of age to exercise plus antihypertensive medication (23 men) or antihypertensive medication alone (23 men). A total of 18 men in the exercise group completed 16 weeks of exercise, and 14 completed 32 weeks of exercise, which was performed three times per week at 60 to 80 percent of the maximal heart rate. RESULTS After 16 weeks, mean (+/- SD) diastolic blood pressure had decreased from 88 +/- 7 to 83 +/- 8 mm Hg in the patients who exercised, whereas it had increased slightly, from 88 +/- 6 to 90 +/- 7 mm Hg, in those who did not exercise (P = 0.002). Diastolic blood pressure remained significantly lower after 32 weeks of exercise, even with substantial reductions in the dose of antihypertensive medication. In addition, the thickness of the interventricular septum (P = 0.03), the left ventricular mass (P = 0.02), and the mass index (P = 0.04) had decreased significantly after 16 weeks in the patients who exercised, whereas there was no significant change in the nonexercisers. CONCLUSIONS Regular exercise reduced blood pressure and left ventricular hypertrophy in African-American men with severe hypertension.

Exercise Capacity and Mortality in Black and White Men

Background— Exercise capacity is inversely related to mortality risk in healthy individuals and those with cardiovascular diseases. This evidence is based largely on white populations, with little information available for blacks. Methods and Results— We assessed the association between exercise capacity and mortality in black (n=6749; age, 58±11 years) and white (n=8911; age, 60±11 years) male veterans with and without cardiovascular disease who successfully completed a treadmill exercise test at the Veterans Affairs Medical Centers in Washington, DC, and Palo Alto, Calif. Fitness categories were based on peak metabolic equivalents (METs) achieved. Subjects were followed up for all-cause mortality for 7.5±5.3 years. Among clinical and exercise test variables, exercise capacity was the strongest predictor of risk for mortality. The adjusted risk was reduced by 13% for every 1-MET increase in exercise capacity (hazard ratio, 0.87; 95% confidence interval, 0.86 to 0.88; P<0.001). Compared with those who achieved <5 METs, the mortality risk was ≈50% lower for those with an exercise capacity of 7.1 to 10 METs (hazard ratio, 0.51; 95% confidence interval, 0.47 to 0.56; P<0.001) and 70% lower for those achieving >10 METs (hazard ratio, 0.31; 95% confidence interval, 0.26 to 0.36; P<0.001). The findings were similar for those with and without cardiovascular disease and for both races. Conclusions— Exercise capacity is a strong predictor of all-cause mortality in blacks and whites. The relationship was inverse and graded, with a similar impact on mortality outcomes for both blacks and whites.

The effect of vardenafil, a potent and highly selective phosphodiesterase-5 inhibitor for the treatment of erectile dysfunction, on the cardiovascular response to exercise in patients with coronary artery disease☆

OBJECTIVES The effect of vardenafil, a potent and highly selective phosphodiesterase-5 (PDE5) inhibitor, on symptom-limited exercise time, time to first awareness of angina, and time to ischemic threshold (ST-segment depression > or =1 mm from baseline) during exercise tolerance testing (ETT) was examined in patients with stable coronary artery disease (CAD). BACKGROUND Erectile dysfunction (ED) is common among men with CAD. PDE5 inhibition is increasingly the preferred treatment option for ED. However, the effect of PDE5 inhibition on exercise-induced ischemia in CAD patients has received limited prospective evaluation. METHODS In this double-blind, crossover, single-dose multicenter study, 41 men with reproducible stable exertional angina due to ischemic CAD received vardenafil 10 mg or placebo, followed by ETT (5 to 10 metabolic equivalents [METS], Bruce protocol) 1 h postdose. Sublingual nitrate use was prohibited for > or =24 h pre- and postexercise study days. End points included symptom-limited treadmill exercise time, time to first awareness of angina, time to ischemic threshold, and safety. RESULTS Relative to placebo, vardenafil 10 mg did not alter exercise treadmill time (427 +/- 105 s vs. 433 +/- 109 s, p = 0.39), or time to first awareness of angina (292 +/- 110 s vs. 291 +/- 123 s, p = 0.59), but significantly prolonged time to ischemic threshold (334 +/- 108 s vs. 381 +/- 108, p = 0.0004). At peak exercise, vardenafil 10 mg did not alter blood pressure, heart rate, or rate-pressure product relative to placebo. The most common adverse events (facial flushing and headache) were of mild or moderate intensity, and short-lived. CONCLUSIONS Vardenafil 10 mg did not impair the ability of patients with stable CAD to exercise at levels equivalent or greater than that attained during sexual intercourse (average of 2.5 to 3.3 METS).

EXERCISE AS HYPERTENSION THERAPY

In conclusion, the findings of most recent studies show that moderate-intensity aerobic exercise training can lower BP in patients with stage 1 and 2 essential hypertension. The average reduction in BP is 10.5 mm Hg for systolic and 7.6 mm Hg for diastolic BP. The reductions do not appear to be gender- or age-specific. Significant reductions in BP and LVH regression in patients with stage 3 hypertension have also been reported following aerobic exercise training. Resistance training exercise has not consistently shown to significantly lower BP and is not recommended as the only form of exercise for hypertensive patients. The exercise training program for optimal benefits should consist of 3 to 5 times per week, 30 to 60 minutes per session, at 50% to 80% of PMHR. However, exercise programs should be individualized to meet the patients needs and abilities. Exercise intensity and duration should be manipulated to promote a safe and effective antihypertensive program. Initially, the exercise intensity should be low and the duration short. Both intensity and duration should progressive increase over a period of weeks until the desired goal, is achieved. The rate of progression must be tailored to meet individual patient needs and abilities. The exercise program for overweight or obese hypertensive patients should aim to promote a caloric expenditure of 300 to 500 Kcal per day and 1000 to 2000 Kcal per week. Such an approach, combined with a prudent diet, is likely to reduce body weight. The mechanisms mediating exercise-induced BP reduction are poorly understood. BP reductions appear to be independent of changes in body weight or body composition. There are also no indications of age- or gender-related differences in BP response to exercise. The use of ambulatory blood pressure measuring devices in exercise studies is not extensive. The few studies available indicate a more moderate reduction in BP than that reported by casual observations.

Exercise Capacity and Mortality in Hypertensive Men With and Without Additional Risk Factors

We assessed the association between exercise capacity and mortality in hypertensive men with and without additional cardiovascular risk factors. A cohort of 4631 hypertensive veterans, who successfully completed a graded exercise test at the Veterans Affairs Medical Center in Washington, DC, and Palo Alto, California, was followed for 7.7±5.4 years (35 629 person-years) for all-cause mortality. Fitness categories were established based on peak metabolic equivalent (MET) levels achieved. In each fitness category, we defined individuals with and without additional cardiovascular risk factors. Exercise capacity was the strongest predictor of all-cause mortality. The adjusted mortality risk was 13% lower for every 1-MET increase in exercise capacity. Compared with the very low fit (≤5.0 MET), the adjusted risk was 34% lower for those achieving 5.1 to 7.0 MET (low fit; hazard ratio: 0.66; CI: 0.58 to 0.76; P<0.001), 59% lower for the moderate fit (7.1 to 10.0 MET; hazard ratio: 0.41; CI: 0.35 to 0.50; P<0.001), and 71% lower for the high-fit category (>10.0 MET; hazard ratio: 0.29; CI: 0.21 to 0.40; P<0.001). Within the very-low-fit category, mortality risk was 47% higher for those with additional risk factors compared with individuals with no risk factors. This risk was eliminated for those in the next fitness category (5.1 to 7.0 MET) and was progressively reduced for the moderate and high-fit categories regardless of the presence or absence of additional risk factors. In conclusion, exercise capacity was the strongest predictor of all-cause mortality in hypertensive men. The increased risk imposed by low fitness and additional cardiovascular risk factors was eliminated by relatively small increases in exercise capacity and declined progressively with higher exercise capacity.

Determinants of exercise blood pressure response in normotensive and hypertensive women: role of cardiorespiratory fitness.

PURPOSE Exaggerated blood pressure (BP) response during physical exertion is associated with increased risk for cardiovascular events. Furthermore, it may be the predisposing factor for myocardial infarction triggered by physical exertion. The authors have shown that systolic BP achieved after 6 minutes of exercise is the strongest predictor of left ventricular hypertrophy. Furthermore, a 37 mm Hg increase in systolic BP above resting BP at 6 minutes of exercise was the threshold for left ventricular hypertrophy. The purpose of this study was to determine predictors of exercise BP response in normotensive and hypertensive women. METHODS An exercise tolerance test (Bruce) was performed by 1411 normotensive (resting BP < 140/90 mm Hg) and hypertensive (resting BP > or = 140/90 mm Hg) women. These women were faculty, students, and staff at the University of Maryland, College Park, Maryland, and the George Washington University Medical Center, as well as patients undergoing a routine exercise tolerance test at West Coast Cardiology, Pinellas Park, Florida. Two fitness categories (low-fit and high-fit) were established on the basis of treadmill time to exhaustion adjusted for age. RESULTS Significant associations were observed among the 6-minute exercise BP and age, body mass index, resting systolic and diastolic BP, heart rate, and exercise time to exhaustion. In a stepwise multiple-regression analysis, the determinants of BP after 6 minutes of exercise were resting systolic BP and treadmill time to exhaustion (R2 = 0.36) for normotensive women and treadmill time to exhaustion and resting systolic BP (R2 = 0.30) for hypertensive women. When fitness categories were contrasted, low-fit women in both the normotensive and hypertensive categories had higher BP and rate-pressure product after 6 minutes of exercise than the high-fit women (P <.05). CONCLUSIONS Resting systolic BP and cardiorespiratory fitness are determinants of a submaximal exercise BP response for both hypertensive and normotensive women. Low cardiorespiratory fitness is associated with a higher BP response during submaximal exercise, suggesting that increased fitness may attenuate this abnormal rise in BP. Thus, low- to moderate-intensity physical activities for most days of the week should be encouraged for all women to increase cardiorespiratory fitness. This is likely to attenuate an abnormal rise in systolic BP that may occur during routine daily activities and protect against the associated health consequences.

Cardiorespiratory fitness and coronary heart disease risk factor association in women

OBJECTIVES The purpose of this study was to examine the association between cardiorespiratory fitness and coronary risk factors in healthy, nonsmoking adult women. BACKGROUND A sedentary life-style is recognized as an independent risk factor for coronary heart disease, and increasing physical activity is strongly recommended to reduce this risk. However, studies examining the effects of increased physical activity on coronary heart disease risk factors in women are relatively few, and the findings have been equivocal. METHODS Subjects provided written informed consent, completed a questionnaire on medical history and performed an exercise tolerance test. Blood chemistry and lipid levels were determined from fasting blood samples. Three fitness categories were established on the basis of treadmill time to exhaustion and were adjusted for age. RESULTS The women in the lowest fitness category had less favorable lipid profiles, blood glucose levels, blood pressures and anthropometric indexes than those in the moderate and high fitness categories. CONCLUSIONS Moderate fitness (equivalent to 10 metabolic equivalents [METs]) is required to improve the coronary risk profile in women.

Exercise Capacity and Blood Pressure Associations With Left Ventricular Mass in Prehypertensive Individuals

Prehypertensive individuals are at increased risk for developing hypertension and cardiovascular disease compared with those with normal blood pressure. Early compromises in left ventricular structure may explain part of the increased risk. We assessed echocardiographic and exercise parameters in prehypertensive individuals (n=790) to determine associations between exercise blood pressure and left ventricular structure. The exercise systolic blood pressure at 5 metabolic equivalents (METs) and the change in blood pressure from rest to 5 METs were the strongest predictors of left ventricular hypertrophy. We identified the systolic blood pressure of 150 mm Hg at the exercise levels of 5 METs as the threshold for left ventricular hypertrophy. There was a 4-fold increase in the likelihood for left ventricular hypertrophy for every 10-mm Hg increment in systolic blood pressure beyond this threshold (OR: 1.15; 95% CI: 1.12 to 1.18). There was also a 42% reduction in the risk for left ventricular hypertrophy for every 1 MET increase in the workload (OR: 0.58; P<0.001). When compared with low-fit, moderate, and high-fit individuals exhibited significantly lower systolic blood pressure at an exercise workload of 5 METs (155±14 versus 146±10 versus 144±10; P<0.05), lower left ventricular mass index (48±12 versus 41±10 versus 41±9; P<0.05), and prevalence of left ventricular hypertrophy (48.3% versus 18.7% versus 21.6%; P<0.001). This suggests that moderate improvements in cardiorespiratory fitness achieved by moderate intensity physical activity can improve hemodynamics and cardiac performance in prehypertensive individuals and reduce the work of the left ventricle, ultimately resulting in lower left ventricular mass.

Effects of Moderate Intensity Exercise on Serum Lipids in African-American Men With Severe Systemic Hypertension

The prevalence of systemic hypertension and its cardiovascular consequences is higher in African-Americans than in whites. Low to moderate intensity aerobic exercise lowers blood pressure (BP) in African-American patients with severe hypertension. It is not known whether such exercise can improve lipid metabolism in these patients. Thirty-six African-American men with established essential hypertension, aged 35 to 76 years, were randomly assigned to an exercise (n = 17) or no exercise (n = 19) group. The exercise group exercised for 16 weeks, 3 times/week, at 60% to 80% of maximum heart rate. After 16 weeks, peak oxygen uptake in the exercise group improved (21+/-4 vs 23+/-3 ml/kg/min; p <0.001). Body weight did not change. Exercise intensity correlated with high-density lipoprotein (HDL) cholesterol changes from baseline to 16 weeks (r = 0.65; p <0.01) and was the strongest predictor of these changes (R2 = 0.4; p = 0.009). Lipoprotein-lipid changes in the 2 randomized groups did not differ significantly. A 10% increase in HDL cholesterol--42+/-19 versus 46+/-19 mg/dl; p = 0.003--noted in 10 patients who exercised > or = 75% of maximal heart rate suggested the existence of an exercise intensity threshold. Thus low to moderate intensity aerobic exercise may not be adequate to modify lipid profiles favorably in patients with severe hypertension. However, substantial changes in HDL cholesterol were noted in patients exercising at intensities > or = 75% of age-predicted maximum heart rate, suggesting an exercise-intensity threshold.

Hydrochlorothiazide Is Superior to Isradipine for Reduction of Left Ventricular Mass: Results of a Multicenter Trial

OBJECTIVES We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.