Cardiorespiratory Fitness and Health Outcomes: A Call to Standardize Fitness Categories.

An inverse association between physical activity or fitness status and health outcomes has been reported by several cohort studies. When fitness categories are established in quartiles or quintiles based on the peak exercise capacity achieved, the association is graded. Although significant health benefits of increased cardiorespiratory fitness (CRF) have been uniformly reported, the degree of protection has varied substantially between studies. This variability is likely due to varying methods used to define CRF categories, and not considering age, despite its strong effect on CRF. To ameliorate these methodological discrepancies, we propose standardized guidelines by which age-specific CRF categories should be defined.

Lifestyle Modifications in Non-Alcoholic Fatty Liver Disease and Non- Alcoholic Steatohepatitis.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common diseases worldwide, affecting more than 30% of general population. High-fat diets, physical inactivity and obesity, all prevalent in the western societies, are strongly associated with the development and progression of NAFLD. Current drug therapies have not consistently shown substantial beneficial effects. Thus, lifestyle modification appears to be the optimal intervention in combating the disease. Accordingly, several studies have concluded that weight loss, via increase in physical activity, and dietary interventions could potential ameliorate biochemical, histological, and structural abnormalities of non-alcoholic fatty liver disease. The aim of this review is to summarize the findings of these lifestyle intervention studies and discuss the implementation of each intervention, and its effectiveness in the management of the disease in everyday clinical practice.

Impact of Cardiorespiratory Fitness on Mortality in Black Male Veterans With Resistant Systemic Hypertension.

Patients with resistant systemic hypertension have poorer outcomes than nonresistant hypertensives. The purpose of this study was to evaluate the association between cardiorespiratory fitness and all-cause mortality in black male Veterans with resistant systemic hypertension. Patients were identified from a cohort undergoing exercise tolerance test at the department of Veterans Affairs Medical Center in Washington, DC. Patients were divided into 4 cardiorespiratory fitness categories based on age-specific peak metabolic equivalents achieved on a standard Bruce protocol. Multivariate Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality across all fitness categories. A total of 1,276 patients out of 9,068 hypertensives had resistant hypertension defined as systolic and/or diastolic blood pressure >140 and/or >90 mm Hg, respectively, on 3 antihypertensive medications, one of which was a diuretic or use of >4 antihypertensive medications. During a follow-up of 9.5 ± 4.2 years, an inverse association was observed between cardiorespiratory fitness and all-cause mortality in patients with resistant hypertension. Compared with the least-fit group, mortality was reduced by 21% in the low-fit group (HR 0.79, CI 0.60 to 1.05; p value: 0.280), 36% in the moderate-fit group (HR 0.64, CI 0.48 to 0.87; p value 0.001), and 62% in the high-fit group (HR 0.38, CI 0.25 to 0.56; p value <0.001). In conclusion, an inverse association was observed between the level of cardiorespiratory fitness and all-cause mortality in patients with resistant systemic hypertension. Compared with the least-fit referent group, the high-fit group had a significant 62% lower risk of all-cause mortality.

Cardiorespiratory Fitness and Incidence of Type 2 Diabetes in United States Veterans on Statin Therapy.

BACKGROUND: Impact of cardiorespiratory fitness on statin-related incidence of type 2 diabetes has not been assessed. We assessed the cardiorespiratory fitness and diabetes incidence association in dyslipidemic patients on statins. METHODS: We identified dyslipidemic patients with a normal exercise test performed during 1986 and 2014 at the Veterans Affairs Medical Centers in Washington, DC or Palo Alto, Calif. The statin-treated patients (n = 4092; age = 58.8 ± 10.9 years) consisted of 2701 Blacks and 1391 Whites. None had evidence of type 2 diabetes prior to statin therapy. We formed 4 fitness categories based on age and peak metabolic equivalents achieved: Least-fit (n = 954), Low-fit (n = 1201), Moderate-fit (n = 1242), and High-fit (n = 695). The non-statin-treated cohort (n = 3001; age = 57.2 ± 11.2 years) with no evidence of type 2 diabetes prior to the exercise test served as controls. RESULTS: Diabetes incidence was 24% higher in statin-treated compared with non-statin-treated patients (P <.001). In the statin-treated cohort, 1075 (26.3%) developed diabetes (average annual incidence rate of 30.6 events/1000 person-years). Compared with the Least-fit, adjusted risk decreased progressively with increasing fitness and was 34% lower for High-fit patients (hazard ratio [HR] 0.66; 95% confidence interval [CI], 0.53-0.82; P <.001). Compared with the nonstatin cohort, elevated risk was evident only in the Least-fit (HR 1.50; 95% CI, 1.30-1.73; P <.001) and Low-fit patients (HR 1.22; 95% CI, 1.06-1.41; P = .006). CONCLUSIONS: Risk of diabetes in statin-treated dyslipidemic patients was inversely and independently associated with cardiorespiratory fitness. The increased risk was evident only in relatively low-fitness patients. Improving fitness may modulate the potential diabetogenic effects of statins.

Left ventricular hypertrophy in athletes and hypertensive patients.

Systemic hypertension and physical exercise are both associated with cardiac adaptations. The impact is most prominent on the left side of the heart, which hypertrophies leading to left ventricular hypertrophy. This article reviews structural and functional cardiac changes seen in hypertensive and athlete's hearts.

Cardiorespiratory Fitness and Incidence of Major Adverse Cardiovascular Events in US Veterans: A Cohort Study.

OBJECTIVE: To assess the association between exercise capacity and the risk of major adverse cardiovascular events (MACEs). PATIENTS AND METHODS: A symptom-limited exercise tolerance test was performed to assess exercise capacity in 20,590 US veterans (12,975 blacks and 7615 whites; mean ± SD age, 58.2±11.0 years) from the Veterans Affairs medical centers in Washington, District of Columbia, and Palo Alto, California. None had a history of MACE or evidence of ischemia at the time of or before their exercise tolerance test. We established quintiles of cardiorespiratory fitness (CRF) categories based on age-specific peak metabolic equivalents (METs) achieved. We also defined the age-specific MET level associated with no risk for MACE (hazard ratio [HR], 1.0) and formed 4 additional CRF categories based on METs achieved below (least fit and low fit) and above (moderately fit and highly fit) that level. Multivariate Cox models were used to estimate HR and 95% CIs for mortality across fitness categories. RESULTS: During follow-up (median, 11.3 years; range, 0.3-33.0 years), 2846 individuals experienced MACEs. The CRF-MACE association was inverse and graded. The risk for MACE declined precipitously for those with a CRF level of 6.0 METs or higher. When considering CFR categories based on the age-specific MET threshold, the risk increased for those in the 2 CFR categories below that threshold (HR, 1.95; 95% CI, 1.73-2.21 and HR, 1.41; 95% CI, 1.27-1.56 for the least-fit and low-fit individuals, respectively) and decreased for those above it (HR, 0.77; 95% CI, 0.68-0.87 and HR, 0.57; 95% CI, 0.48-0.67 for moderately fit and highly fit, respectively). CONCLUSION: Increased CRF is inversely and independently associated with the risk for MACE. When an age-specific MET threshold was defined, the risk for MACE increased significantly for those below that threshold and decreased for those above it (P<.001).

Exercise capacity and all-cause mortality in male veterans with hypertension aged ≥70 years.

Aging, even in otherwise healthy subjects, is associated with declines in muscle mass, strength, and aerobic capacity. Older individuals respond favorably to exercise, suggesting that physical inactivity plays an important role in age-related functional decline. Conversely, physical activity and improved exercise capacity are associated with lower mortality risk in hypertensive individuals. However, the effect of exercise capacity in older hypertensive individuals has not been investigated extensively. A total of 2153 men with hypertension, aged ≥70 years (mean, 75 ± 4) from the Washington, DC, and Palo Alto Veterans Affairs Medical Centers, underwent routine exercise tolerance testing. Peak workload was estimated in metabolic equivalents (METs). Fitness categories were established based on peak METs achieved, adjusted for age: very-low-fit, 2.0 to 4.0 METs (n=386); low-fit, 4.1 to 6.0 METs (n=1058); moderate-fit, 6.1 to 8.0 METs (n=495); high-fit >8.0 METs (n=214). Cox proportional hazard models were applied after adjusting for age, body mass index, race, cardiovascular disease, cardiovascular medications, and risk factors. All-cause mortality was quantified during a mean follow-up period of 9.0 ± 5.5 years. There were a total of 1039 deaths or 51.2 deaths per 1000 person-years of follow-up. Mortality risk was 11% lower (hazard ratio, 0.89; 95% confidence interval, 0.86-0.93; P<0.001) for every 1-MET increase in exercise capacity. When compared with those achieving ≤4.0 METs, mortality risk was 18% lower (hazard ratio, 0.82; 95% confidence interval, 0.70-0.95; P=0.011) for the low-fit, 36% for the moderate-fit (hazard ratio, 0.64; 95% confidence interval, 0.52-0.78; P<0.001), and 48% for the high-fit individuals (hazard ratio, 0.52; 95% confidence interval, 0.39-0.69; P<0.001). These findings suggest that exercise capacity is associated with lower mortality risk in elderly men with hypertension.

Heart rate recovery, exercise capacity, and mortality risk in male veterans.

BACKGROUND: Both impaired heart rate recovery (HRR) and low fitness are associated with higher mortality risk. In addition, HRR is influenced by fitness status. The interaction between HRR, mortality, and fitness has not been clearly defined. Thus, we sought to evaluate the association between HRR and all-cause mortality and to assess the effects of fitness on this association. METHODS: Treadmill exercise testing was performed in 5974 male veterans for clinical reasons at two Veterans Affairs Medical Centers (Washington, DC and Palo Alto, CA). HRR was calculated at 1 and 2 min of recovery. All-cause mortality was determined over a mean 6.2-year follow-up period. RESULTS: Mortality risk was significantly and inversely associated with HRR, only at 2 min. A cut-off value of 14 beats/min at 2 min recovery was the strongest predictor of mortality for the cohort (hazard ratio = 2.4; CI 1.6-3.5). The mortality risk was overestimated when exercise capacity was not considered. When both low fitness and low HRR were present (≤6 metabolic equivalents and ≤14 beats/min), mortality risk was approximately seven-fold higher compared to the High-fit + High-HRR group (>6 metabolic equivalents and >14 beats/min). CONCLUSIONS: HRR at 2 min post exercise is strongly and inversely associated with all-cause mortality. Exercise capacity affects HRR-associated mortality substantially and should be considered when applying HRR to estimate mortality.

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 (< or =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.

Prognostic importance of hemoglobin in hypertensive patients with electrocardiographic left ventricular hypertrophy: the Losartan Intervention For End point reduction in hypertension (LIFE) study.

BACKGROUND: The prognostic importance of hemoglobin is controversial. We investigated the prognostic importance of baseline and in-treatment hemoglobin in the LIFE study. METHODS: Eight thousand one hundred ninety-four LIFE patients with hypertension and left ventricular hypertrophy with available baseline hemoglobin measurements were randomized to losartan- or atenolol-based treatment and followed for 4.8 years for end points of all-cause mortality and composite of cardiovascular death, nonfatal stroke, or nonfatal myocardial infarction. RESULTS: U-shaped relations were observed between deciles of baseline hemoglobin and all-cause mortality and the composite end point. In univariate Cox models, baseline hemoglobin in the lowest gender-specific decile (women/men: <12.5/13.4 g/dL) was associated with all-cause mortality (hazard ratio [HR] 2.01, 95% CI 1.64-2.64) and the composite end point (HR 1.53, 95% CI 1.27-1.85, both P < .001), whereas hemoglobin in the highest gender-specific decile (women/men: > or =15.0/16.2 g/dL) was not. The decrease in hemoglobin was higher (P < .001) in patients allocated to losartan- (14.3-13.8 g/dL) versus atenolol-based treatment (14.3-14.0 g/dL). In Cox models with the same gender-specific definitions for high and low hemoglobin as time-varying covariates with adjustment for treatment allocation and established risk factors and diseases, hemoglobin in the lowest decile was associated with higher rates of all-cause mortality (HR 3.03, 95% CI 1.89-4.85, P < .001) and the composite end point (HR 1.36, 95% CI 1.08-1.71, P < .01), whereas hemoglobin in the highest decile was not. CONCLUSIONS: After adjusting for other risk factors, relatively low, but not high, hemoglobin during antihypertensive treatment was associated with higher incidence of all-cause mortality and the composite end point.

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 approximately 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.

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.

Association of hemoglobin delivery with left ventricular structure and function in hypertensive patients: Losartan Intervention for End Point Reduction in Hypertension Study.

Several studies have shown associations of high levels of hemoglobin (Hgb) or blood viscosity with cardiac events and with left ventricular (LV) hypertrophy (LVH). To assess the relations of LV mass and function with Hgb delivery (ie, the physiological carrier of oxygen), we calculated the product of Hgb concentration and Doppler-derived cardiac output in 864 hypertensive participants with electrocardiographic LVH (359 women) in the Losartan Intervention for End Point Reduction in Hypertension echocardiography substudy. Among women, Hgb delivery was positively related to internal dimension, septal and posterior wall thicknesses, LV mass, endocardial and midwall fractional shortening, and peak A wave velocity and negatively to total peripheral resistance index, E/A ratio, deceleration time, and the isovolumic relaxation time. Among men, Hgb delivery was positively related to LV internal dimension, LV mass, and A velocity, and negatively to LV midwall shortening, relative wall thickness, peripheral resistance index, and E/A ratio. In multivariable analyses that adjusted for age, diastolic blood pressure, body mass index, and total cholesterol, hemoglobin delivery in women was related positively to LV fractional shortening, midwall shortening, LV mass mitral valve A velocity, and LV internal dimension and negatively to mitral valve deceleration time and isovolumic relaxation time. Among men, Hgb delivery had positive independent relations to mitral valve A velocity, LV internal dimension, midwall shortening, and LV mass and negative relations to the E/A ratio and relative wall thickness. Thus, in hypertensive LVH, higher oxygen delivery capacity is associated with higher LV mass and impaired early diastolic LV filling.

Beta-blockade mitigates exercise blood pressure in hypertensive male patients.

OBJECTIVES: The purpose of this study was to determine the antihypertensive agent(s) more likely to mitigate an exaggerated rise in exercise blood pressure (BP) in hypertensive patients. BACKGROUND: An exaggerated rise in exercise BP is associated with increased cardiovascular risk. There are no recommendations for treating such response. METHODS: Participants were hypertensive men (n = 2,318; age 60 +/- 10 years), undergoing a routine exercise test at the Veterans Affairs Medical Center, Washington, DC. Antihypertensive therapy included angiotensin-converting enzyme inhibitors (n = 437), calcium-channel blockers (n = 223), diuretics (n = 226), and combinations (n = 1,442), beta-blockers alone (n = 201) or in combination with other antihypertensive agents (n = 467), and none (n = 208). Exercise BP, heart rate (HR) and rate-pressure product (RPP) at maximal and submaximal workloads were assessed. RESULTS: After adjusting for covariates, patients treated with beta-blockers or beta-blocker-based therapy had significantly lower BP, HR, and RPP at 5 and 7 metabolic equivalents (METs) and peak exercise than those treated with any other antihypertensive agent or combination (p < 0.05). The likelihood of achieving an exercise systolic BP of >/=210 mm Hg was 68% lower (odds ratio = 0.32, 96% confidence interval 0.2 to 0.53) in the beta-blocker-based therapy versus other medications. African Americans exhibited higher BP and HR than Caucasians at all exercise workloads regardless of antihypertensive therapy and had over a 90% higher likelihood for an abnormal exercise BP response. This risk was attenuated by 35% with a beta-blocker-based therapy. CONCLUSIONS: Significantly lower exercise BP, HR, and RPP levels are achieved with beta-blocker-based therapy than with other antihypertensive agents regardless of race. However, BP was better controlled in Caucasians than in African Americans regardless of antihypertensive therapy.

Exercise capacity and 24-h blood pressure in prehypertensive men and women.

BACKGROUND: Prehypertensive individuals are at increased risk for developing hypertension and cardiovascular disease compared to those with normal blood pressure (BP). Physically active, normotensive individuals are also at lower risk for developing hypertension than sedentary individuals. We assessed the relationship between fitness and 24-h ambulatory BP in prehypertensive men and women. METHODS: We assessed exercise capacity and 24-h BP in 407 men (age 51 +/- 11 years) and 243 women (age 54 +/-10 years) with resting systolic BP 120 to 139 mm Hg and diastolic BP of 80 to 89 mm Hg, defined as prehypertension. Fitness categories (low, moderate, and high) were established according to exercise time and age. RESULTS: Multiple regression analysis revealed that fitness status was inversely associated with ambulatory BP in both genders (P < .001). After adjusting for various confounders, individuals in the lowest fitness category had significantly higher 24-h, daytime, and night-time BP than those in the moderate and high fitness categories. For men, differences between low and moderate fitness categories were 6/4 mm Hg, 8/4 mm Hg, and 7/3 mm Hg for 24-h, daytime, and night-time BP, respectively (P < .05). For women, the differences were 8/5 mm Hg, 9/5 mm Hg, and 8/7 mm Hg for 24-h, daytime, and night-time BP, respectively. Similar differences were evident in both genders between low and high fitness category (P < .05). CONCLUSIONS: Moderate physical activity promotes lower BP during a 24-h period in prehypertensive men and women. The risk for developing hypertension is likely to be lowered if moderate intensity physical activity in this vulnerable population is encouraged.

Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in African-American patients with hypertension.

African-American patients with hypertension are less responsive to blockers of the renin-angiotensin system than white patients. The relative efficacy of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers and the extent of cross-resistance to these agents has not been studied. Fifty-one African-American patients with stage 1-2 hypertension were randomly assigned to enalapril or candesartan cilexetil for 8 weeks and then crossed over to the other treatment. Nonresponders to enalapril and candesartan used a combination of the two. Of the 51 patients randomized (average age 61.2+/-9 years, blood pressure 148/100 mm Hg, heart rate 74 bpm, and body weight 92.8 kg), 44 completed the study. At Week 8, systolic blood pressure (SBP) was reduced by 4.8 mm Hg with enalapril and by 4.7 mm Hg with candesartan (p=NS), and diastolic blood pressure (DBP) was reduced by 4.4 mm Hg and 5.6 mm Hg, respectively (p<0.04). Of these 44 patients, 11 (25%) responded to enalapril by SBP criteria and 19 (43%) by DBP criteria. Seven patients (16%) responded by both SBP and DBP criteria, and 21 patients (48%) were nonresponders. With candesartan, 13 patients (29%) responded by SBP criteria, 20 (45%) by DBP criteria and 12 (27%) by both SBP and DBP criteria (p<0.04, compared with enalapril). Only six patients (14%) responded to both enalapril and candesartan by both SBP and DBP criteria. Of the 18 nonresponders to either enalapril or candesartan, the combination of the two had minimal additional effect. Significant changes in plasma-renin activity and angiotensin II levels were noted only with the high dose of each drug. In this small group of patients, treatment with candesartan resulted in slightly higher response and control rates than enalapril, more than 40% of patients who responded to enalapril did not respond to candesartan and vice versa, and in nonresponders, a combination of candesartan and enalapril offered little additional antihypertensive effect.

Characteristics and lipid distribution of a large, high-risk, hypertensive population: the lipid-lowering component of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) consisted of 42,418 participants randomized to one of four antihypertensive treatment groups: chlorthalidone, amlodipine, lisinopril, or doxazosin. A subset of these participants with fasting low-density lipoprotein cholesterol levels 100-189 mg/dL were randomized into a lipid-lowering component: 5170 to receive pravastatin (40 mg daily) and 5185 to receive usual care. This report describes the characteristics and lipid distribution of these participants. There were no important differences between the randomized treatment groups. Women had higher total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol than men. There was a similar finding for black participants compared with whites, except blacks had lower triglycerides. Diabetics had lower high-density lipoprotein cholesterol and higher triglycerides than nondiabetics, and patients with body mass index <25 kg/m(2) had higher high-density lipoprotein cholesterol but lower low-density lipoprotein cholesterol and triglycerides than patients with higher body mass index. The success of the randomization of this large, diverse population and the differences in the lipid distributions among its subgroups will allow further understanding of optimal lipid-lowering treatment.

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).

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.