Association of fasting glucose with subclinical cerebrovascular disease in older adults without Type 2 diabetes.

AIMS: To examine how fasting glucose and glucose tolerance are related to magnetic resonance imaging-assessed indicators of subclinical cerebrovascular disease and brain atrophy and their variation according to age, sex and education. METHODS: Participants in the present study were 172 healthy, community-dwelling older adults. An oral glucose tolerance test was administered and magnetic resonance imaging performed. Fasting, 2-h, and 2-h area-under-the-curve glucose levels, their associations with subclinical cerebrovascular disease and brain atrophy, and their respective interactions with age, sex and education were examined. RESULTS: A positive association between fasting glucose and subclinical cerebrovascular disease (but not brain atrophy) emerged; this association was more pronounced for participants with < 12 years of education; however, glucose tolerance was not related to subclinical cerebrovascular disease or brain atrophy. CONCLUSIONS: Findings revealed a potential link between fasting glucose levels and the presence of subclinical cerebrovascular disease indicators - white matter hyperintensities and silent brain infarction - in older adults without diabetes and with an education level below high school. Additional research is needed to confirm these associations and to determine the need for interventions aimed at closely monitoring and preventing elevated glucose levels in this population to reduce the prevalence of subclinical cerebrovascular disease.

How should adverse events be reported in US clinical trials?: ethical considerations.

Research with human subjects, including clinical trials, forms the cornerstone of the development of knowledge on the safety and efficacy of potential drugs and devices. During the conduct of clinical trials, human subjects may experience adverse events ranging from trivial side effects such as mild discomfort to severe complications, including death. Three of the regulatory criteria set forth in the 45 Code of Federal Regulations 46.111 for approval of research(1) focus on risk assessment and minimization of risks. The accurate and full reporting of these adverse events and the assessment of the risk attributable to participation in research are therefore crucial components in the ethical conduct of research.

Reduced aerobic capacity and physical functioning in older HIV-infected men.

Aerobic capacity and physical functioning decline with age and chronic illness. The extent of physical disability is unknown in older HIV-infected adults, who represent a rapidly growing proportion of HIV/AIDS patients in the United States. We performed functional performance testing including treadmill testing in 32 HIV-infected male veterans aged 40-69 years. Controls were 47 healthy male subjects tested previously in the same exercise laboratory. HIV-infected subjects were classified as younger (40-49 years, n = 12) or older age (50+ years, n = 20). Peak aerobic capacity (VO2peak) was significantly reduced in the older vs. younger HIV subjects [19.1 mL/kg/min +/- 5.7 (mean, SD) vs. 25.2 +/- 4.2, p = 0.01]. VO2peak was reduced 41% +/- 15% (mean, SD) in HIV-infected subjects compared to expected values from age-matched healthy controls. Regression analyses show a similar decline in VO2peak with age in HIV-infected and healthy controls. Mean 6-min walk distance was not significantly different between the HIV-infected age groups, and was reduced only 8% compared to expected values for healthy adults. Current CD4 count and HAART exposure were similar in the two age groups and were not significantly associated with VO2peak. Anemia (HCT <35%) was significantly associated with reduced VO2peak (p = 0.02), but this association was not independent of the effect of age (p = 0.1). We conclude that older HIV-infected adults have markedly impaired aerobic capacity but maintain the capacity to undertake day-to-day activities. Additional physiologic and metabolic testing is needed to measure the effect of HAART toxicity and primary aging on aerobic capacity, and to determine if older HIV-infected adults are at greater risk.

Interactive relations of central versus total obesity and blood pressure to cognitive function.

OBJECTIVE: To examine the potential interactive relations of central versus total obesity and blood pressure (BP) to cognitive function. METHOD: In all, 90 healthy, stroke, and dementia-free middle-aged and older adults (ages 54-81 years; 63% male; 93% White) underwent biomedical and neuropsychological assessment. Relations of central obesity (assessed by waist circumference (WC)) and systolic or diastolic BP to cognitive function were examined in multiple regression models. Next, body mass index (BMI) was substituted for WC in the models. RESULTS: After statistical adjustment for age, education, gender, and other potential confounders including components of the metabolic syndrome (depending on the model), significant interactions of WC and systolic (or diastolic) BP were noted for the Grooved Pegboard - Dominant Hand and Stroop Interference scores, with marginally significant results for Grooved Pegboard - Nondominant Hand. In general, individuals with greater WC and higher BP performed most poorly on these measures. Similar results were obtained for BMI. CONCLUSION: Independent of other confounders including facets of the metabolic syndrome, the combination of greater WC (or BMI) and higher (systolic or diastolic) BP was associated with diminished performance on tests of motor speed and manual dexterity, and executive function (i.e. response inhibition) accounting for 3-13% of the variance in these measures. In healthy older adults, there are similar, negative relations of central and total obesity to cognitive function that are potentiated by higher BP levels.

Body fat distribution and flow-mediated endothelium-dependent vasodilation in older men.

OBJECTIVE: Recent studies indicate that abdominal fat accumulation, in particular intra-abdominal fat, is related to impaired endothelial function in young healthy volunteers. The aim of this study was to examine whether the distribution of body fat depots is related to impaired endothelial function in older men. METHODS: Cross-sectional sample of 38 older (68+/-1 y) sedentary (VO(2max)=2.4+/-0.1 l/min) men. Flow-mediated endothelial dependent vasodilation (EDD) was assessed in the brachial artery in response to reactive hyperemia using high-resolution ultrasound. Abdominal subcutaneous and visceral fat depots were assessed by computed tomography scan (CT-scan) at the L(4)-L(5) region in the supine position. Percentage body fat was assessed via dual-energy X-ray absorptiometry (DEXA). RESULTS: Flow-mediated percentage change in brachial artery was 7.6+/-0.7%, suggesting an impaired flow-mediated EDD. Using simple linear regression analysis, there were no statistically significant relationship observed between flow-mediated EDD and the indices of total and abdominal adiposity (percentage body fat=29.3+/-0.9%, r=-0.11; total abdominal fat area=465+/-23 cm(2), r=-0.1; intra-abdominal fat area=200+/-14 cm(2), r=-0.14; subcutaneous fat area=265+/-13 cm(2), r=-0.05; BMI=29.3+/-0.9 kg/m(2), r=-0.07; and waist to hip ratio=0.98+/-0.01, r=-0.20). CONCLUSION: These findings suggest that in older sedentary men there is no clear correlation between adiposity and body fat distribution and impairment of flow-mediated endothelium dependent vasodilation.

Exercise rehabilitation improves functional outcomes and peripheral circulation in patients with intermittent claudication: a randomized controlled trial.

OBJECTIVE: To determine the effects of a 6-month exercise program on ambulatory function, free-living daily physical activity, peripheral circulation, and health-related quality of life (QOL) in disabled older patients with intermittent claudication. DESIGN: Prospective, randomized controlled trial. SETTING: University Medical (Center and Veterans Affairs Medical Center, Baltimore, Maryland. PARTICIPANTS: Thirty-one of 61 patients with Fontaine stage II peripheral arterial occlusive disease (PAOD) were randomized to exercise rehabilitation and 30 to usual-care control. Three patients from the exercise group and six patients from the control group dropped out, leaving 28 and 24 patients, respectively, completing the study in each group. INTERVENTION: Six months of exercise rehabilitation. MEASUREMENTS: Treadmill distance walked to onset of claudication and to maximal claudication, ambulatory function, peripheral circulation, perceived QOL, and daily physical activity. RESULTS: Compliance with the exercise program was 73% of the possible sessions. Exercise rehabilitation increased treadmill distance walked to onset of claudication by 134% (P < .001) and to maximal claudication by 77% (P < .001), walking economy by 12% (P = .003), 6-minute walk distance by 12% (P < .001), and maximal calf blood flow by 30% (P < .001). Changes in distance walked to maximal pain correlated with changes in walking economy (r = -.50, P = .013) and changes in maximal calf blood flow (r = .38, P = .047). Exercise rehabilitation increased accelerometer-derived daily physical activity by 38% (P < .001); this change correlated with the change in distance walked to maximal pain (r = .45, P = .020). These improvements were significantly better than the changes in the control group (P < .05). CONCLUSION: Improvements in claudication following exercise rehabilitation in older PAOD patients are dependent on improvements in peripheral circulation and walking economy. Improvement in treadmill claudication distances in these patients translated into increased accelerometer-derived physical activity in the community, which enabled the patients to become more functionally independent.

Effects of exercise rehabilitation on endothelial reactivity in older patients with peripheral arterial disease.

Peripheral arterial disease (PAD) is a major cause of morbidity and mortality. Endothelial function, which is a measure of vascular health, is impaired in patients with PAD. We examined the effects of 6 months of aerobic exercise rehabilitation on brachial artery endothelial function, assessed using high-frequency ultrasonography, and calf blood flow in 19 older PAD patients (age 69 +/- 1 years, mean +/- SEM) with intermittent claudication (ankle to brachial artery index of 0.73 +/- 0.04). After exercise, the time to onset of claudication pain increased by 94%, from 271 +/- 49 to 525 +/- 80 seconds (p <0.01), and the time to maximal claudication pain increased by 43%, from 623 +/- 77 to 889 +/- 75 seconds (p <0.05). Exercise rehabilitation increased the flow-mediated brachial arterial diameter by 61%, from 0.18 +/- 0.03 to 0.29 +/- 0.04 mm (p <0.005), as well as the relative change in brachial arterial diameter from the resting state by 60%, from 4.81 +/- 0.82% to 7.97 +/- 1.03% (p <0.005). Maximal calf blood flow (14.2 +/- 1.0 vs 19.2 +/- 2.0 ml/100 ml/min; p = 0.04), and postocclusive reactive hyperemic blood flow (9.8 +/- 0.8 vs 11.3 +/- 0.7 ml/100 ml/min; p = 0.1) increased 35% and 15%, respectively. In conclusion, exercise rehabilitation improved ambulatory function, endothelial-dependent dilation, and calf blood flow in older PAD patients with intermittent claudication.

A comparison of longitudinal changes in aerobic fitness in older endurance athletes and sedentary men.

OBJECTIVES: To compare the longitudinal changes in maximal aerobic capacity (VO2max) in healthy middle aged and older athletes and sedentary men. DESIGN: A cohort study with mean follow-up of 8.7 years (range 4.0-12.8). SETTING: Outpatient research at a tertiary hospital. PARTICIPANTS: Forty-two healthy, middle aged, and older athletes (initial age 64 +/- 1 year) and 47 healthy sedentary men of comparable age recruited for research studies. MEASUREMENTS: VO2max during a maximal treadmill test. RESULTS: At baseline, the cross-sectional rates of decline in VO2max with age (slope) were virtually identical in the athletes and sedentary men (-0.42 versus -0.43 mL x kg(-1) x min(-1) x year(-1)). At follow-up, the VO2max had declined by 11.9 +/- 1.1 mL x kg(-1) x min(-1) (22%) in the athletes, a crude average rate of -1.4 +/- 0.14 mL x kg(-1)x min(-1) x year(-1). By comparison, the VO2max declined by 4.4 +/- 0.6 mL x kg(-1) x min(-1) (14%) in the sedentary men, a crude average rate of change of -0.48 +/- 0.07 mL x kg(-1) x min(-1) x year(-1). Therefore, the observed absolute rate of longitudinal decline in VO2max in the athletes was triple that of the sedentary men (P= .001) and significantly greater than the decline predicted by their baseline cross-sectional data (P= .001). Post hoc analyses of the longitudinal data in the athletes based on the training regimens over the follow-up period demonstrated that the seven individuals who continued to train vigorously ("high training") had no significant decline in VO2max (0.28% change in VO2max per year). By contrast, the VO2max declined by 2.6% per year in the "moderate training" group (N=21), 4.6% per year in the "low training" group (N=13), and 4.7% per year in the two individuals who developed cardiovascular disease. CONCLUSION: The longitudinal decline in VO2max in older male endurance athletes is highly dependent upon the continued magnitude of the training stimulus. The majority of the athletes reduced their training levels over time, resulting in longitudinal reductions in VO2max two to three times as large as those predicted by cross-sectional analyses or those observed longitudinally in their sedentary peers.

Comorbidities and exercise capacity in older patients with intermittent claudication.

Patients with peripheral arterial disease (PAD) and intermittent claudication often have coronary artery disease (CAD) and other comorbid medical problems. There is a paucity of information on the impact of coexistent medical conditions on exercise capacity and functional status in patients with PAD. This study examined the impact of CAD, diabetes, cigarette smoking, prior peripheral surgical revascularization and other medical conditions on claudication pain times and peak oxygen capacity (VO2) during maximal effort treadmill testing in 119 male outpatient volunteers (ankle-brachial index (ABI) of 0.65 +/- 0.2, mean +/- SEM) with a history of Fontaine Stage II PAD. Smoking status was significantly related to ambulatory function. Current smokers had a lower peak VO2 expressed in l/min than either former or never smokers (ANCOVA adjusted for age, p = 0.003). However, after adjustment for body weight, there was only a trend for a difference in peak VO2 between current (13.2 +/- 0.5 ml/kg per min), former (14.2 +/- 0.4 ml/kg per min) and never (15.4 +/- 1.0 ml/kg per min) smokers (ANCOVA, p = 0.10). Current smokers had a shorter time to onset of claudication pain (p = 0.023) and shorter maximal claudication pain times (p = 0.029) than former or never smokers (p = 0.023). The ABI 1 min after cessation of exercise was also lower in smokers compared to former and never smokers (p = 0.018). There were no significant differences in functional performance measures or time to recovery from maximal claudication pain when patients were categorized on the presence or absence of CAD, diabetes, peripheral revascularization, arthritis, hypertension or dyslipidemia. Therefore, smoking adversely affected exercise capacity in these PAD patients, whereas the presence of CAD, diabetes and other medical problems had a relatively minor impact on exercise capacity. In conclusion, the relatively minor impact of comorbid medical conditions on walking ability in patients with PAD reflects the overwhelming limitation in ambulatory function due to the claudication pain.

Improved functional outcomes following exercise rehabilitation in patients with intermittent claudication.

BACKGROUND: The purposes of this study were to identify predictors of increased claudication distances following exercise rehabilitation in peripheral arterial occlusive disease (PAOD) patients with intermittent claudication and determine whether improved claudication distances translated into increased free-living daily physical activity in the community setting. METHODS: Sixty-three patients were recruited (age, 68+/-1 years, mean +/- standard error). Patients were characterized on treadmill claudication distances, walking economy, peripheral circulation, cardiopulmonary function, self-perceived ambulatory function, body composition, baseline comorbidities, and free-living daily physical activity before and after a 6-month treadmill exercise program. RESULTS: Exercise rehabilitation increased distance to onset of claudication pain by 115% (178+/-22 m to 383+/-34 m; p < .001) and distance to maximal claudication pain by 65% (389+/-29 m to 641+/-34 m; p < .001). The increased distance to onset of pain was independently related to a 27% increase in calf blood flow (r = .42, p < .001) and to baseline age (r = -.26, p < .05), and the increased distance to maximal pain was predicted by a 10% increase in peak oxygen uptake (r = .41, p < .001) and by a 10% improvement in walking economy (r = -.34, p < .05). Free-living daily physical activity increased 31% (337+/-29 kcal/day to 443+/-37 kcal/day; p < .001) and was related to the increases in treadmill distances to onset (r = .24, p < .05) and to maximal pain (r = .45, p < .001). CONCLUSIONS: Increased claudication distances following exercise rehabilitation are mediated through improvements in peripheral circulation, walking economy, and cardiopulmonary function, with younger patients having the greatest absolute ambulatory gains. Furthermore, improved symptomatology translated into enhanced community-based ambulation.

Weight loss, not aerobic exercise, improves pulmonary function in older obese men.

BACKGROUND: We evaluated the effect of weight loss (WL) or aerobic exercise (AEX) on pulmonary function in middle-aged and older (46-80 years) obese, sedentary men to determine the effect of reductions in body weight and increases in cardiorespiratory fitness on pulmonary function. METHODS: Subjects were randomly assigned to WL (n = 73), AEX (n = 71), or control (n = 26) groups. Maximal oxygen uptake (VO2max), body composition and anthropometrics, pulmonary function, and arterial blood gases were measured at baseline and after interventions. RESULTS: The 35 subjects who completed WL decreased weight by 11%, body fat percentage by 21% (p < .001), waist circumference by 8%, waist-hip ratio by 2%, and fat-free mass by 3% (p < .05). This resulted in a 3% increase in forced vital capacity (FVC) (4.08 +/- 0.71 L vs 4.21 +/- 0.76 L), a 5% increase in total lung capacity (6.62 +/- 0.99 L vs 6.94 +/- 0.99 L), an 18% increase in functional residual capacity (3.09 +/- 0.58 L vs 3.66 +/- 0.79 L), and an 8% increase in residual volume (2.20 +/- 0.44 L vs 2.37 +/- 0.52 L), with no change in forced expiratory volume in one second (FEV1), FEV1/FVC ratio, or carbon monoxide diffusing capacity. The change in FVC correlated with change in body weight (r = -.34, p < .05). The 38 subjects who completed AEX increased VO2max by 14%, with no change in pulmonary function. There were no changes in 8 control subjects. CONCLUSIONS: WL changes static lung volumes, not dynamic pulmonary function, in middle-aged and older, moderately obese, sedentary men. Some of the alterations in static lung function associated with aging may be due to the development of obesity and are modifiable by WL.

Comorbidities and the entry of patients with peripheral arterial disease into an exercise rehabilitation program.

BACKGROUND: Exercise rehabilitation is advocated to improve function in patients with peripheral arterial disease (PAD) who have intermittent claudication. Patients with PAD often have comorbid medical problems that may interfere with their ability to safely participate in exercise rehabilitation programs. There is a paucity of information regarding the medical comorbidities and the evaluation of PAD patients before their participation in exercise rehabilitation studies. The purpose of this study was to identify comorbidities that predicted exclusion of PAD patients from participation in an aerobic exercise rehabilitation clinical trial. METHODS: This was a prospective cohort study of 225 consecutive outpatient volunteers (mean age 68 +/- 8 years, SD) with a history of Fontaine Stage II PAD recruited for exercise rehabilitation. Patient eligibility was determined by a history and physical exam, blood chemistries, measurement of ankle to brachial index (ABI), and an exercise treadmill test. RESULTS: Seventy-nine volunteers (35%) were medically ineligible: 22 because of symptomatic coronary artery disease, 12 because of severe PAD, and the rest for a variety of medical problems. In stepwise logistic regression analyses, low ABI and use of insulin were predictors of exclusion, whereas peripheral revascularization was an indicator of inclusion. Age, a history of coronary artery disease, myocardial infarction, coronary bypass surgery, and hypertension were not independent determinants of eligibility. CONCLUSIONS: Insulin-requiring diabetes and a low ABI increase the likelihood that older patients with PAD will be ineligible to participate in a research exercise rehabilitation program, whereas peripheral revascularization was associated with inclusion. Whether intensive medical management and peripheral revascularization would enable the claudicants deemed ineligible for entry into the exercise rehabilitation program to safely exercise remains to be determined.

Determinants of peak V(O2) in peripheral arterial occlusive disease patients.

Peripheral arterial occlusive disease (PAOD) patients with intermittent claudication are functionally limited and deconditioned. This study examined whether peak aerobic capacity (V(O2) peak) was associated with PAOD severity, muscle mass, and comorbidities in 109 PAOD patients (93 men and 16 women) aged 48-86 years. The V(O2) peak (1.12+/-0.34 L/min), percentage body fat (30.6+/-8.3%), lean tissue mass of the total body (51.4+/-8.4 kg), lean tissue mass of the legs (16.6+/-3.0 kg), and appendicular skeletal mass (22.8+/-4.2 kg) were determined. The lean tissue mass of the total body (r = .44), lean tissue of the legs (r = .43) and resting ankle/brachial systolic pressure index (ABI; r = .41) correlated with peak V(O2) (all p < .001). None of the comorbidity variables (obesity, arthritis, coronary artery disease, hypertension, diabetes, and smoking history) were significantly associated with peak V(O2) except smoking status. The final model for the prediction of peak V(O2) included lean tissue mass of the legs, resting ABI, smoking status, and ABI x smoking status (r2 = .37,p < .001). In older patients with intermittent claudication, lean tissue mass is an important determinant of physical performance independent of PAOD severity and smoking status. Prevention of muscle atrophy may preserve ambulatory function and peak exercise capacity in older PAOD patients.

Cardiovascular fitness, body composition, and lipoprotein lipid metabolism in older men.

BACKGROUND: Lipoprotein lipids in older individuals are affected by family history of coronary artery disease (CAD), obesity, diet, and physical activity habits. METHODS: The relationship of obesity and physical fitness (VO2max) to lipoprotein lipids and postheparin lipases was examined in a cross-sectional study of 12 lean (LS) and 26 obese (OS) sedentary men and 18 master athletes (MAs) aged 65+/-1 years (mean +/- SE). The men were healthy, had no family history of CAD, and were weight stable on AHA diets at the time of study. RESULTS: VO2max was similar in LS and OS men but higher in the MAs. The OS men had a higher percentage of body fat (%BF), waist circumference, and waist:hip ratio (WHR) than the MA and LS men, but MA and LS men differed only in waist circumference. Total and LDL-C levels were comparable, but HDL-C, HDL2-C, and %HDL2b subspecies were higher in MAs than in OS and LS men, and in LS than in OS men. Triglyceride (TG) was similar in MAs and LS men but higher in OS men. Across groups, two multiple regression analyses models (VO2max, %BF, and WHR or waist circumference) showed that %BF and VO2max independently predicted HDL-C and HDL2, whereas WHR predicted TG (r2 = .45) more strongly than waist circumference (r2 = .39). Postheparin lipoprotein lipase activity (LPL) was comparable among groups and correlated independently with VO2max. Total postheparin lipolytic activity (PHLA), hepatic lipase activity (HL), and HL:PHLA ratio were similar in MAs and LS men but higher in OS men. In both multiple regression analysis models, only %BF predicted HL activity and the HL:PHLA ratio. The HL:PHLA ratio independently predicted HDL-C, HDL2-C, %HDL2b, %HDL3 subspecies, and the cholesterol:HDL-C ratio, whereas LPL activity predicted TG. CONCLUSIONS: Increased fitness and reduced total and abdominal fatness in MAs are associated with lower HL and higher LPL activities, which may mediate their higher HDL-C and lower TG levels relative to their sedentary peers.

Silent ischemia during voluntary detraining and future cardiac events in master athletes.

OBJECTIVES: To determine whether exercise-induced silent ischemia in older master athletes following a 3-month period of deconditioning is a predictor of future cardiovascular events. DESIGN: A longitudinal study of a cohort of master athletes. SETTING: The Geriatric Research Education and Clinical Center (GRECC), Baltimore VA Medical Center, Baltimore, Maryland. PARTICIPANTS: Ten older (59 +/- 8 years, mean +/- SD), highly conditioned (maximal aerobic capacity VO2max 50 +/- 5 mL/kg/min), aerobically trained athletes. INTERVENTION: Five to eight years of longitudinal follow-up of athletes who had previously participated in a 3-month-long detraining intervention. MEASUREMENTS: At baseline, all 10 athletes had their history taken and underwent physical examinations, metabolic testing, electrocardiogram at rest, exercise treadmill tests, exercise thallium scintigrams, and exercise multigated acquisition scans. After 3 months of deconditioning, they had repeat maximal exercise stress tests. After 5 to 8 years of follow-up, they were re-evaluated, including history and physical examination and measurement of their VO2max. RESULT: All 10 master athletes had normal studies at baseline. At the end of 3 months of detraining, three of these athletes had exercise-induced silent ischemia, which disappeared after retraining in two subjects and persisted at a higher heart rate in one subject. Over a 5- to 8-year period of observation, two of these three athletes with silent ischemia experienced major cardiac events (sudden death, cardiac bypass surgery). The other seven athletes did not have any cardiovascular events. CONCLUSIONS: Exercise-induced silent ischemia after a short period of detraining in highly trained older athletes may be a predictor of future cardiac events. A study with a larger cohort is warranted.

Effects of exercise rehabilitation on cardiovascular risk factors in older patients with peripheral arterial occlusive disease.

OBJECTIVE: The purpose of this study was to determine whether a 6-month exercise rehabilitation program can improve cardiovascular risk factors in patients with peripheral arterial occlusive disease (PAOD). METHODS: Thirty-four patients (mean age, 68 +/- 8 years; range 54-84 years) with PAOD with intermittent claudication (Fontaine stage II) and 14 longitudinal controls of comparable age with stage II PAOD enrolled in an exercise intervention at the University Medical Center and Veterans Affairs Medical Center at Baltimore, Maryland. The main outcome measures were lipid profile (total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol [LDL-C]), fasting glucose, blood pressure, body mass index, treadmill times to onset and maximal claudication pain, cardiopulmonary function (peak oxygen uptake), and ankle/brachial index. RESULTS: With exercise rehabilitation, treadmill times to onset and maximal claudication pain increased by 106% and 64% (P <.0001), whereas peak oxygen uptake increased 7% (P <.05). Exercise rehabilitation lowered total cholesterol and LDL-C levels by 5.2% (P <.005) and 8% (P <.01), respectively. Systolic blood pressure declined by 5.7% (P <.05) with no change in diastolic blood pressure. These changes in cholesterol and LDL-C concentrations were related to their initial values. All other cardiovascular risk factors measured did not change. There was no correlation between improvement of cardiovascular risk factors and functional performance measurements. None of the variables measured changed significantly in the control group. CONCLUSIONS: Exercise rehabilitation not only improves functional performance, but also results in favorable alterations in cardiovascular risk factor profile, which is an important element in the management of PAOD.

Enhanced endothelial vasoreactivity in endurance-trained older men.

Using external vascular ultrasound, we measured brachial artery diameter (Diam) at rest, after release of 4 min of limb ischemia, i. e., endothelium-dependent dilation (EDD), and after sublingual nitroglycerin, i.e., non-endothelium-dependent dilation (NonEDD), in 35 healthy men aged 61-83 yr: 12 endurance athletes (A) and 23 controls (C). As anticipated, treadmill exercise maximal oxygen consumption (VO(2 max)) was significantly higher in A than in C (40. 2 +/- 6.6 vs. 27.9 +/- 3.8 ml. kg(-1). min(-1); respectively, P < 0. 0001). With regard to arterial physiology, A had greater EDD (8.9 +/- 4.2 vs. 5.7 +/- 3.5%; P = 0.02) and a tendency for higher NonEDD (13.9 +/- 6.7 vs. 9.7 +/- 4.2%; P = 0.07) compared with C. By multiple linear regression analysis in the combined sample of older men, only baseline Diam (beta = -2.0, where beta is the regression coefficient; P = 0.005) and VO(2 max) (beta = 0.23; P = 0.003) were independent predictors of EDD; similarly, only Diam (beta = -4.0; P = 0.003) and VO(2 max) (beta = 0.27; P = 0.01) predicted NonEDD. Thus endurance-trained older men demonstrate both augmented EDD and NonEDD, consistent with a generalized enhanced vasodilator responsiveness, compared with their sedentary age peers.

Exercise-induced silent myocardial ischemia and future cardiac events in healthy, sedentary, middle-aged and older men.

OBJECTIVES: Before men older than age 45 participate in vigorous exercise programs, the American Heart Association and the American College of Sports Medicine recommend they undergo a screening maximal exercise treadmill test. We examined the predictive value for subsequent cardiac events of exercise-induced silent myocardial ischemia (SI) during the exercise treadmill test in healthy, sedentary, obese, middle-aged and older men recruited for research studies. DESIGN: A cohort study with 7 years of follow-up. SETTING: Out-patient research at a tertiary hospital. PARTICIPANTS: 170 healthy, sedentary, obese, middle-aged and older (ages 45-79 years) men with no prior history of coronary artery disease (CAD) recruited for research studies. MEASUREMENTS: Cardiac risk factors, exercise-induced SI (ST segment depression on the electrocardiogram during a maximal exercise treadmill test), maximal aerobic capacity (VO2max), and 7- year follow-up data on incident CAD. RESULTS: At baseline, 37 of the men (22%) had exercise-induced SI on their treadmill tests. Seven-year follow-up data was obtained in 97% of the patients. In the interim, 31 men had cardiac endpoints (sudden cardiac death, myocardial infarction, angioplasty, coronary artery bypass graft surgery, angina), and four had noncardiac deaths. Seventeen of the 37 men (46%) with exercise-induced SI on their baseline exercise tests had cardiac endpoints compared with 14 of 133 (11%) men with normal exercise tests (P < .001). Compared with the men with no cardiac endpoints, the men with subsequent cardiac endpoints were older (63 +/- 1 vs 58 +/- 1 years, mean +/- SEM, P < .001) and had a lower maximal aerobic capacity (VO2max) (24 +/- 1 vs 29 +/- 1 mL/kg/min, P < .001). In Cox proportional hazards analysis, exercise-induced SI and a low VO2max were independent predictors of subsequent cardiac endpoints. CONCLUSION: In a healthy population of obese, sedentary, middle-aged and older men, exercise-induced SI and low VO2max were predictors of incident CAD. This suggests that exercise treadmill testing is beneficial in assessing risk for future cardiac events in obese, sedentary individuals.

Apolipoprotein E genotype and exercise training-induced increases in plasma high-density lipoprotein (HDL)- and HDL2-cholesterol levels in overweight men.

We determined if the apolipoprotein E (APO E) genotype affects the exercise training-induced increase in plasma high-density lipoprotein cholesterol (HDL-C) and HDL2-C. Sedentary overweight men on an American Heart Association (AHA) step I diet had plasma lipoprotein-lipids measured before and after 9 months of endurance exercise training. APO E2 (n = 6), E3 (n = 33), and E4 (n = 12) groups were similar at baseline in terms of age, body weight and composition, and plasma lipoprotein-lipid profiles. APO E2 men had a larger increase in plasma HDL-C and HDL2-C with exercise training than APO E3 and E4 men (HDL-C, 8 +/- 4 v 3 +/- 1 v 2 +/- 1 mg/dL; HDL2-C, 5 +/- 3 v 1 +/- 1 v -1 +/- 1 mg/dL; mean +/- SE, all P < .01). After adjusting for body weight changes, the increases in plasma HDL-C and HDL2-C remained greater in APO E2 versus E3 and E4 men (all P < .03). These results indicate that APO E2 men may have greater plasma HDL-C and HDL2-C increases with endurance exercise training.

Weight loss due to energy restriction suppresses cholesterol biosynthesis in overweight, mildly hypercholesterolemic men.

Mechanisms explaining the decrease in circulatory cholesterol levels after weight loss remain ill defined. The objective was to examine effects of weight loss as achieved through energy restriction upon human in vivo cholesterol biosynthesis. Six subjects (64-77 y, body mass index, 30.3 +/- 3.8 kg/m(2)) were recruited into a two-phase prospective clinical trial. In the first phase, subjects complied with American Heart Association (AHA) Step I diets for 3 mo with no change in their usual energy intake. After this weight-stable phase, subjects consumed an AHA Step I diet with a targeted reduction in energy intake of approximately 1000 kJ/d for 6 mo to achieve negative energy balance leading to weight loss. The incorporation rate of deuterium from body water into erythrocyte membrane free cholesterol over 24 h was utilized as an index of cholesterogenesis at the end of both phases. Subjects' mean weights decreased (P < 0.05) from 89.3 +/- 12.5 kg to 83.2 +/- 11.5 kg (6.8 +/- 2.6% of initial body weight) across phases. Circulating concentrations of total and LDL-cholesterol, and triglycerides also decreased (P < 0. 05) across phases. HDL-cholesterol concentrations were unchanged (P > 0.05). Cholesterol fractional synthetic rate (FSR) after phase 2 (3.04 +/- 1.90%/d) was lower (P < 0.05) than that after phase 1 (8. 42 +/- 3.90%/d). Absolute synthesis rate (ASR) after phase 2 [0.59 +/- 0.38 g/(kg. d)] also was lower (P < 0.05) than that after phase 1 [1.66 +/- 0.84 g/(kg. d)]. These data suggest that, in obese men, energy restriction resulting in even modest weight loss suppresses endogenous cholesterol synthesis, which contributes to a decline in circulating lipid concentrations.