The influence of obesity and consequent insulin resistance on coronary risk factors in medically treated patients with coronary disease.

OBJECTIVE: Obesity promotes the development and progression of coronary heart disease (CHD), in part, through its association with hyperlipidemia, hypertension, clotting abnormalities and insulin resistance. We assessed whether these relationships persist in patients with established CHD treated with evidence-based preventive pharmacologic therapies. DESIGN AND SUBJECTS: We performed a cross-sectional study of 74 adults with CHD and a body mass index (BMI) of >27 kg m(-2) (mean 32+/-4). The mean age of subjects was 64+/-9 years (range 44-84 years). MEASUREMENTS: Obesity measures included weight, BMI, waist, fat mass, intra-abdominal fat and subcutaneous fat. Risk factor measures included insulin sensitivity, fasting insulin level, lipid profiles, blood pressure, C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI-1) and platelet reactivity. Medication use included aspirin (99%), statin (84%), beta-blocker (71%), ACE inhibitor or blocker (37%) and clopidogrel (28%). RESULTS: There was no direct relationship between obesity parameters and risk factor measures of lipid concentrations, blood pressure, clotting abnormalities or platelet reactivity except for a modest relationship between visceral fat and hs-CRP (r=0.30, P=0.02). However, increased BMI, waist circumference, fat mass, total abdominal fat and abdominal subcutaneous fat all correlated with insulin sensitivity (r-values -0.30 to -0.45, P-values 0.01 to <0.001) and insulin concentrations. Insulin sensitivity, in turn, was the best predictor of PAI-1, triglycerides, high-density lipoprotein (HDL) levels, cholesterol/HDL levels (all P<0.01) and platelet reactivity (R=0.34, P=0.02). CONCLUSIONS: Use of preventive pharmacologic therapies obviated the expected relationship between adiposity and CHD risk factors. However, a residual effect of insulin resistance is left untreated. Total adiposity and central adiposity were strong predictors of insulin sensitivity, which in turn predicted cardiac risk factors such as lipid concentrations, PAI-1 and platelet reactivity. Thus, while evidence-based pharmacologic treatments may diminish the statistical relationship between obesity and many cardiac risk factors, adiposity negatively impacts CHD risk by reducing tissue insulin sensitivity.

Phenotypic characteristics associated with insulin resistance in metabolically obese but normal-weight young women.

Metabolically obese, normal-weight (MONW) individuals are a hypothesized subgroup of the general population. These normal-weight individuals potentially display a cluster of obesity-related features, although this has not been systematically tested in young women. We hypothesized that MONW young women would display higher levels of total and visceral fat and lower levels of physical activity than normal women. In a cohort of 71 healthy nonobese women (21-35 years old), we identified MONW women based on cut points for insulin sensitivity (normal = glucose disposal >8 mg x min(-1) x kg(-1) of fat-free mass [FFM], n = 58; impaired = glucose disposal <8 ml x min(-1) x kg(-1) of FFM, n = 13). Thereafter, we measured body composition (dual energy X-ray absorptiometry) and body fat distribution (computed tomography), cardiorespiratory fitness (VO2max on a treadmill), physical activity energy expenditure (doubly labeled water and indirect calorimetry), glucose tolerance (oral glucose tolerance test), serum lipid profile, and dietary intake. We found a higher body fat percentage (32 +/- 6 vs. 27 +/- 6%, P = 0.01) and higher subcutaneous (213 +/- 61 vs. 160 +/- 78 cm2, P = 0.03) and visceral (44 +/- 16 vs. 35 +/- 14 cm2, P < 0.05) abdominal adiposity in the MONW group versus the normal group. The MONW group showed a lower physical activity energy expenditure (2.66 +/- 0.92 vs. 4.39 +/- 1.50 MJ/day, P = 0.01), but no difference in cardiorespiratory fitness was noted between groups. In conclusion, despite a normal body weight, a subset of young, apparently healthy women displayed a cluster of risky phenotypic characteristics that, if left untreated, may eventually predispose them to type 2 diabetes and cardiovascular disease.

Prevalence, predisposing factors, and prognosis of clinically unrecognized myocardial infarction in the elderly.

OBJECTIVES: This study was designed to determine the prevalence of unrecognized myocardial infarction (UMI), as well as risk factors, and to compare prognosis after detection of previously UMI to that after recognized myocardial infarction (RMI). BACKGROUND: Past studies revealed that a significant proportion of MIs escape recognition, and that prognosis after such events is poor, but the epidemiology of UMI has not been reassessed in the contemporary era. METHODS: The Cardiovascular Health Study (CHS) database, composed of individuals > or =65, was queried for participants who, at entry, demonstrated electrocardiographic evidence of a prior Q-wave MI, but who lacked a history of this diagnosis. The features and outcomes of this group were compared to those of individuals with prevalent RMI. RESULTS: Of 5,888 participants, 901 evidenced a past MI, and 201 (22.3%) were previously unrecognized. The independent predictors of UMI were the absence of angina and the absence of congestive heart failure (CHF). Six-year mortality did not significantly differ between the two groups. CONCLUSIONS: 1) In the elderly, UMI continues to represent a significant proportion of all MIs; 2) associations with angina and CHF may reflect complex neurological issues, but they also may represent diagnosis bias; 3) these individuals can otherwise not be distinguished from those with recognized infarctions; and 4) mortality rates after UMI and RMI are similar. Future studies should address screening for UMI, risk stratification after detection of previously UMI, and the role of standard post-MI therapies.

Determinants of physical functioning in coronary patients: response to cardiac rehabilitation.

BACKGROUND: Coronary heart disease is a major cause of disability. There has been little study of the effect of cardiac rehabilitation on measures of self-reported physical functioning. METHODS: Physical functioning was measured using the Medical Outcomes Study-Short-Form Questionnaire. Determinants of physical function were analyzed in 303 patients with coronary heart disease. Response of physical function to a 3-month exercise rehabilitation program was then determined. RESULTS: At baseline, women had lower physical function scores than men, despite similar age and diagnostic distribution. Older patients had lower physical function than younger patients. Aerobic exercise capacity, leg and arm strength, and comorbidity and depression scores were all significant predictors of baseline physical function (r range, 0.46 to -0.22). Physical function score increased significantly after exercise conditioning, with a mean (+/- SD) overall score increase from 66 +/- 23 to 80 +/- 20 on a scale of 0 to 100. The best baseline determinant of a favorable physical function improvement after rehabilitation was a low baseline physical function score. The best training-related correlate of improved physical function score was a decrease in mental depression score. CONCLUSIONS: Self-reported physical function in coronary patients is related to age, sex, fitness, and mood state. Physical functioning improves after cardiac rehabilitation in all age, sex, and diagnostic groups, but particularly in patients with low baseline values. These data support the concept that cardiac rehabilitation effectively prevents and treats cardiac disability.

Predictors of cardiac rehabilitation participation in older coronary patients.

BACKGROUND: While older coronary patients have a lower exercise capacity than younger coronary patients and have been demonstrated to improve exercise capacity to a degree similar to younger coronary patients, they are less likely to be referred to an outpatient cardiac rehabilitation program. The goal of this study was to determine demographic, medical, and psychosocial predictors of outpatient cardiac rehabilitation participation in hospitalized older post--coronary event patients. METHODS: An in-hospital-guided interview was performed by the clinical research nurse of the cardiac rehabilitation program with 226 hospitalized patients, aged 62 years and older, who had recently suffered a myocardial infarction or coronary bypass surgery. Demographic, medical, and psychosocial data were analyzed. RESULTS: Overall cardiac rehabilitation participation rate in a population with a mean age of 70.4 +/- 6 years (range, 62 to 92 years) was 21%. By multivariate analysis, the strength of the primary physician's recommendation for participation was the most powerful predictor of cardiac rehabilitation entry. Also, significant predictors of participation included commute time, patient "denial" of severity of illness, and history of depression. Medical factors such as cardiac diagnosis and left ventricular ejection fraction did not predict participation. CONCLUSIONS: Demographic, medical, and psychosocial data, collected in hospitalized post-coronary event patients are powerful predictors of subsequent participation in cardiac rehabilitation.

Physiological predictors of increasing total and central adiposity in aging men and women.

BACKGROUND: Increasing levels of total and central body fat with advancing age contribute to the development of cardiovascular and metabolic disease. We examined gender-related differences and physiological predictors of the rate of increase in total and central body fat in men and women. METHODS: We studied 427 healthy men (age range, 17 to 90 years) and 293 women (age range, 18 to 88 years). We measured body fatness by hydrostatic weighing, central adiposity from the waist circumference, peak volume of oxygen utilization (VO2) from a treadmill test, leisure time physical activity (LTA) from a questionnaire, resting metabolic rate and respiratory quotient from indirect calorimetry, and energy intake from 3-day food diaries. RESULTS: Fat mass increased with age, and the rate was greater in women (r = .61; slope = 0.25 kg/y; P < .01) than in men (r = .43; slope = 0.16 kg/y; P < .01). Increasing fat mass in men and women was most strongly associated with declines in peak VO2 and LTA. Controlling for these variables reduced the increase in fat mass from 17% to 3% per decade in men and from 26% to 5% per decade in women. The increase in waist circumference with age was also greater in women (r = .53; slope = 0.28 cm/y) than in men (r = .39; slope = 0.18 cm/y; P < .01). Increasing waist circumference with age in men and women was most strongly associated with declines in LTA and peak VO2, respectively. Control for these variables reduced the age-related increase in waist circumference from 2% to 1% per decade in men and from 4% to 1% per decade in women. We observed no independent contribution of resting metabolic rate, respiratory quotient, menopause status, energy, or macronutrient intake to the age-related increase in fat mass and waist circumference. CONCLUSIONS: Our findings suggest that (1) the age-related increase in fat mass and waist circumference is greater in women than in men and (2) the physiological characteristics that reflect a decline in physical activity-related energy expenditure, rather than resting energy expenditure, are important predictors of the increases in total and central fatness. Lifestyle changes that increase the level of physical activity may be advantageous in blunting age-related increases in total and central body fatness.

Contribution of abdominal adiposity to age-related differences in insulin sensitivity and plasma lipids in healthy nonobese women.

OBJECTIVE: We examined the hypothesis that an age-related increase in the compartments of visceral fat would account, in part, for the deleterious changes in insulin sensitivity and blood lipid profile in nonobese women. RESEARCH DESIGN AND METHODS: We directly assessed visceral and subcutaneous abdominal adipose tissue areas (computed tomography), glucose disposal (hyperinsulinemic-euglycemic clamp), body composition (dual energy X-ray absorptiometry), blood-lipid profile, and aerobic fitness (VO2max) in 178 nonobese women categorized into four age groups: group 1, 28 +/- 4 years, n = 88; group 2, 46 +/- 2 years, n = 38; group 3, 53 +/- 2 years, n = 31; and group 4. 67 +/- 6 years, n = 21. RESULTS: Visceral abdominal adipose tissue area increased with age (2.36 cm2 per year, P < 0.0001). We noted an age-related increase in total cholesterol (P < 0.0003), triglycerides (P < 0.0009), LDL cholesterol (P < 0.027), and the ratio of total cholesterol to HDL cholesterol (P < 0.042). However, age-related changes in insulin sensitivity exhibited a different age-related pattern. That is, insulin sensitivity, expressed on an absolute basis or indexed per kilogram of fat-free mass, was lowest in group 4 but was not significantly different among groups 1, 2, and 3. After statistical control for visceral fat, lower insulin sensitivity persisted in group 4, although differences were diminished relative to other groups. However, the effect of visceral fat on age-related changes in the blood-lipid profile was stronger. That is, differences in visceral and deep subcutaneous adipose tissue area abolished age-related differences in total cholesterol, triglycerides, and LDL cholesterol. No independent effects of VO2max or leisure-time physical activity on age-related changes in insulin sensitivity or on the blood-lipid profile were noted. CONCLUSIONS: We conclude that 1) visceral fat shows an increase with advancing age, whereas a decrease in insulin sensitivity was noted only in older women; 2) age-related differences in visceral fat explain only a modest part of the decline in insulin sensitivity in nonobese women; and 3) unfavorable changes in plasma lipids were strongly associated with the age-related increase in visceral abdominal adipose tissue.

The safety and efficacy of early-initiation exercise training after acute venous thromboembolism: a randomized clinical trial.

BACKGROUND: Exercise training after myocardial infarction is the standard of care within a cardiac rehabilitation setting. However, there is scant evidence regarding the safety and efficacy of early exercise training following a venous thromboembolism (VTE). METHODS: Eligible consenting participants were randomly allocated, on an individual basis, to either a 3-month exercise and behavioral weight loss intervention group or a control group. The primary clinical outcomes were change in health behavior (body weight and physical activity) and objectively measured fitness (Vo2peak ). RESULTS: From 2013 to 2014, 239 patients presented to a community-based specialty clinic after an acute VTE; 43 (18%) of these met the eligibility criteria for inclusion in the study. Of these, 19 (44%) consented to participate (nine in the intervention group; 10 in the control group). There were no adverse events in either group over a 3-month period. The mean difference in body weight between the intervention and control groups was - 4.6 kg (95% confidence interval [CI] - 11.4 to 2.2) in favor of the intervention. The mean difference in duration of physical activity from baseline to 3 months between the intervention and control groups was 133 min (95% CI 7-248) in favor of the intervention. There was a significant change in fitness over a 3-month period for the intervention group (baseline Vo2peak , 26.1 ± 5.4 mL O2 kg(-1)  min(-1) ; postintervention Vo2peak , 29.8 ± 5.4 mL O2 kg(-1)  min(-1) ). CONCLUSION: Early initiation of exercise training resulted in improvements in physical activity and fitness, and did not result in adverse events while individuals were receiving therapeutic anticoagulation. These are the first data on initiation of an exercise training and behavioral weight loss program in the early post-VTE setting.

Are aerobically fit older individuals more physically active in their free-living time? A doubly labeled water approach.

There is considerable controversy regarding factors regulating free-living physical activity energy expenditure (PAEE) in older individuals. This component is highly variable, is difficult to accurately assess, and reflects both volitional and nonvolitional activities. We examined the association between maximal aerobic fitness (peak VO2) and free-living PAEE in older individuals. One hundred and eighty healthy older patients (96 females and 84 males) between 45-90 yr of age were studied. Total energy expenditure was measured from doubly labeled water. PAEE was calculated as the difference between total energy expenditure, resting metabolic rate, and estimated thermic effect of a meal. Peak VO2 was assessed from an exercise test to volitional fatigue. Fat mass and fat-free mass were assessed from dual energy x-ray absorptiometry. After correction for age, fat mass, and fat-free mass, significant correlations were observed between peak VO2 and PAEE for older males (r = 0.42; P < 0.0001) and females (r = 0.24; P < 0.05), although significant variation among volunteers was noted. When subjects were subdivided by tertiles based on their peak VO2 (liters per min), males with the highest peak VO2 showed greater free-living PAEE than individuals with low peak VO2 (P < 0.01). Similar results were observed in females (P < 0.05). Our results suggest a positive association between higher levels of peak VO2 and greater free-living PAEE in older individuals. This relationship is stronger in older men than in women. These additional energy-dissipating properties during their free-living time may serve to preserve leanness and buffer fat gain with age.

Effects of resistance training and endurance training on insulin sensitivity in nonobese, young women: a controlled randomized trial.

We examined the effects of a 6-month randomized program of endurance training (n = 14), resistance training (n = 17), or control conditions (n = 20) on insulin sensitivity in nonobese, younger women (18-35 yr). To examine the possible mechanism(s) related to alterations in insulin sensitivity, we measured body composition, regional adiposity, and skeletal muscle characteristics with computed tomography. We observed no changes in total body fat, sc abdominal adipose tissue, or visceral adipose tissue with endurance or resistance training. Insulin sensitivity, however, increased with endurance training (pre, 421 +/- 107; post, 490 +/- 133 mg/min; P < 0.05) and resistance training (pre, 382 +/- 87; post, 417 +/- 89 mg/min; P = 0.06). When the glucose disposal rate was expressed per kg fat-free mass (FFM), the improved insulin sensitivity persisted in endurance-trained (pre, 10.5 +/- 2.7; post, 12.1 +/- 3.3 mg/min x kg FFM; P < 0.05), but not in resistance-trained (pre, 9.7 +/- 1.9; post, 10.2 +/- 1.8 mg/min x kg FFM; P = NS) women. Muscle attenuation ratios increased (P < 0.05) in both endurance- and resistance-trained individuals, but this was not related to changes in insulin sensitivity. Moreover, the change in insulin sensitivity was not related to the increased maximum aerobic capacity in endurance-trained women (r = 0.24; P = NS). We suggest that both endurance and resistance training improve glucose disposal, although by different mechanisms, in young women. An increase in the amount of FFM from resistance training contributes to increased glucose disposal probably from a mass effect, without altering the intrinsic capacity of the muscle to respond to insulin. On the other hand, endurance training enhances glucose disposal independent of changes in FFM or maximum aerobic capacity, suggestive of an intrinsic change in the muscle to metabolize glucose. We conclude that enhanced glucose uptake after physical training in young women occurs with and without changes in FFM and body composition.

Respiratory fitness, free living physical activity, and cardiovascular disease risk in older individuals: a doubly labeled water study.

The objective of this study was to examine the importance of cardiorespiratory fitness vs. physical activity energy expenditure on selected cardiovascular disease risk factors in older individuals. One hundred and seventeen older individuals, 53 men (68 +/- 9 yr) and 63 women (67 +/- 7 yr), participated in the study. This cohort was divided into 4 groups: 1) high cardiorespiratory fitness and high physical activity, 2) high cardiorespiratory fitness and low physical activity, 3) low cardiorespiratory fitness and high physical activity, and 4) low cardiorespiratory fitness and low physical activity. Cardiorespiratory fitness (VO2max) was determined from a graded exercise test, physical activity energy expenditure was measured by doubly labeled water and indirect calorimetry, body composition was determined by dual energy x-ray absorptiometry, and dietary practices were determined by a 3-day recall. Cardiorespiratory fitness exerted greater effects on the cardiovascular disease risk profile than physical activity. That is, older individuals with higher levels of cardiorespiratory fitness, regardless of their physical activity levels, showed lower levels of fasting insulin (P < 0.01), triglycerides (P < 0.05), total cholesterol (P < 0.05), total to high density lipoprotein cholesterol ratio (P < 0.05), low density lipoprotein (P < 0.05), and lower waist circumference (P < 0.01). Moreover, individuals with a high cardiorespiratory fitness but low physical activity energy expenditure displayed a more favorable cardiovascular disease risk profile than individuals with low cardiorespiratory fitness and high physical activity energy expenditure. The results suggest that higher levels of cardiorespiratory fitness have greater cardioprotective effects than higher levels of free living physical activity in older individuals. Although these findings do not discount the health benefits of being physically active, it is possible that greater emphasis should be placed on aerobic exercise to increase cardiorespiratory fitness in the elderly.

Physical activity, protein intake, and appendicular skeletal muscle mass in older men.

BACKGROUND: Aging is associated with physical inactivity, low energy intake, and loss of skeletal muscle mass. It is not clear whether regular physical activity and adequate dietary protein intake can attenuate the loss of skeletal muscle mass. OBJECTIVE: We hypothesized that the maintenance of physical activity and dietary protein intake would attenuate the age-related decline in total appendicular skeletal muscle mass. DESIGN: Total appendicular skeletal muscle mass was determined by dual-energy X-ray absorptiometry in 44 healthy, older white men aged 49-85 y. Physical activity level was determined by using a uniaxial accelerometer over a 9-d period. Dietary protein intake was estimated from a 3-d food record. RESULTS: Aging was inversely associated with total appendicular skeletal muscle mass in older men (r = -0.43; slope: -0. 119 +/- 0.039 kg/y; P < 0.01). An effect of age on appendicular skeletal muscle mass persisted after standing height and physical activity were controlled for (r = -0.34; slope: -0.120 +/- 0.052 kg/y; P = 0.03). Furthermore, an effect of age on appendicular skeletal muscle mass persisted after standing height and dietary protein intake per kilogram body mass was controlled for (r = -0.41; slope: -0.127 +/- 0.045 kg/y; P < 0.01). CONCLUSIONS: Maintaining regular physical activity and adequate protein intake may not offset the age-related loss of appendicular skeletal muscle mass in older men. Prospective studies are needed to confirm these results and to determine whether anabolic physical activity (eg, strength training) can attenuate the age-related loss of muscle mass in the elderly.

Relationship between physical activity and HDL-cholesterol in healthy older men and women: a cross-sectional and exercise intervention study.

We used cross-sectional and exercise intervention studies to examine whether physical activity levels or increases in peak aerobic capacity (peak VO2) explain variation in high density lipoprotein cholesterol (HDL-C) levels in older men and women. In the cross-sectional study, 307 older individuals (169 men; 138 women; 67 +/- 7 years) were characterized for HDL-C, leisure time physical activity, peak VO2, body composition, body fat distribution and dietary intake. HDL-C was 19% higher (P < 0.001) in women (57 +/- 14 mg/dl) versus men (48 +/- 14 mg/dl). Thirty-two percent of the variation in HDL-C in older men was explained by the waist circumference (r2 = 16%), percent dietary intake of alcohol (r2 = 11%), and carbohydrate (r2 = 6%). Waist circumference was also the best predictor of HDL-C in older women, (r2 = 7%); with percent dietary intake of carbohydrate adding an additional 6% to the model. Neither peak VO2 nor leisure time physical activity were independent predictors of HDL-C. Statistical control for the aforementioned variables diminished, but did not abolish gender differences in HDL-C. Thirty-seven older individuals (23 men; 14 women) participated in a 2-month exercise program in which individuals by week eight were expending approximately 900 kcal per week in exercise energy expenditure. Subjects were maintained in energy balance throughout the exercise program. Endurance training significantly increased peak VO2 by 15% in both men and women, and by design, body composition and body fat distribution did not change. No changes in HDL-C levels were noted. In conclusion, variations in leisure time physical activity or increases in peak VO2 are not independent predictors of HDL-C levels in healthy older men and women. Instead, central adiposity, as estimated by the waist circumference, and to a lesser extent, dietary intake of carbohydrate and alcohol, are significant predictors of variation in plasma HDL-C levels. Furthermore, short-term exercise training, generating less than 900 kcal per week in exercise energy expenditure, in the absence of weight loss, fails to influence HDL-C levels.

Cardiac and skeletal muscle adaptations to training in systemic hypertension and effect of beta blockade (metoprolol or propranolol).

Cardiovascular and peripheral adaptations to an aerobic conditioning program were studied in 30 hypertensive adults taking either placebo, beta 1-selective beta-adrenergic blocker (metoprolol) or beta 1-nonselective beta-adrenergic blocker (propranolol). The placebo group increased aerobic capacity (VO2max) 24% (p less than 0.002), largely explained by an increased peripheral arteriovenous (AV) oxygen difference with minimal changes in cardiac size and function. Resting blood pressure and total systemic resistance also decreased. The group taking a beta 1-selective beta blocker increased VO2max 8% (p less than 0.05), reduced resting blood pressure but had no significant change of AV oxygen difference or cardiac size or function. The group taking the beta 1-nonselective beta blocker propranolol had no increase in VO2max, no decrease in resting blood pressure and no cardiovascular or peripheral adaptations to the exercise program. Thus, beta 1-selective and beta 1-nonselective beta blockers attenuate conditioning in hypertensive patients to differing degrees, in each case by blocking peripheral mechanisms of conditioning.

Referral patterns and exercise response in the rehabilitation of female coronary patients aged greater than or equal to 62 years.

Gender-related differences in cardiac rehabilitation referral patterns and response to an aerobic conditioning program were examined in 226 hospitalized older coronary patients (aged greater than or equal to 62 years). Overall, the outpatient cardiac rehabilitation participation rate in this population was 21%. Older women were less likely to enter cardiac rehabilitation than were older men (15 vs 25%; p = 0.06), despite similar clinical profiles. This was explained primarily by a greater likelihood of primary physicians to strongly recommend cardiac rehabilitation to men. Before conditioning, women who entered cardiac rehabilitation were less fit than were men; peak oxygen consumption was 18% lower in women (16 +/- 5 vs 20 +/- 5 ml/kg/min; p = 0.02). However, both groups improved aerobic capacity similarly in response to a 12-week aerobic conditioning program, with maximal oxygen consumption increasing by 17% in women and by 19% in men. Thus, older female coronary patients are less likely to be referred for cardiac rehabilitation, despite a similar clinical profile and improvement in functional capacity from the training component.

Effect of metoprolol on the submaximal stress test performed early after acute myocardial infarction.

To determine the effect of beta-adrenergic blockade on the submaximal stress test after acute myocardial infarction (AMI), 36 post-AMI patients performed their treadmill test on 2 separate days, with and without metoprolol, in a double-blind, placebo-controlled, crossover design study. Rest and peak submaximal exercise heart rate was diminished by 100 mg of metoprolol administered twice daily (from 84 +/- 3 to 68 +/- 2 beats/min, p less than 0.001, and from 126 +/- 3 to 97 +/- 2 beats/min, p less than 0.001, respectively) compared with placebo. Rest and peak submaximal systolic blood pressure was also decreased (from 121 +/- 3 to 108 +/- 2 mm Hg, p less than 0.001, and from 151 +/- 4 to 124 +/- 3 mm Hg, p less than 0.001). Exercise-induced ST-segment depression of 1 mm or more from baseline occurred in 12 patients taking placebo. However, only 4 of these patients had ST depression when they exercised while taking metoprolol (p less than 0.05). Angina pectoris occurred in 4 patients taking placebo but in only 1 of these taking a beta-blocking drug. It is concluded that beta-blocking therapy renders the post-AMI submaximal stress test less sensitive for markers of exercise-induced ischemia than if the test is performed without the drug. Therefore, when using the prognostic information of published studies, it is important to define the conditions surrounding the exercise test.

Usefulness of myocardial ischemia as predictor of training effect in cardiac rehabilitation after acute myocardial infarction or coronary artery bypass grafting.

Exercise capacity increases to a variable degree in coronary patients during cardiac rehabilitation. The effect of baseline exercise-induced ischemia on the response to a 12-week conditioning program was evaluated in 106 coronary patients. The magnitude of exercise conditioning response was greater in nonischemic patients than in ischemic patients, with maximal exercise intensity increasing 69 versus 50% (7.2 to 12.1 vs 7.1 to 10.6 METs) (p less than 0.05) and maximal oxygen consumption increasing 28 versus 10% (23.1 to 29.6 vs 23.0 to 25.4 cc/kg/min) (p less than 0.05). Markers of conditioning during submaximal exercise such as heart rate and heart rate-systolic blood pressure product were similarly reduced in both groups. The groups did not differ by age, diagnosis, resting ejection fraction, incidence of beta-blocker use, maximal exercise capacity, maximal exercise heart rate, blood pressure or intensity of actual exercise training. These results suggest that exercise-induced ischemia alters the stimulus to adapt to exercise training.

Effect of beta blockade and intrinsic sympathomimetic activity on exercise performance.

Beta-adrenergic receptor blocking drugs with intrinsic sympathomimetic activity may have the advantage of not depressing myocardial function and pulse rate at rest. Little is known about their effects during exercise. Thus, the effects of small and large doses of pindolol, a nonselective beta-adrenergic blocking drug with intrinsic sympathomimetic activity, were compared with the effects of small and large doses of propranolol in 13 normal men during treadmill exercise. Compared with placebo, all drug regimens decreased exercise duration (p less than 0.001). There were no significant differences in duration between pindolol and propranolol, or between the small and large dose of each drug. Maximal oxygen consumption tended to be lower with all preparations compared with placebo (p less than 0.10). With smaller doses, decrements of maximal heart rate (HR) and HR-blood pressure (BP) product were equivalent for pindolol and propranolol (decreases of 46 vs 43 beats/min, and 13,000 vs 12,000 units). The HR-BP product decreased more with high-dose propranolol than high-dose pindolol (decrease of 18,000 vs 14,800 units) due to a greater decrement in HR with propranolol (decrease of 65 +/- 3 vs 53 +/- 3 beats/min). At both submaximal levels, for both low- and high-dose preparations, HR, BP and HR-BP product were lower for propranolol than for pindolol. Thus, in healthy subjects, pindolol and propranolol at doses that produced equivalent reductions in maximal oxygen consumption, exercise duration and, for the smaller dose, HR, had different effects on submaximal HR-BP product, an index of myocardial oxygen consumption, as a result of a higher HR and BP with pindolol.

Central markers of body fat distribution are important predictors of plasma lipids in elderly men and women.

We determined the contribution of body fat distribution, peak VO2, fat mass, and dietary intake to variation in plasma lipids in elderly individuals. Volunteers were a healthy cohort of older Caucasian women (n = 75, mean age +/- SD, 72 +/- 5 years) and older men (n = 101, 72 +/- 5 years). We determined fat mass from underwater weighing, fat patterning from waist circumference, as well as peripheral and truncal skinfolds, exercise capacity from peak VO2, and dietary intake from three-day food diaries. Plasma lipid levels were measured in the fasting state and included total cholesterol, high density lipoprotein (HDL-C), low density lipoprotein (LDL-C), and fasting triglycerides. Older women weighted less than older men, but had higher fat mass, truncal, and peripheral skinfolds. Waist circumference and peak VO2 were lower in older women than older men. Older women had higher total cholesterol (217 +/- 31 vs. 197 +/- 30; p < 0.01), HDL-C (54 +/- 12 vs. 49 +/- 14; p < 0.05), and LDL-C (133 +/- 26 vs. 121 +/- 27; p < 0.01) when compared with older men. No gender differences were noted in fasting triglycerides. Truncal skinfolds were the best predictor of plasma lipids in older men, accounting for between 9% and 30% (r2) of the variation in plasma lipids. Similarly, in older women, central markers of fatness (i.e., waist circumference and truncal skinfolds) were the best predictors of plasma lipids (r2 = 3% to 24%). Total fat mass, peak VO2 and dietary intake were not independent predictors of plasma lipids in older men and women. Indices of central body fatness, rather than total fat mass, peak VO2 or dietary intake are stronger predictors of plasma lipids in healthy older men and women.

Cardiac rehabilitation in older coronary patients.

The majority of patients presenting with acute coronary disease or undergoing coronary revascularization procedures are older than age 65. Disability rates are very high in these patient populations, particularly in women, the older-old, and patients with clinical manifestations of angina pectoris or chronic heart failure. The presence of mental depression is also an important determinant of poor physical functioning. Cardiac rehabilitation has been demonstrated to safely increase aerobic capacity, muscular strength, and endurance in older coronary populations.