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Context: Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease (CVD) risk factors, but the role of physical inactivity is not prominent in these recommendations., Objective: To quantify the influence of low cardiorespiratory fitness, an objective marker of physical inactivity, on CVD and all-cause mortality in normal-weight, overweight, and obese men and compare low fitness with other mortality predictors., Design: Prospective observational data from the Aerobics Center Longitudinal Study., Setting: Preventive medicine clinic in Dallas, Tex., Participants: A total of 25714 adult men (average age, 43.8 years [SD, 10.1 years]) who received a medical examination during 1970 to 1993, with mortality follow-up to December 31, 1994., Main Outcome Measures: Cardiovascular disease and all-cause mortality based on mortality predictors (baseline CVD, type 2 diabetes mellitus, high serum cholesterol level, hypertension, current cigarette smoking, and low cardiorespiratory fitness) stratified by body mass index., Results: During the study period, there were 1025 deaths (439 due to CVD) during 258781 man-years of follow-up. Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors. Using normal-weight men without CVD as the referent, the strongest predictor of CVD death in obese men was baseline CVD (age- and examination year-adjusted relative risk [RR], 14.0; 95% confidence interval [CI], 9.4-20.8); RRs for obese men with diabetes mellitus, high cholesterol, hypertension, smoking, and low fitness were similar and ranged from 4.4 (95% CI, 2.7-7.1) for smoking to 5.0 (95% CI, 3.6-7.0) for low fitness. Relative risks for all-cause mortality in obese men ranged from 2.3 (95% CI, 1.7-2.9) for men with hypertension to 4.7 (95% CI, 3.6-6.1) for those with CVD at baseline. Relative risk for all-cause mortality in obese men with low fitness was 3.1 (95% CI, 2.5-3.8) and in obese men with diabetes mellitus 3.1 (95% CI, 2.3-4.2) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels. Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors. Approximately 50% (n = 1674) of obese men had low fitness, which led to a population-attributable risk of 39% for CVD mortality and 44% for all-cause mortality. Baseline CVD had population attributable risks of 51% and 27% for CVD and all-cause mortality, respectively., Conclusions: In this analysis, low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors.

Objective: To quantify the relation of cardiorespiratory fitness to cardiovascular disease (CVD) mortality and to all-cause mortality within strata of other personal characteristics that predispose to early mortality. DESIGN--Observational cohort study. We calculated CVD and all-cause death rates for low (least fit 20%), moderate (next 40%), and high (most fit 40%) fitness categories by strata of smoking habit, cholesterol level, blood pressure, and health status., Setting: Preventive medicine clinic., Study Participants: Participants were 25341 men and 7080 women who completed preventive medical examinations, including a maximal exercise test., Main Outcome Measures: Cardiovascular disease and all-cause mortality., Results: There were 601 deaths during 211996 man-years of follow-up, and 89 deaths during 52982 woman-years of follow-up. Independent predictors of mortality among men, with adjusted relative risks (RRs) and 95% confidence intervals (CIs), were low fitness (RR, 1.52;95% CI, 1.28-1.82), smoking (RR, 1.65; 95% CI, 1.39-1.97), abnormal electrocardiogram (RR, 1.64;95% CI, 1.34-2.01), chronic illness (RR, 1.63;95% CI, 1.37-1.95), increased cholesterol level (RR, 1.34; 95% CI, 1.13-1.59), and elevated systolic blood pressure (RR, 1.34; 95% CI, 1.13-1.59). The only statistically significant independent predictors of mortality in women were low fitness (RR, 2.10; 95% Cl, 1.36-3.21) and smoking (RR, 1.99; 95% Cl, 1.25-3.17). Inverse gradients were seen for mortality across fitness categories within strata of other mortality predictors for both sexes. Fit persons with any combination of smoking, elevated blood pressure, or elevated cholesterol level had lower adjusted death rates than low-fit persons with none of these characteristics., Conclusions: Low fitness is an important precursor of mortality. The protective effect of fitness held for smokers and nonsmokers, those with and without elevated cholesterol levels or elevated blood pressure, and unhealthy and healthy persons. Moderate fitness seems to protect against the influence of these other predictors on mortality. Physicians should encourage sedentary patients to become physically active and thereby reduce the risk of premature mortality.

Objective: To examine the independent associations of vigorous (> or = 6 resting metabolic rate [MET] score) and nonvigorous (< 6 MET score) physical activity with longevity., Design: Prospective cohort study, following up men from 1962 or 1966 through 1988., Setting/participants: Subjects were Harvard University alumni, without self-reported, physician-diagnosed cardiovascular disease, cancer, or chronic obstructive pulmonary disease (n = 17,321). Men with a mean age of 46 years reported their physical activities on questionnaires at baseline., Main Outcome Measure: All-cause mortality (3728 deaths)., Results: Total energy expenditure and energy expenditure from vigorous activities, but not energy expenditure from nonvigorous activities, related inversely to mortality. After adjustment for potential confounders, the relative risks of dying associated with increasing quintiles of total energy expenditure were 1.00 (referent), 0.94, 0.95, 0.91 and 0.91, respectively (P [trend] < .05). The relative risks of dying associated with less than 630, 630 to less than 1680, 1680 to less than 3150, 3150 to less than 6300, and 6300 or more kJ/wk expended on vigorous activities were 1.00 (referent), 0.88, 0.92, 0.87, and 0.87, respectively (P [trend] = .007). Corresponding relative risks for energy expended on nonvigorous activities were 1.00 (referent), 0.89, 1.00, 0.98, and 0.92, respectively (P [trend] = .36). Analyses of vigorous and nonvigorous activities were mutually adjusted. Among men who reported only vigorous activities (259 deaths), we observed decreasing age-standardized mortality rates with increasing activity (P = .05); among men who reported only nonvigorous activities (380 deaths), no trend was apparent (P = .99)., Conclusions: These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity. These findings pertain only to all-cause mortality; nonvigorous exercise has been shown to benefit other aspects of health.

Objective: To evaluate the relationship between changes in physical fitness and risk of mortality in men., Design: Prospective study, with two clinical examinations (mean interval between examinations, 4.9 years) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination (mean follow-up from subsequent examination, 5.1 years)., Setting: Preventive medicine clinic., Study Participants: Participants were 9777 men given two preventive medical examinations, each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status., Main Outcome Measures: All cause (n = 223) and cardiovascular disease (n = 87) mortality., Results: The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations (122.0/10,000 man-years); the lowest death rate was in men who were physically fit at both examinations (39.6/10,000 man-years). Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10,000 man-years. This is a reduction in mortality risk of 44% (95% confidence interval, 25% to 59%) relative to men who remained unfit at both examinations. Improvement in fitness was associated with lower death rates after adjusting for age, health status, and other risk factors of premature mortality. For each minute increase in maximal treadmill time between examinations, there was a corresponding 7.9% (P = .001) decrease in risk of mortality. Similar results were seen when the group was stratified by health status, and for cardiovascular disease mortality., Conclusions: Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men. Physicians should encourage unfit men to improve their fitness by starting a physical activity program.

Objective: To investigate the nature of the relation between body weight and all-cause mortality., Design: Prospective cohort study, following up men from 1962 or 1966 (1962/1966) through 1988., Setting/participants: Harvard University alumni with a mean age of 46.6 years in 1962/1966 and without self-reported, physician-diagnosed coronary heart disease, stroke, or cancer, who completed questionnaires on weight, height, cigarette smoking habit, and physical activity (n = 19,297). We calculated body mass index (weight in kilograms divided by the square of height in meters) using self-reported measures., Main Outcome Measure: All-cause mortality (4370 deaths)., Results: In multivariate analysis adjusting for age, cigarette smoking habit, and physical activity, we found a J-shaped relation between body mass index and mortality. Relative risks of dying for men with a body mass index of less than 22.5, 22.5 to less than 23.5, 23.5 to less than 24.5, 24.5 to less than 26.0, and 26.0 or greater were 1.00 (referent), 0.99 (95% confidence interval, 0.89 to 1.20), 0.95 (0.87 to 1.05), 1.01 (0.91 to 1.10), and 1.18 (1.08 to 1.28), respectively (P for linear trend = .0008). Among current smokers, the relation between body mass index and mortality was U-shaped, with lowest risk of death at a body mass index of 23.5 to less than 24.5. During early follow-up (1962/1966 through 1974), we also observed a U-shaped curve, this time with lowest mortality risk at a body mass index of 24.5 to less than 26.0. To minimize confounding by cigarette smoking and bias from antecedent disease and early mortality, we conducted analysis only among never smokers and omitted the first 5 years of follow-up (510 deaths). The corresponding relative risks from this analysis, adjusted for age and physical activity, were 1.00, 1.23 (95% confidence interval, 0.90 to 1.67), 1.06 (0.80 to 1.42), 1.27 (0.96 to 1.68), and 1.67 (1.29 to 2.17), respectively (P for linear trend = .0001)., Conclusions: In these prospective data, body weight and mortality were directly related. After accounting for confounding by cigarette smoking and bias resulting from illness-related weight loss or inappropriate control for the biologic effects of obesity, we found no evidence of excess mortality among lean men. Indeed, lowest mortality was observed among men weighing, on average, 20% below the US average for men of comparable age and height.

Objective: To investigate the effect of body weight change on longevity., Design: Cohort analytic study, following men from 1977 through 1988., Setting: The study was conducted among Harvard University alumni with mean age of 58 years., Patients: Alumni, free of cardiovascular disease and cancer, completed questionnaires on weight, height, cigarette habit, and physical activities in 1962 or 1966 and in 1977 (n = 11,703). We assessed weight change between questionnaires, based on self-reported weights., Main Outcome Measure: Mortality from all causes (n = 1441), coronary heart disease (n = 345), and cancer (n = 459), determined from death certificates., Results: Lowest all-cause mortality was among alumni maintaining stable weight (+/- 1 kg). With this category as referent (relative risk = 1.00), relative risks of death associated with losing more than 5 kg, losing between 1 and 5 kg, (more than 1 kg and up to 5 kg) gaining between 1 and 5 kg (more than 1 kg and up to 5 kg), and gaining more than 5 kg were 1.57 (95% confidence interval, 1.34 to 1.84), 1.26 (1.10 to 1.46), 1.06 (0.90 to 1.24), and 1.36 (1.11 to 1.66), respectively. For coronary heart disease mortality, relative risks were 1.75 (1.26 to 2.43), 1.43 (1.05 to 1.93), 1.28 (0.91 to 1.80), and 2.01 (1.36 to 2.97), respectively. Weight change did not predict cancer mortality. Findings were not explained by cigarette habit, physical activity, or body mass index. We observed similar trends for follow-up between 1977 and 1982 and between 1983 and 1988. Those losing or gaining more weight also reported greater total lifetime weight loss, which may indicate weight cycling., Conclusions: Both body weight loss and weight gain are associated with significantly increased mortality from all causes and from coronary heart disease but not from cancer.

We studied physical fitness and risk of all-cause and cause-specific mortality in 10,224 men and 3120 women who were given a preventive medical examination. Physical fitness was measured by a maximal treadmill exercise test. Average follow-up was slightly more than 8 years, for a total of 110,482 person-years of observation. There were 240 deaths in men and 43 deaths in women. Age-adjusted all-cause mortality rates declined across physical fitness quintiles from 64.0 per 10,000 person-years in the least-fit men to 18.6 per 10,000 person-years in the most-fit men (slope, -4.5). Corresponding values for women were 39.5 per 10,000 person-years to 8.5 per 10,000 person-years (slope, -5.5). These trends remained after statistical adjustment for age, smoking habit, cholesterol level, systolic blood pressure, fasting blood glucose level, parental history of coronary heart disease, and follow-up interval. Lower mortality rates in higher fitness categories also were seen for cardiovascular disease and cancer of combined sites. Attributable risk estimates for all-cause mortality indicated that low physical fitness was an important risk factor in both men and women. Higher levels of physical fitness appear to delay all-cause mortality primarily due to lowered rates of cardiovascular disease and cancer.

Epidemiologic studies in Olympic year 1984 suggest that personal athleticism alters trends in life-style and coronary heart disease. Analysis of 572 first attacks among 16,936 Harvard alumni, 1962 to 1972, and 1,413 total deaths, 1962 to 1978, shows that habitual postcollege exercise, not student sports play, predicts low coronary heart disease risk. Sedentary alumni, even ex-varsity athletes, have high risk. Sedentary students becoming physically active alumni acquire low risk. Exercise benefit is independent of contrary life-style elements--smoking, obesity, weight gain, hypertension, and adverse parental disease history--in affecting coronary heart disease incidence. Hypertension is clinically the strongest predictor of coronary attack, but inadequate exercise is strongest on a community basis. Exercise level is inversely related to total, cardiovascular, and respiratory mortality but less related to cancer or unnatural deaths. The current exercise revolution may improve life-style, cardiovascular health, and longevity.