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Background: The association of physical inactivity and elevated body mass index (BMI) with cardiovascular disease (CVD) risk is well established. The relationship of dietary caloric intake and CVD risk is less certain., Methods: The epidemiologic follow-up of the First National Health and Nutrition Examination Survey (1971-1992) was examined to determine the relationship of caloric intake, BMI, and physical activity to CVD mortality. Of 14,407 participants, 9790 subjects aged 25 to 74 years met inclusion criteria. The CVD mortality rate was the outcome., Results: During the 17 years of follow-up, there were 3183 deaths, 1531 of which were due to CVD (9.11/1000 person-years). People with relatively less physical activity, lower caloric intake, and who were overweight (BMI 25 to 29.9 kg/m(2)) and obese (BMI > or =30 kg/m(2)) had a less favorable baseline CVD risk profile than did those who were more active and of normal weight and had greater caloric intake. Age- and race/ethnicity-adjusted CVD mortality rates were highest among those with the least physical activity and lowest caloric intake, and who were overweight or obese. Moreover, subjects of normal weight who exercised most were more likely to have high caloric intake and lower CVD mortality (5.9 vs 14.7 per 1000 person-years, p =0.01) than subjects who were obese and exercised least. In Cox regression analysis, controlling for relevant CVD risk factors, least physical activity was independently associated with increased CVD mortality (hazard ratio=1.32, 95% confidence interval [CI]=1.13-1.53); and obesity was associated with increased CVD mortality (hazard ratio=1.24, 95% CI=1.06-1.44). Although highest dietary caloric intake was associated with reduced CVD mortality (hazard ratio=0.83, 95% CI=0.74-0.93), after adjusting for physical activity and BMI, there was no significant association of highest caloric intake with CVD mortality (hazard ratio=0.91, 95% CI=0.81-1.01)., Conclusions: In this large general population sample, lower levels of physical activity and obesity were independently associated with decreased CVD survival. Moreover, when BMI, physical activity, and other relevant characteristics were taken into account, caloric intake was not related to CVD mortality.