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The aim of this study is to describe the relationship between self-rated physical activity during leisure time and cardiovascular disease mortality in 2936 individuals of the cohort of the Brisighella Heart Study, a prospective, population-based, longitudinal, epidemiological survey.Long-term (1988–2000) prognostic significance of physical activity was determined after adjustments for age, sex, smoking habits, low-density lipoprotein-cholesterol and history of type 2 diabetes.At baseline, 377 (25.3%) male and 496 (34.3%) female participants reported scarce-null physical activity, whereas 1112 (74.7%) men and 951 (65.7%) women reported medium-intense physical activity. In the entire population, cardiovascular mortality was three times higher in participants with sedentary physical activity than in those with medium-intense physical activity (P = 0.0001). These results have been confirmed in both men (P = 0.0001) and women (P = 0.0028). A categorical distribution of the population according to age showed a higher risk of cardiovascular death associated with sedentary physical activity only in the younger male particupants (P = 0.0032).On the basis of our data, physical activity is inversely related to cardiovascular mortality in a sample of the rural Mediterranean population with a highest risk in inactive men aged less than 65 years.