Depressive symptoms and mortality in men results from the multiple risk factor intervention trial

Background and Purpose - Depression may be a risk factor for cardiovascular disease (CVD) mortality. We evaluated long-term mortality risk associated with depressive symptoms measured at middle age among men at high risk for coronary heart disease (CHD). Methods - 12 866 men without definite evidence of CHD at study entry but who had above average risk of CHD based on blood pressure, blood cholesterol levels, and/or cigarette smoking were recruited into the Multiple Risk Factor Intervention Trial (MRFIT). Survivors at the end of the trial were followed-up for mortality for an additional 18 years. Men who had completed the Center for Epidemiologic Studies Depression (CES-D) scale near the end of the trial ( n = 11 216) were used in a prospective analysis of post-trial all-cause and cause-specific mortality during 18-year follow-up after CES-D assessment. Results - Greater depressive symptoms measured at the end of the trial were associated with significantly higher risk of all-cause mortality and for cause-specific death, a higher risk of CVD, and, more specifically, stroke mortality ( all P values < 0.02) but not CHD mortality ( P = 0.48) in linear trend analyses. The significant associations were strongest for those reporting the greatest depression: hazard ratio (HR) = 1.15 ( 95% CI, 1.03 to 1.28; P < 0.01) for all-cause mortality for those in the highest depressive symptom quintile, HR = 1.21 for CVD mortality ( 95% CI, 1.03 to 1.41; P < 0.05), and HR = 2.03 for stroke mortality ( 95% CI, 1.20 to 3.44; P < 0.01) compared with those in the lowest quintile. These associations were adjusted for age, intervention group, race, educational attainment, smoking at baseline and visit 6, trial averaged systolic blood pressure, alcohol consumption, and fasting cholesterol, as well as the occurrence of nonfatal cardiovascular events during the trial. Conclusions - Greater depressive symptoms are associated with an increase in the risk of all-cause and, more specifically, CVD mortality in men. Stroke but not CHD was the form of CVD with which depressive symptoms were associated.