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Mary A. Whooley, MD; Warren S. Browner, MD, MPH; for the Study of Osteoporotic Fractures Research Group

Arch Intern Med. 1998;158:2129-2135.

Background  Major depression is associated with increased mortality, but it is not known whether patients who report depressive symptoms have greater mortality.

Subjects and Methods  We performed a prospective cohort study of 7518 white women 67 years of age or older who were recruited from population-based listings in Baltimore, Md, Minneapolis, Minn, Portland, Ore, and the Monongahela Valley, Pa. Participants completed the Geriatric Depression Scale (short form) and were considered depressed if they reported 6 or more of 15 possible symptoms of depression. Women were followed up for an average of 6 years. If a participant died, we obtained a copy of the official death certificate and hospital records, if available, and used International Classification of Diseases, Ninth Revision, codes to classify death attributable to cardiovascular, cancer, or noncancer, noncardiovascular cause.

Results  Mortality during 7-year follow-up varied from 7% in women with no depressive symptoms to 17% in those with 3 to 5 symptoms to 24% in those with 6 or more symptoms of depression (P<.001). Of 473 women (6.3%) with 6 or more depressive symptoms at baseline, 24% died (111 deaths in 2610 woman-years of follow-up) compared with 11% of women who reported 5 or fewer symptoms of depression (760 deaths in 41460 woman-years of follow-up) (P<.001). Women with 6 or more depressive symptoms had a 2-fold increased risk of death (age-adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.75-2.61; P<.001) compared with those who had 5 or fewer depressive symptoms. This association remained strong after adjusting for potential confounding variables, including history of myocardial infarction, stroke, diabetes mellitus, hypertension, chronic obstructive pulmonary disease, smoking, perceived health, and cognitive function (HR, 1.47; 95% CI, 1.14-1.88; P =.003). Depressive symptoms were associated with an increased adjusted risk of death from cardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.5; P=.003), and noncancer, noncardiovascular diseases (HR, 1.8; 95% CI, 1.2-2.7; P=.01), but were not associated with deaths from cancer (HR, 1.0; 95% CI, 0.6-1.7; P=.93).

Conclusions  Depressive symptoms are a significant risk factor for cardiovascular and noncancer, noncardiovascular mortality but not cancer mortality in older women. Whether depressive symptoms are a marker for, or a cause of, life-threatening conditions remains to be determined.

From the General Internal Medicine Section, San Francisco Department of Veterans Affairs Medical Center, and the Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco.

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