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Sylvia Wassertheil-Smoller, PhD; William B. Applegate, MD; Kenneth Berge, MD; Chee Jen Chang, PhD; Barry R. Davis, MD, PhD; Richard Grimm, Jr, MD, PhD; John Kostis, MD; Sara Pressel, MS; Eleanor Schron, RN, MS

Arch Intern Med. 1996;156(5):553-561.

Abstract
Objective
To determine the relationship between increasing depressive symptoms and cardiovascular events or mortality.

Design
Cohort analytic study of data from randomized placebo-controlled double-blind clinical trial of antihypertensive therapy. Depressive symptoms were assessed semiannually with the Center for Epidemiological Studies— Depression (CES-D) scale during an average follow-up of 4.5 years.

Setting
Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program.

Patients
Generally healthy men and women aged 60 years or older randomized to active antihypertensive drug therapy or placebo who were 79% white and 53% women and had follow-up CES-D scores and no outcome events during the first 6 months (N=4367).

Main Outcome Measures
All-cause mortality, fatal or nonfatal stroke, or myocardial infarction. Results: Baseline depressive symptoms were not related to subsequent events; however, an increase in depression was prognostic. Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable, controlling for multiple covariates, indicated a 25% increased risk of death per 5-unit increase in the CES-D score (relative risk [RR], 1.25; 95% confidence interval [CI], 1.15 to 1.36). The RR for stroke or myocardial infarction was 1.18 (95% CI, 1.08 to 1.30). Increase in CES-D score was an independent predictor in both placebo and active drug groups, and it was strongest as a risk factor for stroke among women (RR, 1.29; 95% CI, 1.07 to 1.34).

Conclusions
Among elderly persons, a significant and substantial excess risk of death and stroke or myocardial infarction was associated with an increase in depressive symptoms over time, which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes. However, further studies of causal pathways are needed before widespread screening for depression in clinical practice is to be recommended.

(Arch Intern Med. 1996;156:553-561)

Author Affiliations
for the SHEP Cooperative Research Group

From the Albert Einstein College of Medicine, Bronx, NY (Drs Wassertheil-Smoller and Chang); University of Tennessee, Memphis (Dr Applegate); Mayo Medical School, Rochester, Minn (Dr Berge); University of Texas Health Science Center at Houston (Dr Davis and Ms Pressel); University of Minnesota, Minneapolis (Dr Grimm); University of Medicine and Dentistry of New Jersey—Robert Wood Johnson Medical School, New Brunswick (Dr Kostis); and the National Institutes of Health, Bethesda, Md (Ms Schron). A list of the participating centers and investigators of the Systolic Hypertension in the Elderly Program (SHEP) appears on pages 559 and 560.

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