Change in depression as a precursor of cardiovascular events. SHEP Cooperative Research Group (Systoloc Hypertension in the elderly)

Arch Intern Med. 1996 Mar 11;156(5):553-61.


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 semi-annually 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 70% 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 casual pathways are needed before wide-spread screening for depression in clinical practice is to be recommended.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antihypertensive Agents / therapeutic use
  • Cardiovascular Diseases / complications*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / psychology
  • Cohort Studies
  • Depression / complications*
  • Depression / epidemiology
  • Depression / psychology
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension / complications*
  • Hypertension / drug therapy
  • Hypertension / mortality
  • Hypertension / psychology
  • Incidence
  • Male
  • Middle Aged
  • Prevalence
  • Prognosis
  • Risk Factors
  • Systole
  • United States / epidemiology


  • Antihypertensive Agents