Depression and risk of stroke morbidity and mortality: a meta-analysis and systematic review

JAMA. 2011 Sep 21;306(11):1241-9. doi: 10.1001/jama.2011.1282.


Context: Several studies have suggested that depression is associated with an increased risk of stroke; however, the results are inconsistent.

Objective: To conduct a systematic review and meta-analysis of prospective studies assessing the association between depression and risk of developing stroke in adults.

Data sources: A search of MEDLINE, EMBASE, and PsycINFO databases (to May 2011) was supplemented by manual searches of bibliographies of key retrieved articles and relevant reviews.

Study selection: We included prospective cohort studies that reported risk estimates of stroke morbidity or mortality by baseline or updated depression status assessed by self-reported scales or clinician diagnosis.

Data extraction: Two independent reviewers extracted data on depression status at baseline, risk estimates of stroke, study quality, and methods used to assess depression and stroke. Hazard ratios (HRs) were pooled using fixed-effect or random-effects models when appropriate. Associations were tested in subgroups representing different participant and study characteristics. Publication bias was evaluated with funnel plots and Begg test.

Results: The search yielded 28 prospective cohort studies (comprising 317,540 participants) that reported 8478 stroke cases (morbidity and mortality) during a follow-up period ranging from 2 to 29 years. The pooled adjusted HRs were 1.45 (95% CI, 1.29-1.63; P for heterogeneity <.001; random-effects model) for total stroke, 1.55 (95% CI, 1.25-1.93; P for heterogeneity = .31; fixed-effects model) for fatal stroke (8 studies), and 1.25 (95% CI, 1.11-1.40; P for heterogeneity = .34; fixed-effects model) for ischemic stroke (6 studies). The estimated absolute risk differences associated with depression were 106 cases for total stroke, 53 cases for ischemic stroke, and 22 cases for fatal stroke per 100,000 individuals per year. The increased risk of total stroke associated with depression was consistent across most subgroups.

Conclusion: Depression is associated with a significantly increased risk of stroke morbidity and mortality.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Review
  • Systematic Review

MeSH terms

  • Adult
  • Depression / epidemiology*
  • Humans
  • Morbidity / trends
  • Mortality / trends
  • Prospective Studies
  • Risk Factors
  • Stroke / mortality*