Depressive Symptoms, Inflammation, and Ischemic Stroke in Older Adults: A Prospective Analysis in the Cardiovascular Health Study

OBJECTIVES: To investigate the mediator role of inflammation in any relationship between depressive symptoms and ischemic stroke. DESIGN: Longitudinal prospective study. SETTING: Review of medical records, death certificates, and the Medicare healthcare utilization database for hospitalizations. PARTICIPANTS: Total of 5,525 elderly men and women aged 65 and older who were prospectively followed from 1989 to 2000 as participants in the Cardiovascular Health Study. MEASUREMENTS: Depression symptom scores, inflammatory markers. RESULTS: Greater depressive symptoms were associated with risk of ischemic stroke (unadjusted hazard ratio (HR)=1.32, 95% confidence interval (CI)=1.09–1.59; HR=1.26, 95% CI=1.03–1.54, adjusted for traditional risk factors). When a term for inflammation (C‐reactive protein (CRP)) was introduced in the model, the HRs were not appreciably altered (unadjusted HR=1.31, 95% CI=1.08–1.58; adjusted HR=1.25, 95% CI=1.02–1.53), indicating that CRP at baseline was not a mediator in this relationship. In analyses stratified according to CRP levels, a J‐shaped relationship between depressive symptoms and stroke was evident in the unadjusted analyses; in the fully adjusted model, only CRP in the highest tertile was associated with a higher risk for stroke in the presence of higher depressive symptoms scores. CONCLUSION: The analyses from this prospective study provide evidence of a positive association between depressive symptoms and risk of incident stroke. Inflammation, as measured according to CRP at baseline, did not appear to mediate the relationship between depressive symptoms and stroke.