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

Authors

  • Jose J. Arbelaez MD, MHS, PhD,

    1. Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland
    2. Welch Center for Prevention, Epidemiology, and Clinical Research,
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  • Abraham A. Ariyo MD, MPH,

    1. Center for Cardiovascular Disease Prevention and Intervention, HeartMasters, Dallas, Texas.
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  • Rosa M. Crum MD, MHS,

    1. Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland
    2. Welch Center for Prevention, Epidemiology, and Clinical Research,
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  • Linda P. Fried MD, MPH,

    1. Department of Medicine, and
    2. Center on Aging and Health, The Johns Hopkins Medical Institutions, Baltimore, Maryland
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  • Daniel E. Ford MD, MPH

    1. Department of Epidemiology, Bloomberg School of Public Health, The Johns Hopkins University, Baltimore, Maryland
    2. Welch Center for Prevention, Epidemiology, and Clinical Research,
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Address correspondence to Jose J. Arbelaez, MD, PhD, Welch Center for Prevention, Epidemiology, and Clinical Research, 2024 E. Monument St., Suite 2-500, Baltimore, MD 21287. E-mail: jarbela1@jhmi.edu; jarbelae@jhsph.edu

Abstract

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.

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