Inflammation and Hemostasis Biomarkers for Predicting Stroke in Postmenopausal Women: The Women's Health Initiative Observational Study

Robert C. Kaplan, Aileen P. McGinn, Alison E. Baird, Susan L. Hendrix, Charles Kooperberg, John Lynch, Daniel M. Rosenbaum, Karen C. Johnson, Howard D. Strickler, Sylvia Wassertheil-Smoller

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Abstract

Background: Inflammatory and hemostasis-related biomarkers may identify women at risk of stroke. Methods: Hormones and Biomarkers Predicting Stroke is a study of ischemic stroke among postmenopausal women participating in the Women's Health Initiative observational study (n = 972 case-control pairs). A Biomarker Risk Score (BRS) was derived from levels of 7 inflammatory and hemostasis-related biomarkers that appeared individually to predict risk of ischemic stroke: C-reactive protein (CRP), interleukin-6, tissue plasminogen activator, D-dimer, white blood cell count, neopterin, and homocysteine. The c index was used to evaluate discrimination. Results: Of all the individual biomarkers examined, CRP emerged as the only independent single predictor of ischemic stroke (adjusted odds ratio comparing Quartile4 v Quartile1 = 1.64, 95% confidence interval: 1.15-2.32, P = .01) after adjustment for other biomarkers and standard stroke risk factors. The BRS identified a gradient of increasing stroke risk with a greater number of elevated inflammatory/hemostasis biomarkers, and improved the c index significantly compared with standard stroke risk factors (P = .02). Among the subset of individuals who met current criteria for high-risk levels of CRP (>3.0 mg/L), the BRS defined an approximately 2-fold gradient of risk. We found no evidence for a relationship between stroke and levels of E-selectin, fibrinogen, tumor necrosis factor-α, vascular cell adhesion molecule-1, prothrombin fragment 1+2, Factor VIIC, or plasminogen activator inhibitor-1 antigen (P > .15). Discussion: The findings support the further exploration of multiple biomarker panels to develop approaches for stratifying an individual's risk of stroke.

Original languageEnglish (US)
Pages (from-to)344-355
Number of pages12
JournalJournal of Stroke and Cerebrovascular Diseases
Volume17
Issue number6
DOIs
StatePublished - Nov 1 2008

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Keywords

  • Stroke
  • epidemiology
  • women

ASJC Scopus subject areas

  • Surgery
  • Rehabilitation
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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