Inflammation and hemostasis biomarkers for predicting stroke in postmenopausal women: the Women's Health Initiative Observational Study

J Stroke Cerebrovasc Dis. 2008 Nov-Dec;17(6):344-55. doi: 10.1016/j.jstrokecerebrovasdis.2008.04.006.

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 Quartile(4)v Quartile(1) = 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-alpha, 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Biomarkers
  • C-Reactive Protein / analysis
  • C-Reactive Protein / metabolism
  • Case-Control Studies
  • Comorbidity
  • Data Interpretation, Statistical
  • Female
  • Hemostatic Disorders / diagnosis*
  • Hemostatic Disorders / epidemiology
  • Homocysteine / analysis
  • Homocysteine / blood
  • Humans
  • Incidence
  • Inflammation / diagnosis*
  • Inflammation / epidemiology
  • Interleukin-6 / analysis
  • Interleukin-6 / blood
  • Leukocyte Count
  • Middle Aged
  • Neopterin / analysis
  • Neopterin / blood
  • Postmenopause / blood*
  • Predictive Value of Tests
  • Risk Factors
  • Stroke / diagnosis*
  • Stroke / epidemiology
  • Tissue Plasminogen Activator / analysis
  • Tissue Plasminogen Activator / blood

Substances

  • Biomarkers
  • Interleukin-6
  • Homocysteine
  • Neopterin
  • C-Reactive Protein
  • Tissue Plasminogen Activator