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


CONCLUSIONS
The findings support the further exploration of multiple biomarker panels to develop approaches for stratifying an individual's risk of stroke.
Kaplan
Robert C
RC
Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
McGinn
Aileen P
AP
Baird
Alison E
AE
Hendrix
Susan L
SL
Kooperberg
Charles
C
Lynch
John
J
Rosenbaum
Daniel M
DM
Johnson
Karen C
KC
Strickler
Howard D
HD
Wassertheil-Smoller
Sylvia
S
D000368:Aged; D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D016022:Case-Control Studies; D015897:Comorbidity; D003627:Data Interpretation, Statistical; D005260:Female; D020141:Hemostatic Disorders / Q000175:diagnosis* / Q000453:epidemiology; D006710:Homocysteine / Q000032:analysis / Q000097:blood; D006801:Humans; D015994:Incidence; D007249:Inflammation / Q000175:diagnosis* / Q000453:epidemiology; D015850:Interleukin-6 / Q000032:analysis / Q000097:blood; D007958:Leukocyte Count; D008875:Middle Aged; D019798:Neopterin / Q000032:analysis / Q000097:blood; D017698:Postmenopause / Q000097:blood*; D011237:Predictive Value of Tests; D012307:Risk Factors; D020521:Stroke / Q000175:diagnosis* / Q000453:epidemiology; D010959:Tissue Plasminogen Activator / Q000032:analysis / Q000097:blood
D015415:Biomarkers; D015850:Interleukin-6; D006710:Homocysteine; D019798:Neopterin; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator