on February 7, 2008
Published online before print February 7, 2008, doi: 10.1161/HYPERTENSIONAHA.107.103721
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Submitted on October 23, 2007
From the Department of Epidemiology and Population Health (S.W-S., A.P.M., R.C.K.), Albert Einstein College of Medicine, Bronx, NY; Fred Hutchinson Cancer Research Center (C.K.), Seattle, Wash; AstraZeneca (J.H.), Wilmington, Del; Department of Obstetrics and Gynecology (S.L.H.), Wayne State University School of Medicine/Hutzel Women’s Hospital, Detroit, Mich; Division of Preventive Medicine (J.E.M.), Brigham & Women’s Hospital, Harvard Medical School, Boston, Mass; Department of Cardiovascular Medicine (J.S.B.), Duke University, Durham, NC; Department of Epidemiology (L.H.K.), University of Pittsburgh School of Public Health, Pa; Department of Family and Preventive Medicine (M.A.A.), University of California at San Diego; and the Stroke Neuroscience Unit (A.E.B.), National Institute of Neurological Disorders and Stroke, Bethesda, Md. * To whom correspondence should be addressed. E-mail: smoller{at}aecom.yu.edu.
Abstract—Few studies have investigated the role of elevated lipoprotein-associated phospholipase A2 (Lp-PLA2) with stroke risk, and those that have are based on small numbers of strokes. No study has evaluated the effect of hormone therapy use on the association of Lp-PLA2 and stroke. We assessed the relationship between Lp-PLA2 and the risk of incident ischemic stroke in 929 stroke patients and 935 control subjects in the Hormones and Biomarkers Predicting Stroke Study, a nested case-control study from the Women’s Health Initiative Observational Study. Mean (SD) levels of Lp-PLA2 were significantly higher among case subjects (309.0 [97.1]) than control subjects (296.3 [87.3]; P<0.01). Odds ratio for ischemic stroke for the highest quartile of Lp-PLA2, compared with lowest, controlling for multiple covariates, was 1.08 (95% CI: 0.75 to 1.55). However, among 1137 nonusers of hormone therapy at baseline, the corresponding odds ratio was 1.55 (95% CI: 1.05 to 2.28),whereas there was no significant association among 737 hormone users (odds ratio: 0.70; 95% CI: 0.42 to 1.17; P for interaction=0.055). Moreover, among nonhormone users, women with high C-reactive protein and high Lp-PLA2 had more than twice the risk of stroke (odds ratio: 2.26; 95% CI: 1.55 to 3.35) compared with women low levels in both biomarkers. Furthermore, different stroke cases were identified as high risk by Lp-PLA2 rather than by C-reactive protein. Lp-PLA2 was associated with incident ischemic stroke independently of C-reactive protein and traditional cardiovascular risk factors among nonusers of hormone therapy with highest risk in those who had both high C-reactive protein and high Lp-PLA2.
Revised on December 4, 2007
Lipoprotein-Associated Phospholipase A2, Hormone Use, and the Risk of Ischemic Stroke in Postmenopausal Women
Sylvia Wassertheil-Smoller*;
Key words: stroke • lipoprotein-associated phospholipase A2 • Lp-PLA2 • postmenopausal women • stroke biomarkers • hormones • Women’s Health Initiative • WHI
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