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(Hypertension. 2008;51:1115.)
© 2008 American Heart Association, Inc.

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Lipoprotein-Associated Phospholipase A₂, Hormone Use, and the Risk of Ischemic Stroke in Postmenopausal Women

Sylvia Wassertheil-Smoller; Charles Kooperberg; Aileen P. McGinn; Robert C. Kaplan; Judith Hsia; Susan L. Hendrix; JoAnn E. Manson; Jeffrey S. Berger; Lewis H. Kuller; Matthew A. Allison; Alison E. Baird

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.

Correspondence to Sylvia Wassertheil-Smoller, Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Ave, Belfer 1312A, Bronx, NY 10461. E-mail smoller{at}aecom.yu.edu

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.

Key Words: stroke • lipoprotein-associated phospholipase A₂ • Lp-PLA₂ • postmenopausal women • stroke biomarkers • hormones • Women’s Health Initiative • WHI

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