Prospective data derived almost exclusively from men indicate that several plasma and genetic markers of thrombosis exist and that affected individuals are at markedly increased risk of future myocardial infarction (MI). However, data describing novel markers for coronary thrombosis among women are scant. The investigators therefore propose to comprehensively evaluate a series of thrombotic, inflammatory, and genetic markers for MI among participants in the Women's Health Initiative Observational Study (WHI-OS), a prospective cohort study of over 90,000 ethnically representative post-menopausal American women aged 50-79 years. Employing a prospective nested case-control design, they will assay baseline plasma and buffy coat samples for nine markers of increased thrombotic potential (tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), total plasma homocysteine, prothrombin fragment F1+2, D-dimer, APC-R, C-reactive protein, interleukin-6, and sICAM-1) to determine whether elevations of these parameters lead to future MI or coronary death. They will also explore common genetic polymorphisms in the tPA, PAI-1, MTHFR, thrombomodulin, prothrombin, and factor V genes so that both inherited and environmental determinants of coronary thrombosis in women can simultaneously be evaluated. Case subjects will be WHI-OS participants who were free of cardiovascular disease at study entry and subsequently developed a documented MI or coronary death during follow-up (N = 650). Control subjects will be selected from study participants who remained free of disease during follow-up; controls will be 1:1 matched to cases by age, smoking status, ethnicity, and follow-up time. Data on usual risk factors, hormone replacement therapy, and standard lipid profiles will be used to evaluate for potential confounding and effect modification. The investigators note that the analyses will take advantage of a unique and unprecedented blood bank from a well-characterized, ethnically diverse, large-scale cohort of post-menopausal women with ongoing follow-up and high quality endpoint verification, thereby providing an efficient way to critically evaluate the hypothesized roles of hemostasis thrombosis and inflammation as risk factors for future MI and coronary death among American women.
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