Drs. Ridker and colleagues comprehensively evaluated a series of thrombotic, inflammatory, and genetic markers for myocardial infarction (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 assayed 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 led to future MI or coronary death. They also explored 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 could simultaneously be evaluated. Case subjects were 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 were selected from study participants who remained free of disease during follow-up; controls were 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 were used to evaluate for potential confounding and effect modification. The analyses took 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.