Associations between sex steroid hormones, hemostatic factors and atherosclerosis

Numerous cardiovascular risk factors have been identified, and lifestyle and drug interventions are available for modification of many of these risk factors. Nevertheless, cardiovascular disease remains the leading cause of death among both men and women in the industrialized world. This has spurred interest in identifying novel risk factors and markers in order to reduce cardiovascular disease morbidity and mortality.;Chapter 1 of this dissertation explores existing knowledge regarding hemostatic factors (factor VII, fibrinogen, tPA, PAI-1 and D-dimer), and how they relate to atherosclerosis measured by angiography, ultrasonography, computed tomography, or ankle/brachial blood pressure ratio. Study results from 23 relevant, published, original research papers were summarized and discussed.;Data analyses based on the Estrogen in the Prevention of Atherosclerosis Trial (EPAT) are included. Chapter 2 analyzes the effect of postmenopausal hormone therapy on levels of hemostatic factors (those listed above, plus albumin) and the relationship between these factors and progression of subclinical atherosclerosis in 186 postmenopausal women. Significant treatment effects on hemostatic factors were found, but no hemostatic factor was associated with CIMT progression.;Chapter 3 compares circulating levels of estrone, estradiol, free estradiol, testosterone, free testosterone, androstenedione, DHEA and SHBG in 179 women from EPAT. Levels of tPA, PAI-1, albumin, and factor VII were related to circulating levels of estrogens in a combined sample of treated and untreated women, but associations were not independent of treatment group. tPA and PAI-1 were related to circulating SHBG independent of treatment group.;Chapter 4 of this dissertation is a grant proposal, Hemostatic Supplement to the ELITE Trial. The Early versus Late Intervention Trial with Estrogen (ELITE) is a randomized, double-blind, placebo-controlled trial of 17-beta estradiol. This supplement will study the effect of hormone therapy on hemostatic factors (factor VII, fibrinogen, tPA antigen, tPA activity, PAI-1, soluble fibrin monomer, global fibrinolytic capacity, and von Willebrand factor), the associations between circulating hormones and hemostatic factors, and the relations between hemostatic factors and atherosclerosis. It will analyze how these relations differ in four subgroups of women studied in ELITE, and will add to our understanding of the role of hemostatic factors in atherosclerosis.