The role of procoagulant hemostatic factors in atherogenesis has been enigmatic. Increased plasma concentrations of procoagulants in youth may reflect early plaque development, and rising levels of procoagulants may mirror the severity and extent of vessel wall involvement by the disease. Insight into these processes may be gained from a longitudinal study of clotting factors in subjects beginning at the earliest stages of atherosclerosis (prior to age 30), and continuing through ages 40 and 50, when subclinical and clinical evidence of disease may be recognized. Such individuals with disease in middle age may have had elevated concentrations of procoagulants in youth and a greater rate of increase in levels over time as compared to those without evidence of atherosclerosis. A unique opportunity to test this hypothesis is presented by the CARDIA study, which for the past twenty years has serially examined a cohort of men and women who were ages 18-30 at inception. In an ancillary study, we measured levels of fibrinogen, factor VII, factor VIII, and von Willebrand factor in blood samples collected 1990-91 (Year 5) and 1992-93 (Year 7). In these Year 5 and 7 samples, obtained when subjects were in their 20's and 30's, cross-sectional analyses revealed that fibrinogen was higher in women than in men, factor VIII and von Willebrand factor were higher in blacks than in whites, and associations were reported of factor VII with cholesterol and triglycerides, and fibrinogen with body mass index, cholesterol, and LDL-cholesterol. Certain correlations were confined to specific sex/race groups, such as fibrinogen with blood pressure, triglycerides, and cigarette smoking in white males. These associations between established risk factors for atherosclerosis and procoagulants suggest common links to atherogenesis. We now wish to extend our previous study to the year 20 examination (2005-6). We shall examine the associations of rate of change in hemostatic factors with clinical and laboratory evidence of atheromatous disease, such as coronary calcification and increased carotid intimal/medial thickness, as well as changes in CARDIA measured lifestyle factors such as diet, physical activity, body mass index, and smoking, and the development of hypertension, hyperlipidemia, and diabetes. In addition, we shall assess whether changes in factor VII and factor VIII coagulant activities over time are associated with particular factor VII or factor VIII haplotypes. Study of CARDIA participants offers a unique opportunity to examine longitudinal changes in hemostatic components linked to atherothrombosis and to correlate their evolution with that of other recognized coronary risk factors during the critical period preceding clinical manifestations of disease.
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