Epidemiologic studies have examined factor VII and fibrinogen, two components of the natural hemostatic mechanism. In the Northwick Park Study (139), factor VII coagulant activity was shown to correlate with cardiovascular mortality. Fibrinogen also corre lated strongly, as did factor VIII, although less strongly than other hemostatic markers. The potential importance of factor VIII, however, is strengthened by the low incidence of atherosclerotic coronary artery disease in hemophiliacs. In the Atherosclerosis Risk Communities study, which included 15,800 individuals from four diverse areas in the United States (140), baseline measurements of factor VIII and von Willebrand factor were performed to determine their relationship to the development of coronary atherosclerosis. In a univariate analysis, both factors were positively associated with plasma triglycerides and negatively associated with high-density lipoprotein cholesterol.
As in the Northwick Park Study, several large-scale epidemiologic studies have identified an association between both factor VIII activity and fibrinogen and the incidence of atherosclerotic coronary artery disease. In the Framingham Study (141), fibrinogen and coronary disease were strongly correlated, and the association was stronger than was the association between cholesterol (and other standard risk factors) and coronary disease.
Involvement of the fibrinolytic system in the development of acute coronary syndromes has recently led investigative groups to explore several markers as predictors of thrombotic cardiovascular events. In a study of 213 consecutive patients with angina pectoris and angiographically confirmed coronary artery disease, tPA mass concentration was the only laboratory marker significantly associated with mortality at a mean follow-up of 7 yr (142).
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