The proposed research is a multidisciplinary, multicenter, collaborative, prospective study to determine if selected circulating blood factors that reflect enhanced thrombogenesis, measured 2 months after an index myocardial infarction, are associated with an increased incidence of recurrent coronary events (cardiac death or non-fatal myocardial reinfarction) during a 1 1/2-3 1/2 year follow-up period. One thousand three hundred patients hospitalized with a myocardial infarction will be enrolled from 10 geographically dispersed centers. Five thrombogenic- related blood factors will be quantitated, and they form the centerpiece of this study: 1) lipoprotein(a) [Lp(a)] - a quantitative genetic factor that contains apololipoprotein B, has a structural homology to plasminogen, interferes with intrinsic thrombolytic activity, and represents a crossover link in the thrombogenesis/atherogenesis hypothesis; 2) soluble fibrin - a system indicator of coagulation activity in the ongoing conversion of fibrinogen to insoluble fibrin strands; 3) plasminogen activator inhibitor-1 (PAI-1) - an important regulator of the fibrinolytic system, it interferes with intrinsic t-PA activity; 4) coagulation Factor VII -high levels lead to increased thrombogenesis and have been associated with an increased risk of ischemic heart disease; and- 5) von Willebrand factor - it binds to platelet glycoproteins, contributes to local thrombus formation, and it is elevated in patients at increased risk of coronary thrombosis. The primary analysis will utilize a time-dependent survivors hip model (Cox regression) to determine the presence or absence of an association between one or more of these factors and subsequent thrombotic-related coronary events. Secondary objectives of this study are: 1) to determine if there is a statistical association between the thrombogenic factors and conventional hematologic/lipid parameters, and to evaluate their interactions regarding coronary events; and 2) to determine if thrombogenic factors have uniform effects on coronary event rates across various subgroups. The findings from this study should provide promising clues about the thrombogenic factors involved in the progression of vascular disease and should help identify high risk coronary patients who might benefit from focused therapies to counter thrombogenic mechanisms.
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