The overall goal of this project are to define the pathophysiologic mechanisms through which lipoprotein (a) (Lp(a)) acts as a risk factor for coronary disease in black Americans, and to delineate the importance of Lp(a) in blacks by contrasting these mechanisms of Lp(a) action in blacks versus whites. To meet this goal, the project has several specific aims. First, the presence, extent, and location of objectively-defined coronary disease will be compared in blacks versus whites. Second, (a) levels, phenotypes, and genotypes will be correlated with the presence and extent coronary atherosclerosis, and the strengths of these correlations will be compared blacks versus whites. Third, Lp(a) levels, phenotypes, and genotypes will be correlated in blacks versus whites with the history of myocardial infarction, adjusted for the presence and extent of coronary atherosclerosis and other coagulation factors. Fourth, the association between Lp(a) and coronary atherosclerosis/ myocardial infarction will be tested for independence by development of multivariate risk factor models. Fifth, Lp(a) levels, phenotypes or genotypes will be examined for synergism with other risk factors. Finally, the role of Lp(a) as a determinant of prognosis will be examined by the follow-up of both cohorts of patients over the course of the study. To accomplish these specific aims, two groups of patients undergoing coronary arteriography will be recruited, one group of black patients (300 men and 200 women) from the Harlem Hospital and a second group of white patients (300 men and 200 women) from the M.I. Bassett Hospital. The presence and extent of coronary disease in these 1000 patients will be defined by masked readings and densitometric quantitation of the coronary arteriograms by two panels of cardiologists. Prior to arteriography, each patient will have clinical and risk factor data collected through an interview and brief physical examination. Blood samples will be collected for state-of-the-art lipid and lipoprotein analyses (M.I. Bassett Lipid Laboratory), LP(a) phenotypes and genotypes (Laboratory of Biochemical Genetics and Metabolism of Rockefeller University), and coagulation and fibrinolysis factors (University of Vermont Laboratory for Clinical Biochemistry Research). Data analyses for case-control studies will be used to test major study hypotheses. The results of this study should establish Lp(a) as a major risk factor in blacks, and elucidate mechanisms determining its elevated levels in blacks, and the way these elevations cause coronary disease.
