RISK FACTORS IN EARLY HUMAN ATHEROGENESIS

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This collaborative project will collect arteries and risk factor data from 1400 young persons 15-34 years of age who die from trauma and are autopsied in medical examiners' laboratories. The data will be analyzed t determine the associations of the risk factors for adult atherosclerotic disease with the various lesions of atherosclerosis which appear during this age period. These cases will supplement 1800 cases that are being collected in the ongoing study Pathobiological Determinants of Atherosclerosis in Youth. The major purposes of the additional cases are to (1) obtain an adequate number of cases of women; (2) increase the power of the study to detect associations of risk factors with raised lesions, which begin to appear in this age group; and (3) increase the power to detect genetic effects on atherosclerosis. Aortic and coronary artery lesions are measured by visual estimation and by gross and histologic morphometry using computerized image analysis. Risk factor measurements include cholesterol and lipoprotein cholesterol concentration in postmortem serum; thiocyanate in postmortem serum as a marker for smoking; blood pressure by wall thickness of renal arteries and arterioles; and DNA polymorphism by analysis of liver DNA. Collection of cases is performed at participating centers in cooperation with local medical examiners; processing of arteries, blood, liver, and other tissue is carried out in central laboratories, and data are managed by a statistical center. The research unit at Louisiana State University Medical Center (LSUMC) will 1. Describe, by gross pathology and chemical techniques, the atherosclerotic lesions to determine characteristics of lesions observed. 2. Determine relationships of classical risk factors, as measured postmortem, to atherosclerotic lesions by applying methods to: a) estimate blood pressure through measurements of renal arteriolar changes in conjunction with heart weight; b) estimate serum cholesterol, HDL-C, apoA-1, apoB and Lp(a) levels; c) differentiate smokers and non-smokers by measuring thiocyanate levels; d) evaluate diabetic status through measurements of glycosylated hemoglobin; e) estimate dietary and metabolic factors through evaluation of adipose tissue fatty acids. 3. Determine markers which may help in understanding white-black, male-female differences in development of atherosclerosis. This study should provide detailed quantitative information concerning association of risk factors with arterial lesions in this important age group.