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 to determine the association of the risk factors for adult atherosclerotic disease with the various lesions of atherosclerosis which appear during this age period. These cases will supplement the 1800 cases 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 polymorphisms by medical examiners; processing of arteries, blood liver, and other tissue is carried out in central laboratories; and data are managed by a statistical center. This application also proposes to investigate the role of biogenic amines in the progression of atherosclerosis: Vascular spasm has been suggested as a possible mechanism of endothelial injury in the presence or absence of established risk factors that may induce atherosclerosis. It has been shown that histamine content of atherosclerotic coronary arteries is increased and vessels are hyperreactive to histamine in vitro. We have observed that early plaque progression correlates with increasing histamine content and mast cell collection in the adventitia in young males. We propose to extend this observation to the study of young women (black and white). We will measure total histamine, serotonin, and catecholamine content in vascular segments (aorta and coronary arteries) and in the serum. We will also correlate the biogenic amine concentration, especially histamine content, to the presence of mast cells and their relationship to the type, extent of atherosclerosis, and risk factor data.
