This proposal is designed as part of an investigator initiated multi-center study entitled """"""""Pathobiological Determinants of Atherosclerosis in Youth"""""""". Autopsies of persons aged 15-34 who die from accidents, suicides, and homicides, performed at multiple centers in the United States, will provide samples of coronary arteries, aortas, blood and other tissues that can be evaluated using a standard protocol. This research unit, composed of three central laboratories (lipid biochemistry center, coronary heart disease risk factors center, and center for processing and evaluating grossly visible lesions in arterial segments), would provide basic data for comparisons and interpretation of findings from the multiple centers.
Our specific aims as related to the questions posed in the research plan for the multi-center study are: 1. Describe, by gross pathology techniques, the atherosclerotic lesions to determine characteristics of lesions observed in later childhood which may indicate progression into those seen in young adults. 2. Identify grossly visible features of arterial lesions which correlate with this progression and the factors responsible for these signs of progression. 3. Determine relationships of classical risk factors, as measured postmortem, to atherosclerotic lesions in children, adolescents, and young adults by continuing to develop, test and apply methods to: a) estimate blood pressure through measurements of renal arteriolar changes in conjunction with heart weight and body measurements; b) estimate serum cholesterol, HDL-C, apoA, apoB, Lp(a), apoE levels through evaluation of postmortem serum samples; c) differentiate smokers and non-smokers by measuring thiocyanate levels; d) evaluate diabetic status through measurements of glycosylated hemoglobin; e) evaluate obesity status by measurements of weight, height, trunk length, and thickness of panniculus adiposus; f) estimate dietary and metabolic factors through evaluation of adipose tissue fatty acids. 4. Define by gross evaluation and microscopic morphometry the features of """"""""transitional lesions"""""""". 5. Determine markers which may help in understanding white-black, male-female differences in development and progression of atherosclerosis. 6. Identify morphological determinants or markers which might be associated with the decline of CHD mortality in the USA and determine if they are associated with the risk factors determined postmortem. This study of the """"""""Pathobiological Determinants of Atherosclerosis in Youth"""""""" should provide detailed quantitative information concerning association of risk factors with arterial lesions in this important age group.
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