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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R10)
Project #
5R10HL033746-02
Application #
3433019
Study Section
(SRC)
Project Start
1985-06-01
Project End
1992-07-31
Budget Start
1986-06-01
Budget End
1987-02-28
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Louisiana State University Hsc New Orleans
Department
Type
School of Medicine & Dentistry
DUNS #
782627814
City
New Orleans
State
LA
Country
United States
Zip Code
70112
McMahan, C Alex; Gidding, Samuel S; Malcom, Gray T et al. (2007) Comparison of coronary heart disease risk factors in autopsied young adults from the PDAY Study with living young adults from the CARDIA study. Cardiovasc Pathol 16:151-8
Zieske, Arthur W; McMahan, C Alex; McGill Jr, Henry C et al. (2005) Smoking is associated with advanced coronary atherosclerosis in youth. Atherosclerosis 180:87-92
Zieske, Arthur W; Tracy, Russell P; McMahan, C Alex et al. (2005) Elevated serum C-reactive protein levels and advanced atherosclerosis in youth. Arterioscler Thromb Vasc Biol 25:1237-43
Scheer, W Douglas; Boudreau, Donald A; Hixson, James E et al. (2005) ACE insert/delete polymorphism and atherosclerosis. Atherosclerosis 178:241-7
McGill Jr, Henry C; McMahan, C Alex; Herderick, Edward E et al. (2002) Obesity accelerates the progression of coronary atherosclerosis in young men. Circulation 105:2712-8
Homma, S; Ishii, T; Malcom, G T et al. (2001) Histopathological modifications of early atherosclerotic lesions by risk factors--findings in PDAY subjects. Atherosclerosis 156:389-99
McGill Jr, H C; McMahan, C A; Zieske, A W et al. (2001) Effects of nonlipid risk factors on atherosclerosis in youth with a favorable lipoprotein profile. Circulation 103:1546-50
Ishikawa, Y; Ishii, T; Akasaka, Y et al. (2001) Immunolocalization of apolipoproteins in aortic atherosclerosis in American youths and young adults: findings from the PDAY study. Atherosclerosis 158:215-25
Zieske, A W; Malcom, G T; Strong, J P (2000) Pathobiological determinants of atherosclerosis in youth (PDAY) cardiovascular specimen and data library. J La State Med Soc 152:296-301
Strong, J P; Malcom, G T; Oalmann, M C (1995) Environmental and genetic risk factors in early human atherogenesis: lessons from the PDAY study. Pathobiological Determinants of Atherosclerosis in Youth. Pathol Int 45:403-8

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