Cardiovascular disease (CVD) is the leading cause of death in the United States. Blacks are affected disproportionately by CVD;age-adjusted coronary heart disease death rates are 29% higher for blacks than for whites. This disparity in risk is only partially explained by racial differences in prevalences of traditional and emerging CVD risk factors. Despite having higher rates of CVD, blacks are less likely than whites to have severe obstructive coronary artery atherosclerosis and coronary artery calcium. This observation is counterintuitive;the less diffuse coronary artery calcification and obstruction observed in blacks would be expected to be associated with a lower prevalence of CVD risk factors and a lower incidence of CVD events, neither of which is observed. In the face of these inconsistencies, we hypothesize that as compared to whites, blacks are more likely to develop vulnerable atherosclerotic plaques that are associated with acute CVD. Our preliminary investigations support this hypothesis by demonstrating that black race is independently associated with less calcified coronary artery plaques, greater positive arterial remodeling, and more endothelial dysfunction. Racial differences in these arterial characteristics, which are associated with increased plaque vulnerability, may be explained by our observations which indicate that blacks have higher levels of circulating modulators of plaque vulnerability. Therefore, the goal of the proposed study is to prospectively investigate race-related differences in the pathophysiology of atherosclerotic plaques in our extensively characterized cohort of 2,000 subjects (43% black) in our Heart SCORE study that has collected a wealth of biological data and plasma over a follow-up period of 6 years. This proposal will compare the prevalence of vulnerable atherosclerotic plaque between blacks and whites who are enrolled in Heart SCORE by using microbubble contrast-enhanced B-mode ultrasonography to quantify carotid artery adventitial vasa vasorum density, which correlates with plaque vulnerability, and to accurately measure intimal-medial thickness of both the far and near walls of the carotid artery (cIMT). The proposed study will also evaluate race-related differences in distributions of modulators of plaque vulnerability, such as inflammatory mediators, matrix metalloproteinases, and markers of endothelial cell activation, and in the predictive value of these modulators for long-term risk of adverse CVD events. Moreover, the study will assess the predictive values of vasa vasorum density and modulators of plaque vulnerability for cIMT (including by race). We anticipate that our findings will demonstrate a link between race, vasa vasorum density, atherosclerosis modulators, and CVD outcome. This finding would suggest that racial disparities in CVD are related, at least in part, to race-related differences in the pathophysiology of atheroscleros

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Clinical and Integrative Cardiovascular Sciences Study Section (CICS)
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Harman, Jane
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University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
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