Mediators of Atherosclerosis in South Asians in America

South Asians (individuals from India, Pakistan, Bangladesh, Nepal, and Sri Lanka) have higher rates of heart disease than other race/ethnic groups that are not fully explained by their higher prevalence of diabetes or other traditional cardiovascular risk factors. Coronary artery calcium (CAC) is a measure of atherosclerosis which improves heart disease risk prediction for many race/ethnic groups. More recently, progression of CAC and plaque calcium density have also been found to be independently associated with cardiovascular disease (CVD) events. No existing studies have examined whether CAC, CAC progression or novel coronary plaque characteristics help to explain the high incidence of heart disease in South Asians. The NIH/NHLBI has supported the creation of a unique South Asian cohort called the Mediators of Atherosclerosis in South Asians Living in America (MASALA study) to establish the prevalence of subclinical atherosclerosis and cardiovascular risk factors (parent R01 Aims 1 and 2) and to begin to determine the prognostic significance of subclinical atherosclerosis for CVD events (exploratory Aim 3) in this high risk population. The objective of the proposed study is to leverage the MASALA cohort baseline data by adding novel measures of coronary plaque and measure progression of plaque characteristics after 4 years of follow-up to investigate the epidemiology, etiology and natural history of heart disease in South Asians. Our central hypotheses are that there will be greater coronary plaque burden based on these advanced plaque characteristics and faster plaque progression which will help explain the higher incidence of coronary heart disease in South Asians. In this renewal of the MASALA study grant, we propose to measure advanced coronary plaque characteristics (calcium density, plaque localization and distribution), determine the progression of coronary plaque and identify the key predictors of coronary and cardiovascular disease events among approximately 875 South Asians. The specific aims of this study are to: 1. Determine the prevalence and correlates of advanced coronary plaque characteristics among South Asians, and compare the prevalence and correlates with the four MESA race/ethnic groups. 2. Investigate the rate of CAC and advanced plaque characteristic progression among South Asians after approximately 4 years of follow-up, and compare annualized progression rates to the four MESA race/ethnic groups. 3. Determine whether CAC and coronary plaque characteristics are associated with incident coronary heart disease and total CVD events among South Asians, and whether these associations are stronger among South Asians than the four MESA race/ethnic groups.