We propose to investigate the association of pericardial fat with subclinical and clinical measures of coronary heart disease. Visceral fat is more detrimental than subcutaneous fat with regard to coronary heart disease. Pericardial fat, a novel fat depot around the heart with properties like visceral fat, may be especially detrimental due to local lipotoxicity and inflammation in coronary arteries. However, epidemiologic evidence is lacking. We hypothesize that increased amounts of pericardial fat accelerates the atherosclerotic process in coronary arteries and that pericardial fat is the primary contributor to the development of coronary heart disease among commonly assessed regional fat depots. The proposed study is an ancillary study to the Multi-Ethnic Study of Atherosclerosis (MESA). We will examine 1) the association of pericardial fat with subclinical coronary heart disease (calcified coronary plaque measured by computed tomography (CT)) at baseline, 2) the association of baseline and changes in pericardial fat with changes in calcified coronary plaque over three years, and 3) the risk of clinical coronary heart disease associated with pericardial fat in a 6 year follow-up among 6,814 white, black, Hispanic, and Asian American men and women, age 45-84. The measures of calcified coronary plaque and clinical coronary heart disease will be obtained from the existing MESA database. We will measure the volume of pericardial fat using the existing CT scans in MESA, from which calcified coronary plaque was quantified, at baseline (N=6,814) and a follow-up exam (N=6,000) three years later. The MESA cohort, with extensive longitudinal assessments of cardiovascular disease, is an ideal study population for assessing the role of pericardial fat in the development of coronary heart disease. The diversified study population will also provide ethnicity-specific information on the relationships to be examined. More importantly, the existing CT scans enable us to cost-effectively measure pericardial fat without extra burden to participants. The recent report of the NIH Obesity Research Task Force indicates that elucidation of differences in various fat depots with regard to their roles in obesity-associated diseases will further our understanding of the link between obesity and its health consequences, which may yield new targets for therapeutics to disrupt this link. Given the health impact of coronary heart disease, there is a pressing need to examine the relationship between pericardial fat and coronary heart disease.

R01HL085323

2006-08-21

2012-05-31