Inflammation and Cardiovascular Disease in RA

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DESCRIPTION (provided by applicant): Cardiovascular disease (CVD) is a major cause of morbidity and mortality in rheumatoid arthritis (RA). CV-related deaths, congestive heart failure, and acute CV events are increased 2-4 fold in RA patients compared to matched controls, but the prevalence of conventional risk factors for CVD is not increased. We hypothesize that inflammation due to RA promotes and exacerbates CVD, independent of conventional CV risk factors. This application is an ancillary proposal to the Multi-Ethnic Study of Atherosclerosis (MESA). We will compare the prevalence and progression of subclinical CVD in 200 RA patients to 1066 non-RA MESA participants from the Hopkins MESA Field Center. The degree to which inflammation contributes to increased CVD in RA patients will be examined, after adjusting for conventional CV risk factors. Our specific aims are as follows: Specific Aim 1. In a cross-sectional analysis we will compare a measure of atherosclerosis (coronary calcium) and measures of left ventricular (LV) dysfunction (by magnetic resonance imaging) between RA patients and controls. We will determine whether differences between the groups in coronary calcium and LV dysfunction are explained by serum markers of inflammation in RA (e.g., CRP, interleukin-6, soluble adhesion molecules). Specific Aim 2. In a prospective analysis, we will compare the changes in coronary calcium between RA patients and controls. We will determine the degree to which elevated serum markers of inflammation contribute to differences in progression of coronary calcium. Specific Aim 3. We will assess the associations of various markers of inflammation and disease activity/severity, as well as conventional CV risk factors, with coronary calcium and LV dysfunction at baseline and over three years, among RA patients. Particularly, the potential dose-response relationships of various markers of inflammation and disease activity/severity to coronary calcium and LV dysfunction will be examined.