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. This suggests that the disease itself, presumably via chronic inflammation, is an important risk factor for accelerated CVD. Our hypothesis is that RA constitutes an independent risk factor for accelerated CVD. We hypothesize further that inflammation due to RA promotes and exacerbates CVD, independent of conventional CV risk factors. This application is an ancillary application to the Multi-Ethnic Study of Atherosclerosis (MESA), a unique prospective multi-center study to identify risk factors for incident and progressive subclinical and clinical CVD in the general population. We will recruit 200 RA patients followed in the Johns Hopkins Arthritis Center and compare the prevalence and progression of subclinical CVD in this population to the 1066 MESA participants, who are not RA patients, from the Hopkins Field Center. The degree to which inflammation contributes to increased CVD in IRA patients will be examined, after adjusting for conventional CVD risk factors.
Our specific aims are as follows: ? ? Specific Aim 1: In a cross-sectional analysis, we will assess and compare the distributions of a measure of atherosclerosis (coronary calcium by computed tomography) and measures of left ventricular (LV) structure and function (by magnetic resonance imaging) between IRA patients and controls. We will determine whether differences between the groups in coronary calcium and LV dysfunction are explained by markers of inflammation in RA. ? ? Specific Aim 2: In a prospective analysis, we will compare the changes in coronary calcium over three years between RA patients and controls. We will determine the degree to which elevated 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 CVD 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. ? ? RA is a chronic inflammatory disease that can be considered to be a model of accelerated CV disease. Lessons learned from the study of CVD in RA may promote the fundamental understanding of inflammatory mechanisms of CVD. ? ?
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