Inflammation and Atherosclerosis in Rheumatoid Arthritis

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DESCRIPTION (provided by applicant): Atherosclerosis and rheumatoid arthritis (RA) are two inflammatory diseases with marked similarities in pathobiology. In the general population, individuals with elevated inflammatory biomarkers (e.g. C- reactive protein, CRP) have increased CV events. Patients with RA have chronic elevations in CRP and other inflammatory markers that are usually higher than the levels associated with increased CV risk in the general population. Indeed, RA patients have accelerated atherosclerosis and increased CV mortality not explained by traditional cardiac risk factors but associated with chronic inflammation. However, the mechanisms by which systemic inflammation leads to atherosclerosis are not well characterized in RA. Moreover, current treatment strategies of RA largely target joint symptoms rather than systemic inflammation, potentially leaving patients at increased risk for CVD. In animal models and in human diseases, inflammation induces pro-atherogenic lipoprotein abnormalities, nitro-oxidative stress and endothelial dysfunction, which are pivotal in the development of atherosclerosis. However, studies of these pro-atherogenic markers in the full spectrum of inflammation and clinical manifestations in RA are missing. We hypothesize that inflammatory markers will be more strongly associated with atherogenic changes in RA patients than any clinical measure of disease activity. This hypothesis will be tested with a cross-sectional study of patients in the UCSF RA cohort. Aim 1 will characterize atherogenic changes across the spectrum of RA disease activity, specifically measuring endothelial function by flow-mediated vasodilation, markers of nitro-oxidative stress, and pro-atherogenic lipoproteins. Aim 2 will identify factors associated with these atherogenic changes across the spectrum of RA disease activity, specifically focusing on the association between inflammatory markers, FMD and pro-atherogenic lipoprotein abnormalities. Rheumatoid arthritis patients have increased inflammation in their bodies, which leads to atherosclerosis, or plaque build-up in blood vessels, the leading cause of death in the United States. By studying inflammation and atherosclerosis in RA, we can understand better what causes clogged arteries in general, as well as improve the standards of treatment for RA to prolong lives in addition to just alleviating symptoms.