Atherosclerosis in Rheumatoid Arthritis: Role of Inflammation, Lipoproteins, and Endothelial Dysfunction

In the general population, individuals with elevated inflammatory markers (e.g. C-reactive protein, CRP) have increased cardiovascular disease. Patients with RA have chronic elevations in CRP and other inflammatory markers that are usually higher than the levels associated with increased cardiovascular risk in the general population. Indeed, RA patients have accelerated disease of their blood vessels, and increased cardiovascular death not explained by traditional cardiac risk factors but associated with chronic inflammation. However, the mechanisms by which inflammation leads to cardiovascular disease are not well characterized in RA. Moreover, current treatment strategies of RA largely target joint symptoms rather than inflammation, potentially leaving patients at increased risk for cardiovascular disease. Studies of markers that increase the risk of heart disease in the full spectrum of RA are missing. We hypothesize that inflammatory markers will be more strongly associated with abnormalities in blood vessels 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 abnormal blood vessel changes across the spectrum of RA disease activity, specifically measuring ultrasound of the upper arm artery, markers of oxidative stress, and abnormalities in cholesterol proteins. Aim 2 will identify factors associated with these changes across the spectrum of RA disease activity, specifically focusing on the association between inflammatory markers, cholesterol, and blood vessel abnormalities.