Imaging Anti-Tumor Necrosis Factor- Therapy Reduces Aortic Inflammation and Stiffness in Patients With Rheumatoid Arthritis

Background—Rheumatoid arthritis (RA) is a systemic inflammatory condition associated with increased cardiovascular risk. This is not fully explained by traditional risk factors, but direct vascular inflammation and aortic stiffening may play a role. We hypothesized that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumor necrosis factortherapy and correlates with aortic stiffness reduction. Methods and Results—Aortic inflammation was quantified in 17 patients with RA, before and after 8 weeks of anti-tumor necrosis factortherapy by using F-fluorodeoxyglucose positron emission tomography with computed tomography coregistration. Concomitantly, 34 patients with stable cardiovascular disease were imaged as positive controls at baseline. Aortic fluorodeoxyglucose target-to-background ratios (TBRs) and aortic pulse wave velocity were assessed. RA patients had higher baseline aortic TBRs in comparison with patients who have cardiovascular disease (2.02 0.22 versus 1.74 0.22, P 0.0001). Following therapy, aortic TBR fell to 1.90 0.29, P 0.03, and the proportion of inflamed aortic slices (defined as TBR 2.0) decreased from 50 33% to 33 27%, P 0.03. Also, TBR in the most diseased segment of the aorta fell from 2.51 0.33 to 2.05 0.29, P 0.0001. Treatment also reduced aortic pulse wave velocity significantly (from 9.09 1.77 to 8.63 1.42 m/s, P 0.04), which correlated with the reduction of aortic TBR (R 0.60, P 0.01). Conclusions—This study demonstrates that RA patients have increased aortic F-fluorodeoxyglucose uptake in comparison with patients who have stable cardiovascular disease. Anti-tumor necrosis factortherapy reduces aortic inflammation in patients with RA, and this effect correlates with the decrease in aortic stiffness. These results suggest that RA patients exhibit a subclinical vasculitis, which provides a mechanism for the increased cardiovascular disease risk seen in RA. (Circulation. 2012;126:2473-2480.)