Anti-Tumor Necrosis Factor-α 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 factor-alpha therapy 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 factor-alpha therapy by using F-18-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-18-fluorodeoxyglucose uptake in comparison with patients who have stable cardiovascular disease. Anti-tumor necrosis factor-alpha therapy 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.)