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 hypothesised that patients with RA exhibit aortic inflammation, which can be reversed with anti-tumour necrosis factor alpha (TNF-α) therapy, and correlates with aortic stiffness reduction.
Methods and Results—Aortic inflammation was quantified in 17 patients with RA, before and after eight weeks of anti-TNF-α therapy, using 18F-fluoro-deoxyglucose positron emission tomography (18F-FDG-PET) with CT co-registration. Concomitantly, 34 patients with stable cardiovascular disease (CVD) were imaged as positive controls at baseline. Aortic FDG target to background ratios (TBR) and aortic pulse wave velocity (aPWV) were assessed. RA patients had higher baseline aortic TBR compared to CVD patients (2.02±0.22 v. 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 aPWV 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 18F-FDG uptake in comparison to stable CVD patients. Anti-TNF-α therapy reduces aortic inflammation in patients with RA, and this effect correlates with the fall in aortic stiffness. These results suggest that RA patients exhibit a sub-clinical vasculitis, which provides a mechanism for the increased CVD risk seen in RA.
- Received June 27, 2012.
- Accepted September 28, 2012.
- Copyright © 2012, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited