Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Circulation. 2012 Nov 20;126(21):2473-80. doi: 10.1161/CIRCULATIONAHA.112.120410. Epub 2012 Oct 24.
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-α therapy and correlates with aortic stiffness reduction.
Aortic inflammation was quantified in 17 patients with RA, before and after 8 weeks of anti-tumor necrosis factor-α therapy by using (18)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).
This study demonstrates that RA patients have increased aortic (18)F-fluorodeoxyglucose uptake in comparison with patients who have stable cardiovascular disease. Anti-tumor necrosis factor-α 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.
类风湿关节炎（RA）是一种与心血管风险增加相关的系统性炎症性疾病。这不能完全用传统的危险因素来解释，但直接的血管炎症和主动脉僵硬可能起作用。我们假设 RA 患者存在主动脉炎症，这种炎症可以通过抗肿瘤坏死因子-α治疗逆转，并与主动脉僵硬的降低相关。
通过使用（18）F-氟脱氧葡萄糖正电子发射断层扫描与计算机断层融合，对 17 例 RA 患者在抗肿瘤坏死因子-α治疗前和治疗 8 周后进行主动脉炎症定量。同时，对 34 例稳定心血管疾病患者进行了基线正电子发射断层扫描。评估主动脉氟脱氧葡萄糖靶-背景比（TBR）和主动脉脉搏波速度。与患有心血管疾病的患者相比，RA 患者的主动脉 TBR 更高（2.02±0.22 与 1.74±0.22，P=0.0001）。治疗后，主动脉 TBR 降至 1.90±0.29，P=0.03，炎症主动脉切片比例（定义为 TBR>2.0）从 50±33%降至 33±27%，P=0.03。此外，主动脉最严重节段的 TBR 从 2.51±0.33 降至 2.05±0.29，P<0.0001。治疗还显著降低了主动脉脉搏波速度（从 9.09±1.77 降至 8.63±1.42 m/s，P=0.04），与主动脉 TBR 的降低相关（R=0.60，P=0.01）。
本研究表明，与稳定心血管疾病患者相比，RA 患者的主动脉（18）F-氟脱氧葡萄糖摄取增加。抗肿瘤坏死因子-α治疗可降低 RA 患者的主动脉炎症，这种作用与主动脉僵硬的降低相关。这些结果表明，RA 患者存在亚临床血管炎，这为 RA 患者心血管疾病风险增加提供了机制。
