Mäki-Petäjä Kaisa M, Hall Frances C, Booth Anthony D, Wallace Sharon M L, Bearcroft Philip W P, Harish Srinivasan, Furlong Anita, McEniery Carmel M, Brown John, Wilkinson Ian B
Clinical Pharmacology Unit, University of Cambridge, Addenbrooke's Hospital, Box 110, Cambridge CB2 2QQ, United Kingdom.
Circulation. 2006 Sep 12;114(11):1185-92. doi: 10.1161/CIRCULATIONAHA.105.601641. Epub 2006 Sep 4.
Rheumatoid arthritis (RA) is associated with increased cardiovascular risk, which is not explained by traditional cardiovascular risk factors but may be due in part to increased aortic stiffness, an independent predictor of cardiovascular mortality. In the present study, our aim was to establish whether aortic stiffness is increased in RA and to investigate the relationship between inflammation and aortic stiffness. In addition, we tested the hypothesis that aortic stiffness could be reduced with anti-tumor necrosis factor-alpha (TNF-alpha) therapy.
Aortic pulse-wave velocity (PWV), augmentation index, and blood pressure were measured in 77 patients with RA and in 142 healthy individuals. Both acute and chronic inflammatory measures and disease activity were determined. The effect of anti-TNF-alpha therapy on PWV and endothelial function was measured in 9 RA patients at 0, 4, and 12 weeks. Median (interquartile range) aortic PWV was significantly higher in subjects with RA than in control subjects (8.35 [7.14 to 10.24] versus 7.52 [6.56 to 9.18] m/s, respectively; P = 0.005). In multiple regression analyses, aortic PWV correlated independently with age, mean arterial pressure, and log-transformed C-reactive protein (R2 = 0.701; P < 0.0001). Aortic PWV was reduced significantly by anti-TNF-alpha therapy (8.82+/-2.04 versus 7.94+/-1.86 versus 7.68+/-1.56 m/s at weeks 0, 4, and 12, respectively; P < 0.001); concomitantly, endothelial function improved.
RA is associated with increased aortic stiffness, which correlates with current but not historical measures of inflammation, suggesting that increased aortic stiffness may be reversible. Indeed, anti-TNF-alpha therapy reduced aortic stiffness to a level comparable to that of healthy individuals. Therefore, effective control of inflammation may be of benefit in reducing cardiovascular risk in patients with RA.
类风湿关节炎（RA）与心血管风险增加相关，传统心血管危险因素无法解释这一现象，但其可能部分归因于主动脉僵硬度增加，而主动脉僵硬度是心血管死亡率的独立预测因素。在本研究中，我们的目的是确定RA患者的主动脉僵硬度是否增加，并研究炎症与主动脉僵硬度之间的关系。此外，我们检验了抗肿瘤坏死因子-α（TNF-α）治疗可降低主动脉僵硬度的假设。
对77例RA患者和142名健康个体测量了主动脉脉搏波速度（PWV）、增强指数和血压。测定了急性和慢性炎症指标以及疾病活动度。在9例RA患者中，于第0、4和12周测量了抗TNF-α治疗对PWV和内皮功能的影响。RA患者的主动脉PWV中位数（四分位间距）显著高于对照组（分别为8.35[7.14至10.24]与7.52[6.56至9.18]m/s；P = 0.005）。在多元回归分析中，主动脉PWV与年龄、平均动脉压和对数转换的C反应蛋白独立相关（R2 = 0.701；P < 0.0001）。抗TNF-α治疗使主动脉PWV显著降低（第0、4和12周分别为8.82±2.04、7.94±1.86和7.68±1.56 m/s；P < 0.001）；同时，内皮功能得到改善。
RA与主动脉僵硬度增加相关，这与当前而非既往炎症指标相关，提示主动脉僵硬度增加可能是可逆的。事实上，抗TNF-α治疗可将主动脉僵硬度降低至与健康个体相当的水平。因此，有效控制炎症可能有助于降低RA患者的心血管风险。
