Dessein Patrick H, Joffe Barry I, Singh Sham
Department of Rheumatology, Johannesburg Hospital and Milpark Hospital, Parktown, South Africa.
Arthritis Res Ther. 2005;7(3):R634-43. doi: 10.1186/ar1717. Epub 2005 Mar 24.
Cardiovascular event rates are markedly increased in rheumatoid arthritis (RA), and RA atherogenesis remains poorly understood. The relative contributions of traditional and nontraditional risk factors to cardiovascular disease in RA await elucidation. The present study comprises three components. First, we compared biomarkers of endothelial dysfunction (vascular cell adhesion molecule [VCAM]-1, intercellular adhesion molecule [ICAM]-1 and endothelial leucocyte adhesion molecule [ELAM]-1) in 74 RA patients and 80 healthy control individuals before and after controlling for traditional and nontraditional cardiovascular risk factors, including high-sensitivity C-reactive protein (hs-CRP), IL-1, IL-6 and tumor necrosis factor-alpha. Second, we investigated the potential role of an extensive range of patient characteristics in endothelial dysfunction in the 74 RA patients. Finally, we assessed associations between biomarkers of endothelial dysfunction and ultrasonographically determined common carotid artery intima-media thickness and plaque in RA. The three biomarkers of endothelial dysfunction, as well as hs-CRP, IL-1, IL-6 and tumor necrosis factor-alpha, were higher in patients than in control individuals (P < 0.0001). Patients were also older, exercised less and had a greater waist circumference, blood pressure and triglyceride levels (P <or= 0.04). Five patients had diabetes. Differences in endothelial function were no longer significant between patients and controls (P = 0.08) only after both traditional and nontraditional cardiovascular risk factors were controlled for. In the 74 RA patients, IL-6 predicted levels of all three biomarkers (P <or= 0.03), and rheumatoid factor titres and low glomerular filtration rate (GFR) both predicted levels of VCAM-1 and ICAM-1, independent of traditional cardiovascular risk factors (P <or= 0.02). VCAM-1 was associated with common carotid artery intima-media thickness (P = 0.02) and plaque (P = 0.04) in RA. Patients had impaired endothelial function, less favourable traditional cardiovascular risk factor profiles, and higher circulating concentrations of hs-CRP and cytokines compared with healthy control individuals. Both traditional and nontraditional cardiovascular risk factors contributed to the differences in endothelial function between RA patients and healthy control individuals. IL-6, rheumatoid factor titres and low GFR were independently predictive of endothelial dysfunction in RA. Disease-modifying agents that effectively suppress both cytokine and rheumatoid factor production, and interventions aimed at preserving renal function may attenuate cardiovascular risk in RA.
类风湿关节炎（RA）患者的心血管事件发生率显著增加，而RA的动脉粥样硬化发生机制仍知之甚少。传统和非传统风险因素对RA患者心血管疾病的相对贡献尚待阐明。本研究包括三个部分。首先，我们比较了74例RA患者和80例健康对照者在控制传统和非传统心血管风险因素（包括高敏C反应蛋白（hs-CRP）、IL-1、IL-6和肿瘤坏死因子-α）前后的内皮功能障碍生物标志物（血管细胞黏附分子[VCAM]-1、细胞间黏附分子[ICAM]-1和内皮白细胞黏附分子[ELAM]-1）。其次，我们研究了74例RA患者中一系列广泛的患者特征在内皮功能障碍中的潜在作用。最后，我们评估了RA患者内皮功能障碍生物标志物与超声测定的颈总动脉内膜中层厚度和斑块之间的关联。患者的三种内皮功能障碍生物标志物以及hs-CRP、IL-1、IL-6和肿瘤坏死因子-α均高于对照个体（P < 0.0001）。患者年龄也更大，运动更少，腰围、血压和甘油三酯水平更高（P≤0.04）。5例患者患有糖尿病。仅在控制了传统和非传统心血管风险因素后，患者与对照之间的内皮功能差异才不再显著（P = 0.08）。在74例RA患者中，IL-6可预测所有三种生物标志物的水平（P≤0.03），类风湿因子滴度和低肾小球滤过率（GFR）均可独立于传统心血管风险因素预测VCAM-1和ICAM-1的水平（P≤0.02）。在RA患者中，VCAM-1与颈总动脉内膜中层厚度（P = 0.02）和斑块（P = 0.04）相关。与健康对照个体相比，患者存在内皮功能受损、传统心血管风险因素状况较差以及hs-CRP和细胞因子循环浓度较高的情况。传统和非传统心血管风险因素均导致了RA患者与健康对照个体在内皮功能方面的差异。IL-6、类风湿因子滴度和低GFR可独立预测RA患者的内皮功能障碍。有效抑制细胞因子和类风湿因子产生的疾病改善药物以及旨在保护肾功能的干预措施可能会降低RA患者的心血管风险。
