Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis.
Biomarkers of endothelial dysfunction, cardiovascular risk factors and atherosclerosis in rheumatoid arthritis.
复制标题
类风湿关节炎中内皮功能障碍，心血管危险因素和动脉粥样硬化的生物标志物。
DOI：
10.1186/ar1717
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发表时间：
2005
影响因子：
4.9
通讯作者：
Singh, Sham
中科院分区：
文献类型：
--
作者：
Dessein, Patrick H;Joffe, Barry I;Singh, Sham
类风湿性关节炎(RA)的心血管事件发生率显著增加，而RA动脉粥样硬化的形成机制仍知之甚少。传统和非传统危险因素对RA心血管疾病的相对贡献有待阐明。本研究包括三个部分。首先，我们比较了74例RA患者和80例健康对照组在控制传统和非传统心血管危险因素(包括高敏C反应蛋白、IL-1、IL-6和肿瘤坏死因子-α)前后内皮功能障碍的生物标志物(血管细胞黏附分子-1、细胞间黏附分子-1和内皮白细胞黏附分子-1)。其次，我们调查了74名RA患者广泛的患者特征在内皮功能障碍中的潜在作用。最后，我们评估了血管内皮功能障碍的生物标志物与超声确定的RA颈总动脉内中膜厚度和斑块之间的关系。内皮功能障碍的三项标志物以及hs-C反应蛋白、IL-1、IL-6和肿瘤坏死因子-α均高于正常对照组(P<；0.0001)。患者年龄更大，运动量更少，腰围、血压和甘油三酯水平更大(P≤0.04)。5名患者患有糖尿病。只有在控制了传统和非传统心血管危险因素后，患者和对照组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预测所有三个生物标志物的水平(P≤0.03)，类风湿因子滴度和低肾小球滤过率均预测VCAM1和ICAM-1的水平，独立于传统的心血管危险因素(P≤0.02)。VCAM-1与RA颈总动脉内中膜厚度(P=0.02)和斑块(P=0.04)相关。与健康对照组相比，患者的内皮功能受损，传统的心血管危险因素特征不那么有利，循环中hs-CRP和细胞因子浓度较高。传统心血管危险因素和非传统心血管危险因素共同导致类风湿关节炎患者和健康对照组血管内皮功能的差异。IL-6、类风湿因子滴度和低GFR是RA患者内皮功能障碍的独立预测指标。有效抑制细胞因子和类风湿因子产生的疾病改良剂，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。
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-α. 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-α, 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 ≤ 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 ≤ 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 ≤ 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.