Department of Public Health and Clinical Medicine/Rheumatology, University Hospital, 901 85 Umeå, Sweden.
Arthritis Res Ther. 2010;12(4):R158. doi: 10.1186/ar3116. Epub 2010 Aug 16.
In this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account.
Patients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months.
There were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001).
We found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.
本研究旨在探讨早期类风湿关节炎（RA）患者是否存在内皮依赖性血流介导的舒张功能（ED-FMD）和内膜中层厚度（IMT）等动脉粥样硬化早期表现，并分析其与内皮功能障碍生物标志物的关系，同时考虑炎症和传统心血管疾病（CVD）危险因素的影响。
在一项正在进行的 CVD 合并症的前瞻性研究中，我们对瑞典北部三个县诊断为早期 RA 的患者进行随访。在此基础上，所有年龄≤60 岁的患者均连续纳入本项 CVD 危险因素调查（n=79）。同时纳入 44 名年龄和性别匹配的对照组。采用超声技术测量颈总动脉 IMT 和肱动脉 ED-FMD。采集血液样本用于分析血脂、红细胞沉降率（ESR）、C 反应蛋白（CRP）、纤溶酶原激活物抑制剂-1（PAI-1）、组织型纤溶酶原激活物（tPA）-质量、血管性血友病因子（VWF）、可溶性细胞间黏附分子-1（sICAM）、可溶性血管细胞黏附分子-1（sVCAM）、可溶性 E-选择素（sE-selectin）、可溶性 L-选择素（sL-selectin）和单核细胞趋化蛋白-1（MCP-1）。在 27 名 RA 患者及其对照组的亚组中，18 个月后重新分析了超声测量结果。
在第一次评估时，RA 患者与对照组在 IMT 或 ED-FMD 方面无显著差异。然而，18 个月后，RA 患者的 IMT 显著升高（P＜0.05）。与对照组相比，RA 患者的 VWF、sICAM-1（P＜0.05）和 MCP-1 水平更高（P=0.001）。在 RA 中，IMT 与传统 CVD 危险因素、tPA-质量、VWF（P＜0.01）和 MCP-1 相关，与 sL-selectin 呈负相关（P＜0.05）。在 RA 中，ED-FMD 与 sL-selectin 相关（P＜0.01）。基线 DAS28 与 PAI-1、tPA-质量呈负相关，与 sVCAM-1（P＜0.05）和 sL-selectin（P=0.001）呈正相关。
与对照组相比，新诊断的 RA 患者并未出现动脉粥样硬化迹象。然而，在早期 RA 患者中，IMT 和 ED-FMD 与已知与内皮功能障碍和动脉粥样硬化相关的生物标志物的相关性，大于对照组。18 个月后，RA 患者的 IMT 显著升高，但对照组无此变化。
