Rheumatology Unit, Department of Medicine Karolinska University Hospital, Solna, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
Arthritis Res Ther. 2009;11(6):R186. doi: 10.1186/ar2878. Epub 2009 Dec 10.
Cardiovascular disease (CVD) is a major cause of premature mortality among Systemic lupus erythematosus (SLE) patients. Many studies have measured and evaluated risk factors for premature subclinical atherosclerosis, but few studies are prospective and few have evaluated risk factors for hard endpoints, i.e. clinically important cardiovascular events (CVE). We investigated the impact of traditional and lupus associated risk factors for the first ever CVE in a longitudinal cohort of SLE patients.
A total of 182 SLE patients (mean age 43.9 years) selected to be free of CVE were included. Cardiovascular and autoimmune biomarkers were measured on samples collected after overnight fasting at baseline. Clinical information was collected at baseline and at follow up. End point was the first ever CVE (ischemic heart, cerebrovascular or peripheral vascular disease or death due to CVD). Impact of baseline characteristics/biomarkers on the risk of having a first CVE was evaluated with Cox regression.
Follow up was 99.5% after a mean time of 8.3 years. Twenty-four patients (13%) had a first CVE. In age-adjusted Cox regression, any positive antiphospholipid antibody (aPL), elevated markers of endothelial activation (von Willebrand factor (vWf), soluble vascular cellular adhesion molecule-1 (sVCAM-1)) and fibrinogen predicted CVEs. Of SLE manifestations, arthritis, pleuritis and previous venous occlusion were positively associated with future CVEs while thrombocytopenia was negatively associated. Among traditional risk factors only age and smoking were significant predictors. In a multivariable Cox regression model age, any positive aPL, vWf and absence of thrombocytopenia were all predictors of the first CVE.
In addition to age, positive aPL, biomarkers indicating increased endothelial cell activity/damage, and absence of thrombocytopenia were independent predictors of CVEs in this prospective study. Our results indicate that activation of the endothelium and the coagulation system are important features in SLE related CVD. Furthermore, we observed that the risk of CVEs seems to differ between subgroups of SLE patients.
心血管疾病（CVD）是红斑狼疮（SLE）患者过早死亡的主要原因。许多研究已经测量和评估了亚临床动脉粥样硬化的危险因素，但很少有前瞻性研究，也很少有研究评估硬终点（即临床重要心血管事件（CVE））的危险因素。我们在 SLE 患者的纵向队列中研究了传统和狼疮相关危险因素对首次 CVE 的影响。
共纳入 182 例 SLE 患者（平均年龄 43.9 岁），入选时无 CVE。在基线时空腹过夜后采集心血管和自身免疫生物标志物样本。基线和随访时收集临床信息。终点是首次 CVE（缺血性心脏病、脑血管或周围血管疾病或 CVD 导致的死亡）。使用 Cox 回归评估基线特征/生物标志物对首次 CVE 风险的影响。
平均随访 8.3 年后，随访率为 99.5%。24 例患者（13%）发生了首次 CVE。在年龄调整的 Cox 回归中，任何阳性抗磷脂抗体（aPL）、升高的内皮细胞激活标志物（血管性血友病因子（vWf）、可溶性血管细胞黏附分子-1（sVCAM-1））和纤维蛋白原预测 CVE。在 SLE 表现中，关节炎、胸膜炎和先前的静脉阻塞与未来的 CVE 呈正相关，而血小板减少与 CVE 呈负相关。在传统危险因素中，只有年龄和吸烟是显著的预测因素。在多变量 Cox 回归模型中，年龄、任何阳性 aPL、vWf 和无血小板减少均为首次 CVE 的预测因素。
除了年龄，阳性 aPL、提示内皮细胞活性/损伤增加的生物标志物以及无血小板减少是本前瞻性研究中 CVE 的独立预测因素。我们的研究结果表明，内皮细胞和凝血系统的激活是 SLE 相关 CVD 的重要特征。此外，我们观察到 CVE 的风险似乎在不同的 SLE 患者亚组之间存在差异。
