From the Department of Epidemiology (Z.Z., D.G., Y.J., K.Z., M.S., P.Y., A.W., T.X., Y.Z.), School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, China; Department of Epidemiology (Z.Z., M.S., J.C., J.H.), Tulane University School of Public Health and Tropical Medicine, New Orleans, LA; Department of Neurology (Y.P.), Affiliated Hospital of North China University of Science and Technology, Hebei; Department of Medicine (J.C., J.H.), Tulane University School of Medicine, New Orleans, LA; and Department of Neurology (J.Z.), the 960th Hospital of People's Liberation Army, Shandong, China.
Neurology. 2022 Aug 30;99(9):e916-e924. doi: 10.1212/WNL.0000000000200783. Epub 2022 Jun 2.
Thrombomodulin has been suggested to be implicated in ischemic stroke because of its anticoagulant, anti-inflammatory, and cytoprotective properties. We aimed to investigate the associations of plasma thrombomodulin levels with clinical outcomes after ischemic stroke in a multicenter prognostic cohort study.
Our multicenter prognostic cohort study included 3,532 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was the composite outcome of death and major disability (modified Rankin Scale [mRS] score ≥3) at 3 months after ischemic stroke. Secondary outcomes included major disability (mRS score 3-5), vascular events, and the ordered 7-level categorical score of the mRS.
During 3 months of follow-up, 867 participants experienced the primary outcome. After multivariate adjustment, the adjusted odds ratios or hazard ratios associated with the highest quartile of plasma thrombomodulin were 0.75 (95% CI 0.59-0.97; = 0.029) for the primary outcome, 0.73 (95% CI 0.56-0.94; = 0.028) for major disability, and 0.80 (95% CI 0.42-1.51; = 0.232) for vascular events. In addition, a significantly better shift in the distribution of the mRS score was observed with higher thrombomodulin quartiles ( = 0.005). A multivariable-adjusted spline regression model showed a linear relationship between plasma thrombomodulin and the risk of primary outcome ( for linearity = 0.027). Subgroup analyses further confirmed these associations.
Increased plasma thrombomodulin levels at baseline were associated with decreased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting a protective role of thrombomodulin in the development of ischemic stroke. Further studies from various populations are needed to replicate our findings.
血栓调节蛋白因其抗凝、抗炎和细胞保护特性而被认为与缺血性脑卒中有关。我们旨在通过一项多中心预后队列研究，调查血浆血栓调节蛋白水平与缺血性脑卒中后临床结局的相关性。
我们的多中心预后队列研究纳入了来自中国急性缺血性脑卒中降压试验（China Antihypertensive Trial in Acute Ischemic Stroke）的 3532 例中国缺血性脑卒中患者。所有患者均在缺血性脑卒中发病后 3 个月进行随访。主要结局为缺血性脑卒中发病后 3 个月时的死亡和主要残疾（改良 Rankin 量表[mRS]评分≥3）复合结局。次要结局包括主要残疾（mRS 评分 3-5 分）、血管事件和 mRS 有序 7 级分类评分。
在 3 个月的随访期间，867 名患者发生了主要结局。经多变量调整后，与血浆血栓调节蛋白最高四分位数相关的调整比值比或风险比为 0.75（95%CI 0.59-0.97；=0.029），主要残疾为 0.73（95%CI 0.56-0.94；=0.028），血管事件为 0.80（95%CI 0.42-1.51；=0.232）。此外，随着血栓调节蛋白四分位数的升高，mRS 评分的分布明显向更好的方向移动（=0.005）。多变量调整后的样条回归模型显示，血浆血栓调节蛋白与主要结局风险之间存在线性关系（线性检验=0.027）。亚组分析进一步证实了这些关联。
基线时血浆血栓调节蛋白水平升高与缺血性脑卒中后 3 个月不良临床结局的风险降低相关，提示血栓调节蛋白在缺血性脑卒中的发生发展中具有保护作用。需要来自不同人群的进一步研究来复制我们的发现。
