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Plasma Thrombomodulin Levels and Ischemic Stroke: A Population-Based Prognostic Cohort Study
Zhengbao Zhu1, Daoxia Guo2, Yiming Jia2
1From 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. yhzhang@suda.edu.cn.
Background And Objectives:
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.
Methods:
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.
Results:
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; p trend = 0.029) for the primary outcome, 0.73 (95% CI 0.56-0.94; p trend = 0.028) for major disability, and 0.80 (95% CI 0.42-1.51; p trend = 0.232) for vascular events. In addition, a significantly better shift in the distribution of the mRS score was observed with higher thrombomodulin quartiles (p trend = 0.005). A multivariable-adjusted spline regression model showed a linear relationship between plasma thrombomodulin and the risk of primary outcome (p for linearity = 0.027). Subgroup analyses further confirmed these associations.
Discussion:
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.
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