High plasma thrombomodulin level is associated with a decreased risk of cognitive impairment after ischemic stroke

Yu He; Xinyue Chang; Yi Liu; Jiawen Fei; Xiaoli Qin; Beiping Song; Quan Yu; Mengyao Shi; Daoxia Guo; Jing Chen; Aili Wang; Tan Xu; Jiang He; Yonghong Zhang; Zhengbao Zhu

doi:10.1016/j.jstrokecerebrovasdis.2024.108172

High plasma thrombomodulin level is associated with a decreased risk of cognitive impairment after ischemic stroke

J Stroke Cerebrovasc Dis. 2024 Dec 2;34(1):108172. doi: 10.1016/j.jstrokecerebrovasdis.2024.108172. Online ahead of print.

Authors

Yu He¹, Xinyue Chang², Yi Liu³, Jiawen Fei⁴, Xiaoli Qin⁵, Beiping Song⁶, Quan Yu⁷, Mengyao Shi⁸, Daoxia Guo⁹, Jing Chen¹⁰, Aili Wang¹¹, Tan Xu¹², Jiang He¹³, Yonghong Zhang¹⁴, Zhengbao Zhu¹⁵

Affiliations

¹ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
² Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
³ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
⁴ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
⁵ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
⁶ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
⁷ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
⁸ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. Electronic address: [email protected].
⁹ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
¹⁰ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: [email protected].
¹¹ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
¹² Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
¹³ Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Department of Medicine, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: [email protected].
¹⁴ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China. Electronic address: [email protected].
¹⁵ Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Major Chronic Non-communicable Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, Jiangsu Province 215123, PR China; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA. Electronic address: [email protected].

PMID: 39631512
DOI: 10.1016/j.jstrokecerebrovasdis.2024.108172

Abstract

Background: Thrombomodulin, a thrombin receptor with anticoagulant, anti-inflammatory, and cytoprotective properties, has been suggested to play a pivotal role in ischemic stroke. However, the association of plasma thrombomodulin with post-stroke cognitive impairment (PSCI) remains unclear. We aimed to prospectively investigate the associations of plasma thrombomodulin with PSCI among ischemic stroke patients in a multicenter cohort study.

Methods: We measured plasma thrombomodulin levels at baseline among 615 ischemic stroke patients from a preplanned ancillary study of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). We used Montreal Cognitive Assessment (MoCA) to evaluate cognitive function at 3-month follow-up after ischemic stroke, and PSCI was defined as MoCA score <23.

Results: Plasma thrombomodulin was inversely associated with PSCI, and the adjusted odds ratio of PSCI for the highest versus lowest quartile of thrombomodulin was 0.50 (95 % CI: 0.28-0.92, P_trend=0.026). Each standard deviation increment of log-transformed thrombomodulin was associated with a 23 % (odds ratio: 0.77, 95 % CI: 0.62-0.97, P=0.029) decreased risk of PSCI. In addition, plasma thrombomodulin could significantly improve the risk reclassification of PSCI beyond established risk factors (net reclassification index: 25.04 %, 95 % CI: 7.20 %-42.87 %, P=0.007; integrated discrimination improvement: 1.13 %, 95 % CI: 0.18 %-2.09 %, P=0.020).

Conclusions: High plasma thrombomodulin levels were associated with a decreased risk of PSCI among ischemic stroke patients. Our findings suggest that plasma thrombomodulin might be a predictive biomarker and potential therapeutic target for PSCI.

Keywords: Biomarker; Cognitive impairment; Ischemic stroke; Prognosis; Thrombomodulin.