Chongke Zhong1, Guangli Wang1, Tan Xu1, Zhengbao Zhu1, Daoxia Guo1, Xiaowei Zheng1, Aili Wang1, Xiaoqing Bu1, Hao Peng1, Jing Chen1, Tian Xu1, Yanbo Peng1, Qunwei Li1, Zhong Ju1, Deqin Geng1, Jiang He2, Yonghong Zhang2. 1. From the Department of Epidemiology (C.Z., G.W., Tan Xu, Z.Z., D. Guo, X.Z., A.W., X.B., H.P., Tian Xu, Y.Z.), School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China; Department of Epidemiology (C.Z., 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, Tangshan; Department of Epidemiology (Q.L.), School of Public Health, Taishan Medical College, Taian; Department of Neurology (Z.J.), Kerqin District First People's Hospital of Tongliao City; Department of Neurology (D. Geng), Affiliated Hospital of Xuzhou Medical College, China; Department of Medicine (J.C., J.H.), Tulane University School of Medicine, New Orleans, LA; and Department of Neurology (Tian Xu), Affiliated Hospital of Nantong University, China. 2. From the Department of Epidemiology (C.Z., G.W., Tan Xu, Z.Z., D. Guo, X.Z., A.W., X.B., H.P., Tian Xu, Y.Z.), School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China; Department of Epidemiology (C.Z., 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, Tangshan; Department of Epidemiology (Q.L.), School of Public Health, Taishan Medical College, Taian; Department of Neurology (Z.J.), Kerqin District First People's Hospital of Tongliao City; Department of Neurology (D. Geng), Affiliated Hospital of Xuzhou Medical College, China; Department of Medicine (J.C., J.H.), Tulane University School of Medicine, New Orleans, LA; and Department of Neurology (Tian Xu), Affiliated Hospital of Nantong University, China. yhzhang@suda.edu.cn jhe@tulane.edu.
Abstract
OBJECTIVE: To prospectively investigate the relationships between serum tissue inhibitor metalloproteinase-1 (TIMP-1) and clinical outcomes in patients with acute ischemic stroke. METHODS: We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline serum TIMP-1 concentrations were measured in 3,342 participants. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events. RESULTS: A total of 843 participants (25.2%) experienced major disability or died within 3 months. After adjustment for age, sex, admission NIH Stroke Scale score, and other important covariates, odds ratios or hazard ratios (95% confidence intervals) of 1-SD (0.17 ng/mL) higher log-TIMP-1 were 1.17 (1.06-1.29) for the primary outcome, 1.13 (1.02-1.25) for major disability, 1.49 (1.19-1.87) for death, and 1.34 (1.11-1.62) for the composite outcome of death and vascular events. The addition of serum TIMP-1 to conventional risk factors model significantly improved risk prediction of the primary outcome (net reclassification index 9.0%, p = 0.02; integrated discrimination improvement 0.2%, p = 0.03). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had the highest risk of all study outcomes. CONCLUSIONS: Higher TIMP-1 levels were associated with increased risk of mortality and major disability after acute ischemic stroke. Our findings provided evidence supporting the important prognostic role of extracellular matrix biomarkers after acute ischemic stroke.
OBJECTIVE: To prospectively investigate the relationships between serum tissue inhibitor metalloproteinase-1 (TIMP-1) and clinical outcomes in patients with acute ischemic stroke. METHODS: We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke. Baseline serum TIMP-1 concentrations were measured in 3,342 participants. The primary outcome was the combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after ischemic stroke, and secondary outcomes included major disability, death, and vascular events. RESULTS: A total of 843 participants (25.2%) experienced major disability or died within 3 months. After adjustment for age, sex, admission NIH Stroke Scale score, and other important covariates, odds ratios or hazard ratios (95% confidence intervals) of 1-SD (0.17 ng/mL) higher log-TIMP-1 were 1.17 (1.06-1.29) for the primary outcome, 1.13 (1.02-1.25) for major disability, 1.49 (1.19-1.87) for death, and 1.34 (1.11-1.62) for the composite outcome of death and vascular events. The addition of serum TIMP-1 to conventional risk factors model significantly improved risk prediction of the primary outcome (net reclassification index 9.0%, p = 0.02; integrated discrimination improvement 0.2%, p = 0.03). Participants with both higher TIMP-1 and matrix metalloproteinase-9 levels simultaneously had the highest risk of all study outcomes. CONCLUSIONS: Higher TIMP-1 levels were associated with increased risk of mortality and major disability after acute ischemic stroke. Our findings provided evidence supporting the important prognostic role of extracellular matrix biomarkers after acute ischemic stroke.