Chongke Zhong1, Zhengbao Zhu1, Aili Wang1, Tan Xu1, Xiaoqing Bu1, Hao Peng1, Jingyuan Yang1, Liyuan Han1, Jing Chen1, Tian Xu1, Yanbo Peng1, Jinchao Wang1, Qunwei Li1, Zhong Ju1, Deqin Geng1, Jiang He2, Yonghong Zhang2. 1. From the Department of Epidemiology (C.Z., Z.Z., A.W., Tan Xu, X.B., H.P., J.Y., L.H., 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 Epidemiology (J.Y.), School of Public Health, Guizhou Medical University, Guiyang; Department of Preventive Medicine (L.H.), Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China; Department of Medicine (J.C., J.H.), Tulane University School of Medicine, New Orleans, LA; Department of Neurology (Tian Xu), Affiliated Hospital of Nantong University, Nantong; Department of Neurology (Y.P.), Affiliated Hospital of North China University of Science and Technology; Department of Neurology (J.W.), Yutian County Hospital, 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, Tongliao; and Department of Neurology (D.G.), Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. 2. From the Department of Epidemiology (C.Z., Z.Z., A.W., Tan Xu, X.B., H.P., J.Y., L.H., 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 Epidemiology (J.Y.), School of Public Health, Guizhou Medical University, Guiyang; Department of Preventive Medicine (L.H.), Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China; Department of Medicine (J.C., J.H.), Tulane University School of Medicine, New Orleans, LA; Department of Neurology (Tian Xu), Affiliated Hospital of Nantong University, Nantong; Department of Neurology (Y.P.), Affiliated Hospital of North China University of Science and Technology; Department of Neurology (J.W.), Yutian County Hospital, 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, Tongliao; and Department of Neurology (D.G.), Affiliated Hospital of Xuzhou Medical College, Xuzhou, China. yhzhang@suda.edu.cn jhe@tulane.edu.
Abstract
OBJECTIVE: To study the prognostic significance of multiple novel biomarkers in combination after ischemic stroke. METHODS: We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke, and 12 informative biomarkers were measured. 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: In 3,405 participants, 866 participants (25.4%) experienced major disability or died within 3 months. In multivariable analyses, elevated high-sensitive C-reactive protein, complement C3, matrix metalloproteinase-9, hepatocyte growth factor, and antiphosphatidylserine antibodies were individually associated with the primary outcome. Participants with a larger number of elevated biomarkers had increased risk of all study outcomes. The adjusted odds ratios (95% confidence intervals) of participants with 5 elevated biomarkers were 3.88 (2.05-7.36) for the primary outcome, 2.81 (1.49-5.33) for major disability, 5.67 (1.09-29.52) for death, and 4.00 (1.22-13.14) for vascular events, compared to those with no elevated biomarkers. Simultaneously adding these 5 biomarkers to the basic model with traditional risk factors led to substantial reclassification for the combined outcome (net reclassification improvement 28.5%, p < 0.001; integrated discrimination improvement 2.2%, p < 0.001) and vascular events (net reclassification improvement 37.0%, p = 0.001; integrated discrimination improvement 0.8%, p = 0.001). CONCLUSION: We observed a clear gradient relationship between the numbers of elevated novel biomarkers and risk of major disability, mortality, and vascular events. Incorporation of a combination of multiple biomarkers observed substantially improved the risk stratification for adverse outcomes in ischemic stroke patients.
OBJECTIVE: To study the prognostic significance of multiple novel biomarkers in combination after ischemic stroke. METHODS: We derived data from the China Antihypertensive Trial in Acute Ischemic Stroke, and 12 informative biomarkers were measured. 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: In 3,405 participants, 866 participants (25.4%) experienced major disability or died within 3 months. In multivariable analyses, elevated high-sensitive C-reactive protein, complement C3, matrix metalloproteinase-9, hepatocyte growth factor, and antiphosphatidylserine antibodies were individually associated with the primary outcome. Participants with a larger number of elevated biomarkers had increased risk of all study outcomes. The adjusted odds ratios (95% confidence intervals) of participants with 5 elevated biomarkers were 3.88 (2.05-7.36) for the primary outcome, 2.81 (1.49-5.33) for major disability, 5.67 (1.09-29.52) for death, and 4.00 (1.22-13.14) for vascular events, compared to those with no elevated biomarkers. Simultaneously adding these 5 biomarkers to the basic model with traditional risk factors led to substantial reclassification for the combined outcome (net reclassification improvement 28.5%, p < 0.001; integrated discrimination improvement 2.2%, p < 0.001) and vascular events (net reclassification improvement 37.0%, p = 0.001; integrated discrimination improvement 0.8%, p = 0.001). CONCLUSION: We observed a clear gradient relationship between the numbers of elevated novel biomarkers and risk of major disability, mortality, and vascular events. Incorporation of a combination of multiple biomarkers observed substantially improved the risk stratification for adverse outcomes in ischemic strokepatients.
Authors: Antonela Bicvic; Natalie Scherrer; Juliane Schweizer; Felix Fluri; Mirjam Christ-Crain; Gian Marco De Marchis; Andreas R Luft; Mira Katan Journal: Eur Stroke J Date: 2022-04-20