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Genetic liability to frailty in relation to functional outcome after ischemic stroke

Dataset

  • Huan Cai (Creator)
  • Hao ZhangNorthwestern Polytechnical University Xian, Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China; Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing , China, Harvard University, Ruijin Hospital, Chinese Academy of Sciences, Dalian University of Technology, Shandong University, University of Arizona, Changhai Hospital, Guangdong Pharmaceutical University, Second Affiliated Hospital of Harbin Medical University, Ocean University of China, Nanjing Agricultural University, Zhejiang University, Shanghai Jiao Tong University, University of Chinese Academy of Sciences, Nanjing Medical University, China agricultural University, Huazhong University of Science and Technology, Jilin University, Urology Department The Affiliated Qingdao Central Hospital of Qingdao University, The Second Affiliated Hospital of Medical College of Qingdao University Qingdao Shandong China, South China University of Technology, Nanyang Technological University, Shanghai Children's Medical Center, Center for Brain Science, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China., McGill University, Sichuan University, Jiangnan University, University of Victoria, Nanchang University, First Affiliated Hospital of Harbin Medical University, Wenzhou Medical University, Zhongnan Hospital of Wuhan University, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Anzhen Hospital, Yunnan Academy of Agricultural Sciences, Chongqing Medical University, Inner Mongolia Academy of Agricultural & Animal Husbandry Sciences, Department of Pathology, The First Affiliated Hospital of Hainan Medical University, Haikou, China;, Shanghai Stomatological Hospital, Pudong Medical Center, Heilongjiang Provincial Hospital, Jinan University, Ruian People's Hospital, Jiangsu Province Hospital, Second Affiliated Hospital of Nanjing Medical University, Hunan Agricultural University, Fudan University, Hubei Academy of Agricultural Sciences, Cornell University, Guangdong University of Petrochemical Technology, Henan Normal University (Creator)
  • Jialin Liang (Creator)
  • Zhonghua Liu (Creator)
  • Guozhi Huang (Creator)

Description

Background:Frailty appears to be associated with unfavorable prognosis after stroke in observational studies, but the causality remains largely unknown.Aims:The aim of this study is to investigate the potential causal effect of frailty on functional outcome at 3 months after ischemic stroke using the Mendelian randomization (MR) framework.Methods:Genetic instruments for frailty index were identified in a genome-wide association study meta-analysis including 175,226 individuals of European descent. Corresponding genetic association estimates for functional outcome after ischemic stroke at 90 days were taken from the Genetic of Ischemic Stroke Functional Outcome (GISCOME) network of 6021 patients. We performed inverse-variance weighted MR as the main analyses, followed by several alternate methods and sensitivity analyses.Results:In univariable MR, we found evidence that genetically predicted higher frailty index (odds ratio (OR) = 5.12; 95% confidence interval (CI) = 1.31–20.09; p = 0.019) was associated with worse functional outcome (modified Rankin Scale score ⩾3) after ischemic stroke. In further multivariable MR adjusting for potential confounding traits including body mass index, C-reactive protein, inflammatory bowel disease, and smoking initiation, the overall patterns between genetic liability to frailty and poor functional outcome status remained. Sensitivity analyses with complementary methods and with model unadjusted for baseline stroke severity (OR = 4.19; 95% CI = 1.26–13.90; p = 0.019) yielded broadly concordant results.Conclusions:The present MR study suggested a possible causal effect of frailty on poor functional outcome after ischemic stroke. Frailty might represent a potential target for intervention to improve recovery after ischemic stroke.
Date made available2023
PublisherSAGE Journals

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