Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke:a prospective cohort study  

作　　者：Xin Qiu Yalun Dai Si Cheng Hong-Qiu Gu Yong Jiang Xia Meng Yilong Wang Xingquan Zhao Yingyu Jiang Zhe Xu Xinying Huang Meng Wang Tian Jie Lyu Yubo Wang Jiaxu Weng Lingyun Cui Yi Shangguan Hao Li Yongjun Wang Zixiao Li 

机构地区：[1]Department of Neurology,Beijing Tiantan Hospital,Capital Medical University,Beijing,China [2]China National Clinical Research Center for Neurological Diseases,Beijing,China [3]Advanced Innovation Center for Human Brain Protection,Capital Medical University,Beijing,China [4]Research Unit of Artificial Intelligence in Cerebrovascular Disease,Chinese Academy of Medical Sciences,Beijing,China [5]Center for Excellence in Brain Science and Intelligence Technology Shanghai,Chinese Academy of Sciences,Shanghai,China [6]Chinese Institute for Brain Research,Beijing,China

出　　处：《Stroke & Vascular Neurology》2023年第2期103-110,共8页卒中与血管神经病学（英文）

基　　金：supported by grants from National Natural Science Foundation of China(grant number 82171270,81870905,U20A20358);Natural Science Foundation of Beijing(Z200016);Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2019-I2M 5-029).

摘　　要：Background Somatic mutation contributes to clonal haematopoiesis of indeterminate potential(CHIP)is related to age and associated with a higher risk of stroke and atherosclerotic cardiovascular disease.Here,we investigated the prognostic significance of CHIP in a large first-ever acute ischaemic stroke(AIS)cohort and explored the underlying mechanisms.Methods We studied a prospective cohort of 6016 patients who had a first-ever AIS in China.Whole-genome sequencing was performed to identify CHIP.High-sensitivity C reactive protein(hs-CRP)levels above 3 mg/L at baseline were defined as hyperinflammation.Recurrent stroke during the 3-month follow-up was the primary outcome.Results Among the 6016 patients who had a first-ever AIS,with a median age was 62 years(IQR,54.0‒70.0),3.70%were identified as CHIP carriers.The most common mutations occurred in the DNMT3A(30.0%)and TET2(11.4%)genes.During a follow-up of 3 months,the presence of CHIP was associated with recurrent stroke(HR 1.62,95%CI 1.04 to 2.51,p=0.03),recurrent ischaemic stroke(HR 1.64,95%CI 1.04 to 2.58,p=0.03)and combined vascular events(HR 1.58,95%CI 1.02 to 2.44,p=0.04)after adjusting for hsCRP levels at baseline in patients who had a first-ever AIS.Subgroup analysis demonstrated that CHIP was only associated with recurrent stroke when patients under hyperinflammation(OR 3.10,95%CI 1.92 to 5.00,p<0.001)but not in those without hyperinflammation(OR 0.18,95%CI 0.03 to 1.04,p=0.06,Pinteraction=0.002).Conclusion Our results suggest that somatic mutations contributing to CHIP increase the risk of short-term recurrent stroke in patients who had a first-ever AIS.Hyperinflammation may be important in the relationship between CHIP and recurrent stroke.

关 键 词：INFLAMMATION PROSPECTIVE acute 

分 类 号：R743.3[医药卫生—神经病学与精神病学]