{"title":"体细胞突变促进克隆造血是首次急性缺血性卒中复发的危险因素:一项前瞻性队列研究。","authors":"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","doi":"10.1136/svn-2022-001756","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>DNMT3A</i> (30.0%) and <i>TET2</i> (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, P<sub>interaction</sub>=0.002).</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":22021,"journal":{"name":"Stroke and Vascular Neurology","volume":"8 2","pages":"103-110"},"PeriodicalIF":4.4000,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/03/svn-2022-001756.PMC10176982.pdf","citationCount":"1","resultStr":"{\"title\":\"Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study.\",\"authors\":\"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\",\"doi\":\"10.1136/svn-2022-001756\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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 <i>DNMT3A</i> (30.0%) and <i>TET2</i> (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, P<sub>interaction</sub>=0.002).</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":22021,\"journal\":{\"name\":\"Stroke and Vascular Neurology\",\"volume\":\"8 2\",\"pages\":\"103-110\"},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2023-04-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9d/03/svn-2022-001756.PMC10176982.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Stroke and Vascular Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/svn-2022-001756\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Stroke and Vascular Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/svn-2022-001756","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 1
摘要
背景:体细胞突变导致克隆性不确定潜能造血(CHIP)与年龄有关,并与卒中和动脉粥样硬化性心血管疾病的高风险相关。在这里,我们研究了CHIP在首次急性缺血性卒中(AIS)队列中的预后意义,并探讨了其潜在机制。方法:我们研究了6016例中国首次AIS患者的前瞻性队列。全基因组测序鉴定CHIP。高敏C反应蛋白(hs-CRP)在基线水平高于3mg /L被定义为高炎症。3个月随访期间卒中复发是主要结局。结果:6016例首次AIS患者中,年龄中位数为62岁(IQR, 54.0-70.0), 3.70%为CHIP携带者。最常见的突变发生在DNMT3A(30.0%)和TET2(11.4%)基因。在3个月的随访中,CHIP的存在与卒中复发(HR 1.62, 95% CI 1.04 - 2.51, p=0.03)、缺血性卒中复发(HR 1.64, 95% CI 1.04 - 2.58, p=0.03)和合并血管事件(HR 1.58, 95% CI 1.02 - 2.44, p=0.04)相关,在首次AIS患者中调整基线hsCRP水平后。亚组分析显示,CHIP仅与高脂血症患者的卒中复发相关(OR 3.10, 95% CI 1.92 ~ 5.00, p互作=0.002)。结论:我们的研究结果表明,在首次AIS患者中,导致CHIP的体细胞突变增加了短期复发性卒中的风险。在CHIP与卒中复发之间的关系中,高炎症可能是重要的。
Somatic mutation contributing to clonal haematopoiesis is a risk factor of recurrent stroke in first-ever acute ischaemic stroke: a prospective cohort study.
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.
期刊介绍:
Stroke and Vascular Neurology (SVN) is the official journal of the Chinese Stroke Association. Supported by a team of renowned Editors, and fully Open Access, the journal encourages debate on controversial techniques, issues on health policy and social medicine.