首次中风幸存者的遗传风险和预后:来自中国嘉理生物银行和英国生物银行的研究结果。

IF 7.7 1区 医学 Q1 CLINICAL NEUROLOGY
Neurology Pub Date : 2025-07-22 Epub Date: 2025-06-27 DOI:10.1212/WNL.0000000000213832
Yuting Han, Hongjing Shi, Canqing Yu, Pei Pei, Ling Yang, Iona Y Millwood, Robin G Walters, Yiping Chen, Huaidong Du, Meiyu Guan, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Li, Dianjianyi Sun, Jun Lv
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引用次数: 0

摘要

背景和目的:卒中以预后不良而闻名。尽管遗传仪器在对普通人群的首次中风风险进行分层方面显示出了希望,但它们是否与中风预后相关尚不清楚。我们的研究旨在探讨卒中的遗传风险在中国和英国从无卒中到首次卒中再到复发性卒中、随后的冠心病(CHD)和死亡的进展中的作用。方法:我们使用来自中国嘉道理生物银行(CKB)和英国生物银行(UKB)两个前瞻性人群队列的数据。受试者在基线时没有中风和冠心病。使用综合多基因风险评分(iprs)对卒中的遗传风险进行量化,该评分纳入了卒中结局及其亚型和血管风险特征的多个全基因组关联研究的汇总统计数据。我们使用了一个多状态模型来分析遗传风险在从基线到首次卒中,再到复发性卒中,随后的冠心病和死亡的转变中的作用。结果:我们的研究包括80,908名CKB参与者和380,348名UKB参与者,平均年龄(女性百分比)分别为54.0岁(58.6%)和56.1岁(55.4%)。在中位随访期间,CKB和UKB分别为11.9年和13.4年,13,481和5,772名参与者首次中风,没有经历冠心病,也没有在28天内死亡。这些幸存者分别有5707和943例复发性中风,以及1196和418例冠心病事件。在这两个人群中,卒中幸存者的iprs与卒中复发和冠心病相关。CKB组相应的风险比(HRs)和95% ci / SD分别为1.08(1.05 ~ 1.11)和1.08 (1.02 ~ 1.15),UKB组分别为1.11(1.03 ~ 1.19)和1.23(1.10 ~ 1.37)。iprs与死亡风险之间没有关联。当我们进一步将首次卒中分为4种病理亚型时,两种人群都显示iprs与首次缺血性卒中向复发性卒中和冠心病转变之间存在统计学意义上的相关性。讨论:我们的研究表明,首次卒中的遗传风险也会影响卒中幸存者的预后,提示PRS具有改善卒中预后的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic Risk and Prognosis of the First Incident Stroke Survivors: Findings from China Kadoorie Biobank and UK Biobank.

Background and objectives: Stroke is known for its poor prognosis. Although genetic instruments have shown promise in stratifying first stroke risk in the general population, it is unknown whether they are associated with stroke prognosis. Our study aims to explore the role of genetic risk of stroke in the progression from stroke-free to first stroke and then to recurrent stroke, subsequent coronary heart disease (CHD), and death in China and the United Kingdom.

Methods: We used data from 2 prospective population-based cohorts, China Kadoorie Biobank (CKB) and UK Biobank (UKB). Participants who were unrelated and free of stroke and CHD at baseline were included. Genetic risks of stroke were quantified using integrative polygenic risk scores (iPRSs), which incorporated summary statistics from multiple genome-wide association studies for stroke outcomes and its subtypes, and vascular-risk traits. We used a multistate model to analyze the roles of genetic risk in the transitions from baseline to first incident stroke and then to recurrent stroke, subsequent CHD, and death.

Results: Our study included 80,908 CKB participants and 380,348 UKB participants, with mean ages (% female) of 54.0 years (58.6%) and 56.1 years (55.4%). During median follow-ups of 11.9 years and 13.4 years in the CKB and UKB, respectively, 13,481 and 5,772 participants had their first stroke, neither experienced a CHD, or died within 28 days. These survivors had 5,707 and 943 recurrent strokes, as well as 1,196 and 418 CHD events, respectively. iPRSs were associated with recurrent stroke and CHD among stroke survivors in both populations. The corresponding hazard ratios (HRs) and 95% CIs per SD of iPRSs were 1.08 (1.05-1.11) and 1.08 (1.02-1.15) in CKB and 1.11 (1.03-1.19) and 1.23 (1.10-1.37) in UKB, respectively. There was no association between iPRSs and mortality risk. When we further divided the first stroke into 4 pathologic subtypes, both populations revealed statistically significant associations between iPRSs and the transitions from first ischemic stroke to recurrent stroke and CHD.

Discussion: Our study shows that the genetic risk of first stroke also influences the prognosis of stroke survivors, indicating that PRS has the potential to improve stroke prognosis.

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来源期刊
Neurology
Neurology 医学-临床神经学
CiteScore
12.20
自引率
4.00%
发文量
1973
审稿时长
2-3 weeks
期刊介绍: Neurology, the official journal of the American Academy of Neurology, aspires to be the premier peer-reviewed journal for clinical neurology research. Its mission is to publish exceptional peer-reviewed original research articles, editorials, and reviews to improve patient care, education, clinical research, and professionalism in neurology. As the leading clinical neurology journal worldwide, Neurology targets physicians specializing in nervous system diseases and conditions. It aims to advance the field by presenting new basic and clinical research that influences neurological practice. The journal is a leading source of cutting-edge, peer-reviewed information for the neurology community worldwide. Editorial content includes Research, Clinical/Scientific Notes, Views, Historical Neurology, NeuroImages, Humanities, Letters, and position papers from the American Academy of Neurology. The online version is considered the definitive version, encompassing all available content. Neurology is indexed in prestigious databases such as MEDLINE/PubMed, Embase, Scopus, Biological Abstracts®, PsycINFO®, Current Contents®, Web of Science®, CrossRef, and Google Scholar.
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