Han Yuting, Shi Hongjing, Yu Canqing, Pei Pei, Yang Ling, Millwood Iona Y, Walters Robin G, Chen Yiping, Du Huaidong, Guan Meiyu, Avery Daniel, Chen Junshi, Chen Zhengming, Li Liming, Sun Dianjianyi, Lv Jun
Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing, China.
Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.
Neurology. 2025 Jul 22;105(2):e213832. doi: 10.1212/WNL.0000000000213832. Epub 2025 Jun 27.
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.
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.
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.
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.
中风预后较差。尽管基因工具在对普通人群首次中风风险进行分层方面显示出前景，但尚不清楚它们是否与中风预后相关。我们的研究旨在探讨中风遗传风险在中国和英国从无中风到首次中风、再到复发性中风、随后的冠心病（CHD）及死亡过程中的作用。
我们使用了来自两项基于人群的前瞻性队列研究的数据，即中国嘉道理生物银行（CKB）和英国生物银行（UKB）。纳入了基线时无亲属关系且无中风和冠心病的参与者。使用综合多基因风险评分（iPRSs）对中风的遗传风险进行量化，该评分纳入了多个全基因组关联研究针对中风结局及其亚型以及血管风险特征的汇总统计数据。我们使用多状态模型分析遗传风险在从基线到首次中风事件、再到复发性中风、随后的冠心病及死亡转变过程中的作用。
我们的研究纳入了80,908名CKB参与者和380,348名UKB参与者，平均年龄（女性比例）分别为54.0岁（58.6%）和56.1岁（55.4%）。在CKB和UKB中，分别进行了11.9年和13.4年的中位随访，13,481名和5,772名参与者首次中风，均未发生冠心病，或在28天内死亡。这些幸存者分别发生了5,707次和943次复发性中风，以及1,196次和418次冠心病事件。iPRSs与两个队列中中风幸存者的复发性中风和冠心病相关。在CKB中，iPRSs每标准差的相应风险比（HRs）和95%置信区间分别为1.08（1.05 - 1.11）和1.08（1.02 - 1.15），在UKB中分别为1.11（1.03 - 1.19）和1.23（1.10 - 1.37）。iPRSs与死亡风险之间无关联。当我们将首次中风进一步分为4种病理亚型时，两个队列均显示iPRSs与从首次缺血性中风到复发性中风及冠心病的转变之间存在统计学显著关联。
我们的研究表明，首次中风的遗传风险也会影响中风幸存者的预后，这表明多基因风险评分有改善中风预后的潜力。
