Genetic Risk and Prognosis of the First Incident Stroke Survivors

作者：Yuting Han, Hongjing Shi, Canqing Yu, Pei Pei, Ling Yang, Iona Y. Millwood, Robin Walters, Yiping Chen, Huaidong Du, Meiyu Guan, Daniel Avery, Junshi Chen, Zhengming Chen, Liming Li, Dianjianyi Sun, Jun Lv, for the China Kadoorie Biobank Collaborative Group · 发表于：Neurology · 年份：2025 · DOI：10.1212/wnl.0000000000213832 · 被引用次数：5 · 研究领域：Genetic Associations and Epidemiology、Renin-Angiotensin System Studies、Acute Ischemic Stroke Management

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,...