Clonal Hematopoiesis and Risk of Stroke: Evidence From Over 800 000 Individuals Across 3 Cohorts.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition that increases risk for cardiovascular disease. However, its relationship with stroke remains uncertain. METHODS: To resolve these conflicting findings, we analyzed genomic and clinical data from 800 160 participants with genetic sequencing and medical records across 3 large-scale cohorts: the Vanderbilt BioVU biobank (United States; enrollment 2007-2022), the National Institutes of Health All of Us Research Program (United States; enrollment 2018-2023), and the UK Biobank (United Kingdom; enrollment 2006-2010). The median follow-up time was 4.4 years (interquartile range, 1.8-10.2) in BioVU, 1.9 years (interquartile range, 0.4-3.9) in All of Us, and 12.4 years (interquartile range, 11.7-13.1) in UK Biobank. Stroke events were identified and classified as ischemic or hemorrhagic using RESULTS: CHIP was associated with increased risk of incident stroke in the meta-analysis (hazard ratio [HR], 1.20 [95% CI, 1.14-1.27]; CONCLUSIONS: Our large-scale, multicohort study establishes CHIP as a determinant of incident stroke risk and IL (interleukin)-1-mediated inflammation as a targetable pathway to reduce this risk.