Longevity & AgingBlood Cell Mutations Linked to 27–52% Higher Heart Failure Risk in 417K Adults
A large UK Biobank study of 417,616 adults found that clonal hematopoiesis of indeterminate potential (CHIP)—age-related mutations in blood stem cells—raises heart failure risk by 27% overall. Non-DNMT3A CHIP variants (TET2, ASXL1, JAK2, spliceosome genes) drove the strongest associations, with up to 4-fold elevated risk for JAK2 CHIP. DNMT3A CHIP showed a more modest 15% increased risk, significant only for the R882 hotspot variant. Importantly, known CHIP-related comorbidities like coronary artery disease, atrial fibrillation, diabetes, and chronic kidney disease explained only about 28% of the non-DNMT3A CHIP-heart failure link, suggesting direct cardiac mechanisms are at play.
