Association of Life's Essential 8 With Clonal Hematopoiesis and Coronary Artery Disease.

BACKGROUND: Clonal hematopoiesis (CH), characterized by clonal expansion of hematopoietic stem cells harboring preleukemic mutations, is an emerging cardiovascular disease risk factor. The American Heart Association's Life's Essential 8 (LE8) score is the contemporary standard for quantifying cardiovascular health. However, the interplay between this novel genetic risk factor and classical health metrics remains unknown. OBJECTIVES: This study sought to examine the association between LE8 score and CH prevalence, and determine their joint effects on incident coronary artery disease (CAD). METHODS: We analyzed 427,295 UK Biobank participants. Exposures included LE8 score and CH (evaluated as a composite and by common drivers: DNMT3A, TET2, ASXL1). Associations with CH prevalence and incident CAD over a median 13.6-year follow-up were evaluated using multivariable regression. RESULTS: = 0.005). Participants with ASXL1 CH subtype and low LE8 scores experienced the highest absolute CAD risk (18.7 vs 2.0 events/1,000 person-years in noncarriers with high LE8). CONCLUSIONS: Optimal cardiovascular health is associated with a lower prevalence of CH. Although maintaining ideal cardiovascular health is associated with lower CAD risk in CH carriers, this protective benefit is attenuated compared with noncarriers.