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

CH prevalence was 3.4%. A higher LE8 score was associated with significantly lower odds of CH and examined driver mutations, strongest for ASXL1 (OR: 0.79; 95% CI: 0.75-0.83; P < 0.001). CH significantly modified the protective effect of LE8 on CAD incidence on multiplicative and additive scales. A 1-SD increase in LE8 yielded an adjusted CAD HR of 0.74 (95% CI: 0.70-0.78) in CH carriers vs 0.68 (95% CI: 0.67-0.69) in noncarriers (Pinteraction = 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.