DNMT3A clonal hematopoiesis is associated with cardiovascular disease in women

BACKGROUND: Clonal hematopoiesis (CH) is an independent risk factor for cardiovascular disease (CVD). Targeted next generation sequencing (NGS) studies have highlighted the contribution of smaller clones to CVD, particularly for DNMT3A and TET2 CH, the most frequent CH mutations. DNMT3A CH occurs more frequently in women than men. Whether sex affects the association between CH and CVD is unknown. METHODS: We included 5508 participants from the Lifelines cohort, who had previously undergone targeted NGS. Our cohort is enriched for blood count abnormalities. We investigated the sex-specific associations between CH and prior myocardial infarction (MI) or coronary artery calcium (CAC) and evaluated the association of sex or prior MI with clonal expansion. RESULTS: ). CONCLUSIONS: DNMT3A CH is associated with previous MI and higher atherosclerotic burden only in women, highlighting the need to better understand the sex-specific risks that CH may confer on CVD.