This AHA scientific statement reviewed the emerging evidence on clonal hematopoiesis and its cardiovascular implications, describing how somatic mutations in hematopoietic stem cells drive inflammation and increase cardiovascular risk independent of traditional risk factors.
Clonal hematopoiesis (CH), the benign clonal expansion of hematopoietic stem cells, is often caused by somatic sequence variations in genes associated with hematologic malignancies. Over the past decade, CH has emerged as a risk factor for a wide range of cardiovascular diseases (CVDs), including atherosclerosis, heart failure, atrial fibrillation, and thrombosis. The cardiovascular risk associated with CH is heterogeneous; it varies on the basis of specific genes and variants, clone size, and various extrinsic features. Mechanistic studies suggest that CH contributes to CVDs through both gene-specific pathways and broader inflammatory processes. These include aberrant cytokine production, inflammasome activation, and other proinflammatory mechanisms, which can accelerate atherosclerosis, promote thrombogenesis, and impair vascular or myocardial function. These findings underscore the importance of addressing CH as a potential contributor to CVDs. CH is predominantly considered an age-
