Abstract
Clonal hematopoiesis arises from somatic mutations that provide a fitness advantage to hematopoietic stem cells and the outgrowth of clones of blood cells. Clonal hematopoiesis commonly involves mutations in genes that are involved in epigenetic modifications, signaling and DNA damage repair. Clonal hematopoiesis has emerged as a major independent risk factor in atherosclerotic cardiovascular disease, thrombosis and heart failure. Studies in mouse models of clonal hematopoiesis have shown an increase in atherosclerosis, thrombosis and heart failure, involving increased myeloid cell inflammatory responses and inflammasome activation. Although increased inflammatory responses have emerged as a common underlying principle, some recent studies indicate mutation-specific effects. The discovery of the association of clonal hematopoiesis with cardiovascular disease and the recent demonstration of benefit of anti-inflammatory treatments in human cardiovascular disease converge to suggest that anti-inflammatory treatments should be directed to individuals with clonal hematopoiesis. Such treatments could target specific inflammasomes, common downstream mediators such as IL-1β and IL-6, or mutations linked to clonal hematopoiesis.