Clonal hematopoiesis at the crossroads of Inflammaging and cardiovascular disease: Mechanistic insights and translational horizons.

Abstract

Clonal Hematopoiesis of indeterminate potential (CHIP) has been increasingly recognised as a risk factor for cardiovascular disease (CVD). Recent epidemiological and experimental studies have linked CHIP as an independent risk factor for myocardial infarction, stroke, and coronary artery disease, with specific mutations carrying a higher CVD risk. During the aging process, somatic mutations in genes, including DNMT3A and TET2, accumulate in the hematopoietic stem cells (HSCs), conferring both epigenetic and metabolic advantages that not only drive hematopoiesis towards a pro-inflammatory myeloid lineage but also reprogram innate immune cells, promoting a persistent inflammatory state. These myeloid derivatives, via increased IL-1β and IL-6 production, establish a pro-atherogenic environment and contribute to plaque instability, leading to an increased thrombotic risk and accelerated vascular aging. Although routine screening is not recommended for asymptomatic adults, targeted detection in high-risk individuals could benefit from preventive strategies. Incorporating CHIP into risk models may enable precision prevention, but prospective trials are needed to determine whether CHIP-guided interventions improve cardiovascular outcomes.