Emerging Role of Acquired Mutations and Clonal Hematopoiesis in Atherosclerosis

Accumulating evidence suggests that conventional cardiovascular risk factors are incompletely predictive of cardiovascular disease, as a substantial risk remains even when these factors are apparently managed well. In this context, clonal hematopoiesis has emerged as a new and potent risk factor for atherosclerotic cardiovascular disease and other cardiometabolic conditions. Clonal hematopoiesis typically arises from somatic mutations that confer a competitive advantage to a mutant hematopoietic stem cell, leading to its clonal expansion in the stem cell population and its progeny of blood leukocytes. Human sequencing studies and experiments in mice suggest that clonal hematopoiesis, at least when driven by certain mutations, contributes to accelerated athero-sclerosis development. However, the epidemiology, biology and clinical implications of this phenomenon remain incompletely under-stood. Here, we review the current understanding of the connection between clonal hematopoiesis and atherosclerosis, and highlight knowledge gaps in this area of research.

Automated summary

Accumulating evidence suggests that conventional cardiovascular risk factors are incomplete predictors of cardiovascular disease, as a substantial risk remains even when these factors are well-managed. Clonal hematopoiesis has emerged as a new and potent risk factor for atherosclerotic cardiovascular disease and other cardiometabolic conditions. However, the understanding of the epidemiology, biology, and clinical implications of this phenomenon remains incomplete.