Cardiovascular Disease, Aging, and Clonal Hematopoiesis

Annu Rev Pathol. 2020 Jan 24:15:419-438. doi: 10.1146/annurev-pathmechdis-012419-032544. Epub 2019 Nov 5.

Abstract

Traditional risk factors are incompletely predictive of cardiovascular disease development, a leading cause of death in the elderly. Recent epidemiological studies have shown that human aging is associated with an increased frequency of somatic mutations in the hematopoietic system, which provide a competitive advantage to a mutant cell, thus allowing for its clonal expansion, a phenomenon known as clonal hematopoiesis. Unexpectedly, these mutations have been associated with a higher incidence of cardiovascular disease, suggesting a previously unrecognized connection between somatic mutations in hematopoietic cells and cardiovascular disease. Here, we provide an up-to-date review of clonal hematopoiesis and its association with aging and cardiovascular disease. We also give a detailed report of the experimental studies that have been instrumental in understanding the relationship between clonal hematopoiesis and cardiovascular disease and have shed light on the mechanisms by which hematopoietic somatic mutations contribute to disease pathology.

Keywords: ARCH; CHIP; DNMT3A; IL-1β; TET2; age-related clonal hematopoiesis; clonal hematopoiesis of indeterminate potential; somatic mutations.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aging / genetics
  • Aging / physiology*
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / etiology*
  • Cells, Cultured
  • Clonal Evolution / physiology*
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology*
  • Humans
  • Incidence
  • Mutation / physiology
  • Risk Factors