Clonal Hematopoiesis Is Associated With Higher Risk of Stroke

Stroke. 2022 Mar;53(3):788-797. doi: 10.1161/STROKEAHA.121.037388. Epub 2021 Nov 8.


Background and purpose: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel age-related risk factor for cardiovascular disease-related morbidity and mortality. The association of CHIP with risk of incident ischemic stroke was reported previously in an exploratory analysis including a small number of incident stroke cases without replication and lack of stroke subphenotyping. The purpose of this study was to discover whether CHIP is a risk factor for ischemic or hemorrhagic stroke.

Methods: We utilized plasma genome sequence data of blood DNA to identify CHIP in 78 752 individuals from 8 prospective cohorts and biobanks. We then assessed the association of CHIP and commonly mutated individual CHIP driver genes (DNMT3A, TET2, and ASXL1) with any stroke, ischemic stroke, and hemorrhagic stroke.

Results: CHIP was associated with an increased risk of total stroke (hazard ratio, 1.14 [95% CI, 1.03-1.27]; P=0.01) after adjustment for age, sex, and race. We observed associations with CHIP with risk of hemorrhagic stroke (hazard ratio, 1.24 [95% CI, 1.01-1.51]; P=0.04) and with small vessel ischemic stroke subtypes. In gene-specific association results, TET2 showed the strongest association with total stroke and ischemic stroke, whereas DMNT3A and TET2 were each associated with increased risk of hemorrhagic stroke.

Conclusions: CHIP is associated with an increased risk of stroke, particularly with hemorrhagic and small vessel ischemic stroke. Future studies clarifying the relationship between CHIP and subtypes of stroke are needed.

Keywords: brain ischemia; cardiovascular diseases; clonal hematopoiesis; humans; prospective studies.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Clonal Hematopoiesis / genetics
  • Clonal Hematopoiesis / physiology*
  • DNA Methyltransferase 3A / genetics
  • DNA-Binding Proteins / genetics
  • Dioxygenases / genetics
  • Female
  • Hemorrhagic Stroke / epidemiology*
  • Hemorrhagic Stroke / genetics
  • Hemorrhagic Stroke / physiopathology
  • Humans
  • Incidence
  • Ischemic Stroke / epidemiology*
  • Ischemic Stroke / genetics
  • Ischemic Stroke / physiopathology
  • Male
  • Middle Aged
  • Prevalence
  • Repressor Proteins / genetics
  • Risk


  • ASXL1 protein, human
  • DNA-Binding Proteins
  • Repressor Proteins
  • Dioxygenases
  • TET2 protein, human
  • DNA Methyltransferase 3A

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