Faculty, Staff and Student Publications
Publication Date
3-1-2022
Journal
Stroke
Abstract
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
Adult, Aged, Aged, 80 and over, Clonal Hematopoiesis, DNA Methyltransferase 3A, DNA-Binding Proteins, Dioxygenases, Female, Hemorrhagic Stroke, Humans, Incidence, Ischemic Stroke, Male, Middle Aged, Prevalence, Repressor Proteins, Risk, brain ischemia, cardiovascular diseases, clonal hematopoiesis, humans, prospective studies
DOI
10.1161/STROKEAHA.121.037388
PMID
34743536
PMCID
PMC8885769
PubMedCentral® Posted Date
3-1-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Included in
Cardiology Commons, Cardiovascular Diseases Commons, Hematology Commons, Hemic and Lymphatic Diseases Commons, Public Health Commons