Clonal Hematopoiesis Is Associated with Higher Risk of Stroke

Romit Bhattacharya, Seyedeh M. Zekavat, Jeffrey Haessler, Myriam Fornage, Laura Raffield, Md Mesbah Uddin, Alexander G. Bick, Abhishek Niroula, Bing Yu, Christopher Gibson, Gabriel Griffin, Alanna C. Morrison, Bruce M. Psaty, William T. Longstreth, Joshua C. Bis, Stephen S. Rich, Jerome I. Rotter, Russell P. Tracy, Adolfo Correa, Sudha SeshadriAndrew Johnson, Jason M. Collins, Kathleen M. Hayden, Tracy E. Madsen, Christie M. Ballantyne, Siddhartha Jaiswal, Benjamin L. Ebert, Charles Kooperberg, Joann E. Manson, Eric A. Whitsel, Pradeep Natarajan, Alexander P. Reiner

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)788-797
Number of pages10
JournalStroke
Volume29
Issue number2
DOIs
StatePublished - Mar 1 2022

Keywords

  • brain ischemia
  • cardiovascular diseases
  • clonal hematopoiesis
  • humans
  • prospective studies

ASJC Scopus subject areas

  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine
  • Advanced and Specialized Nursing

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