Related Experiment Video
Updated: Jul 30, 2025
Bone Marrow Transplantation Procedures in Mice to Study Clonal Hematopoiesis
Published on: May 26, 2021
Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic
Esra D Gumuser1, Art Schuermans2, So Mi Jemma Cho3
1Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Insights
Clonal hematopoiesis of indeterminate potential (CHIP) predicts adverse cardiovascular events and mortality in patients with established atherosclerotic cardiovascular disease (ASCVD). Specific mutations like TET2 and spliceosome gene alterations indicate particularly high risks.
Area of Science:
- Cardiovascular Medicine
- Hematology
- Genetics
Background:
- Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related condition involving blood stem cells with leukemia-associated mutations.
- CHIP is recognized as a cardiovascular risk factor, but its prognostic significance in patients with existing atherosclerotic cardiovascular disease (ASCVD) requires further investigation.
Purpose of the Study:
- To determine if CHIP predicts adverse outcomes in individuals already diagnosed with established ASCVD.
Main Methods:
- Analysis of UK Biobank participants aged 40-70 with established ASCVD and whole-exome sequencing data.
- Primary outcome: composite of ASCVD events and all-cause mortality.
- Cox regression models assessed associations of CHIP (≥2% variant allele fraction), large CHIP clones (≥10%), and specific driver gene mutations with incident outcomes.
Main Results:
- Out of 13,129 individuals, 5.1% had CHIP. Over 10.8 years, CHIP was associated with increased risk of the primary outcome (adjusted HR: 1.23).
- Large CHIP clones showed a higher risk (adjusted HR: 1.34).
- TET2 and spliceosome gene CHIP, particularly large clones, were strongly linked to adverse outcomes (large TET2 CHIP HR: 1.89; large spliceosome CHIP HR: 3.02).
Conclusions:
- CHIP is an independent predictor of adverse outcomes in individuals with established ASCVD.
- Patients with TET2 or spliceosome gene CHIP, especially large clones, face significantly elevated risks.
Background:
Clonal hematopoiesis of indeterminate potential (CHIP)-the age-related clonal expansion of blood stem cells with leukemia-associated mutations-is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear.
Objectives:
This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD.
Methods:
Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression.
Results:
Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001).
Conclusions:
CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.
More Related Videos
08:14Lentiviral CRISPR/Cas9-Mediated Genome Editing for the Study of Hematopoietic Cells in Disease Models
Published on: October 3, 2019
09:32Clonal Analysis of Embryonic Hematopoietic Stem Cell Precursors Using Single Cell Index Sorting Combined with Endothelial Cell Niche Co-culture
Published on: May 8, 2018
Related Concept Videos
01:19Multipotency of Hematopoietic Stem Cells
01:21Lineage Commitment
01:01Regulation of Hematopoietic Stem Cells
01:34Production of Formed Elements
Most HSCs commit to...
01:21Hematopoiesis
01:20Overview of Hematopoiesis
Developmental Phases of Hematopoiesis
Initially, HSCs are formed in the embryonic yolk sac, a critical site for early blood cell production. These stem cells subsequently migrate to other...