Clonal haematopoiesis of indeterminate potential and mortality in coronary artery disease
Main finding · All-cause mortalityResult — go to the resultHazard ratio 1.39 95% CI 1.16–1.65Authors' conclusion
Clonal haematopoiesis of indeterminate potential is a predictor of mortality in CAD patients. TET2 mutations promote a pro-atherogenic macrophage phenotype via LDLR up-regulation and inflammatory activation, linking epigenetic dysregulation to adverse outcomes in CAD.
Study context
- Population
- Patients with angiographically confirmed coronary artery disease (CAD)
- Participants
- 8,612 patients2,389 matched pairs
- Exposure
- Clonal haematopoiesis of indeterminate potential (CHIP) carriers vs non-carriers
- Outcome
- All-cause mortality
- Follow-up
- 3 years
Methodological detailspropensity-score matched 1:1, targeted deep sequencing of 13 CHIP driver genes, multi-omics (MISSION, Athero-Express, STARNET) and CRISPR/Cas9 TET2+/- macrophages in vitro
- Propensity-score matched 1:1
- Targeted deep sequencing of 13 CHIP driver genes
- Multi-omics (MISSION, Athero-Express, STARNET) and CRISPR/Cas9 TET2+/- macrophages in vitro
Main finding
As reported in the abstract
Hazard ratio
1.39
95% CI 1.16–1.65
P < 0.001
CHIP carriers vs non-carriers
HR 1.39 (95% CI 1.16–1.65); P < 0.001
Observational data: associations, not effects.
Further findings
Mortality by mutated gene
- Mutations in TET2, ASXL1, DNMT3A, JAK2, PPM1D, SF3B1, SRSF2 and U2AF1 individually conferred higher mortality risk
Plaque and macrophage mechanisms (TET2)
- CHIP mutations found in lesional macrophages in human plaques
- TET2 CHIP carriers: increased necrotic core size, inflammation, reduced plaque stability
- Multi-omics: up-regulation of lipid metabolism and inflammatory pathways
- TET2+/- macrophages: increased LDLR expression and lipid uptake, enhanced chromatin accessibility at LDLR promoter
- Carotid plaques of TET2 CHIP carriers: increased LDLR and inflammasome-related gene expression
Original publication
Clonal haematopoiesis of indeterminate potential and mortality in coronary artery disease. Eur Heart J. Published 3 September 2025. doi:10.
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