What question did this study set out to answer?

This study aims to determine if clonal hematopoiesis of indeterminate potential (CHIP) predicts adverse outcomes in patients with established atherosclerotic cardiovascular disease (ASCVD).

May 21, 2026Open Access

Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Atherosclerotic cardiovascular disease (ASCVD) (n=13129). Intervention: Clonal hematopoiesis of indeterminate potential (CHIP) vs. No CHIP. Primary outcome: Composite of ASCVD events and all-cause mortality (HR 1.23, 95% CI 1.10-1.38, p=< 0.001).

Key Result

Any CHIP was associated with an increased risk of ASCVD events and all-cause mortality in patients with established ASCVD (HR 1.23; 95% CI 1.10-1.38; P<0.001).

Key Points

This study aims to determine if clonal hematopoiesis of indeterminate potential (CHIP) predicts adverse outcomes in patients with established atherosclerotic cardiovascular disease (ASCVD).
Analyzed individuals aged 40 to 70 from the UK Biobank with ASCVD and available whole-exome sequences.
Compared outcomes in individuals with any CHIP and large CHIP clones using unadjusted and multivariable-adjusted Cox regression.
Primary outcome was a composite of ASCVD events and all-cause mortality.
5.1% of individuals had CHIP, with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) for any CHIP and 1.34 (95% CI: 1.17-1.53; P < 0.001) for large CHIP.
Large TET2 CHIP had an HR of 1.89 (95% CI: 1.40-2.55; P <0.001) and large spliceosome CHIP had HR of 3.02 (95% CI: 1.95-4.70; P < 0.001), indicating particularly high risks.

Study Design

Type

Cohort (n=13,129)

PICO

Population

Atherosclerotic cardiovascular disease (ASCVD) (n=13,129)

Intervention / Comparator

Clonal hematopoiesis of indeterminate potential (CHIP) vs No CHIP

Primary Outcome

Composite of ASCVD events and all-cause mortality — HR 1.23 (1.10-1.38), p=< 0.001

Main Result

Effect estimate: HR 1.23 (95% CI 1.10-1.38)

p-value: p=< 0.001

Abstract

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.

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