Association of Clonal Hematopoiesis With Incident Heart Failure
Key result
CHIP linked to ~25% higher risk of incident heart failure.
- HR 1.25
- 95% CI 1.13-1.38
- n=56,597
Why the study?
Age-related clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular events including recurrent heart failure, but its association with incident heart failure is unclear.
Does clonal hematopoiesis of indeterminate potential (CHIP) increase the risk of incident heart failure in individuals without prevalent HF?
Population
56,597 individuals without prevalent HF or hematologic malignancy from five cohorts
Comparison
Presence of CHIP vs absence of CHIP
Design
Meta-analysis of cohort studies
Follow-up
Up to 20 years
Authors
Discussion
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Implication
Clonal hematopoiesis of indeterminate potential (CHIP), particularly mutations in ASXL1, TET2, and JAK2, is independently associated with an increased risk of incident heart failure.
Key Points
- To determine whether age-related clonal hematopoiesis of indeterminate potential is prospectively associated with the development of incident heart failure in individuals free of baseline heart failure.
- Analyzed 56,597 participants (59% female, mean age 58 years at baseline) without prevalent heart failure or hematologic malignancy across five cohorts followed for up to 20 years.
- Determined clonal hematopoiesis of indeterminate potential (CHIP) status using whole-exome or whole-genome sequencing of blood DNA.
- Estimated heart failure risk using cohort-specific multivariable Cox proportional hazards models adjusted for demographic and clinical risk factors, pooled via fixed-effect meta-analyses.
- Among 56,597 individuals, 3,406 (6%) had CHIP, and 4,694 (8.3%) developed incident heart failure during follow-up.
- CHIP was prospectively associated with a 25% increased risk of incident heart failure (HR=1.25, 95% CI 1.13, 1.38), with large clones (variant allele frequency >10%) conferring higher risk (HR=1.29, 95% CI 1.15, 1.44).
- Mutations in ASXL1, TET2, and JAK2 were each significantly associated with increased heart failure risk, and ASXL1 mutations associated with reduced left ventricular ejection fraction, whereas DNMT3A mutations showed no association.
Study Design
Type
Cohort (n=56,597)
Multicenter
Yes
Structured PICO
Does clonal hematopoiesis of indeterminate potential (CHIP) increase the risk of incident heart failure in individuals without prevalent HF?
P
Population
56,597 individuals without prevalent heart failure or hematologic malignancy (mean age 58 years, 59% female) followed for up to 20 years.
E
Exposure
Presence of clonal hematopoiesis of indeterminate potential (CHIP)
C
Comparator
Absence of CHIP
O
Outcome
Incident heart failurehard clinical
Main Result
Hazard Ratio: 1.25 (95% CI 1.13–1.38)
Clonal hematopoiesis of indeterminate potential (CHIP), particularly mutations in ASXL1, TET2, and JAK2, is independently associated with an increased risk of incident heart failure.
Cite This Study
Yu et al. (2021) conducted a cohort in Incident Heart Failure (n=56,597). Clonal hematopoiesis of indeterminate potential (CHIP) vs. No CHIP was evaluated on Incident heart failure (HR 1.25, 95% CI 1.13-1.38). Clonal hematopoiesis of indeterminate potential (CHIP) was associated with a 25% increased risk of incident heart failure over up to 20 years of follow-up (HR 1.25; 95% CI 1.13-1.38).