| Title: | Clonal haematopoiesis of indeterminate potential predicts incident cardiac arrhythmias |
| Journal: | European Heart Journal |
| Published: | 11 Nov 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37952204/ |
| DOI: | https://doi.org/10.1093/eurheartj/ehad670 |
Publication 8348
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Abstract
BACKGROUND AND AIMS: Clonal haematopoiesis of indeterminate potential (CHIP), the age-related expansion of blood cells with preleukemic mutations, is associated with atherosclerotic cardiovascular disease and heart failure. This study aimed to test the association of CHIP with new-onset arrhythmias.</p>
METHODS: UK Biobank participants without prevalent arrhythmias were included. Co-primary study outcomes were supraventricular arrhythmias, bradyarrhythmias, and ventricular arrhythmias. Secondary outcomes were cardiac arrest, atrial fibrillation, and any arrhythmia. Associations of any CHIP [variant allele fraction (VAF) ≥ 2%], large CHIP (VAF ≥10%), and gene-specific CHIP subtypes with incident arrhythmias were evaluated using multivariable-adjusted Cox regression. Associations of CHIP with myocardial interstitial fibrosis [T1 measured using cardiac magnetic resonance (CMR)] were also tested.</p>
RESULTS: This study included 410 702 participants [CHIP: n = 13 892 (3.4%); large CHIP: n = 9191 (2.2%)]. Any and large CHIP were associated with multi-variable-adjusted hazard ratios of 1.11 [95% confidence interval (CI) 1.04-1.18; P = .001] and 1.13 (95% CI 1.05-1.22; P = .001) for supraventricular arrhythmias, 1.09 (95% CI 1.01-1.19; P = .031) and 1.13 (95% CI 1.03-1.25; P = .011) for bradyarrhythmias, and 1.16 (95% CI, 1.00-1.34; P = .049) and 1.22 (95% CI 1.03-1.45; P = .021) for ventricular arrhythmias, respectively. Associations were independent of coronary artery disease and heart failure. Associations were also heterogeneous across arrhythmia subtypes and strongest for cardiac arrest. Gene-specific analyses revealed an increased risk of arrhythmias across driver genes other than DNMT3A. Large CHIP was associated with 1.31-fold odds (95% CI 1.07-1.59; P = .009) of being in the top quintile of myocardial fibrosis by CMR.</p>
CONCLUSIONS: CHIP may represent a novel risk factor for incident arrhythmias, indicating a potential target for modulation towards arrhythmia prevention and treatment.</p>
23 Authors
- Art Schuermans
- Caitlyn Vlasschaert
- Victor Nauffal
- So Mi Jemma Cho
- Md Mesbah Uddin
- Tetsushi Nakao
- Abhishek Niroula
- Marcus D R Klarqvist
- Lachelle D Weeks
- Amy E Lin
- Seyedmohammad Saadatagah
- Kim Lannery
- Megan Wong
- Whitney Hornsby
- Steven A Lubitz
- Christie Ballantyne
- Siddhartha Jaiswal
- Peter Libby
- Benjamin L Ebert
- Alexander G Bick
- Patrick T Ellinor
- Pradeep Natarajan
- Michael C Honigberg
1 Application
| Application ID | Title |
|---|---|
| 7089 | Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank |
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