| Title: | Effect of clonal hematopoiesis of indeterminate potential on long-term survival in patients with arrhythmias |
| Journal: | Journal of Translational Medicine |
| Published: | 8 Aug 2026 |
| DOI: | https://doi.org/10.1186/s12967-026-08748-0 |
Publication 21038
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BackgroundClonal hematopoiesis of indeterminate potential(CHIP), defined by somatic mutations within hematopoietic clones, has emerged as a novel risk factor for cardiovascular disease. While cardiac arrhythmias are a major global health concern, the factors contributing to outcome variability remain unclear. The study aimed to investigate the association between CHIP and mortality in patients with arrhythmias.MethodsThis study analyzed UK Biobank participants hospitalized with arrhythmias who had whole-exome sequencing data. Arrhythmia subtypes were classified using ICD-10 codes. Outcomes, including all-cause, cardiovascular, and cancer-related mortality, were obtained from national registries. CHIP was defined as any CHIP as variant allele fraction(VAF) ≥ 2%, large CHIP as VAF ≥ 10%. Cox regression models adjusted for confounders were used.ResultsAmong 53,149 individuals (median age 69 years), 3,315 carried CHIP mutations. Both any and large CHIP were independently associated with higher mortality: adjusted hazard ratios (HRs) for all-cause mortality were 1.26 (1.19-1.34) and 1.44 (1.33-1.55), respectively; for cardiovascular mortality, 1.14 (1.02-1.27) and 1.31 (1.14-1.52); and for cancer-related mortality, 1.36 (1.23-1.51) and 1.65 (1.45-1.87). Associations persisted across arrhythmia subtypes, with the strongest effects in ventricular arrhythmias. In gene-specific analyses, TET2, TP53 and spliceosome genes appeared to be the strongest deleterious genes for all-cause mortality [large TET2 CHIP: HR 1.63 (1.40-1.90); large TP53 CHIP: 1.83 (1.18-2.84); large spliceosome CHIP: HR 1.85 (1.32-2.59)].ConclusionsCHIP is independently associated with increased mortality in patients with arrhythmias across different subtypes. These findings suggest that CHIP may serve as a potential prognostic marker and therapeutic target.</p>
12 Authors
- Lei Ding
- Panhui Tian
- Fengyuan Yu
- Zihan Jiang
- Yingjie Qi
- Aikai Zhang
- Yuandong Liu
- Yujing Shen
- Hongda Zhang
- Min Tang
- Tianyun Wang
- Junqing Xie
1 Application
| Application ID | Title |
|---|---|
| 217390 | Further understanding of cardiovascular and metabolic disorders using large cohort and multimodal data in the UK Biobank |
Enabling scientific discoveries that improve human health