The effect of clonal hematopoiesis on long-term outcomes in patients undergoing coronary artery bypass grafting

作者：Zhiwei Zeng, F Li, Shujie Gai, Runze Chen, Peng Wang, Juncheng Wang, Yuhui Yang, Jin-Hua Chen, Xingyi Zhang, Yuqin Wang, Yi Han, Chuxiang Lei, Xi Li, Hanning Liu, Zhe Zheng · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-04140-9 · 被引用次数：8 · 研究领域：Acute Myeloid Leukemia Research、Angiogenesis and VEGF in Cancer、Myeloproliferative Neoplasms: Diagnosis and Treatment

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP), characterized by age-related somatic mutations in hematopoietic stem and progenitor cells, has been identified as a potential risk factor for cardiovascular events and mortality. However, the significance of CHIP in the context of coronary artery bypass grafting (CABG) remains unexplored. We aim to investigate the potential impact of CHIP on long-term outcomes of patients who underwent CABG. METHODS: We conducted a nested case-control study with 497 patients from the randomized Statin Therapy in Cardiac Surgery (STICS) cohort (ClinicalTrials.gov number NCT01573143). CHIP mutations were identified using ultra-deep sequencing of a targeted panel of 23 genes, with a mean depth of coverage of 16,043x. The relationship between CHIP and major adverse cardiovascular and cerebrovascular events (MACCE), including all-cause death, non-fatal ischemic stroke (IS), and non-fatal myocardial infarction (MI), was analyzed using Cox proportional hazards models and Fine-Gray regression to account for competing risks. We also validated our findings using data from the selected UK Biobank cohort of CABG to assess the generalizability. RESULTS: CHIP with a variant allele frequency (VAF) ≥ 2% was detected in 91 patients (18.3%), while CHIP with lower VAF (≥ 0.1%) was present in 46.3% of patients. DNMT3A and TET2 were the most frequently mutated genes. Over a median follow-up of 6.0 years (interquartile range [IQR], 3.5-6.5 years),...