Prognostic significance of clonal hematopoiesis in STEMI: a 10-year follow-up reveals high-risk gene mutations

• Published in: Human genomics Vol. 19; no. 1; pp. 51 - 14
• Main Authors: Fan, Wen-Lang, Yeh, Jih-Kai, Hsieh, Li-Ching, Tsai, Ming-Lung, Ho, Ming-Yun, Huang, Yi-Chun, Hsieh, I-Chang, Wen, Ming-Shien, Wang, Chao-Yung
• Format: Journal Article
• Language: English
• Published: London BioMed Central 12.05.2025; BMC
• Subjects: Aged; Bioinformatics; Biomedical and Life Sciences; Biomedicine; Blood; Cardiovascular disease; Clonal hematopoiesis; Clonal Hematopoiesis - genetics; Comparative analysis; Exome Sequencing; Female; Follow-Up Studies; Gene frequency; Genes; Genetic Predisposition to Disease; Genomes; Genomics; Heart attacks; Heart failure; Hemopoiesis; Human Genetics; Humans; Ischemia; Major adverse cardiovascular events; Male; Middle Aged; Mortality; Mutation; Mutation - genetics; Myocardial infarction; Patients; Percutaneous Coronary Intervention; Point mutation; Prognosis; Proteomics; Repressor Proteins - genetics; Risk Factors; ST Elevation Myocardial Infarction - genetics; ST Elevation Myocardial Infarction - pathology; ST-segment elevation myocardial infarction; Survival analysis; Whole genome sequencing; Major adverse cardiovascular events; Clonal hematopoiesis; ST-segment elevation myocardial infarction
• ISSN: 1479-7364; 1473-9542; 1479-7364
• DOI: 10.1186/s40246-025-00757-2

Background To elucidate the extent and clinical implications of clonal hematopoiesis of indeterminate potential (CHIP) prevalence in patients with ST-segment elevation myocardial infarction (STEMI), and to evaluate its utility as a contributory factor for risk stratification in long-term outcomes. Methods Whole-exome sequencing was performed in a cohort of 101 patients presenting with STEMI who underwent emergency percutaneous coronary intervention. These patients were longitudinally followed for over 120 months. Their genomic data were compared with those from a control group of 706 individuals without cardiovascular events. Comparative analyses were conducted to identify patterns of CHIP between the STEMI and control cohorts. Results In our cohort, 37.6% (n = 38) of STEMI patients exhibited somatic mutations associated with CHIP at a variant allele frequency of 1% or greater, compared to 22.8% (n = 161) in the control group. The most frequently detected mutations in STEMI patients were in the ASXL1 and CREBBP genes, each present in 5.0% of this cohort. Long-term follow-up revealed that STEMI patients with CHIP had a higher incidence of major adverse cardiovascular events (MACEs), with an adjusted hazard ratio of 2.23 (95% confidence interval (CI) 1.16–4.28, p = 0.015). Conclusion CHIP is prevalent in the STEMI patient cohort and is significantly correlated with adverse clinical outcomes. Incorporating CHIP status could enhance the risk stratification process, thus informing more tailored clinical management strategies for STEMI patients.