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Background <p>Clonal Hematopoiesis of Indeterminate Potential (CHIP) has emerged as a novel, non-traditional risk factor for atherosclerotic cardiovascular disease (ASCVD), driven by somatic mutations in hematopoietic stem cells. However, its role in South Asian populations with disproportionately high rates of premature coronary artery disease (CAD) remains underexplored.</p> Aim <p>To assess the prevalence of CHIP among Indian patients presenting with acute coronary syndrome (ACS) and explore its association with clinical, biochemical, and angiographic characteristics.</p> Methods <p>In this prospective, case-control study, 72 patients aged ≥ 40 years with ACS and 36 age- and sex-matched healthy controls were enrolled. Individuals with traditional risk factors or prior CAD were excluded. Peripheral blood samples underwent targeted next-generation sequencing for CHIP-associated mutations in 42 genes. Comparative analyses were performed between CHIP-positive and CHIP-negative participants.</p> Results <p>CHIP mutations were detected in 11.1% of ACS patients and 2.8% of controls (odds ratio: 4.4; p: 0.26). The most frequently mutated genes were TET2, DNMT3A, and ASXL1. CHIP carriers had significantly lower mean LDL levels (79.8 ± 36.6 vs. 109.9 ± 36.1&#xa0;mg/dL; <i>p</i> = 0.03) and higher prevalence of premature CAD family history (62.5% vs. 12.5%; <i>p</i> = 0.004). No significant differences were noted in CRP levels, echocardiographic findings, or angiographic severity between the two groups.</p> Conclusions <p>CHIP mutations are more prevalent in Indian ACS patients and may contribute to CAD via lipid-independent, pro-inflammatory mechanisms. These findings support incorporating CHIP into cardiovascular risk stratification, particularly in younger patients lacking traditional risk factors.</p>

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Genomic Insights into Acute Coronary Syndrome: Role of Clonal Hematopoiesis of Indeterminate Potential

  • 期刊论文

  • 发表日期：

    2026年1月16日

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  • Mayank Saini,
  • Sarthak Wadhera,
  • Rudra Narayan Swain,
  • Anand Balakrishnan,
  • Prabhjot Kaur,
  • Sreejesh Sreedharanunni,
  • Arihant Jain,
  • Rajesh Vijayvergiya,
  • Pankaj Malhotra

摘要

Background

Clonal Hematopoiesis of Indeterminate Potential (CHIP) has emerged as a novel, non-traditional risk factor for atherosclerotic cardiovascular disease (ASCVD), driven by somatic mutations in hematopoietic stem cells. However, its role in South Asian populations with disproportionately high rates of premature coronary artery disease (CAD) remains underexplored.

Aim

To assess the prevalence of CHIP among Indian patients presenting with acute coronary syndrome (ACS) and explore its association with clinical, biochemical, and angiographic characteristics.

Methods

In this prospective, case-control study, 72 patients aged ≥ 40 years with ACS and 36 age- and sex-matched healthy controls were enrolled. Individuals with traditional risk factors or prior CAD were excluded. Peripheral blood samples underwent targeted next-generation sequencing for CHIP-associated mutations in 42 genes. Comparative analyses were performed between CHIP-positive and CHIP-negative participants.

Results

CHIP mutations were detected in 11.1% of ACS patients and 2.8% of controls (odds ratio: 4.4; p: 0.26). The most frequently mutated genes were TET2, DNMT3A, and ASXL1. CHIP carriers had significantly lower mean LDL levels (79.8 ± 36.6 vs. 109.9 ± 36.1 mg/dL; p = 0.03) and higher prevalence of premature CAD family history (62.5% vs. 12.5%; p = 0.004). No significant differences were noted in CRP levels, echocardiographic findings, or angiographic severity between the two groups.

Conclusions

CHIP mutations are more prevalent in Indian ACS patients and may contribute to CAD via lipid-independent, pro-inflammatory mechanisms. These findings support incorporating CHIP into cardiovascular risk stratification, particularly in younger patients lacking traditional risk factors.