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Clonal hematopoiesis of indeterminate potential in patients with acute coronary syndrome undergoing percutaneous coronary intervention in the absence of traditional risk factors

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Abstract

Aims

To investigate the frequency of clonal hematopoiesis of indeterminate potential (CHIP) and evaluate its impacts on outcomes in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) in the absence of traditional cardiovascular risk factors (CVRFs).

Methods

Whole-exome sequencing was performed to detect the presence of CHIP in 183 patients underwent PCI for the treatment of ACS. The association between CHIP-related mutations and major adverse cardiac or cerebral events (MACCEs, a composite of all-cause mortality, coronary revascularization, myocardial infarction, or stroke) was analyzed in such cohort.

Results

Of 179 patients [median age, 65 years; 84 female (46.9%)] included in this analysis, CHIP-related mutations were detected in 36 (20.1%) patients. The somatic mutations most frequently occurred in the genes DNMT3A (17 mutations), TET2 (6 mutations), and ASXL1 (4 mutations). Clinical outcomes at median 635 follow-up days showed that DNMT3A/TET2/ASXL1-CHIP mutations were associated with significantly higher risk of MACCEs, compared with non-CHIP carriers in the CVRFs-absent ACS cohort (26.1% vs. 4.2%, log-rank P = 0.001). Multivariable regression showed that DNMT3A/TET2/ASXL1-CHIP driver mutations (HR 4.015; 95% CI 1.236–13.046; P = 0.021) were independent predictors of adverse clinical outcomes.

Conclusion

The most frequent CHIP-related mutations, DNMT3A, TET2, and ASXL1 are significantly associated with increased risk of recurrent cardiovascular events. Our study may be valuable target to reduce residual risk in patients with ACS carrying specific mutations.

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Acknowledgements

We thank Prof. Siddhartha Jaiswal (Department of Pathology, Stanford University School of Medicine, USA) for constructive suggestions on CHIP-related gene list aspects.

Funding

This study was supported by the National Key Research and Development Project in China, Grant/Award Numbers: 2016YFC1301300, 2016YFC1301303.

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Author notes

  1. Zaixin Jiang and Yi Li contributed equally to this work.

Authors and Affiliations

  1. The Department of Cardiology, General Hospital of Northern Theater Command, No. 83 Wenhua Road, Shenyang, 110016, Liaoning Province, China

    Zaixin Jiang, Yi Li, Chenghui Yan, Xiaolin Zhang, Quanyu Zhang, Jing Li, Xiaoxiang Tian, Miaohan Qiu, Zhenyang Liang, Sichong Ma, Kun Na, Ziqi Li, Sanbao Chen, Yu Zhao, Zizhao Qi, Xiying Liu & Yaling Han

  2. The Department of Cardiology, Naval Medical University Changhai Hospital, Shanghai, China

    Zaixin Jiang

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  1. Zaixin Jiang
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Contributions

ZXJ and YL: designed the study, acquired and analyzed data, and wrote the manuscript; CHY, XLZ, QYZ, JL, XXT, MHQ and ZYL: assisted with study design; MHQ: assisted with data analysis; SCM, KN, ZQL, SBC, YZ, ZZQ and XYL: clinically examined study participants; and YLH: supervised the study, critically revised the manuscript, and obtained research funding.

Corresponding author

Correspondence to Yaling Han.

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The authors have declared that no conflict of interest exists.

Ethical approval

This study have been approved by the ethics review board of the General Hospital of Northern Theater Command and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments.

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Jiang, Z., Li, Y., Yan, C. et al. Clonal hematopoiesis of indeterminate potential in patients with acute coronary syndrome undergoing percutaneous coronary intervention in the absence of traditional risk factors. Clin Res Cardiol 112, 506–517 (2023). https://doi.org/10.1007/s00392-022-02039-6

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  • DOI: https://doi.org/10.1007/s00392-022-02039-6

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