Annals of Laboratory Medicine

Korean Society for Laboratory Medicine (대한진단검사의학회)
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Association Between Aortic Valve Sclerosis and Clonal Hematopoiesis of Indeterminate Potential

  • Minkwan Kim (Division of Cardiology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine and Cardiovascular Center) ;
  • Jin Ju Kim (Department of Laboratory Medicine, Yongin Severance Hospital, Yonsei University College of Medicine) ;
  • Seung-Tae Lee (Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • Yeeun Shim (Department of Laboratory Medicine, Graduate School of Medical Sciences, Brain Korea 21 PLUS Project, Yonsei University College of Medicine) ;
  • Hyeonah Lee (Department of Laboratory Medicine, Graduate School of Medical Sciences, Brain Korea 21 PLUS Project, Yonsei University College of Medicine) ;
  • SungA Bae (Division of Cardiology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine and Cardiovascular Center) ;
  • Nak-Hoon Son (Department of Statistics, Keimyung University) ;
  • Saeam Shin (Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine) ;
  • In Hyun Jung (Division of Cardiology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine and Cardiovascular Center)
  • Received : 2023.07.11
  • Accepted : 2023.12.14
  • Published : 2024.05.01
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Abstract

Background: The mechanism and medical treatment target for degenerative aortic valve disease, including aortic stenosis, is not well studied. In this study, we investigated the effect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aortic valve sclerosis (AVS), a calcified aortic valve without significant stenosis. Methods: Participants with AVS (valves ≥2 mm thick, high echogenicity, and a peak transaortic velocity of <2.5 m/sec) and an age- and sex-matched control group were enrolled. Twenty-four CHIP genes with common variants in cardiovascular disease were used to generate a next-generation sequencing panel. The primary endpoint was the CHIP detection rate between the AVS and control groups. Inverse-probability treatment weighting (IPTW) analysis was performed to adjust for differences in baseline characteristics. Results: From April 2020 to April 2022, 187 participants (125 with AVS and 62 controls) were enrolled; the mean age was 72.6±8.5 yrs, and 54.5% were male. An average of 1.3 CHIP variants was observed. CHIP detection, defined by a variant allele frequency (VAF) of ≥0.5%, was similar between the groups. However, the AVS group had larger CHIP clones: 49 (39.2%) participants had a VAF of ≥1% (vs. 13 [21.0%] in the control group; P=0.020), and 25 (20.0%) had a VAF of ≥2% (vs. 4 [6.5%]; P=0.028). AVS is independently associated with a VAF of ≥1% (adjusted odds ratio: 2.44, 95% confidence interval: 1.11-5.36; P=0.027). This trend was concordant and clearer in the IPTW cohort. Conclusions: Participants with AVS more commonly had larger CHIP clones than age- and sex-matched controls. Further studies are warranted to identify causality between AVS and CHIP.

Keywords

Acknowledgement

The authors thank Medical Illustration and Design (MID), a part of the Medical Research Support Services of the Yonsei University College of Medicine, for providing excellent support with the medical illustrations.

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