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Association Between Aortic Valve Sclerosis and Clonal Hematopoiesis of Indeterminate Potential

 Minkwan Kim  ;  Jin Ju Kim  ;  Seung-Tae Lee  ;  Yeeun Shim  ;  Hyeonah Lee  ;  SungA Bae  ;  Nak-Hoon Son  ;  Saeam Shin  ;  In Hyun Jung 
 ANNALS OF LABORATORY MEDICINE, Vol.44(3) : 279-288, 2024-05 
Journal Title
Issue Date
Aged ; Aged, 80 and over ; Aortic Valve / diagnostic imaging ; Aortic Valve / pathology ; Aortic Valve Stenosis* / diagnosis ; Aortic Valve Stenosis* / genetics ; Aortic Valve Stenosis* / pathology ; Calcinosis* / pathology ; Clonal Hematopoiesis ; Female ; Humans ; Male ; Middle Aged ; Sclerosis / pathology
Aortic valve sclerosis ; Clonal hematopoiesis ; High-throughput nucleotide sequencing ; Inflammation ; Variant allele frequency
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 ef?fect of clonal hematopoiesis of indeterminate potential (CHIP) on the development of aor?tic valve sclerosis (AVS), a calcified aortic valve without significant stenosis.

Methods: Participants with AVS (valves ≥2 mm thick, high echogenicity, and a peak trans?aortic 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 gen?erate 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 associ?ated 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

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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Laboratory Medicine (진단검사의학교실) > 1. Journal Papers
Yonsei Authors
Kim, Minkwan(김민관) ORCID logo https://orcid.org/0000-0002-4079-8219
Kim, Jin Ju(김진주) ORCID logo https://orcid.org/0000-0001-9166-1848
Bae, SungA(배성아) ORCID logo https://orcid.org/0000-0003-1484-4645
Shin, Saeam(신새암) ORCID logo https://orcid.org/0000-0003-1501-3923
Lee, Seung-Tae(이승태) ORCID logo https://orcid.org/0000-0003-1047-1415
Jung, In Hyun(정인현) ORCID logo https://orcid.org/0000-0002-1793-215X
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