Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studies Article Swipe
Sami Fawaz
,
Severine Marti
,
Mélody Dufossée
,
Yann Pucheu
,
Astrid Gaufroy
,
Jean Broitman
,
Audrey Bidet
,
Aïcha Soumaré
,
Gaëlle Munsch
,
Christophe Tzourio
,
Stéphanie Debette
,
David‐Alexandre Trégouët
,
Chloé James
,
Olivier Mansier
,
Thierry Couffinhal
·
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.7554/elife.96150
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.7554/elife.96150
Background: Clonal hematopoiesis of indeterminate potential (CHIP) was initially linked to a twofold increase in atherothrombotic events. However, recent investigations have revealed a more nuanced picture, suggesting that CHIP may confer only a modest rise in myocardial infarction (MI) risk. This observed lower risk might be influenced by yet unidentified factors that modulate the pathological effects of CHIP. Mosaic loss of the Y chromosome (mLOY), a common marker of clonal hematopoiesis in men, has emerged as a potential candidate for modulating cardiovascular risk associated with CHIP. In this study, we aimed to ascertain the risk linked to each somatic mutation or mLOY and explore whether mLOY could exert an influence on the cardiovascular risk associated with CHIP. Methods: We conducted an examination for the presence of CHIP and mLOY using targeted high-throughput sequencing and digital PCR in a cohort of 446 individuals. Among them, 149 patients from the CHAth study had experienced a first MI at the time of inclusion (MI(+) subjects), while 297 individuals from the Three-City cohort had no history of cardiovascular events (CVE) at the time of inclusion (MI(-) subjects). All subjects underwent thorough cardiovascular phenotyping, including a direct assessment of atherosclerotic burden. Our investigation aimed to determine whether mLOY could modulate inflammation, atherosclerosis burden, and atherothrombotic risk associated with CHIP. Results: CHIP and mLOY were detected with a substantial prevalence (45.1% and 37.7%, respectively), and their occurrence was similar between MI(+) and MI(-) subjects. Notably, nearly 40% of CHIP(+) male subjects also exhibited mLOY. Interestingly, neither CHIP nor mLOY independently resulted in significant increases in plasma hs-CRP levels, atherosclerotic burden, or MI incidence. Moreover, mLOY did not amplify or diminish inflammation, atherosclerosis, or MI incidence among CHIP(+) male subjects. Conversely, in MI(-) male subjects, CHIP heightened the risk of MI over a 5 y period, particularly in those lacking mLOY. Conclusions: Our study highlights the high prevalence of CHIP and mLOY in elderly individuals. Importantly, our results demonstrate that neither CHIP nor mLOY in isolation substantially contributes to inflammation, atherosclerosis, or MI incidence. Furthermore, we find that mLOY does not exert a significant influence on the modulation of inflammation, atherosclerosis burden, or atherothrombotic risk associated with CHIP. However, CHIP may accelerate the occurrence of MI, especially when unaccompanied by mLOY. These findings underscore the complexity of the interplay between CHIP, mLOY, and cardiovascular risk, suggesting that large-scale studies with thousands more patients may be necessary to elucidate subtle correlations. Funding: This study was supported by the Fondation Cœur & Recherche (the Société Française de Cardiologie), the Fédération Française de Cardiologie, ERA-CVD (« CHEMICAL » consortium, JTC 2019) and the Fondation Université de Bordeaux. The laboratory of Hematology of the University Hospital of Bordeaux benefitted of a convention with the Nouvelle Aquitaine Region (2018-1R30113-8473520) for the acquisition of the Nextseq 550Dx sequencer used in this study. Clinical trial number: NCT04581057 .
Related Topics
Concepts
Medicine
Myocardial infarction
Internal medicine
Digital polymerase chain reaction
Prospective cohort study
Oncology
Biology
Bioinformatics
Genetics
Gene
Polymerase chain reaction
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.7554/elife.96150
- OA Status
- gold
- References
- 47
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4396570751
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4396570751Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.7554/elife.96150Digital Object Identifier
- Title
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Evaluation of clonal hematopoiesis and mosaic loss of Y chromosome in cardiovascular risk: An analysis in prospective studiesWork title
- Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2024Year of publication
- Publication date
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2024-05-02Full publication date if available
- Authors
-
Sami Fawaz, Severine Marti, Mélody Dufossée, Yann Pucheu, Astrid Gaufroy, Jean Broitman, Audrey Bidet, Aïcha Soumaré, Gaëlle Munsch, Christophe Tzourio, Stéphanie Debette, David‐Alexandre Trégouët, Chloé James, Olivier Mansier, Thierry CouffinhalList of authors in order
- Landing page
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https://doi.org/10.7554/elife.96150Publisher landing page
- Open access
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YesWhether a free full text is available
- OA status
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goldOpen access status per OpenAlex
- OA URL
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https://doi.org/10.7554/elife.96150Direct OA link when available
- Concepts
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Medicine, Myocardial infarction, Internal medicine, Digital polymerase chain reaction, Prospective cohort study, Oncology, Biology, Bioinformatics, Genetics, Gene, Polymerase chain reactionTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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47Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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