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.96150.2
YOU?
·
· 2024
· Open Access
·
· DOI: https://doi.org/10.7554/elife.96150.2
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 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 myocardial infarction (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 hsCRP 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 five-year period, particularly in those lacking mLOY. Conclusion 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 contribute 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.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.7554/elife.96150.2
- OA Status
- gold
- References
- 39
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4402926685
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4402926685Canonical identifier for this work in OpenAlex
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https://doi.org/10.7554/elife.96150.2Digital 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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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2024Year of publication
- Publication date
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2024-09-27Full publication date if available
- Authors
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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
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https://doi.org/10.7554/elife.96150.2Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.7554/elife.96150.2Direct OA link when available
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Mosaic, Biology, Genetics, Medicine, History, ArchaeologyTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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