| Title: | Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease |
| Journal: | Journal of the American College of Cardiology |
| Published: | 1 May 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37197843/ |
| DOI: | https://doi.org/10.1016/j.jacc.2023.03.401 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10249057 |
Publication 11402
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Abstract
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP)-the age-related clonal expansion of blood stem cells with leukemia-associated mutations-is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear.</p>
OBJECTIVES: This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD.</p>
METHODS: Individuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression.</p>
RESULTS: Of 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001).</p>
CONCLUSIONS: CHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.</p>
18 Authors
- Esra D Gumuser
- Art Schuermans
- So Mi Jemma Cho
- Zachary A Sporn
- Md Mesbah Uddin
- Kaavya Paruchuri
- Tetsushi Nakao
- Zhi Yu
- Sara Haidermota
- Whitney Hornsby
- Lachelle D Weeks
- Abhishek Niroula
- Siddhartha Jaiswal
- Peter Libby
- Benjamin L Ebert
- Alexander G Bick
- Pradeep Natarajan
- Michael C Honigberg
1 Application
| Application ID | Title |
|---|---|
| 7089 | Exome Sequencing of All Premature Coronary Artery Disease Participants in UK Biobank |
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