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Clonal Hematopoiesi...
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Gumuser, Esra D.Massachusetts General Hospital
(författare)
Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease
- Artikel/kapitelEngelska2023
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Nummerbeteckningar
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LIBRIS-ID:oai:lup.lub.lu.se:a1559a34-b8c3-4727-9466-37c08bc4c20e
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https://lup.lub.lu.se/record/a1559a34-b8c3-4727-9466-37c08bc4c20eURI
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https://doi.org/10.1016/j.jacc.2023.03.401DOI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Ämneskategori:ref swepub-contenttype
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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. Objectives: This study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD. 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. 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). 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.
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Biuppslag (personer, institutioner, konferenser, titlar ...)
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Schuermans, ArtMassachusetts Institute of Technology,Catholic University of Leuven,Massachusetts General Hospital
(författare)
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Cho, So Mi JemmaMassachusetts Institute of Technology,Massachusetts General Hospital
(författare)
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Sporn, Zachary A.Massachusetts General Hospital
(författare)
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Uddin, Md MesbahMassachusetts General Hospital,Massachusetts Institute of Technology
(författare)
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Paruchuri, KaavyaMassachusetts Institute of Technology,Massachusetts General Hospital
(författare)
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Nakao, TetsushiBrigham and Women's Hospital / Harvard Medical School,Massachusetts Institute of Technology,Dana-Farber Cancer Institute,Massachusetts General Hospital
(författare)
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Yu, ZhiMassachusetts General Hospital,Massachusetts Institute of Technology
(författare)
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Haidermota, SaraMassachusetts Institute of Technology,Massachusetts General Hospital
(författare)
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Hornsby, WhitneyMassachusetts Institute of Technology,Massachusetts General Hospital
(författare)
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Weeks, Lachelle D.Dana-Farber Cancer Institute
(författare)
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Niroula, AbhishekLund University,Lunds universitet,Hematogenomics,Forskargrupper vid Lunds universitet,Lund University Research Groups,Dana-Farber Cancer Institute,Massachusetts Institute of Technology(Swepub:lu)med-anu
(författare)
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Jaiswal, SiddharthaStanford University School of Medicine
(författare)
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Libby, PeterBrigham and Women's Hospital / Harvard Medical School
(författare)
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Ebert, Benjamin L.Dana-Farber Cancer Institute
(författare)
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Bick, Alexander G.Vanderbilt University Medical Center
(författare)
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Natarajan, PradeepMassachusetts General Hospital,Massachusetts Institute of Technology
(författare)
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Honigberg, Michael C.Massachusetts Institute of Technology,Massachusetts General Hospital
(författare)
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Massachusetts General HospitalMassachusetts Institute of Technology
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of the American College of Cardiology81:20, s. 1996-20090735-1097
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Gumuser, Esra D.
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Schuermans, Art
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Cho, So Mi Jemma
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Sporn, Zachary A ...
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Uddin, Md Mesbah
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Paruchuri, Kaavy ...
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Nakao, Tetsushi
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Yu, Zhi
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Haidermota, Sara
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Hornsby, Whitney
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Weeks, Lachelle ...
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Niroula, Abhishe ...
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Jaiswal, Siddhar ...
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Libby, Peter
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Ebert, Benjamin ...
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Bick, Alexander ...
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