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Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure.
Monday,2021-08-23 22:45 America/Los_Angeles — ecterry
| Title | Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure. |
| Publication Type | Journal Article |
| Year of Publication | 2021 |
| Authors | Yu, B, Roberts, MB, Raffield, LM, Zekavat, SMaryam, Nguyen, NQuynh H, Biggs, ML, Brown, MR, Griffin, G, Desai, P, Correa, A, Morrison, AC, Shah, AM, Niroula, A, Uddin, MMesbah, Honigberg, MC, Ebert, BL, Psaty, BM, Whitsel, EA, Manson, JAE, Kooperberg, C, Bick, AG, Ballantyne, CM, Reiner, AP, Natarajan, P, Eaton, CB |
| Corporate/Institutional Authors | National Heart, Lung, and Blood Institute TOPMed Consortium |
| Journal | J Am Coll Cardiol |
| Volume | 78 |
| Issue | 1 |
| Pagination | 42-52 |
| Date Published | 2021 07 06 |
| ISSN | 1558-3597 |
| Keywords | Aged, Clonal Hematopoiesis, Correlation of Data, Demography, DNA-Binding Proteins, Female, Heart Failure, Humans, Janus Kinase 2, Male, Middle Aged, Mutation, Proportional Hazards Models, Proto-Oncogene Proteins, Repressor Proteins, Risk Factors, Stroke Volume, Ventricular Dysfunction, Left, Whole Exome Sequencing |
| Abstract | <p><b>BACKGROUND: </b>Age-related clonal hematopoiesis of indeterminate potential (CHIP), defined as clonally expanded leukemogenic sequence variations (particularly in DNMT3A, TET2, ASXL1, and JAK2) in asymptomatic individuals, is associated with cardiovascular events, including recurrent heart failure (HF).</p><p><b>OBJECTIVES: </b>This study sought to evaluate whether CHIP is associated with incident HF.</p><p><b>METHODS: </b>CHIP status was obtained from whole exome or genome sequencing of blood DNA in participants without prevalent HF or hematological malignancy from 5 cohorts. Cox proportional hazards models were performed within each cohort, adjusting for demographic and clinical risk factors, followed by fixed-effect meta-analyses. Large CHIP clones (defined as variant allele frequency >10%), HF with or without baseline coronary heart disease, and left ventricular ejection fraction were evaluated in secondary analyses.</p><p><b>RESULTS: </b>Of 56,597 individuals (59% women, mean age 58 years at baseline), 3,406 (6%) had CHIP, and 4,694 developed HF (8.3%) over up to 20 years of follow-up. CHIP was prospectively associated with a 25% increased risk of HF in meta-analysis (hazard ratio: 1.25; 95% confidence interval: 1.13-1.38) with consistent associations across cohorts. ASXL1, TET2, and JAK2 sequence variations were each associated with an increased risk of HF, whereas DNMT3A sequence variations were not associated with HF. Secondary analyses suggested large CHIP was associated with a greater risk of HF (hazard ratio: 1.29; 95% confidence interval: 1.15-1.44), and the associations for CHIP on HF with and without prior coronary heart disease were homogenous. ASXL1 sequence variations were associated with reduced left ventricular ejection fraction.</p><p><b>CONCLUSIONS: </b>CHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.</p> |
| DOI | 10.1016/j.jacc.2021.04.085 |
| Alternate Journal | J Am Coll Cardiol |
| PubMed ID | 34210413 |
| PubMed Central ID | PMC8313294 |
| Grant List | F30 HL149180 / HL / NHLBI NIH HHS / United States HHSN268201800012C / HL / NHLBI NIH HHS / United States R01 HL120393 / HL / NHLBI NIH HHS / United States HHSN268201600002C / HL / NHLBI NIH HHS / United States HHSN268201600018C / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States R01 HL148565 / HL / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States HHSN268201700002C / HL / NHLBI NIH HHS / United States HHSN268201600004C / HL / NHLBI NIH HHS / United States HHSN268201800011C / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States HHSN268201100037C / HL / NHLBI NIH HHS / United States T32 HL094301 / HL / NHLBI NIH HHS / United States RC2 HL102419 / HL / NHLBI NIH HHS / United States R01 HL151283 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States U54 HG003273 / HG / NHGRI NIH HHS / United States HHSN268201800014C / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States T32 HL129982 / HL / NHLBI NIH HHS / United States R01 HL142711 / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States HHSN268201700001I / HL / NHLBI NIH HHS / United States HHSN268201800013I / MD / NIMHD NIH HHS / United States HHSN268201500015C / HL / NHLBI NIH HHS / United States HHSN268201600003C / HL / NHLBI NIH HHS / United States HHSN268201600033C / ES / NIEHS NIH HHS / United States HHSN268201700004I / HL / NHLBI NIH HHS / United States HHSN268201500014C / HL / NHLBI NIH HHS / United States HHSN268201600001C / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States HHSN268201700005C / HL / NHLBI NIH HHS / United States HHSN268201700001C / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States HHSN268201700003C / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States HHSN268201800015I / HB / NHLBI NIH HHS / United States R01 HL141824 / HL / NHLBI NIH HHS / United States HHSN268201700004C / HL / NHLBI NIH HHS / United States HHSN268201700002I / HL / NHLBI NIH HHS / United States HHSN268201700005I / HL / NHLBI NIH HHS / United States R01 HL117626 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States HHSN268201700003I / HL / NHLBI NIH HHS / United States R01 HL148050 / HL / NHLBI NIH HHS / United States |
ePub date:
21/07