Evidence map›Paper›PMID 34210413›Full record

ArticleJournal of the American College of Cardiology2021

Supplemental Association of Clonal Hematopoiesis With Incident Heart Failure.

Bing Yu, Mary B Roberts, Laura M Raffield, Seyedeh Maryam Zekavat, Ngoc Quynh H Nguyen, Mary L Biggs, Michael R Brown, Gabriel Griffin, Pinkal Desai, Adolfo Correa and 16 more

Erratum issuedOpen access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 150 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
150citing papers in PubMed, 2 pooled it
20.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

150 citing papers in PubMed, 2 syntheses or guidelines pooled it, 205 citations in OpenAlex.

  1. Pooled it
  2. Clonal Hematopoiesis of Indeterminate Potential and Kidney Function Decline in the General Population.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2023
    Pooled it
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90 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 11 institutions in 2 countries.

Bing YuSchool of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Mary B RobertsCenter for Primary Care and Prevention, Brown University, Pawtucket, Rhode Island, USA.
Laura M RaffieldDepartment of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Seyedeh Maryam ZekavatYale School of Medicine, New Haven, Connecticut, USA; Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Ngoc Quynh H NguyenSchool of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Mary L BiggsDepartment of Biostatistics, University of Washington, Seattle, Washington, USA; Department of Epidemiology, Gillings School of Global Public Health and Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Michael R BrownSchool of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Gabriel GriffinBroad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Pinkal DesaiDivision of Hematology and Oncology, Weill Cornell Medical College, New York, New York, USA.
Adolfo CorreaDepartment of Pediatric and Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Alanna C MorrisonSchool of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Amil M ShahDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Abhishek NiroulaBroad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA; Department of Laboratory Medicine, Lund University, Lund, Sweden.
Md Mesbah UddinProgram in Medical and Population Genetics and the Cardiovascular Disease Initiative, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA.
Michael C HonigbergBroad Institute of Harvard and MIT, Cambridge, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Benjamin L EbertDivision of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA; Harvard Medical School, Boston, Massachusetts, USA; Howard Hughes Medical Institute, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington, Seattle, Washington, USA.
Eric A WhitselDepartment of Epidemiology, Gillings School of Global Public Health and Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
JoAnn E MansonHarvard Medical School, Boston, Massachusetts, USA; Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Charles KooperbergPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Alexander G BickDivision of Genetic Medicine, Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Christie M BallantyneSection of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA.
Alex P ReinerPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Pradeep NatarajanHarvard Medical School, Boston, Massachusetts, USA; Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Cardiovascular Disease Initiative of the Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA. Electronic address: pnatarajan@mgh.harvard.edu.
Charles B EatonDepartment of Epidemiology, Brown University, Providence, Rhode Island, USA; Care New England, Center for Primary Care and Prevention, Pawtucket, Rhode Island, USA; Department of Family Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA. Electronic address: cbeaton51@gmail.com.
National Heart, Lung, and Blood Institute TOPMed Consortium
Broad Institute · USThe University of Texas Health Science Center at Houston · USBrigham and Women's Hospital · USUniversity of North Carolina at Chapel Hill · USBrown University · USFred Hutch Cancer Center · USBaylor College of Medicine · USCornell University · USUniversity of Mississippi Medical Center · USUniversity of Washington · USVanderbilt University · US

Funding

The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3M
Building on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
Studies of Rare Genetic Variation in the Isolated Population of SardiniaR01HL117626 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ABECASIS, GONCALO · 2013 to 2016
$10.5M
Exceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5M
Rare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9M
CARDIOVASCULAR HEALTH STUDY (CHS) - TASK AREA C, STUDY CLOSEOUT75N92021D00006 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE · 2021 to 2024
$8.4M
Noninvasive Cardiovascular Imaging Research Training ProgramT32HL094301 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Marcelo F DI CARLI · 2010 to 2026
$7.8M
CHS research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6M
Clonal hematopoiesis in the Womens Health Initiative Memory StudyR01HL148565 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ALEXANDER P REINER, Eric A. Whitsel · 2019 to 2026
$5.9M
Clonal hematopoiesis in humans: determinants of development and progressionR01HL148050 · NHLBI · BAYLOR COLLEGE OF MEDICINE · PI BALLANTYNE, CHRISTIE MITCHELL, NATARAJAN, PRADEEP · 2019 to 2022
$5.9M
Whole genome sequences in individuals to comprehensively characterize the genetic mechanisms of dyslipidemiasR01HL142711 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Satoshi Koyama, Gina Marie Peloso · 2019 to 2026
$4.7M
NHGRI NIH HHS U54 HG003273NHLBI NIH HHS 75N92021D00006NHLBI NIH HHS F30 HL149180NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100037CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201500014CNHLBI NIH HHS HHSN268201500015CNHLBI NIH HHS HHSN268201600001CNHLBI NIH HHS HHSN268201600002CNHLBI NIH HHS HHSN268201600003CNHLBI NIH HHS HHSN268201600004CNHLBI NIH HHS HHSN268201600018CNHLBI NIH HHS HHSN268201700001CNHLBI NIH HHS HHSN268201700001INHLBI NIH HHS HHSN268201700002CNHLBI NIH HHS HHSN268201700002INHLBI NIH HHS HHSN268201700003CNHLBI NIH HHS HHSN268201700003INHLBI NIH HHS HHSN268201700004CNHLBI NIH HHS HHSN268201700004INHLBI NIH HHS HHSN268201700005CNHLBI NIH HHS HHSN268201700005INHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS HHSN268201800010INHLBI NIH HHS HHSN268201800011CNHLBI NIH HHS HHSN268201800011INHLBI NIH HHS HHSN268201800012CNHLBI NIH HHS HHSN268201800012INHLBI NIH HHS HHSN268201800014CNHLBI NIH HHS HHSN268201800014INHLBI NIH HHS HHSN268201800015INHLBI NIH HHS K24 HL152008NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL141824NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL148050NHLBI NIH HHS R01 HL148565NHLBI NIH HHS R01 HL151283NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS T32 HL094301NHLBI NIH HHS T32 HL129982NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL130114NIA NIH HHS R01 AG023629NIEHS NIH HHS HHSN268201600033CNIMHD NIH HHS HHSN268201800013I
6 · The paper itself

Abstract

backgroundAge-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).

objectivesThis study sought to evaluate whether CHIP is associated with incident HF.

methodsCHIP 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.

resultsOf 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.

conclusionsCHIP, particularly sequence variations in ASXL1, TET2, and JAK2, represents a new risk factor for HF.

Indexed as

Heart FailureVentricular Dysfunction, LeftAgedClonal HematopoiesisCorrelation of DataDemographyDioxygenasesDNA-Binding ProteinsExome SequencingFemaleHumansJanus Kinase 2MaleMiddle AgedMutationProportional Hazards ModelsASXL1 protein, humanDioxygenasesDNA-Binding ProteinsJAK2 protein, humanJanus Kinase 2Proto-Oncogene ProteinsRepressor ProteinsTET2 protein, humanclonal hematopoiesis of indeterminate potentialheart failurerisk factor

Identifiers

PMID34210413
PMCPMC8313294
OpenAlexW3173789154

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.