Evidence map›Paper›PMID 40864016›Full record

ArticleJournal of the American College of Cardiology2025

Clonal Hematopoiesis and Cardiovascular Outcomes in Older Women.

Daniel Ezzat, Md Mesbah Uddin, Liying Xue, Yash Pershad, Shengruo Zhang, Jason M Collins, Jacob O Kitzman, Siddhartha Jaiswal, Pinkal Desai, Charles Kooperberg and 6 more

Registry-linked trialAbstract read
In one paragraph

Article in Journal of the American College of Cardiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00000611 (Women's Health Initiative), which is not on this map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
–field-weighted citation impact
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.

NCT00000611 phase3completednot on this map

Women's Health Initiative (WHI)

TypeinterventionalSponsorNational Heart, Lung, and Blood Institute (NHLBI)ConditionsBone Diseases, Breast Neoplasms, Cardiovascular Diseases, Colonic NeoplasmsArmshormone replacement therapy, estrogens, progestins, estrogen replacement therapy, diet, fat-restricted
3 · Its place in the literature

Who cites it

13 citing papers in PubMed.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Daniel EzzatCardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA; Faculty of Medicine, KU Leuven, Leuven, Belgium.
Md Mesbah UddinCardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Liying XueCardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Yash PershadDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Shengruo ZhangDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Jason M CollinsDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Jacob O KitzmanDepartment of Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
Siddhartha JaiswalDepartment of Pathology, Stanford University School of Medicine, Stanford, California, USA.
Pinkal DesaiDivision of Hematology and Medical Oncology, Weill Cornell Medicine, The New York Presbyterian Hospital, New York, New York, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Alexander G BickDivision of Genetic Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Pradeep NatarajanCardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
JoAnn E MansonDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Eric A WhitselDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA; Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
Alexander P ReinerDepartment of Epidemiology, University of Washington, Seattle, Washington, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Michael C HonigbergCardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA; Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. Electronic address: mhonigberg@mgh.harvard.edu.

Funding

WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WACTAWSKI-WENDE, JEAN · 2021 to 2025
$6.9M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00004 · NHLBI · STANFORD UNIVERSITY · PI STEFANICK, MARCIA · 2021 to 2025
$6.5M
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
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00003 · NHLBI · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA · 2021 to 2025
$5.0M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI VITOLINS, MARA · 2021 to 2025
$4.2M
Effects of IL-1 beta inhibition on vascular inflammation in TET2 clonal hematopoiesisR01HL173028 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Michael Honigberg, Mabel Toribio · 2025 to 2026
$1.7M
NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS R01 HL148565NHLBI NIH HHS R01 HL173028WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

backgroundClonal hematopoiesis of indeterminate potential (CHIP) is an emerging aging-related risk factor for cardiovascular disease (CVD). However, previous studies suggest that CHIP's relevance to CVD may diminish with advancing age.

objectivesThis study aimed to test the association of CHIP and its key subtypes with incident CVD in an older population.

methodsParticipants in the Women's Health Initiative Long Life Study completed study assessments in 2012-2013 and underwent high-coverage sequencing (median depth 4,580×). The co-primary exposures were composite CHIP and TET2 CHIP. DNMT3A, ASXL1, JAK2, and non-DNMT3A CHIP were examined as secondary exposures. The primary outcome was incident coronary heart disease. Secondary outcomes were incident heart failure with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF), ischemic stroke, venous thromboembolism, and cardiovascular death. Multivariable-adjusted Cox models tested associations between CHIP and incident CVD.

resultsAmong 6,677 women (median age 80 years; median follow-up 10.1 years), 2,176 (32.6%) had any CHIP. TET2 CHIP was independently associated with incident coronary heart disease (aHR: 1.36 [95% CI: 1.05-1.77]; P = 0.02), whereas composite CHIP was not (aHR: 1.07 [95% CI: 0.89-1.28]; P = 0.49). Secondarily, TET2 CHIP was associated with HFpEF (aHR: 1.40 [95% CI: 1.03-1.90]; P = 0.03), ASXL1 CHIP with HFrEF (aHR: 3.16 [95% CI: 1.53-6.55]; P = 0.002), and JAK2 CHIP with ischemic stroke (aHR: 2.49 [95% CI: 1.17-5.30]; P = 0.02), venous thromboembolism (aHR: 2.71 [95% CI: 1.11-6.65]; P = 0.03), and cardiovascular death (aHR: 2.62 [95% CI: 1.68-4.11]; P < 0.001). No other significant associations were observed for composite or DNMT3A CHIP.

conclusionsIn an older female cohort, key CHIP subtypes (TET2, ASXL1, and JAK2) were associated with incident CVD, with associations that appeared to differ by CVD outcome. These findings suggest that CHIP remains associated with cardiovascular health into later life. (Women's Health Initiative [WHI]; NCT00000611).

Indexed as

Cardiovascular DiseasesClonal HematopoiesisAgedAged, 80 and overDioxygenasesDNA-Binding ProteinsDNA Methyltransferase 3AFemaleHumansIncidenceJanus Kinase 2Proto-Oncogene ProteinsRepressor ProteinsASXL1 protein, humanDioxygenasesDNA-Binding ProteinsDNA Methyltransferase 3AJanus Kinase 2Proto-Oncogene ProteinsRepressor ProteinsTET2 protein, humancardiovascular diseasesclonal hematopoiesiscoronary diseaseheart failureischemic strokevenous thromboembolism

Identifiers

PMID40864016
PMCPMC12557340

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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 Socratic graph.