Evidence map›Paper›PMID 33161765›Full record

ArticleCirculation2021

Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women.

Michael C Honigberg, Seyedeh M Zekavat, Abhishek Niroula, Gabriel K Griffin, Alexander G Bick, James P Pirruccello, Tetsushi Nakao, Eric A Whitsel, Leslie V Farland, Cecelia Laurie and 8 more

Open access · greenAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
90citing papers in PubMed, 4 pooled it
15.8field-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

90 citing papers in PubMed, 4 syntheses or guidelines pooled it, 137 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Trial
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Clonal Hematopoiesis and Cardiovascular Outcomes in Older Women.Journal of the American College of Cardiology · 2025
    Article
  20. Cardiovascular Consequences of Premature Menopause.Current cardiology reports · 2025
    Review

30 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 2 countries.

Michael C HonigbergCardiology Division (M.C.H., J.P.P., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
Seyedeh M ZekavatBroad Institute of Harvard and MIT, Cambridge, MA (M.C.H., S.M.Z., A.N., G.K.G., A.G.B., J.P.P., T.N., S.G., B.L.E., P.N.).
Abhishek NiroulaBroad Institute of Harvard and MIT, Cambridge, MA (M.C.H., S.M.Z., A.N., G.K.G., A.G.B., J.P.P., T.N., S.G., B.L.E., P.N.).
Gabriel K GriffinBroad Institute of Harvard and MIT, Cambridge, MA (M.C.H., S.M.Z., A.N., G.K.G., A.G.B., J.P.P., T.N., S.G., B.L.E., P.N.).
Alexander G BickBroad Institute of Harvard and MIT, Cambridge, MA (M.C.H., S.M.Z., A.N., G.K.G., A.G.B., J.P.P., T.N., S.G., B.L.E., P.N.).
James P PirruccelloCardiology Division (M.C.H., J.P.P., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
Tetsushi NakaoCardiovascular Research Center and Center for Genomic Medicine (M.C.H., J.P.P., T.N., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
Eric A WhitselGillings School of Global Public Health and School of Medicine, University of Chapel Hill, NC (E.A.W.).
Leslie V FarlandDepartment of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson (L.V.F.).
Cecelia LaurieDepartment of Biostatistics, University of Washington, Seattle (C.L.).
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (C.K., A.P.R.).
JoAnn E MansonDivision of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
Stacey GabrielBroad Institute of Harvard and MIT, Cambridge, MA (M.C.H., S.M.Z., A.N., G.K.G., A.G.B., J.P.P., T.N., S.G., B.L.E., P.N.).
Peter LibbyCardiovascular Division, Brigham and Women's Hospital Heart & Vascular Center, Boston, MA (P.L.).
Alexander P ReinerDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (C.K., A.P.R.).
Benjamin L EbertBroad Institute of Harvard and MIT, Cambridge, MA (M.C.H., S.M.Z., A.N., G.K.G., A.G.B., J.P.P., T.N., S.G., B.L.E., P.N.).
NHLBI Trans-Omics for Precision Medicine Program
Pradeep NatarajanCardiology Division (M.C.H., J.P.P., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
Broad Institute · USBrigham and Women's Hospital · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAUniversity of Arizona · USUniversity of North Carolina at Chapel Hill · USUniversity of Washington · US

Funding

SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI Xinxin Ding · 1994 to 2026
$36.7M
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
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
Noninvasive Cardiovascular Imaging Research Training ProgramT32HL094301 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI Marcelo F DI CARLI · 2010 to 2026
$7.8M
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
Rare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6M
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
Clonal hematopoiesis of indeterminate potential and HIV in the REPRIEVE trialR01HL151283 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI NATARAJAN, PRADEEP · 2020 to 2023
$2.5M
Targeting Clonal Hematopoiesis of Indeterminate Potential Using Human GeneticsDP5OD029586 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BICK, ALEXANDER · 2020 to 2024
$2.3M
Novel mechanisms of the thrombotic complications of atherosclerosisR01HL134892 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIBBY, PETER · 2019 to 2022
$1.7M
Medical Research Council MC_PC_17228Medical Research Council MC_QA137853NHLBI NIH HHS HHSN268201500014CNHLBI NIH HHS HHSN268201600001CNHLBI NIH HHS HHSN268201600002CNHLBI NIH HHS HHSN268201600003CNHLBI NIH HHS HHSN268201600004CNHLBI NIH HHS HHSN268201600018CNHLBI NIH HHS HHSN268201800001CNHLBI NIH HHS R01 HL117626NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL134892NHLBI NIH HHS R01 HL142711NHLBI NIH HHS R01 HL148050NHLBI NIH HHS R01 HL148565NHLBI NIH HHS R01 HL151283NHLBI NIH HHS T32 HL094301NHLBI NIH HHS U01 HL120393
6 · The paper itself

Abstract

backgroundPremature menopause is an independent risk factor for cardiovascular disease in women, but mechanisms underlying this association remain unclear. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic cells with leukemogenic mutations without detectable malignancy, is associated with accelerated atherosclerosis. Whether premature menopause is associated with CHIP is unknown.

methodsWe included postmenopausal women from the UK Biobank (n=11 495) aged 40 to 70 years with whole exome sequences and from the Women's Health Initiative (n=8111) aged 50 to 79 years with whole genome sequences. Premature menopause was defined as natural or surgical menopause occurring before age 40 years. Co-primary outcomes were the presence of any CHIP and CHIP with variant allele frequency >0.1. Logistic regression tested the association of premature menopause with CHIP, adjusted for age, race, the first 10 principal components of ancestry, smoking, diabetes, and hormone therapy use. Secondary analyses considered natural versus surgical premature menopause and gene-specific CHIP subtypes. Multivariable-adjusted Cox models tested the association between CHIP and incident coronary artery disease.

resultsThe sample included 19 606 women, including 418 (2.1%) with natural premature menopause and 887 (4.5%) with surgical premature menopause. Across cohorts, CHIP prevalence in postmenopausal women with versus without a history of premature menopause was 8.8% versus 5.5% (

conclusionsPremature menopause, especially natural premature menopause, is independently associated with CHIP among postmenopausal women. Natural premature menopause may serve as a risk signal for predilection to develop CHIP and CHIP-associated cardiovascular disease.

Indexed as

AdultAgedClonal HematopoiesisCoronary Artery DiseaseFemaleHumansMenopause, PrematureMiddle AgedPostmenopauseProspective StudiesRisk FactorsWomen's Healthclonal hematopoiesiscoronary artery diseasehematologyinflammationmenopause, prematurewomen

Identifiers

PMID33161765
PMCPMC7911856
OpenAlexW3103515997

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.