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Honigberg MC, Zekavat SM, Niroula A, et al. Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women. Circulation. 2020;143(5):410-423doi: 10.1161/CIRCULATIONAHA.120.051775.
Honigberg, M. C., Zekavat, S. M., Niroula, A., Griffin, G. K., Bick, A. G., Pirruccello, J. P., Nakao, T., Whitsel, E. A., Farland, L. V., Laurie, C., Kooperberg, C., Manson, J. E., Gabriel, S., Libby, P., Reiner, A. P., Ebert, B. L., & Natarajan, P. (2021). Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women. Circulation, 143(5), 410-423. https://doi.org/10.1161/CIRCULATIONAHA.120.051775
Honigberg, Michael C, et al. "Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women." Circulation vol. 143,5 (2021): 410-423. doi: https://doi.org/10.1161/CIRCULATIONAHA.120.051775
Honigberg MC, Zekavat SM, Niroula A, Griffin GK, Bick AG, Pirruccello JP, Nakao T, Whitsel EA, Farland LV, Laurie C, Kooperberg C, Manson JE, Gabriel S, Libby P, Reiner AP, Ebert BL, Natarajan P. Premature Menopause, Clonal Hematopoiesis, and Coronary Artery Disease in Postmenopausal Women. Circulation. 2021 Feb 02;143(5):410-423. doi: 10.1161/CIRCULATIONAHA.120.051775. Epub 2020 Nov 09. PMID: 33161765; PMCID: PMC7911856.
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Circulation. 2021 Feb 02;143(5):410-423. doi: 10.1161/CIRCULATIONAHA.120.051775. Epub 2020 Nov 09.

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

Circulation

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, Charles Kooperberg, JoAnn E Manson, Stacey Gabriel, Peter Libby, Alexander P Reiner, Benjamin L Ebert, Pradeep Natarajan

Affiliations

  1. Cardiology Division (M.C.H., J.P.P., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
  2. Department of Medicine (M.C.H., J.P.P., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
  3. Cardiovascular Research Center and Center for Genomic Medicine (M.C.H., J.P.P., T.N., P.N.), Massachusetts General Hospital, Harvard Medical School, Boston.
  4. Broad 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.).
  5. Yale University School of Medicine, New Haven, CT (S.M.Z.).
  6. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA (A.N., T.N., B.L.E.).
  7. Department of Pathology (G.K.G., T.N.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  8. Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN (A.G.B.).
  9. Gillings School of Global Public Health and School of Medicine, University of Chapel Hill, NC (E.A.W.).
  10. Department of Epidemiology and Biostatistics, Mel and Enid Zuckerman College of Public Health, University of Arizona, Tucson (L.V.F.).
  11. Department of Biostatistics, University of Washington, Seattle (C.L.).
  12. Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA (C.K., A.P.R.).
  13. Division of Preventive Medicine (J.E.M.), Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
  14. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA (J.E.M.).
  15. Cardiovascular Division, Brigham and Women's Hospital Heart & Vascular Center, Boston, MA (P.L.).

PMID: 33161765 PMCID: PMC7911856 DOI: 10.1161/CIRCULATIONAHA.120.051775

Abstract

BACKGROUND: Premature 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.

METHODS: We 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.

RESULTS: The 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% (

CONCLUSIONS: Premature 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.

Keywords: clonal hematopoiesis; coronary artery disease; hematology; inflammation; menopause, premature; women

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