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Author Notes:

Erin D. Michos, MD, MHS, FACC, FAHA, Associate Professor of Medicine, Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Blalock 524-B, 600 N. Wolfe Street, Baltimore, MD 21287, USA. E-mail: edonnell@jhmi.edu

The authors thank the other investigators, the staff, and the participants of the ARIC study for their important contributions. A full list of participating ARIC investigators and institutions can be found at https://www2.cscc.unc.edu/aric/.

Dr. Hoogeveen has received grant support and consulting fees from Denka Seiken outside the submitted work. Dr. Ballantyne: grants/research support (paid to institution, not individual) and consultant: Abbott Diagnostic, Denka Seiken, Roche Diagnostic. Drs. Hoogeveen and Ballantyne are coinventors on a provisional patent (patent #61721475) entitled Biomarkers to Improve Prediction of Heart Failure Risk filed by Roche and Baylor College of Medicine on their behalf.

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Research Funding:

This work was funded by the American Heart Association Go Red for Women Strategically Focused Research Network grant 16SFRN27870000. The Atherosclerosis Risk in Communities study has been funded in whole or in part with Federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health, Department of Health and Human Services, under Contract nos. (HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, HHSN268201700004I).

Dr. Zhao is also funded by the Blumenthal Scholars Preventive Cardiology Fund and Dr. Michos is funded by the Amato Fund for Women’s Cardiovascular Health Research, both at Johns Hopkins University.

Keywords:

  • testosterone
  • DHEA-S
  • SHBG
  • sex hormone
  • heart failure
  • HFpEF
  • HFrEF

Sex Hormones and Incident Heart Failure in Men and Postmenopausal Women: The Atherosclerosis Risk in Communities Study

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Journal Title:

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Volume:

Volume 105, Number 10

Publisher:

, Pages e3798-e3807

Type of Work:

Article | Final Publisher PDF

Abstract:

Context Sex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes. Objective To examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF). Design Atherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years. Setting General community. Participants 4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation [SD] 5.7) and 62.8 (5.5) years, respectively. Exposure Plasma sex hormone levels were measured at visit 4 (1996-1998). Main Outcome Measures Incident HF events were identified through hospital discharge codes and death certificates. Results The Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant. Conclusion In this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex.

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