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

• Type of Material: Article
• Authors: Di Zhao, Johns Hopkins University; Eliseo Guallar, Johns Hopkins University; Christie M Ballantyne, Methodist DeBakey Heart Center; Wendy S Post, Johns Hopkins University; Pamela Ouyang, Johns Hopkins University; Dhananjay Vaidya, Johns Hopkins University; Xiaoming JIa, Baylor College of Medicine, Houston; Wendy Ying, Johns Hopkins University; Vinita Subramanya, Emory University; Chiadi E Ndumele, Johns Hopkins University; Ron C Hoogeveen, Methodist DeBakey Heart Center; Erin D Michos, Johns Hopkins University Bloomberg
• Language: English
• Date: 2020-10-01
• Publisher: Oxford University Press (OUP)
• Publication Version: Final Published Version
• Copyright Statement: © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: [e-mail]
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1210/clinem/dgaa500
• Title of Journal or Parent Work: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
• Volume: 105
• Issue: 10
• Start Page: e3798
• End Page: e3807
• Grant/Funding Information: 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: DHEA-S; SHBG; heart failure; HFpEF; testosterone; sex hormone; HFrEF
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

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.