Author + information
- Received November 10, 2017
- Revision received January 13, 2018
- Accepted January 18, 2018
- Published online May 28, 2018.
- Di Zhao, PhDa,
- Eliseo Guallar, MD, DrPHa,
- Pamela Ouyang, MB BSb,
- Vinita Subramanya, MB BS, MPHb,
- Dhananjay Vaidya, PhD, MB BSa,c,
- Chiadi E. Ndumele, MD, MHSa,b,
- Joao A. Lima, MDb,
- Matthew A. Allison, MD, MPHd,
- Sanjiv J. Shah, MDe,
- Alain G. Bertoni, MD, MPHf,
- Matthew J. Budoff, MDg,
- Wendy S. Post, MD, MSa,b and
- Erin D. Michos, MD, MHSa,b,∗ (, )@ErinMichos
- aDepartment of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland
- bDivision of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
- cDivision of General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
- dDivision of Preventive Medicine, University of California-San Diego, La Jolla, California
- eDivision of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
- fDepartment of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, North Carolina
- gLos Angeles Biomedical Research Center at Harbor-UCLA, Torrance, California
- ↵∗Address for correspondence:
Dr. Erin D. Michos, Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Blalock 524-B, 600 North Wolfe Street, Baltimore, Maryland 21287.
Background Higher androgen and lower estrogen levels are associated with cardiovascular disease (CVD) risk factors in women. However, studies on sex hormones and incident CVD events in women have yielded conflicting results.
Objectives The authors assessed the associations of sex hormone levels with incident CVD, coronary heart disease (CHD), and heart failure (HF) events among women without CVD at baseline.
Methods The authors studied 2,834 post-menopausal women participating in the MESA (Multi-Ethnic Study of Atherosclerosis) with testosterone, estradiol, dehydroepiandrosterone, and sex hormone binding globulin (SHBG) levels measured at baseline (2000 to 2002). They used Cox hazard models to evaluate associations of sex hormones with each outcome, adjusting for demographics, CVD risk factors, and hormone therapy use.
Results The mean age was 64.9 ± 8.9 years. During 12.1 years of follow-up, 283 CVD, 171 CHD, and 103 HF incident events occurred. In multivariable-adjusted models, the hazard ratio (95% confidence interval [CI]) associated with 1 SD greater log-transformed sex hormone level for the respective outcomes of CVD, CHD, and HF were as follows: total testosterone: 1.14 (95% CI: 1.01 to 1.29), 1.20 (95% CI: 1.03 to 1.40), 1.09 (95% CI: 0.90 to 1.34); estradiol: 0.94 (95% CI: 0.80 to 1.11), 0.77 (95% CI: 0.63 to 0.95), 0.78 (95% CI: 0.60 to 1.02); and testosterone/estradiol ratio: 1.19 (95% CI: 1.02 to 1.40), 1.45 (95% CI: 1.19 to 1.78), 1.31 (95% CI: 1.01 to 1.70). Dehydroepiandrosterone and SHBG levels were not associated with these outcomes.
Conclusions Among post-menopausal women, a higher testosterone/estradiol ratio was associated with an elevated risk for incident CVD, CHD, and HF events, higher levels of testosterone associated with increased CVD and CHD, whereas higher estradiol levels were associated with a lower CHD risk. Sex hormone levels after menopause are associated with women’s increased CVD risk later in life.
- cardiovascular disease
- coronary heart disease
- heart failure
- sex hormone binding globulin
- sex hormones
This work was partly supported by the American Heart Association (AHA) Go Red for Women Strategic Focused Research Network contract AHA 16SFRN27870000. Drs. Zhao and Michos are also supported by the Blumenthal Scholars Fund for Preventive Cardiology Research. Dr. Shah is supported by National Institutes of Health/National Heart, Lung, and Blood Institute (NIH/NHLBI) grants R01 HL107577 and R01 HL127028, and by AHA grant #16SFRN28780016. The MESA study was supported by NHLBI contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169, and by NIH grants R01 HL074406 and R01 HL074338. Dr. Ouyang has received research grant support from Cordex Systems, Inc. Dr. Budoff has received research funds from GE Healthcare. Dr. Michos has received an honorarium from Siemens Diagnostics for being a blinded events adjudicator in a clinical trial. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Puja K. Mehta, MD, served as Guest Editor for this paper.
- Received November 10, 2017.
- Revision received January 13, 2018.
- Accepted January 18, 2018.
- 2018 American College of Cardiology Foundation
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