Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

Di Zhao; Eliseo Guallar; Pamela Ouyang; Vinita Subramanya; Dhananjay Vaidya; Chiadi E. Ndumele; Joao A. Lima; Matthew A. Allison; Sanjiv J. Shah; Alain G. Bertoni; Matthew J. Budoff; Wendy S. Post; Erin D. Michos

doi:10.1016/j.jacc.2018.01.083

Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

Di Zhao, Eliseo Guallar, Pamela Ouyang, Vinita Subramanya, Dhananjay Vaidya, Chiadi E. Ndumele, Joao A. Lima, Matthew A. Allison, Sanjiv J. Shah, Alain G. Bertoni, Matthew J. Budoff, Wendy S. Post, Erin D. Michos

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2555-2566
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	71
Issue number	22
DOIs	https://doi.org/10.1016/j.jacc.2018.01.083
State	Published - Jun 5 2018

Keywords

cardiovascular disease
coronary heart disease
estradiol
heart failure
sex hormone binding globulin
sex hormones
testosterone

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.jacc.2018.01.083

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Zhao, D., Guallar, E., Ouyang, P., Subramanya, V., Vaidya, D., Ndumele, C. E., Lima, J. A., Allison, M. A., Shah, S. J., Bertoni, A. G., Budoff, M. J., Post, W. S., & Michos, E. D. (2018). Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women. Journal of the American College of Cardiology, 71(22), 2555-2566. https://doi.org/10.1016/j.jacc.2018.01.083

@article{0e36918480314cd38d4528b13505dbc2,

title = "Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women",

abstract = "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.",

keywords = "cardiovascular disease, coronary heart disease, estradiol, heart failure, sex hormone binding globulin, sex hormones, testosterone",

author = "Di Zhao and Eliseo Guallar and Pamela Ouyang and Vinita Subramanya and Dhananjay Vaidya and Ndumele, {Chiadi E.} and Lima, {Joao A.} and Allison, {Matthew A.} and Shah, {Sanjiv J.} and Bertoni, {Alain G.} and Budoff, {Matthew J.} and Post, {Wendy S.} and Michos, {Erin D.}",

note = "Funding Information: 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. Publisher Copyright: {\textcopyright} 2018 American College of Cardiology Foundation",

year = "2018",

month = jun,

day = "5",

doi = "10.1016/j.jacc.2018.01.083",

language = "English (US)",

volume = "71",

pages = "2555--2566",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier USA",

number = "22",

}

TY - JOUR

T1 - Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

AU - Zhao, Di

AU - Guallar, Eliseo

AU - Ouyang, Pamela

AU - Subramanya, Vinita

AU - Vaidya, Dhananjay

AU - Ndumele, Chiadi E.

AU - Lima, Joao A.

AU - Allison, Matthew A.

AU - Shah, Sanjiv J.

AU - Bertoni, Alain G.

AU - Budoff, Matthew J.

AU - Post, Wendy S.

AU - Michos, Erin D.

N1 - Funding Information: 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. Publisher Copyright: © 2018 American College of Cardiology Foundation

PY - 2018/6/5

Y1 - 2018/6/5

N2 - 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.

AB - 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.

KW - cardiovascular disease

KW - coronary heart disease

KW - estradiol

KW - heart failure

KW - sex hormone binding globulin

KW - sex hormones

KW - testosterone

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Endogenous Sex Hormones and Incident Cardiovascular Disease in Post-Menopausal Women

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