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Sex hormones and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Purpose

Atrial fibrillation is more prevalent in men than women. Due to these sex differences in atrial fibrillation susceptibility, we examined whether sex hormones have differing associations with atrial fibrillation risk in men and women.

Methods

This analysis included 4883 (mean age = 63 ± 10 years; 39% women; 64% non-white) participants from the Multi-Ethnic Study of Atherosclerosis. Sex hormones (total testosterone, bioavailable testosterone, estradiol, and sex hormone binding globulin) were measured at baseline (2000-2002) for all male and all postmenopausal female participants. Atrial fibrillation was ascertained by hospital discharge records, Medicare claims data, and study electrocardiograms through December 31, 2012.

Results

Over a median follow-up of 10.9 years, a total of 613 (13%) atrial fibrillation cases were detected. A higher incidence rate of atrial fibrillation was observed for males (n = 385, age-standardized incidence rate per 1000 person-years = 12.3, 95%CI = 11.1, 13.6) than females (n = 228, age-standardized incidence rate per 1000 person-years = 9.0, 95%CI = 7.9, 10.3). In men, higher bioavailable testosterone levels were associated with increased atrial fibrillation risk (HR = 1.32, 95%CI = 1.01, 1.74; p = 0.044; comparing 3rd to 1st tertile), while an association in the opposite direction was observed for women (HR = 0.81, 95%CI = 0.58, 1.13; p = 0.22; comparing 3rd to 1st tertile). Other hormones were not associated with atrial fibrillation in men or women.

Conclusion

Higher levels of endogenous bioavailable testosterone contribute to atrial fibrillation development in men. The combination of endogenous bioavailable testosterone and other risk factors potentially are important for atrial fibrillation development in men.

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Acknowledgements

The authors thank the other investigators, the staff, and the participants of the MESA study for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

Funding

This research was supported by 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 from the National Heart, Lung, and Blood Institute. This research was supported by grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources, 16EIA26410001 from the American Heart Association, and R01-HL-127659 from the National Heart, Lung, and Blood Institute. W.T.O. is supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number F32-HL-134290. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Correspondence to Wesley T. O’Neal.

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Conflict of interest

Dr. Nazarian is principal investigator for research funds awarded to Johns Hopkins University from Biosense Webster Inc and is also a consultant to Biosense Webster, St Jude Medical, CardioSolv, and Spectranetics. The other authors declare that they have no competing interests.

Ethical approval

All procedures in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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O’Neal, W.T., Nazarian, S., Alonso, A. et al. Sex hormones and the risk of atrial fibrillation: The Multi-Ethnic Study of Atherosclerosis (MESA). Endocrine 58, 91–96 (2017). https://doi.org/10.1007/s12020-017-1385-3

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Keywords

  • Sex hormones
  • Atrial fibrillation
  • Epidemiology
  • Risk