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Endogenous androgen exposures and ischemic heart disease, a separate sample Mendelian randomization study.
Int J Cardiol 2016; 222:940-945IJ

Abstract

BACKGROUND

Evolutionary biology suggests growth and reproduction trade-off against longevity. Correspondingly estrogen supplementation failed to increase lifespan. Testosterone supplementation is widely used by older men, although regulators have warned of its cardiovascular risk. No large trial of testosterone exists. We examined how genetic determinants of up-regulation (follicle-stimulating hormone (FSH)) and down-regulation (anti-Müllerian hormone (AMH) and testicular dysgenesis syndrome (TDS)) of mainly the male reproductive system are associated with ischemic heart disease (IHD).

METHODS

Separate sample instrumental variable analysis with genetic instruments, i.e., Mendelian randomization, was used to obtain unconfounded estimates using large case-control studies of coronary artery disease/myocardial infarction (CAD/MI) with extensive genotyping, i.e., CARDIoGRAMplusC4D (64,374 CAD/MI cases, 130,681controls), or CARDIoGRAMplusC4D 1000 Genomes (60,801 cases, 123,504 controls).

RESULTS

Genetically predicted FSH was positively associated with CAD/MI (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.03 to 1.13 per mIU/mL FSH). Genetically predicted AMH and TDS were inversely associated with CAD/MI (OR 0.93, 95% CI 0.87 to 0.998 per ng/mL log AMH and OR 0.89, 95% CI 0.81 to 0.98 per log OR higher risk of TDS).

CONCLUSIONS

As expected from evolutionary biology, genetically predicted FSH, related to higher androgens in men and women, was positively associated with IHD, while genetically predicted AMH and TDS, related to lower androgens in men, were inversely associated with IHD. Androgens might be a modifiable causal factor underlying men's greater vulnerability to IHD, with corresponding implications for use of testosterone supplementation as well as for prevention and treatment of IHD.

Authors+Show Affiliations

School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Electronic address: janezhao@hku.hk.School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; City University of New York, School of Public Health and Health Policy, New York, NY, USA. Electronic address: cms1@hku.hk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27526363

Citation

Zhao, Jie V., and C Mary Schooling. "Endogenous Androgen Exposures and Ischemic Heart Disease, a Separate Sample Mendelian Randomization Study." International Journal of Cardiology, vol. 222, 2016, pp. 940-945.
Zhao JV, Schooling CM. Endogenous androgen exposures and ischemic heart disease, a separate sample Mendelian randomization study. Int J Cardiol. 2016;222:940-945.
Zhao, J. V., & Schooling, C. M. (2016). Endogenous androgen exposures and ischemic heart disease, a separate sample Mendelian randomization study. International Journal of Cardiology, 222, pp. 940-945. doi:10.1016/j.ijcard.2016.07.174.
Zhao JV, Schooling CM. Endogenous Androgen Exposures and Ischemic Heart Disease, a Separate Sample Mendelian Randomization Study. Int J Cardiol. 2016 Nov 1;222:940-945. PubMed PMID: 27526363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endogenous androgen exposures and ischemic heart disease, a separate sample Mendelian randomization study. AU - Zhao,Jie V, AU - Schooling,C Mary, Y1 - 2016/07/29/ PY - 2016/06/03/received PY - 2016/07/27/accepted PY - 2016/8/16/entrez PY - 2016/8/16/pubmed PY - 2017/9/30/medline KW - Androgens KW - Ischemic heart disease KW - Mendelian randomization SP - 940 EP - 945 JF - International journal of cardiology JO - Int. J. Cardiol. VL - 222 N2 - BACKGROUND: Evolutionary biology suggests growth and reproduction trade-off against longevity. Correspondingly estrogen supplementation failed to increase lifespan. Testosterone supplementation is widely used by older men, although regulators have warned of its cardiovascular risk. No large trial of testosterone exists. We examined how genetic determinants of up-regulation (follicle-stimulating hormone (FSH)) and down-regulation (anti-Müllerian hormone (AMH) and testicular dysgenesis syndrome (TDS)) of mainly the male reproductive system are associated with ischemic heart disease (IHD). METHODS: Separate sample instrumental variable analysis with genetic instruments, i.e., Mendelian randomization, was used to obtain unconfounded estimates using large case-control studies of coronary artery disease/myocardial infarction (CAD/MI) with extensive genotyping, i.e., CARDIoGRAMplusC4D (64,374 CAD/MI cases, 130,681controls), or CARDIoGRAMplusC4D 1000 Genomes (60,801 cases, 123,504 controls). RESULTS: Genetically predicted FSH was positively associated with CAD/MI (odds ratio (OR) 1.08, 95% confidence interval (CI) 1.03 to 1.13 per mIU/mL FSH). Genetically predicted AMH and TDS were inversely associated with CAD/MI (OR 0.93, 95% CI 0.87 to 0.998 per ng/mL log AMH and OR 0.89, 95% CI 0.81 to 0.98 per log OR higher risk of TDS). CONCLUSIONS: As expected from evolutionary biology, genetically predicted FSH, related to higher androgens in men and women, was positively associated with IHD, while genetically predicted AMH and TDS, related to lower androgens in men, were inversely associated with IHD. Androgens might be a modifiable causal factor underlying men's greater vulnerability to IHD, with corresponding implications for use of testosterone supplementation as well as for prevention and treatment of IHD. SN - 1874-1754 UR - https://www.unboundmedicine.com/medline/citation/27526363/Endogenous_androgen_exposures_and_ischemic_heart_disease_a_separate_sample_Mendelian_randomization_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0167-5273(16)31567-4 DB - PRIME DP - Unbound Medicine ER -