Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project

J Endocrinol Invest. 2022 Jul;45(7):1367-1377. doi: 10.1007/s40618-022-01771-0. Epub 2022 Mar 9.

Abstract

Background: Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking.

Objective: To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes.

Methods: The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B2 (TxB2) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up.

Results: Among 509 adults with IHD (mean age 67 ± 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB2 and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB2 production.

Conclusion: Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding.

Keywords: Estradiol; Ischemic heart disease; Mortality; Testosterone; Thromboxane.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Blood Platelets*
  • Estradiol
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Ischemia*
  • Testosterone
  • Thromboxanes

Substances

  • Estradiol
  • Testosterone
  • Thromboxanes