Dataset Information

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

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.

SUBMITTER: Raparelli V

PROVIDER: S-EPMC9184432 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Raparelli V V Nocella C C Proietti M M Romiti G F GF Corica B B Bartimoccia S S Stefanini L L Lenzi A A Viceconte N N Tanzilli G G Cammisotto V V Pilote L L Cangemi R R Basili S S Carnevale R R

Journal of endocrinological investigation 20220309 7

<h4>Background</h4>Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking.<h4>Objective</h4>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.<h4>Methods</h4>The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary an ...[more]

PMID: 35262860

Similar Datasets

Project description:Background and Purpose- Although exogenous hormone therapy (HT) use has been associated with increased risk of ischemic stroke in postmenopausal women, it remains unknown whether sex hormone levels contribute to ischemic stroke risk. We aimed to estimate associations between plasma sex hormone levels and ischemic stroke risk, by HT status, in a nested case-control study of postmenopausal women from the NHS (Nurses' Health Study). Methods- Women with confirmed incident ischemic stroke (n=419) were matched with controls (n=419) by age, HT use, and other factors. Plasma estradiol and testosterone levels were measured using liquid chromatography tandem mass spectrometry; SHBG (sex hormone-binding globulin) was assayed by electrochemiluminescence immunoassay. Associations of total and free estradiol and testosterone, the estradiol/testosterone ratio, and SHBG with ischemic stroke were estimated using conditional logistic regressions stratified by HT status with adjustment for matching and cardiovascular risk factors. Results- Current HT users had different hormone profiles from never/past users. No clear linear trends were observed between estradiol (total or free) levels or the estradiol/testosterone ratio and ischemic stroke risk among either current users (Ptrend>0.1) or never/past users (Ptrend>0.6). For both current and never/past users, the associations between some of the sex hormones and ischemic stroke differed by body mass index categories (Pinteraction≤0.04). For women with a body mass index <25 kg/m2, a higher estradiol/testosterone ratio was associated with significantly elevated ischemic stroke risk among current users (Ptrend=0.01), and higher levels of total and free estradiol were significantly associated with higher ischemic stroke risk among never/past users (Ptrend≤0.04). Testosterone and SHBG were not associated with ischemic stroke in either current or never/past users. Conclusions- Our findings do not support a role of sex hormone levels in mediating ischemic stroke risk among postmenopausal women. Replications in additional larger studies are required.

Project description:IntroductionSex hormones are hypothesized to drive sex-specific health disparities. Here, we study the association between sex steroid hormones and DNA methylation-based (DNAm) biomarkers of age and mortality risk including Pheno Age Acceleration (AA), Grim AA, and DNAm-based estimators of Plasminogen Activator Inhibitor 1 (PAI1), and leptin concentrations.MethodsWe pooled data from three population-based cohorts, the Framingham Heart Study Offspring Cohort (FHS), the Baltimore Longitudinal Study of Aging (BLSA), and the InCHIANTI Study, including 1,062 postmenopausal women without hormone therapy and 1,612 men of European descent. Sex hormone concentrations were standardized with mean 0 and standard deviation of 1, for each study and sex separately. Sex-stratified analyses using a linear mixed regression were performed, with a Benjamini-Hochberg (BH) adjustment for multiple testing. Sensitivity analysis was performed excluding the previously used training-set for the development of Pheno and Grim age.ResultsSex Hormone Binding Globulin (SHBG) is associated with a decrease in DNAm PAI1 among men (per 1 standard deviation (SD): -478 pg/mL; 95%CI: -614 to -343; P:1e-11; BH-P: 1e-10), and women (-434 pg/mL; 95%CI: -589 to -279; P:1e-7; BH-P:2e-6). The testosterone/estradiol (TE) ratio was associated with a decrease in Pheno AA (-0.41 years; 95%CI: -0.70 to -0.12; P:0.01; BH-P: 0.04), and DNAm PAI1 (-351 pg/mL; 95%CI: -486 to -217; P:4e-7; BH-P:3e-6) among men. In men, 1 SD increase in total testosterone was associated with a decrease in DNAm PAI1 (-481 pg/mL; 95%CI: -613 to -349; P:2e-12; BH-P:6e-11).ConclusionSHBG was associated with lower DNAm PAI1 among men and women. Higher testosterone and testosterone/estradiol ratio were associated with lower DNAm PAI and a younger epigenetic age in men. A decrease in DNAm PAI1 is associated with lower mortality and morbidity risk indicating a potential protective effect of testosterone on lifespan and conceivably cardiovascular health via DNAm PAI1.

Dataset Information

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

Background

Objective

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets