Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project
Valeria Raparelli, Cristina Nocella, Marco Proietti, Giulio Francesco Romiti, Bernadette Corica, Simona Bartimoccia, Lucia Stefanini, Andrea Lenzi, Nicola Viceconte, Gaetano Tanzilli, Vittoria Cammisotto, Louise Pilote, Roberto Cangemi, Stefania Basili, Roberto Carnevale, The EVA Collaborators, Claudio Tiberti, Federica Panimolle, Andrea Isidori, Elisa Giannetta, Mary Anna Venneri, Laura Napoleone, Marta Novo, Silvia Quattrino, Simona Ceccarelli, Eleni Anastasiadou, Francesca Megiorni, Cinzia Marchese, Enrico Mangieri, Gaetano Tanzilli, Nicola Viceconte, Francesco Barillà, Carlo Gaudio, Vincenzo Paravati, Guglielmo Tellan, Evaristo Ettorre, Adriana Servello, Fabio Miraldi, Andréa Moretti, Alessandra Tanzilli, Piergiovanni Mazzonna, Suleyman Al Kindy, Riccardo Iorio, Martina Di Iorio, Gennaro Petriello, L Gioffrè, Eleonora Indolfi, Gaetano Pero, Nino Cocco, Loredana Iannetta, Sara Giannuzzi, Emilio Centaro, Sonia Cristina Sergi, Pasquale Pignatelli, Daria Amoroso, Simona Bartimoccia, Giovanni Talerico, Salvatore Minisola, Sergio Morelli, Antonio Fraioli, Silvia Nocchi, Mario Fontana, Filippo Toriello, Eleonora Ruscio, Tommaso Todisco, Nicolò Sperduti, Giuseppe Santangelo, Giacomo Visioli, Marco Vano, Marco Borgi, Ludovica Maria Antonini, Silvia Robuffo, Claudia Tucci, Agostino Rossoni, Valeria Spugnardi, A Vernile, Mariateresa Santoliquido, Verdiana Santori, Giulia Tosti, Fabrizio Recchia, Francesco Morricone, Roberto Scacciavillani, Alice Lipari, Andrea Zito, Floriana Testa, Giulia Ricci, Ilaria Vellucci, Marianna Vincenti, Silvia Pietropaolo, Camilla Scala, Nicolò Rubini, Marta Tomassi, Gloria Rozzi, Floriana Santomenna, Claudio Cantelmi, Giacomo Costanzo, Lucas Rumbolà, Salvatore Giarrizzo, Carlotta Sapia, Biagio Scotti
Abstract
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 B 2 (TxB 2 ) 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 TxB 2 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 TxB 2 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.