Sex and Gender Differences in Ischemic Heart Disease: Endocrine Vascular Disease Approach (EVA) Study Design

Improvements in ischemic heart disease (IHD) management have been unbalanced between sexes, with coronary microvascular dysfunction considered the likely underlying reason. The Endocrine Vascular disease Approach (EVA) is an observational study (Clinicaltrial.gov NCT02737982) aiming to assess sex and gender interactions between coronary circulation, sexual hormones, and platelet function. Consecutive patients with IHD undergoing coronary angiography will be recruited: (1) to assess sex and gender differences in angiographic reperfusion indexes; (2) to evaluate the effects of estrogen/androgen on sex-related differences in myocardial ischemia; (3) to investigate the platelet biology differences between men and women with IHD; (4) to verify sex- and gender-driven interplay between response to percutaneous coronary intervention, platelets, sex hormones, and myocardial damage at baseline and its impact on 12-month outcomes. The integration of sex and gender in this translational project on IHD will contribute to the identification of new targets for further innovative clinical interventions

Epigenetics of human cutaneous melanoma: setting the stage for new therapeutic strategies

Cutaneous melanoma is a very aggressive neoplasia of melanocytic origin with constantly growing incidence and mortality rates world-wide. Epigenetic modifications (i.e., alterations of genomic DNA methylation patterns, of post-translational modifications of histones, and of microRNA profiles) have been recently identified as playing an important role in melanoma development and progression by affecting key cellular pathways such as cell cycle regulation, cell signalling, differentiation, DNA repair, apoptosis, invasion and immune recognition. In this scenario, pharmacologic inhibition of DNA methyltransferases and/or of histone deacetylases were demonstrated to efficiently restore the expression of aberrantly-silenced genes, thus re-establishing pathway functions. In light of the pleiotropic activities of epigenetic drugs, their use alone or in combination therapies is being strongly suggested, and a particular clinical benefit might be expected from their synergistic activities with chemo-, radio-, and immuno-therapeutic approaches in melanoma patients. On this path, an important improvement would possibly derive from the development of new generation epigenetic drugs characterized by much reduced systemic toxicities, higher bioavailability, and more specific epigenetic effects

Sex effects on statin therapy. Effetti del sesso sulla risposta alle statine

Le statine rappresentano uno degli approcci terapeutici più efficaci e diffusi nella prevenzione primaria e secondaria delle malattie cardiovascolari (CVD), in base all’azione di riduzione del colesterolo e ad altri effetti pleiotropici; di fatto, il loro utilizzo è attualmente supportato dalle più importanti linee guida internazionali per la prevenzione e il trattamento delle malattie cardiovascolari. Uomini e donne sono diversamente interessati dalla CVD da diversi punti di vista, compresi gli aspetti epidemiologici, clinici e farmacologici. Il sesso è stato considerato come uno dei fattori che potrebbero influenzare la farmacodinamica e la farmacocinetica delle statine, nonché la loro risposta differente nelle donne e negli uomini. Tuttavia, i meccanismi e le grandezze delle ipotizzate differenze dipendenti dal sesso nell’efficacia e nella sicurezza delle statine sono, finora, ancora da chiarire. Le donne non solo sono sottorappresentate nella maggior parte degli studi delle statine, ma anche sotto-trattate e meno aderenti alla terapia con statine, portando ad una minore riduzione del colesterolo LDL e a disuguaglianze tra i sessi nella gestione delle malattie cardiovascolari. Lo scopo della presente rassegna è di riassumere le prove sull’uso delle statine nella prevenzione primaria e secondaria, specifiche per sesso. Ci siamo anche proposti di valutare le raccomandazioni, specifiche per sesso, delle linee guida internazionali, concentrandoci sulle prospettive future della gestione specifica per sesso della cardiopatia ischemica.Statins represent one of the most effective and widespread therapeutic approach in both primary and secondary prevention of cardiovascular disease (CVD), according to their cholesterol-lowering action and other pleiotropic effects; as a matter of fact, their use is currently endorsed by the most important international guidelines for prevention and treatment of CVD. Men and women are differently affected by CVD from several point of view, including epidemiological, clinical and pharmacological aspects. Sex was addressed as one of the factors that could affect pharmacodynamics and pharmacokinetics of statins, as well as their differential response in women and men. However, mechanisms and magnitudes of the hypothesized sex-dependent differences in statins’ efficacy and safety are, to date, far to be elucidated. Women are not only underrepresented in most statins’ trials, but are also reported to be undertreated and less adherent to statins therapy, perhaps leading to lower rate of LDL-cholesterol target achievements and inequalities across sexes in the management of CVD. The aim of the present review is to summarize the evidence on the use of statins in primary and secondary prevention from a sex-specific point of view. We also aim at evaluating sex-specific recommendations currently endorsed by international guidelines, focusing on future perspectives on sex-tailored management of CVD