Although health disparities in women presenting with acute coronary syndrome (ACS) have received growing attention in recent years, clinical outcomes from ACS are still worse for women than for men. Women continue to experience higher patient and system delays and receive less aggressive invasive treatment and pharmacotherapies. Gender- and sex-specific variables that contribute to ACS vulnerability remain largely unknown. Notwithstanding the sex differences in baseline coronary anatomy and function, women and men are treated the same based on guidelines that were established from experimental and clinical trial data over-representing the male population. Importantly, younger women have a particularly unfavourable prognosis and a plethora of unanswered questions remains in this younger population. The present review summarizes contemporary evidence for gender and sex differences in vascular biology, clinical presentation, and outcomes of ACS. We further discuss potential mechanisms and non-traditional risk conditions modulating the course of disease in women and men, such as unrecognized psychosocial factors, sex-specific vascular and neural stress responses, and the potential impact of epigenetic modifications.

Sex and gender in cardiovascular medicine: presentation and outcomes of acute coronary syndrome

Although the female gender is generally less represented in cardiovascular studies, observational and randomized investigations suggest that-compared with men-women may obtain different benefits from antiplatelet therapy. Multiple factors, including hormonal mechanisms and differences in platelet biology, might contribute to such apparent gender peculiarities. The thrombotic and bleeding risks, as well as outcomes after a cardiovascular event, appear to differ between genders, partly in relation to differences in age, comorbidities and body size. Equally, the benefits of antiplatelet therapy may differ in women compared with men in different vascular beds, during primary or secondary prevention and according to the type of an antiplatelet agent used. This document is an attempt to bring together current evidence, clinical practices and gaps of knowledge on gender-specific platelet function and antiplatelet therapy. On the basis of the available data, we provide suggestions on current indications of antiplatelet therapy for cardiovascular prevention in women with different clinical features; no strong recommendation may be given because the available data derive from observational studies or post hoc/subgroup analyses of randomized studies without systematic adjustments for baseline risk profiles.

/pdf/platelet-function-and-long-term-antiplatelet-therapy-in-vjc3sgvhbz.pdf

Platelet function and long-term antiplatelet therapy in women: is there a gender-specificity? A ‘state-of-the-art’ paper

https://www.onlinelibrary.wiley.com/doi/pdf/10.1111/jth.13177

Advanced age and high-residual platelet reactivity in patients receiving dual antiplatelet therapy with clopidogrel or ticagrelor.

There is considerable interest in defining new agents or targets for antithrombotic purposes. The 5-HT2A receptor is a G-protein coupled receptor (GPCR) expressed on many cell types, and a known therapeutic target for many disease states. This serotonin receptor is also known to regulate platelet function. Thus, in our FDA-approved drug repurposing efforts, we investigated the antiplatelet activity of cyproheptadine and pizotifen, two antidepressant 5-HT2A Receptor antagonists. Our results revealed that cyproheptadine and pizotifen reversed serotonin-enhanced ADP-induced platelet aggregation in vitro and ex vivo. And the inhibitory effects of these two agents were found to be similar to that of EMD 281014, a 5-HT2A Receptor antagonist under development. In separate experiments, our studies revealed that these 5-HT2A receptor antagonists have the capacity to reduce serotonin-enhanced ADP-induced elevation in intracellular calcium levels and tyrosine phosphorylation. Using flow cytometry, we also observed that cyproheptadine, pizotifen, and EMD 281014 inhibited serotonin-enhanced ADP-induced phosphatidylserine (PS) exposure, P-selectin expression, and glycoprotein IIb-IIIa activation. Furthermore, using a carotid artery thrombosis model, these agents prolonged the time for thrombotic occlusion in mice in vivo. Finally, the tail-bleeding time was investigated to assess the effect of cyproheptadine and pizotifen on hemostasis. Our findings indicated prolonged bleeding time in both cyproheptadine- and pizotifen-treated mice. Notably, the increases in occlusion and bleeding times associated with these two agents were comparable to that of EMD 281014, and to clopidogrel, a commonly used antiplatelet drug, again, in a fashion comparable to clopidogrel and EMD 281014. Collectively, our data indicate that the antidepressant 5-HT2A antagonists, cyproheptadine and pizotifen do exert antiplatelet and thromboprotective effects, but similar to clopidogrel and EMD 281014, their use may interfere with normal hemostasis.

/pdf/the-antidepressant-5-ht2a-receptor-antagonists-pizotifen-and-23nwjpke1z.pdf

The antidepressant 5-HT2A receptor antagonists pizotifen and cyproheptadine inhibit serotonin-enhanced platelet function.

Potent P2Y12 Inhibitors in Men Versus Women: A Collaborative Meta-Analysis of Randomized Trials

Background
Previous studies have suggested that women do not accrue equal therapeutic benefit from antiplatelet medication as compared with men. The physiological mechanism and clinical implications behind this gender disparity have yet to be established.

/pdf/effect-of-gender-difference-on-platelet-reactivity-1f34k9zymh.pdf

Effect of gender difference on platelet reactivity

Hart- en vaatziekten zijn de eerste doodsoorzaak onder vrouwen en het aantal doden neemt minder af dan onder mannen.


Er wordt steeds meer bekend over de pathofysiologische achtergrond van genderverschillen bij hart- en vaatziekten.


Mannen en vrouwen kunnen een verschillende klachtenpresentatie hebben: vrouwen hebben minder vaak last van pijn op de borst en van transpireren, en hebben vaker atypische klachten als misselijkheid.


Vrouwen krijgen coronarialijden op latere leeftijd dan mannen, en hebben dan vaak meer risicofactoren voor hart- en vaatziekten.


Diabetes en in mindere mate hypertensie zijn sterkere risicofactoren voor vrouwen; zwangerschapsdiabetes en het polycysteusovariumsyndroom kunnen voorboden zijn van diabetes.


Voor exogene oestrogenen is geen beschermend effect tegen hart- en vaatziekten bewezen.


Diagnostisch onderzoek is bij vrouwen lastiger te interpreteren, met meer foutpositieve en foutnegatieve uitslagen. Het mag daarom echter niet achterwege worden gelaten.


Vrouwen worden minder vaak dan mannen volgens de richtlijnen behandeld en ondergaan minder vaak een interventie.


De kortetermijnmortaliteit na een myocardinfarct of een coronaire bypass (CABG) lijkt hoger voor vrouwen.

M. A. Sluman

Papers

Effect of gender difference on platelet reactivity

Pathofysiologie, risicofactoren, diagnostiek en therapie van hart- en vaatziekten: mannen en vrouwen zijn anders