Abstract
Cardiovascular diseases (CVD) represent one of the biggest causes of death globally, and their prevalence, aetiology, and outcome are related to genetic, metabolic, and environmental factors, among which sex- and age-dependent differences may play a key role. Among CVD risk factors, platelet hyperactivity deserves particular mention, as it is involved in the pathophysiology of main cardiovascular events (including stroke, myocardial infarction, and peripheral vascular injury) and is closely related to sex/age differences. Several determinants (e.g., hormonal status and traditional cardiovascular risk factors), together with platelet-related factors (e.g., plasma membrane composition, receptor signaling, and platelet-derived microparticles) can elucidate sex-related disparity in platelet functionality and CVD onset and outcome, especially in relation to efficacy of current primary and secondary interventional strategies. Here, we examined the state of the art concerning sex differences in platelet biology and their relationship with specific cardiovascular events and responses to common antiplatelet therapies. Moreover, as healthy nutrition is widely recognized to play a key role in CVD, we also focused our attention on specific dietary components (especially polyunsaturated fatty acids and flavonoids) and patterns (such as Mediterranean diet), which also emerged to impact platelet functions in a sex-dependent manner. These results highlight that full understanding of gender-related differences will be useful for designing personalized strategies, in order to prevent and/or treat platelet-mediated vascular damage.
Highlights
Noncommunicable diseases (mostly, cardiovascular disease (CVD), cancer, diabetes, and chronic respiratory disease) are the leading cause of mortality worldwide: with 41 million deaths, they were responsible for 71% of all global deaths in 2016 [1]
Cardiovascular diseases (CVD) remains the biggest cause of death globally in the last 20 years: according to the last World Health Organization Report, ischemic heart disease and stroke collectively accounted for 15.2 million deaths in 2016 [1]
Life expectancy is greater for women than men, but CVD, including myocardial infarction, stroke, cardiomyopathy, and hypertensive heart disease, displays sex- and age-related incidence: it accounts for 40% of all deaths in men and up to 49% of all deaths in women over the age of 65 years [2]
Summary
Noncommunicable diseases (mostly, cardiovascular disease (CVD), cancer, diabetes, and chronic respiratory disease) are the leading cause of mortality worldwide: with 41 million deaths, they were responsible for 71% of all global deaths in 2016 [1]. Plasma pMP levels are high in healthy subjects showing high coronary heart disease risk score [77], and their number and phenotype (i.e., surface expression of P-selectin and phosphatidylserine) positively correlate with recurrent CVD events [78, 79] According to their parental origin, a significant genderspecific difference has been found, with the amount of pMPs significantly greater in healthy women than in the corresponding counterparts [80]. A menstrual cycle-dependent difference in pMPs exists: a case-control study enrolling 27 healthy women and 18 healthy men demonstrated increased pMP release in females, especially in the luteal phase [81] This finding suggests, that higher circulating pMPs (together with other risk factors, including pregnancy, oral contraceptives, and hormone therapy) may contribute to higher risk of developing venous thromboembolism observed in women < 45 years [49, 82, 83]. Given these gender-related divergences, physicians are encouraged to take care of sex-specific risks in primary cardiovascular prevention and for design of personalized therapeutic strategies [90]
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