Gender medicine: effects of sex and gender on cardiovascular disease manifestation and outcomes

Abstract

Despite a growing body of evidence, the distinct contributions of biological sex and the sociocultural dimension of gender to the manifestations and outcomes of ischaemic heart disease and heart failure remain unknown. The intertwining of sex-based differences in genetic and hormonal mechanisms with the complex dimension of gender and its different components and determinants that result in different disease phenotypes in women and men needs to be elucidated. The relative contribution of purely biological factors, such as genes and hormones, to cardiovascular phenotypes and outcomes is not yet fully understood. Increasing awareness of the effects of gender has led to efforts to measure gender in retrospective and prospective clinical studies and the development of gender scores. However, the synergistic or opposing effects of sex and gender on cardiovascular traits and on ischaemic heart disease and heart failure mechanisms have not yet been systematically described. Furthermore, specific considerations of sex-related and gender-related factors in gender dysphoria or in heart–brain interactions and their association with cardiovascular disease are still lacking. In this Review, we summarize contemporary evidence on the distinct effects of sex and gender as well as of their interactions on cardiovascular disease and how they favourably or unfavourably influence the pathogenesis, clinical manifestations and treatment responses in patients with ischaemic heart disease or heart failure.

Why you should pay more attention to your cells’ sex

“…Myocardial infarction is usually caused by plaque rupture in men, while plaque erosions or coronary dissections occur frequently in women. In heart failure, women are more likely to develop cardiac hypertrophy, diastolic dysfunction and heart failure with preserved ejection fraction (Regitz‐Zagrosek & Gebhard, 2023; Vogel et al., 2021). Sex and gender differences are also described for neurological and psychiatric disorders, pulmonary and gastrointestinal diseases as well as for cancer, among others.…”

“…Sex and gender differences are also described for neurological and psychiatric disorders, pulmonary and gastrointestinal diseases as well as for cancer, among others. In general, harmful pharmacological side effects are more common in women (Regitz‐Zagrosek & Gebhard, 2023; Seydel, 2021). Therefore, including sex in preclinical and clinical drug development studies is critical.…”

Effects of Sex on the Susceptibility for Atrial Fibrillation in Pigs with Ischemic Heart Failure

“…In particular, an analysis of all studies cited by the “2020 Canadian Cardiovascular Society/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of Atrial Fibrillation” showed that only 39.1% of the study population were women [ 3 , 6 ]. In recent years, research began setting a greater focus on investigating differences between men and women concerning pathophysiology, treatment, and prevention [ 7 ]. It has been observed that treatment strategies and outcome of cardiovascular diseases are influenced by the gender of patients: women less often receive electrical cardioversion or catheter ablation upon the diagnosis of AF [ 8 ] and a nationwide study in Germany showed that the in-hospital mortality of patients with AF, who underwent atrial ablation or atrial appendage occlusion therapy, is also associated with the female sex [ 9 ].…”

Sex-Specific Differences in Lipoprotein Production and Clearance

“…3,4 In addition to sex hormones, there are genetic, behavioral, and socioeconomic factors associated with sex that influence health disparities among sexes. 5…”

“…3,4 In addition to sex hormones, there are genetic, behavioral, and socioeconomic factors associated with sex that influence health disparities among sexes. 5 Seminal scientific advancements in the last century achieved a profound reduction in the incidence of cardiovascular disease (CVD); however, there is an increased awareness that addressing remaining residual risk will require the use of personalized strategies of which sex as a biological variable in both basic and human studies will have to be considered. 6,7 Studies highlight sex differences in many factors implicated in the development of atherosclerosis, the main underlying cause of CVD.…”