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. Sex-related and gender-related factors often have opposite effects on the clinical manifestations and outcomes of cardiovascular disease. Some sex-related differences in the human cardiovascular system already exist at birth and are due to purely biological mechanisms, that is, genes and sex hormones. Gender-related variables or scores allow for the characterization of individuals beyond their biological sex, and the effects of gender might even oppose the effects of biological sex on clinical outcomes. The predominantly male leadership and workforce in clinical cardiology is a disadvantage for women as patients. Cardiovascular disease risk factors related to female biological sex or feminine gender include, among others, pregnancy complications, breast cancer therapy, autoimmune and rheumatic diseases, depression, and household-related stress. Despite a more favourable biology, gender-related factors impair outcomes in women with coronary artery disease or heart failure compared with those in men. In this Review, the authors summarize the evidence on the different effects of sex and gender on the pathogenesis, clinical manifestations and treatment responses of patients with ischaemic heart disease or heart failure. In addition, they highlight unexplored areas of sex-related and gender-related factors in cardiovascular disease such as in individuals with gender dysphoria.