The Impact of Sex and Gender on Heart-Brain Axis Dysfunction: Current Concepts and Novel Perspectives

The Heart-Brain Axis (HBA) recapitulates all the circuits that regulate bidirectional flow of communication between heart and brain. Several mechanisms may underlie the interdependent relationship involving heterogeneous tissues at rest and during specific target organ injury, such as myocardial infarction, heart failure, arrhythmia, stroke, mood disorders or dementia. In-depth translational studies of the HBA dysfunction under single-organ injury should include both male and female animals to develop sex/gender-oriented prevention, diagnosis and treatment strategies. Indeed, sex and gender are determining factors since females and males exhibit significant differences in terms of susceptibility to risk factors, age of onset, severity of symptoms and outcome. Despite most studies have focused on the male population, we have conducted a careful appraisal of the literature investigating HBA in females. In particular, we have i) analysed sex-related heart and brain illnesses, ii) recapitulated the most significant studies simultaneously conducted on cardio- and cerebrovascular systems in female population, iii) hypothesised future perspectives for the development of gender-based approach to HBA dysfunction. Although sex/gender-oriented research is at its infancy, the impact of sex on HBA dysfunction is opening unexpected new avenues for managing health of female subjects exposed to risk of lifestyle multi-organ disease.