Heart-brain interactions in cardiac and brain diseases: why sex matters

Mechanisms involved in the heart-brain crosstalk. Simplified representation of sex differences seen in the main mechanisms and neurohumoral circuits involved in heart-brain interactions. The intensity of activation is represented by a colour code scale, with red indicating the maximal activation. In brief, specific triggers (e.g. stress, acute myocardial infarction) induce the activation of the amygdala via the central autonomic system. Efferent projections increase the activation of the sympathetic nervous system and initiate neurohormonal output through the hypothalamic-pituitary-adrenal axis leading to catecholamine release, myelopoiesis activation, and release of pro-inflammatory cytokines with deleterious effect on the heart. This pro-inflammatory state initiates and promotes atherosclerosis. Current evidence on the pathophysiology of the specific heart and brain disease discussed in this review has shown that the activation of all thesemechanisms ismore pronounced in women as compared with men. The bidirectionality of heart-brain interactions is still under investigation. Cardiovascular disease and brain disorders, such as depression and cognitive dysfunction, are highly prevalent conditions and are among the leading causes limiting patient's quality of life. A growing body of evidence has shown an intimate crosstalk between the heart and the brain, resulting froma complex network of several physiological and neurohumoral circuits. From a pathophysiological perspective, both organs share common risk factors, such as hypertension, diabetes, smoking or dyslipidaemia, and are similarly affected by systemic inflammation, atherosclerosis, and dysfunction of the neuroendocrine system. In addition, there is an increasing awareness that physiological interactions between the two organs play important roles in potentiating disease and that sex- and gender-related differences modify those interactions between the heart and the brain over the entire lifespan. The present review summarizes contemporary evidence of the effect of sex on heart-brain interactions and how these influence pathogenesis, clinical manifestation, and treatment responses of specific heart and brain diseases.

Automated summary

There is a close interaction between the heart and the brain, regulated by various physiological and neurohumoral circuits. Current evidence suggests that this interaction is more pronounced in women. Cardiovascular and brain diseases are common conditions, and gender differences can affect the pathogenesis, clinical manifestation, and treatment responses of these diseases.