Cardiac effects of aldosterone: Does gender matter?

• A significant gender bias exists in the outcome of cardiovascular disease.
• Aldosterone negatively effects myocardial health to promote cardiovascular disease.
• Sex hormones alter the release of, and response to, aldosterone in multiple tissues.
• Such mechanisms represent a new homeostatic mechanism regulating aldosterone.

Ischemic heart disease (IHD) continues to be the most common cause of death globally, although mortality rates are decreasing with significant advances in treatment. Higher prevalence of co-morbidities in women only partly explains the lack of decrease in mortality rates in younger women due to. Until recently there has been gender bias in pre-clinical studies and many clinical trials, resulting in a significant gap in knowledge whether there are differential responses to therapy for women, particularly younger women. There is increasing evidence that there are significant gender-specific differences in the outcome of post-infarction remodelling, prevalence of hypertension and sudden cardiac death. These differences indicate that cardiac tissue in females displays significant physiological and biochemical differences compared to males. However, the mechanisms mediating these differences, and how they change with age, are poorly understood. Circulating levels and physiological effects of aldosterone vary across the menstrual cycle suggesting female steroid sex hormones may not only regulate production of, but also responses to, aldosterone in pre-menopausal women. This modified tissue response may foster a homeostatic environment where higher levels of aldosterone are tolerated without adverse cardiac effect. Moreover, there is limited data on the direct regulation of this signalling axis by androgens in female animals/subjects. This review explores the relationship between gender and the effects of aldosterone in cardiovascular disease (CVD), an issue of significant need that may lead to changes in best practice to optimise clinical care and improve outcomes for females with CVD.