Sex-Related Differences In Calcific Aortic Valve Stenosis: Pathophysiology, Epidemiology, Etiology, Diagnosis, Presentation, And Outcomes

Although sex-related differences in aortic valve stenosis (AS) have been published since the 1990s, the extent and complexity of the impact of sex on AS remains incompletely understood. Indeed, male sex has been a well-known risk factor of AS for several years. Thus, AS pathophysiology has been traditionally studied in male cohorts or in cohorts with a large majority of men, explaining the very scarce data regarding sex-specific pathophysiology of AS. However, recent evidence demonstrated the existence of sex differences in AS lesion and thus probably pathophysiology. Moreover, in recent population-based studies, AS occurred more often for men only in young patients (linked to bicuspid aortic valve) while after 75 years of age, female sex seems to be more prevalent. Interestingly, at diagnosis, comorbidities, symptoms or AS severity may be different according to the sex of the patients. Moreover, due to a sex-specific remodeling of the left ventricle, the pattern of AS itself is different, with more women presenting paradoxical low flow low gradient AS. Interestingly, outcomes are also sex-specific, and probably therapy-specific too, with a better outcome in men after open heart surgery but a better outcome in women after transcatheter aortic valve replacement. The aim of this review is to report the impact of sex on AS etiology, epidemiology, management, and outcome, and explore the hypotheses on sex-related differences in the pathophysiology's mechanisms of AS. In particular, sex hormones, sex chromosomes, and the renin-angiotensin-aldosterone system will be discussed.