Molecular Features of Calcific Aortic Stenosis in Female and Male Patients

Over the past 15 years, sex-related differences in aortic valve (AV) stenosis (AS) have been highlighted, affecting various aspects of AS, such as the pathophysiology, AV lesions, left ventricle remodelling, and outcomes. Female patients were found to present a more profibrotic pattern of leaflet remodelling and/or thickening, whereas male patients have a preponderance of calcification within stenosed leaflets. The understanding of these sex differences is still limited, owing to the underrepresentation of female patients in many basic and clinical research studies and trials. A better understanding of sex differences in the pathophysiology of AS may highlight new therapeutic targets that potentially could be sex-specific. This review aims to summarize sex-related differences in AS, as discovered from basic research experiments, covering aspects of the disease ranging from leaflet composition to signalling pathways, sex hormones, genetics and/or transcriptomics, and potential sex-adapted medical treatments.