Women with severe aortic stenosis had significantly higher indexed aortic valve fibrosis volume (83 vs 63 mm3/cm2) and lower calcium content compared to men.
Observational (n=56)
No
Are there sex-specific differences in aortic valve fibrosis, calcification, and molecular pathways in patients with severe aortic stenosis?
Severe aortic stenosis exhibits sex-specific pathophysiological differences, with women showing predominantly fibrotic remodeling and men showing more calcific and inflammatory changes.
Absolute Event Rate: 83% vs 63%
p-value: p=0.026
Background: Aortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related difference in AS development and progression. Fibrotic remodeling is peculiar in women's aortic valves, while men's leaflets are more calcified. Our study aimed to assess aortic valve fibrosis (AVF) in a severe AS cohort using non-invasive diagnostic tools and determine whether sex-specific pathological pathways and cell types are associated with severe AS. Materials and Methods: We have included 28 men and 28 women matched for age with severe AS who underwent echocardiography and cardiac contrast-enhanced computed tomography (CT) before intervention. The calcium and fibrosis volumes were assessed and quantified using the ImageJ thresholding method, indexed calcium and fibrosis volume were calculated by dividing the volume by the aortic annular area. For a deeper understanding of molecular mechanisms characterizing AS disorder, differentially expressed genes and functional inferences between women and men's aortic valves were carried out on a publicly available microarray-based gene expression dataset (GSE102249). Cell types enrichment analysis in stenotic aortic valve tissues was used to reconstruct the sex-specific cellular composition of stenotic aortic valves. Results: In agreement with the literature, our CT quantifications showed that women had significantly lower aortic valve calcium content compared to men, while fibrotic tissue composition was significantly higher in women than men. The expression profiles of human stenotic aortic valves confirm sex-dependent processes. Pro-fibrotic processes were prevalent in women, while pro-inflammatory ones, linked to the immune response system, were enhanced in men. Cell-type enrichment analysis showed that mesenchymal cells were over-represented in AS valves of women, whereas signatures for monocytes, macrophages, T and B cells were enriched men ones. Conclusions: Our data provide the basis that the fibro-calcific process of the aortic valve is sex-specific, both at gene expression and cell type level. The quantification of aortic valve fibrosis by CT could make it possible to perform population-based studies and non-invasive assessment of novel therapies to reduce or halt sex-related calcific aortic valve stenosis (CAVS) progression, acting in an optimal window of opportunity early in the course of the disease.
Myasoedova et al. (Thu,) conducted a observational in Severe aortic stenosis (n=56). Female sex vs. Male sex was evaluated on Indexed aortic valve fibrosis (iAVF) volume (mm3/cm2) (p=0.026). Women with severe aortic stenosis had significantly higher indexed aortic valve fibrosis volume (83 vs 63 mm3/cm2) and lower calcium content compared to men.