The influence of sex and valve phenotype on fibrocalcific composition in severe aortic stenosis evolves with age

While sex and valve phenotype influence fibrocalcific composition in older patients with aortic stenosis (AS), their roles in younger individuals remain unclear. We investigated the impact of sex, valve phenotype, and age on computed tomography (CT)-derived aortic valve composition in a relatively younger cohort with severe AS.

This study included 221 patients with severe AS (mean age 64.0 ± 7.6 years; 102 women; 151 bicuspid aortic valve [BAV]) who underwent echocardiography and cardiac CT. CT quantified calcific density, fibrotic density, and fibrotic percentage. Group comparisons and Pearson correlations were performed.

Compared to men, women had lower calcific density (p < 0.001), higher fibrotic density (p = 0.001), and a higher fibrotic percentage (p < 0.001). These sex differences were more pronounced in patients aged < 65 years. Age correlated positively with calcific density (R = 0.225, p < 0.001) and negatively with fibrotic percentage (R = -0.280, p < 0.001) overall, driven primarily by women, whereas no significant correlations were observed in men. BAV-women exhibited higher fibrosis than BAV-men (p < 0.001), while TAV-women had lower calcification than TAV-men (p = 0.005). Valve phenotype (BAV vs. TAV) showed no significant association with tissue composition in the overall cohort or among patients < 65 years. However, among women aged ≥ 65 years, those with BAV had higher fibrotic and fibrocalcific densities than those with TAV.

In our relatively younger severe AS cohort, sex is the primary determinant of fibrocalcific composition, particularly in patients under 65 years. In women aged ≥ 65 years, valve phenotype re-emerges as a significant factor.