Sex-Related Discordance Between Aortic Valve Calcification and Hemodynamic Severity of Aortic Stenosis

Abstract

In this series of patients with tricuspid aortic valve and similar AS severity, women have less valvular calcification but more fibrosis compared with men. These findings suggest that the pathophysiology of AS and thus potential targets for drug development may be different according to sex.

H19 is not hypomethylated or upregulated with age or sex in the aortic valves of mice

“…For example, male mice had higher overall PSV values that trended upwards with age and higher Bmp2 expression, indicative of onset of stenosis with activation of calcific pathways. This matches with clinical data showing that men are more likely to develop CAVD than women and that features of the disease (fibrosis and calcification) differ between sexes (Owens et al ; Simard et al ). Still, CAVD is relatively prevalent in women, and the differences in disease progression between sexes may direct more personalized treatment strategies.…”

“…Because H19 is known to be involved in other cardiovascular diseases, expression levels were also assessed in ventricular tissue and the aortic arch, as well as the liver, which is known to express higher levels of H19 and was previously shown to exhibit age‐related loss of imprint. While many existing mouse models of CAVD consider only male mice, CAVD is also highly prevalent in women, thus motivating our investigation into the effect of sex on H19 ‐driven calcification (Owens et al ; Simard et al ). Because our primary interest was in the effects of age and sex (rather than genetic mutation or chronic injury through diet) on H19 expression in the aortic valve, these experiments were conducted in healthy C57BL/6 mice maintained on a normal diet.…”

Calcific Aortic Valve Disease

“…Specifically, for an equivalent degree of aortic stenosis, men had significantly greater valve calcification than women, as measured by multidetector CT (MDCT) imaging of patients [7]. This intriguing discovery sets the stage for the current work by Simard et al [8], whose research builds upon the earlier finding to uncover further differences in pathology between male and female valves with CAVD.…”

“…In their study, Simard et al [8] merge in vivo quantification of stenosis severity and calcification with ex vivo evaluation of explanted leaflets for evidence of calcification and fibrosis. After controlling for patient comorbidities, study participants were evaluated using echocardiography and MDCT imaging to assess aortic stenosis severity and valve calcification, and to frequency-match patients according to demographics and extent of disease.…”

Gender-specific differences in valvular heart disease

“…Quantification of AVC by CT is of particular clinical importance in low-flow AS, if dobutamine stress echocardiography is not possible/inconclusive, and in patients with paradoxical low-flow AS. Here, gender-specific cut-off values should be applied as women reach the same hemodynamic AS severity with less AVC [4], due to more pronounced valvular fibrosis instead of calcification [5]. With the onset of cardinal symptoms, such as angina, exertional dyspnea and syncope, AS patients face a dismal prognosis and should receive valvular replacement according to current recommendations [6].…”