Sex Differences in Phenotypes of Bicuspid Aortic Valve and Aortopathy

Abstract

Background-This large multicenter, international bicuspid aortic valve (BAV) registry aimed to define the sex differences in prevalence, valve morphology, dysfunction (aortic stenosis/regurgitation), aortopathy, and complications (endocarditis and aortic dissection). Methods and Results-Demographic, clinical, and echocardiographic data at first presentation of 1992 patients with BAV (71.5% men) were retrospectively analyzed. BAV morphology and valve function were assessed; aortopathy configuration was defined as isolated dilatation of the sinus of Valsalva or sinotubular junction, isolated dilatation of the ascending aorta distal to the sinotubular junction, or diffuse dilatation of the aortic root and ascending aorta. New cases of endocarditis and aortic dissection were recorded. There were no significant sex differences regarding BAV morphology and frequency of normal valve function. When presenting with moderate/severe aortic valve dysfunction, men had more frequent aortic regurgitation than women (33.8% versus 22.2%, P<0.001), whereas women were more likely to have aortic stenosis (34.5% versus 44.1%, P<0.001). Men had more frequently isolated dilatation of the sinus of Valsalva or sinotubular junction (14.2% versus 6.7%, P<0.001) and diffuse dilatation of the aortic root and ascending aorta (16.2% versus 7.3%, P<0.001) than women. Endocarditis (4.5% versus 2.5%, P=0.037) and aortic dissections (0.5% versus 0%, P<0.001) occurred more frequently in men. Conclusions-Although there is a male predominance among patients with BAV, men with BAV had more frequently moderate/severe aortic regurgitation at first presentation compared with women, whereas women presented more often with moderate/severe aortic stenosis compared with men. Furthermore, men had more frequent aortopathy than women. (Circ Cardiovasc Imaging. 2017;10:e005155.

Age- and Sex-Related Aortic Valve Dysfunction and Aortopathy Difference in Patients with Bicuspid Aortic Valve

“…Higher frequency of aortopathy in men with BAV compared with women has been previously described. 4) Prior study showed impaired AA function in clinically normal patients, and larger aortic dimension in men compared with women was reported. 19,20) In our study, the diameter of aortic sinus and AA was higher in men but with no significance difference.…”

“…3) Prior studies showed BAV was three times more prevalent in men than women, and male patients had more frequent AR compared with female. 4) In addition, male patients were referred to aortic valve replacement (AVR) at younger age and combined with more frequent aortopathy. 5) Whereas elderly patients with AS were referred to transcatheter aortic valve replacement (TAVR), the proportion of women was higher in patients with BAV than those with TAV.…”

Bicuspid Aortic Valve Disease: New Insights

“…In the study by Kong and coworkers, moderate and severe AR was slightly more common among BAV patients with 2 raphes. 10 However, the incidence of significant AR was similar across patients with type 0 BAV and type 1 regardless of the raphe location ( Figure 4). In contrast, an association between the type of aortopathy and AR has been described.…”

“…9 In addition, a gender difference in the development of AS has been found, with women more likely to present with moderate to severe AS than men. 10 However, there is conflicting data regarding the association of BAV leaflet morphology and the potential for AS. Beppu and colleagues reported that BAV with left-right cusp fusion was more likely to be associated with rapid development of AS.…”

Unanswered Questions Regarding Sex and BMP/TGF-&beta; Signaling

“…Recent reports described dissimilarities in the ratios of fibrotic to calcified tissue in equally stenotic valves from men versus women [4][5][6][7]. Because TGF-β signaling is generally pro-fibrotic and BMP signaling is generally anti-fibrotic, we wondered if sex-associated changes in this balance contributed to the skewed sex distribution of valvular heart disease [4,[7][8][9][10][11]. Here we review the current state of understanding regarding the impact of sex on BMP and TGF-β signaling and identify several unanswered questions.…”