Sex differences in aortopathy, arteriopathy, and mortality in vascular Ehlers-Danlos syndrome

Vascular Ehlers-Danlos syndrome (VEDS) is a rare autosomal dominant disorder due to pathogenic alterations in type III collagen structure and production, which results in increased risk of aortopathy and arteriopathy. Given the documented sex-related differences in aortic and other arterial aneurysms and dissections in non-VEDS populations, the potential influence of sex on the incidence of aortopathy, arteriopathy, and mortality in individuals with VEDS was examined.

A cross-sectional analysis on a cohort of 557 individuals with VEDS with COL3A1 pathogenic variants was performed as part of the VEDS Collaborative Natural History Study. Primary outcomes were all-cause mortality and time to first aortopathy or arteriopathy diagnosis. Statistical analysis was performed using the Student t test (continuous data), Pearson χ² test (categorical data), and log-rank test (Kaplan-Meier survival data). Data were analyzed using STATA version 16 for Windows (STATA Inc).

Male patients comprised 44.5% of the cohort (n = 248) and female patients 55.7% (n = 309). At enrollment, the mean age of male patients was younger than that of female patients (35.8 ± 16.6 vs 39.2 ± 16.0 years; P = .017). The mean age at genetic diagnosis did not differ (30.8 ± 17.9 vs 33.5 ± 17.7 years; P = .110). Aortopathy and iliac or visceral arteriopathy were more frequent in male patients (74.2% vs 57.9%; P < .001), whereas female patients had higher rates of carotid-cavernous fistulas and spontaneous coronary artery dissections. The mean age at first aortopathy or arteriopathy diagnosis trended younger in male patients (34.4 vs 37.3 years; P = .057), as confirmed by Kaplan-Meier analysis (P < .001). Male patients also had higher all-cause mortality (32.3% vs 20.4%; P = .001) and a trend toward increased aortic-related mortality (53.8% vs 38.1%; P = .063).

Male patients presented at younger ages with earlier disease onset and higher all-cause mortality. The distribution of vascular pathology varied by sex: aortopathy and iliac or visceral arteriopathy were more common in male patients, whereas carotid-cavernous fistulas and spontaneous coronary artery dissection occurred more frequently in female patients.