Work

Sex-associated territory-specific vascular phenotypes in genetically confirmed vascular Ehlers-Danlos syndrome

Year: 2026

Type: article

Abstract: Objective To characterise territory-specific sex-associated vascular phenotypes in genetically confirmed vascular Ehlers-Danlos syndrome and assess whether associations persisted after accounting for COL3A1 molecular mechanism.Methods In this retrospective multicentre cohort, clinical-genomics review identified 95 eligible patients from 110 source records. 18 prespecified vascular outcomes were evaluated using Firth bias-reduced logistic regression adjusted for completed age per 10-year increment. Sensitivity analyses among 75 patients with classifiable dominant-negative or haploinsufficient mechanisms additionally adjusted for molecular mechanism.Results The cohort included 34 male and 61 female patients. Male sex was associated with ascending aortic dilation or aneurysm (adjusted OR 4.88, 95% CI 1.68 to 15.41), iliac/femoral aneurysm (4.61, 95% CI 1.79 to 12.52), extra-aortic dissection (3.93, 95% CI 1.61 to 10.24), renal dissection (10.08, 95% CI 3.08 to 42.11) and splanchnic dissection (5.84, 95% CI 2.27 to 15.90). Aortic dissection and cervical aneurysm or dissection were not associated with male sex. In the imaging-restricted unadjusted comparison, head and neck tortuosity, ectasia or dilation was present in 23/44 (52.3%) female and 7/29 (24.1%) male patients (p=0.028). In genotype sensitivity analyses, associations remained for iliac/femoral, renal and splanchnic aneurysms and for extra-aortic, renal, splanchnic and iliac dissections, whereas several broader aneurysm and intervention estimates became less precise.Conclusions Male sex was associated with a territory-specific vascular phenotype, with the most consistent genotype-adjusted associations involving renal, splanchnic, iliac/femoral and broader extra-aortic dissection territories. Surveillance should remain comprehensive rather than sex restricted.

Source: Open Heart

DOI: 10.1136/openhrt-2026-004552