Sex-associated territory-specific vascular phenotypes in genetically confirmed vascular Ehlers-Danlos syndrome
- 1Department of Cardiovascular Medicine, Mayo Clinic, Phoenix, Arizona, USA
- 2Department of Clinical Genomics, Mayo Cinic, Rochester, Minnesota, USA
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.
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BibTeX
@article{nabi2026sexassociated,
title = {{Sex-associated territory-specific vascular phenotypes in genetically confirmed vascular Ehlers-Danlos syndrome}},
author = {Hussein Abdul Nabi and Luke Arnulfo Dreher and Vinícius de Sousa Barzon Serra and Sammudeen Ibrahim and Luis R Scott and Chadi Ayoub and Hicham Z El Masry and Linnea M Baudhuin and Fadi E Shamoun},
journal = {Open Heart},
year = {2026},
month = nov,
doi = {10.1136/openhrt-2026-004552},
url = {https://doi.org/10.1136/openhrt-2026-004552},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Sex-associated territory-specific vascular phenotypes in genetically confirmed vascular Ehlers-Danlos syndrome
AU - Hussein Abdul Nabi
AU - Luke Arnulfo Dreher
AU - Vinícius de Sousa Barzon Serra
AU - Sammudeen Ibrahim
AU - Luis R Scott
AU - Chadi Ayoub
AU - Hicham Z El Masry
AU - Linnea M Baudhuin
AU - Fadi E Shamoun
PY - 2026
DA - 2026/11/02
JO - Open Heart
DO - 10.1136/openhrt-2026-004552
UR - https://doi.org/10.1136/openhrt-2026-004552
AB - 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.
SN - 2053-3624
ER -