%0 Journal Article
%T Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.
%A Stephens SB
%A Shalhub S
%A Dodd N
%A Li J
%A Huang M
%A Oda S
%A Kancherla K
%A Doan TT
%A Prakash SK
%A Weigand JD
%A Asch FM
%A Beecroft T
%A Cecchi A
%A Shittu T
%A Preiss L
%A LeMaire SA
%A Devereux RB
%A Pyeritz RE
%A Holmes KW
%A Roman MJ
%A Lacro RV
%A Shohet RV
%A Krishnamurthy R
%A Eagle K
%A Byers P
%A Milewicz DM
%A Morris SA
%J J Am Heart Assoc
%V 12
%N 19
%D 2023 10 3
%M 37776192
%F 6.106
%R 10.1161/JAHA.123.029518
%X Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.