Three-Dimensional Curvature of the Cervical Carotid Artery Predicts Long-Term Neurovascular Risk in Loeys-Dietz Syndrome

BACKGROUND: Although the relationship between cervical carotid tortuosity and cardiovascular risk in patients with Loeys-Dietz syndrome has been studied, it is unclear whether cervical carotid tortuosity influences the risk of neurovascular events. METHODS: This is a single-institution retrospective cohort study. Cervical carotid tortuosity and morphology were assessed in patients with Loeys-Dietz syndrome who underwent baseline computed tomography/magnetic resonance imaging of the cervical and cerebral arteries from 2010 to 2022. The primary end point was a composite of adverse neurovascular events (multiple vessel cervical artery dissection, ischemic stroke, intracerebral hemorrhage, and any neurovascular intervention) at 5- and 10-year follow-ups. Independent risk factors were identified using univariate and multivariate logistic regression analyses. Single-variable predictors of 5- and 10-year outcomes were analyzed via receiver operating curve analyses. Cutoff values were determined per the Youden J index. Stratification analyses were performed for ages <60 and ≥60 years. RESULTS: Of 105 eligible participants, 63 were included (mean age, 40±17 years; 52% female). During a mean follow-up of 8.7±4.1 years, 23 (37%) developed an adverse neurovascular event. Five-year follow-up was achieved in 86% and 10-year follow-up in 48%. Carotid total absolute curvature (TAC; P=0.008), coiling morphology (P=0.012), and TGFBR1/2 genetic variant (P=0.037) were independently associated with 5-year events. Stratification analyses revealed that the age group <60 years was more vulnerable to high TAC (unadjusted odds ratio, 7.2 [95% CI, 2.0-25.4]; P=0.002). Baseline TAC was the only independent predictor of adverse events at 5 years (area under the curve, 0.84; P<0.001) and 10 years (area under the curve, 0.75; P=0.007) in this age group. An optimal threshold for predicting neurovascular events was TAC ≥16.5. None were predictive in the age group ≥60 years. CONCLUSIONS: Cervical carotid tortuosity is associated with a long-term increased risk of neurovascular events in Loeys-Dietz syndrome. Angiographic findings of high-risk features such as increased TAC and coiling morphology may help to identify neurovascular vulnerability noninvasively at an early stage.