Cervical Artery Tortuosity Is Associated With Dissection Occurrence and Late Recurrence: A Nested Case-Control Study

BACKGROUND: The pathogenesis of spontaneous cervical artery dissection remains unclear, and no established predictors of recurrence exist. Our goal was to investigate the potential association between cervical artery tortuosity, a characteristic of patients with connective tissue disorder, and spontaneous cervical artery dissection. METHODS: The ReSect study (Risk Factors for Recurrent Cervical Artery Dissection) is an observational study that invited all spontaneous cervical artery dissection patients treated at the Innsbruck University Hospital between 1996 and 2018 for clinical and radiological follow-up. Internal carotid and vertebral artery tortuosity was assessed on magnetic resonance angiography using a validated 3-dimensional algorithm. Differences between patients and healthy controls as well as dependent on recurrence status were assessed by applying χ 2 , Mann-Whitney U test, and Kruskal-Wallis test where applicable, and confounders were established by bivariable Pearson correlation. Logistic regression was used to address the impact of tortuosity on dissection occurrence and recurrence as well as its association to extracellular matrix proteome data derived from skin biopsies in a subset of patients. RESULTS: Magnetic resonance angiography was performed a median of 6.5 years after dissection in the included dissection patients. Patients with dissection (n=125) had significantly increased values of internal carotid artery tortuosity compared with healthy controls (n=24; odds ratio, 2.65 [95% CI, 1.68–3.86], 1 SD increase; P <0.01). This was also true for patients with long-term dissection recurrence (n=7) when compared with those with single time-point dissection (n=118; odds ratio, 2.00 [95% CI, 1.47–3.99], 1 SD increase; P <0.01). In patients with dissection and available extracellular matrix protein data (n=37), 6 of 13 (46.2%) proteins previously found linked with dissection recurrence were also associated with increased tortuosity. All 3 proteins associated with both anterior and posterior circulation tortuosity belonged to the desmosome-related cluster. CONCLUSIONS: Internal carotid artery tortuosity is elevated in spontaneous cervical artery dissection patients compared with healthy controls, and this difference is most pronounced if individuals suffer from long-term dissection recurrence. Additionally, an association between tortuosity, being a readily measurable biomarker in routine magnetic resonance angiography, and proteomic markers of dissection recurrence exists, further enhancing the prospect of underlying subclinical connective tissue disease in dissection patients.