GENOTYPE-PHENOTYPE RELATIONSHIP IN ARTERIAL REMODELING: CAROTID WCSA AND CIRCUMFERENTIAL WALL STRESS PREDICT COL3A1 MUTATION IN PATIENTS WITH VASCULAR EHLERS-DANLOS SYNDROME: PP.10.394

Abstract

Background: Vascular Ehlers-Danlos syndrome (vEDS) resulting from mutations in the gene encoding type III procollagen (COL3A1) is clinically characterized by four major and nine minor criteria. The diagnosis is improved by genetic detection of COL3A1 mutations. We aim to assess the genotype-phenotype relationship in vEDS patients. Methods: 132 vEDS patients, diagnosed from clinical criteria, had carotid measurement. Genetic testing was realized in all patients. 57 patients (43%) presented COL3A1 mutations (COL3A1+). Arterial parameters were determined with high-resolution echo-tracking system coupled with applanation tonometry. Statistical analysis was performed using general linear model ANOVA, logistic regression and receiver-operating characteristic (ROC) curves. Results: Demographic data did not differ between COL3A1+ and COL3A1- patients. Patients with COL3A1+ were significantly leaner than COL3A1- patients (-6 kg, p < 0.05). Heart rate, brachial BP, central PP, carotid diameter, distensibility, and Young's elastic modulus were not significantly different between the two groups. Carotid intima-media thickness (IMT) and carotid wall cross-sectional area (WCSA) were significantly lower (-12%, p < 0.001; and -15%, p < 0.001, respectively) in COL3A1+ than COL3A1- patients. Carotid circumferential wall stress was higher (+17%, p < 0.001) in COL3A1+ than COL3A1- patients. Carotid WCSA and circumferential wall stress independently discriminated between COL3A1+ and COL3A1- patients. They were scored from 1 to 3 depending on their threshold values for sensitivity/specificity, and then combined into a total ultrasound (US) score (from 2 to 6). A total US score ≥5 had a high positive predictive value (>75% certainty of COL3A1+ mutations). The area under the ROC curves for the total US score was 0.73 (95% CI, 0.64 to 0.81). Odds ratio for total US score ≥5 was 7.1 (95% CI, 3 to 16.9). Conclusions: An ultrasound score combining carotid WCSA and circumferential wall stress is highly predictive of a COL3A1 mutation in vEDS patients.