I033 Celiprolol increases the elasticity of the radial artery in vascular Ehlers-Danlos syndrome : a randomized controlled clinical trial

IntroductionVascular Ehlers-Danlos syndrome (vEDS) is an autosomal dominant inherited disorder of connective tissue. This syndrome results from mutations in the gene encoding type III procollagen. The patients can present with spontaneous arterial rupture or dissection. We had previously described that celiprolol stiffened large-sized elastic artery (common carotid artery) in vEDS. We tested the effects of celiprolol, a beta1-adrenoceptor antagonist with a beta2-adrenoceptor agonist action in small-sized muscular artery (radial artery) in vEDS.Methods47 vEDS patients with no previous beta-blocker were randomized to 5 years treatment. According to a PROBE design, they were allocated either to celiprolol (50 to 200mg once a day, n=23) or no treatment (n=24). Radial internal diameter, intimamedia thickness (IMT) and distension were measured on the right arm with a 10-MHz ultrasound system analyzing the radiofrequency signal. Radial blood pressures were obtained with applanation tonometry. Other radial parameters (wall cross-sectional area, wall-to-lumen ratio, distensibility, Young's elastic modulus and circumferential wall stress) were calculated from radial internal diameter, IMT, distension, mean blood pressure and pulse pressure. We used MIXED procedure of the SAS® System through the repeated statements to compare serial changes in blood pressure and arterial parameters in two groups.ResultsAfter 12 months, heart rate, radial systolic and mean blood pressure, pulse pressure, IMT, Young's elastic modulus and circumferential wall stress did not change in both groups. Radial diastolic blood pressure decreased significantly (p=0.03) and to the same extent in both groups (−5 % in the celiprolol group and −6 % in the control group) (period effect). Radial internal diameter, wall cross-sectional area increased significantly (+5 %, p=0.04 and +12 %, p=0.04 respectively) and wall-to-lumen ratio decreased significantly (−2 %, p=0.04) in celiprolol group but not in control group (periodby-group interaction). Significant increase in distensibility was observed in celiprolol group (+18 %, p=0.04) but not in control group (group effect).Conclusionscompared to no treatment, celiprolol induced a moderate dilation and an important augmentation of elasticity of the radial artery with no change in radial blood pressure. The results proposed the pleiotropic effect of celiprolol in small-sized muscular artery