P2621Improvement of endothelial glycocalyx thickness after anti-inflammatory treatment is related with reduced arterial blood pressure, stiffness and wave reflections in psoriasis

Abstract

Psoriasis has been associated with an increasing risk for atherosclerosis. The glycocalyx, is an integral component of the endothelial surface layer, composed of glycoconjugates and proteoglycans and an important element in inter‐ and intracellular communication and tissue homeostasis We investigated whether there was a greater improvement of endothelial glycocalyx aortic elastic properties and vascular function, post ‐treatment with IL12/23 antagonists, in patients with psoriasis (PS), compared to treatment with anti‐TNFa agents or cyclosporine. Methods: 130 patients (age:50±12 yrs) with psoriasis (PS) (PASI disease activity score:11.5±8) were randomized to receive an anti‐TNF‐a agent (n=49),an anti‐IL12/23 regimen Ustekinumab, (n=33) or a combined cyclosporine and methotrexate (n=48). At baseline and after 4 months of treatment, we measured a)the carotid‐femoral pulse wave velocity (Complior‐PWVc) and augmentation index (AIx) and brachial systolic blood pressure (SBP) b) perfused boundary region (PBR) of the sublingual arterial microvessels (ranged from 5‐25μm) using Sideview Darkfield imaging (Microscan, Glycocheck). Increased PBR is considered an accurate index of reduced endothelial glucocalyx thickness because of a deeper RBC penetration in the glycocalyx. Forty normal subjects (N) served as controls Risk factors age and sex were similar between the treatment groups Results: At baseline patients with psoriasis had higher (PBR) (5‐25μm) (2.12±0.27 vs. 1.77±0.3), SBP (135±20 vs. 120±10 mmHg), PWV (11±2.4 vs. 9.9±5.1 m/sec) and AIx, (28.3±37 vs. 23.5±16%) than normals (p<0.05 for all comparison) Four months post‐treatment, patient, treated with anti‐IL12/23 regimen showed a significant improvement of (PBR) (5‐25μm) (2.13±0.37 vs. 2.09±0.31, p=0.03) compared to patients treated with anti‐TNFa agents (2.14±0.23 vs. 2.11±0.27) or those treated with non‐biological drugs (PBR) ( 5‐ 25μm) (2.04±0.3 vs. 1.97±0.34) who showed a small non‐significant reduction of PBR (p>0.05). Risk factors age and sex were similar between the treatment groups. Post‐treatment improved (PBR) (5‐25μm) and (PBR) (5‐9μm) were associated with lower brachial systolic (r=0.31 and r=0.28) and diastolic brachial blood pressure (r=0.20 and r=0.22) as well as reduced PWV (r=0.19 and r=0.167) and Aix (r=0.17 and r=0.28) (p<0.05 for all associations) in all patients. Conclusion: Improvement of endothelial glycocalyx post‐treatment is associated with reduced arterial blood pressure, stiffness and wave reflection. Treatment with IL‐12/23 antagonist appears to have a greater effect on endothelial glycocalyx than treatment with anti‐TNF antagonists or cyclosporine/methotrexate in psoriasis.