OP0006 IMPROVEMENT OF ENDOTHELIAL DYSFUNCTION AND INFLAMMATION IN PSORIATIC ARTHRITIS: IMPROVE – PSA STUDY
Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Cardiovascular (CV) disease is leading cause of death in Psoriatic Arthritis (PsA)<sup>1</sup>. Chronic inflammation in PsA is associated with vascular endothelial dysfunction and enhanced CV risk. However, the therapeutic options to treat this enhanced CV risk are limited. <h3>Objectives</h3> To investigate the impact of Olmesartan and Rosuvastatin on endothelial dysfunction and inflammation in PsA. <h3>Methods</h3> 54 PsA patients randomized to receive 24 weeks of treatment with Olmesartan (OLME) (10mg/day, n=18), Rosuvastatin (Rvs) (10mg/day, n=18), and placebo (PL) (n=18) as an adjunct to existing stable antirheumatic drugs. FMD assessed by AngioDefender. EPCs estimated by flow cytometry. Serum nitrite, TBARS, ICAM-1, VCAM-1 and lipids levels estimated at baseline and after treatment. Inflammatory measures included DAS28, DAPSA, ESR and CRP, pro-inflammatory cytokines. Quality of life and CV 10-year risk (SCORE high risk charts) were estimated using standard tools. <h3>Results</h3> Baseline levels of FMD and EPC population were impaired indicating endothelial dysfunction. Basal concentrations of inflammatory markers, pro-inflammatory cytokines and markers of endothelial dysfunction were elevated among three groups. After 24 weeks treatment, FMD improved significantly in rosuvastatin and olmesartan group as compared to placebo. {OLME vs. PL (p≤0.01), Rvs vs. PL (p&lt;0.01), Rvs vs. OLME (p=0.10)} (Fig.1A). EPCs and nitrite (Fig.1B) levels improved significantly in both rosuvastatin and olmesartan groups. Significant reduction found in ICAM-1 after rosuvastatin treatment (p&lt;0.01) where as olmesartan significantly decreased VCAM-1 (p=0.04) and TBAR levels (p≤0.05). Both rosuvastatin and olmesartan resulted in significant reductions of DAS28, DAPSA, ESR, CRP, IL-6 (Fig.1C) and TNF-α (Fig.1D) as compared to placebo. There was a significant reduction in SCORE, HAQ-DI and SF-36 (PH) score after treatment with rosuvastatin and olmesartan. <h3>Conclusion</h3> Olmesartan and rosuvastatin improve endothelial dysfunction, inflammation, CV risk and quality of life in PsA patients. Olmesartan and Rosuvastatin lower the proinflammatory cytokines, especially TNF-α, that down regulates production of CRP, adhesion molecules and nitric oxide which in turn improves endothelial dysfunction. Both drugs also decrease nitrite concentration and improve the EPC population in PsA patients. The augmentation of EPCs by olmesartan and rosuvastatin represents a fascinating new approach for the management of PsA. However, Rosuvastatin in addition also favourably impacted ICAM-1 and lipid abnormalities. In contrast, olmesartan has beneficial effect on blood pressure. Thus, both rosuvastatin and olmesartan demonstrate immunomodulatory, vasculoprotective and cardioprotective potential in PsA mediated through anti-proinflammatory cytokine action. <h3>Reference</h3> [1] Haroon M, Gallagher P, Heffernan E and FitzGerald O. The Journal of Rheumatology. 2014; 41:7. <h3>Acknowledgement</h3> None <h3>Disclosure of Interests</h3> None declared