ORIGINAL ARTICLE Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis Ashit SYNGLE, 1,2 Kanchan VOHRA, 3 Nidhi GARG, 3 Ladbans KAUR 4 and Prem CHAND 3 1 Healing Touch City Clinic, Chandigarh, 2 Department of Internal Medicine and Rheumatology, Fortis Multispeciality Hospital, Mohali, 3 Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, and 4 Department of Radiology, Prime Diagnostics, Chandigarh, India Abstract Aim: Chronic inflammation in rheumatoid arthritis is associated with vascular endothelial dysfunction. The objective was to study the efficacy and safety of advanced glycation end products (AGEs) inhibitor (benfoti- amine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 lg, Vonder Ò (ACME Lifescience, Baddi, Himachal Pradesh, India)) on endothelial function in rheumatoid arthritis (RA). Methods: Twenty-four patients with established active RA with high disease activity (Disease Activity Score of 28 joints [DAS28 score] > 5.1) despite treatment with stable doses of conventional disease-modifying anti- rheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Question- naire-Disability Index [HAQ-DI] scores, erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), markers of endothelial dysfunction, serum nitrite concentration and endothelium-dependent and -indepen- dent vasodilation of the brachial artery were measured before and after 12 weeks therapy with twice a day oral AGEs inhibitor. Results: After treatment, flow-mediated vasodilation improved from 9.64  0.65% to 15.82  1.02% (P < 0.01), whereas there was no significant change in endothelium-independent vasodilation with nitroglyc- erin and baseline diameter; serum nitrite concentration significantly reduced from 5.6  0.13 to 5.1  0.14 lmol/L (P = 0.004), ESR from 63.00  3.5 to 28.08  1.5 mm in the first h (P < 0.01) and CRP levels from 16.7  4.1 to 10.74  2.9 mg/dL (P < 0.01). DAS28 and HAQ-DI scores were significantly reduced, from 5.9  0.17 to 3.9  0.17 (P < 0.01) and 4.6  0.17 to 1.7  0.22 (P < 0.01), respectively. Conclusions: Advanced glycation end products inhibitor improves endothelial dysfunction and inflammatory disease activity in RA. In RA, endothelial dysfunction is part of the disease process and is mediated by AGEs- induced inflammation. Key words: advanced glycation end-products (AGEs) inhibitor, endothelial dysfunction, rheumatoid arthritis. INTRODUCTION Rheumatoid arthritis (RA) is a chronic progressive autoimmune inflammatory disease of unknown etiology that attacks the synovial tissue leading to irreversible joint damage, chronic pain, stiffness, func- tional impairment and premature death. 1 RA patients are 2–5 times more prone to cardiovascular morbidity and mortality as compared to the general population and cardiovascular disease contributes to one-third to one-half of premature deaths in RA. 2 The chronic sys- temic inflammatory process in RA initiates atheroscle- rosis in these patients through its actions on the vascular endothelium. 3 The endothelium is a major Correspondence: Dr Ashit Syngle, Healing Touch City Clinic H. No 547, Sector 16-D, Chandigarh 160015, India. Email: ashitsyngle@yahoo.com International Journal of Rheumatic Diseases 2012; 15: 45–55 ª 2011 The Authors International Journal of Rheumatic Diseases ª 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd