Advanced glycation end-products inhibition improves endothelial dysfunction in rheumatoid arthritis

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 (benfotiamine 50 mg + pyridoxamine 50 mg + methylcobalamin 500 mu g, Vonder (R) (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 antirheumatic drugs were investigated. Inflammatory disease activity (DAS28 and Health Assessment Questionnaire- 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 -independent 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 nitroglycerin and baseline diameter; serum nitrite concentration significantly reduced from 5.6 +/- 0.13 to 5.1 +/- 0.14 mu mol/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 AGEsinduced inflammation.