Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis

Objective: Chronic inflammation in rheumatoid arthritis (RA) is associated with vascular endothelial dysfunction. The aim of this study was to determine the effect of spironolactone on endothelial function in anti-tumour necrosis factor (TNF)-naive RA patients. Methods: Twenty-four anti-TNF-naive RA patients (mean age 491.8 years; disease duration 8.55.8 years) with high disease activity [Disease Activity Score including a 28-joint count (DAS285.1)] despite treatment with stable doses of conventional disease-modifying anti-rheumatic drugs (DMARDs) were investigated. Inflammatory disease activity [DAS28 and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP)], serum markers of endothelial dysfunction, serum nitrite concentration, and endothelium-dependent and -independent vasodilation of the brachial artery were measured before and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. Results: After treatment with spironolactone, flow-mediated vasodilation (FMD) improved from 3.180.46% to 3.950.49% (p0.001) whereas there was no significant change in endothelium-independent vasodilation with nitroglycerin and baseline diameter (18.41.15% vs. 18.31.13%, p=0.046, and 3.50.1 vs. 3.520.1 mm, p=0.952, respectively); serum nitrite concentration was reduced significantly from 6.90.34 to 6.80.33 mol/L (p0.001), ESR from 59.904.86 to 51.224.26 mm in the first hour (p0.001), and CRP level from 15.23.8 to 9.42.6 mg/dL (p=0.019). DAS28 and HAQ-DI scores were significantly reduced, from 6.90.25 to 4.10.31 (p0.05) and from 1.470.09 to 0.690.1 (p0.05), respectively. Conclusions: The study suggests that, in RA, endothelial dysfunction is part of the disease process and treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in RA.