Effect of spironolactone on endothelial dysfunction in rheumatoid arthritis

Abstract

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 49±1.8 years; disease duration 8.5±5.8 years) with high disease activity [Disease Activity Score including a 28‐joint count (DAS28>5.1)] 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 3.18±0.46% to 3.95±0.49% (p<0.001) whereas there was no significant change in endothelium‐independent vasodilation with nitroglycerin and baseline diameter (18.4±1.15% vs. 18.3±1.13%, p = 0.046, and 3.5±0.1 vs. 3.52±0.1 mm, p = 0.952, respectively); serum nitrite concentration was reduced significantly from 6.9±0.34 to 6.8±0.33 µmol/L (p<0.001), ESR from 59.90±4.86 to 51.22±4.26 mm in the first hour (p<0.001), and CRP level from 15.2±3.8 to 9.4±2.6 mg/dL (p = 0.019). DAS28 and HAQ‐DI scores were significantly reduced, from 6.9±0.25 to 4.1±0.31 (p<0.05) and from 1.47±0.09 to 0.69±0.1 (p<0.05), 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.