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.
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.
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 micromol/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.
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.