Spironolactone improves endothelial dysfunction in ankylosing spondylitis

Abstract

Chronic inflammation in ankylosing spondylitis (AS) is associated with vascular endothelial dysfunction which leads to accelerated atherosclerosis. Accelerated atherosclerosis contributes to premature cardiovascular disease and increased cardiovascular mortality in AS. Spironolactone inhibits the production of proinflammatory cytokines and improves endothelial dysfunction in rheumatoid arthritis. This study aimed to determine the effect of spironolactone in antitumor necrosis factor (TNF)-naive AS patients. Twenty anti-TNF-naive AS patients (M/F = 15/5) with high disease activity (Bath ankylosing spondylitis disease activity index, BASDAI >4) despite treatment with stable doses of conventional disease-modifying antirheumatic drugs were investigated. Inflammatory disease activity (BASDAI and Bath ankylosing spondylitis functional index (BASFI) scores, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels), serum nitrite concentration, and endothelium-dependent and -independent vasodilatation of the brachial artery were measured at baseline and after 12 weeks of therapy with oral spironolactone 2 mg/kg/day. Ten healthy subjects matched for age and sex acted as the control. Flow-mediated dilation (FMD) in AS patients at baseline was significantly impaired compared with healthy control group (p < 0.001). After treatment, FMD improved from 11.3 ± 1.70 to 24.69 ± 2.34% (p < 0.001); nitrite concentration reduced from 7.9 ± 0.28 to 4.79 ± 0.19 μmol/L (p < 0.001); ESR from 33.8 ± 4.38 to 15.13 ± 1.30 mm in the first hour, (p < 0.001); and CRP level from 22.39 ± 3.80 to 6.3 ± 1.29 mg/dL, (p < 0.001). BASDAI and BASFI also reduced significantly (p < 0.001). The study suggests that in AS endothelial dysfunction is a part of the disease process. This is the first study to show that treatment with spironolactone improves both endothelial dysfunction and inflammatory disease activity in AS.

Effect of spironolactone for 1 yr on endothelial function and vascular inflammation biomarkers in renal transplant recipients

“…Also in line with these observations was the unchanged level of cGMP. By contrast, Syngle et al described a decrease in plasma nitrite without changes in blood pressure after spironolactone in patients with active rheumatoid arthritis (51) and ankylosing spondylitis (52) and normal renal function. These subjects were characterized by active inflammation at inclusion and exhibited markedly higher baseline and follow-up nitrite levels (up to 7.9 µmol/L) than the present patient group (range 0.1-1.7 µmol/L).…”

The Relationship of Ankylosing Spondylitis and Subclinical Atherosclerosis: A Systemic Review and Meta-Analysis

“…All of the 35 studies included in the meta-analysis were analyzed using the Stata 12.0 (Stata Corp, College Station, Texas) software. 5 -39 The values of continuous parameters (cIMT, PWV, FMD) were expressed as mean and standard deviation (SD). Median or interquartile range values were transformed into mean and SD forms.…”

Low vaspin levels are related to endothelial dysfunction in patients with ankylosing spondylitis

“…Ankylosing spondylitis is associated with accelerated atherosclerosis and increased risk of metabolic syndrome ( 11 - 13 ). Clinical studies have shown that the impairment of flow-mediated dilation (FMD) is present in patients with ankylosing spondylitis ( 14 - 16 ). Sari et al, in a study where they excluded patients who had common cardiovascular risk factors, reported that ankylosing spondylitis had a role in the development of endothelial impairment ( 15 ).…”