Rosuvastatin improves endothelial dysfunction in ankylosing spondylitis

Abstract

Enhanced cardiovascular risk in ankylosing spondylitis (AS) provides a strong rationale for early therapeutical intervention. In view of the proven benefit of statins in atherosclerotic vascular disease, we aimed to investigate the effect of rosuvastatin on endothelial dysfunction (ED) and inflammatory disease activity in AS. In a single-blind, placebo-controlled, parallel study, 32 AS patients were randomized to receive 24 weeks of treatment with rosuvastatin (10 mg/day, n = 17) and placebo (n = 15) as an adjunct to existing stable antirheumatic drugs. Flow-mediated dilatation (FMD) was assessed by AngioDefender™ (Everest Genomic Ann Arbor, USA). Inflammatory measures (BASDAI, BASFI, CRP and ESR) and pro-inflammatory cytokines (tumour necrosis factor-alpha [TNF-α], interleukin-6 [IL-6] and interleukin-1 [IL-1]) were measured at baseline and after treatment. Lipids and adhesion molecules (intracellular adhesion molecule [ICAM-1] and vascular cell adhesion molecule [VCAM-1]) were estimated at baseline and after treatment. At baseline, inflammatory measures, pro inflammatory cytokines and adhesion molecules were elevated among both groups. After treatment with rosuvastatin, FMD improved significantly (p < 0.01). Levels of inflammatory measures, TNF-α, IL-6 and ICAM-1 decreased significantly (p < 0.01) after treatment with rosuvastatin. Rosuvastatin exerted positive effect on lipid spectrum. No significant change in the placebo group. Significant negative correlation was observed between FMD and IL-6, ICAM-1, CRP after treatment with rosuvastatin. First study to show that rosuvastatin improves inflammatory disease activity and ED in AS. Rosuvastatin lowers the proinflammatory cytokines, especially IL-6 and TNF-α, which downregulates adhesion molecules and CRP production which in turns improves ED. Improvement in ED in AS occurs through both cholesterol-independent and cholesterol-dependent pathways. Rosuvastatin can mediate modest but clinically apparent anti-inflammatory effects with modification of vascular risk factors in the context of high-grade autoimmune inflammation of AS.

Nitric Oxide: Link between Inflammation and Endothelial Dysfunction in Rheumatoid Arthritis

“…A reduction in the FMD, reflecting ED, has been demonstrated in early stages of atherosclerosis and in patients with inflammatory rheumatic diseases such as ankylosing spondylitis (AS) and RA. 19,24 In this study, we corroborated these results, finding a reduction in FMD in patients with RA with respect to controls. Increased production of NO in RA due to the activation of iNOS and an attenuation of eNOS activity reduces basal FMD.…”

Predisposing factors, pathogenesis and therapeutic intervention of Kawasaki disease

“…Atorvastatin is a selective competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. In addition to cholesterol-lowering effects, statins exert improvement in endothelial function and reduction in proinflammatory cytokines and chemokines [88,89]. An open-label, noncomparative Phase II trial is ongoing to evaluate the effect of atorvastatin on the persistent coronary arterial aneurysm in children with KD (clinicaltrials.gov NCT02114099).…”

Endothelial Progenitor Cells as a Marker of Endothelial Dysfunction and Atherosclerosis in Ankylosing Spondylitis: A Cross-Sectional Study

“…AngioDefender test results are not dependent on user technique or operator proficiency. 11 The mean of the two measures was considered for analysis. The intra-and interobserver variability had the coefficient of variations as 1.50 and 2.25%, respectively, for the measurements of FMD.…”