title: 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.
authors.affiliation: Department of Pharmaceutical Sciences & Drug Research, Punjabi University, Patiala, Punjab, India.
authors.forename: Nidhi
authors.initials: N
authors.lastname: Garg
authors.forename: Pawan
authors.initials: P
authors.lastname: Krishan
authors.forename: Ashit
authors.initials: A
authors.lastname: Syngle
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007375:Interleukin-1 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D008297:Male; D063177:Pulse Wave Analysis; D000068718:Rosuvastatin Calcium / Q000627:therapeutic use*; D016037:Single-Blind Method; D013167:Spondylitis, Ankylosing / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014664:Vasodilation / Q000502:physiology*
chemical_list: D018501:Antirheumatic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C573420:ICAM1 protein, human; C508600:IL6 protein, human; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000068718:Rosuvastatin Calcium