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BACKGROUND: Endothelial vasomotor dysfunction and markers of systemic inflammation are independent determinants of cardiovascular risk. However, the link between clinical inflammation and endothelial dysfunction is unclear. The aim of this study was to use anti-neutrophil cytoplasmic antibody-associated systemic vasculitis (AASV) as a model of systemic inflammation in which to test the hypothesis that inflammation is associated with endothelial dysfunction and can be reversed with anti-tumor necrosis factor-alpha (TNF-alpha) therapy. METHODS AND RESULTS: Fourteen patients with active AASV and 21 age-matched control subjects were studied. Endothelial function was assessed through the use of forearm plethysmography and related to clinical disease activity: Birmingham Vasculitis Activity Score (BVAS) and serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), and TNF-alpha. The effects of anti-TNF-alpha therapy (infliximab), either alone (n=6) or in combination with standard treatment (n=4), on endothelial function were subsequently determined. Patients had a mean BVAS of 11+/-1, and CRP and IL-6 were higher in the AASV group than in control subjects (34.8+/-10.5 versus 1.6+/-0.2 pg/mL, P<0.001; 9.0+/-0.7 versus 6.7+/-0.6 pg/mL, P=0.02). Forearm blood flow response to acetylcholine (ACh) was reduced in the patients compared with control subjects (P=0.002), but sodium nitroprusside (SNP) responses were not (P=0.3). The response to ACh improved with infliximab treatment (P=0.004) in particular, with infliximab alone (P=0.03). CONCLUSIONS: AASV is associated with endothelial dysfunction. Anti-TNF-alpha therapy, alone or in combination with standard treatment, results in clinical remission, reduced inflammation, and improved endothelium-dependent vasomotor responses.

Original publication

DOI

10.1161/01.CIR.0000124720.18538.DD

Type

Journal article

Journal

Circulation

Publication Date

13/04/2004

Volume

109

Pages

1718 - 1723

Keywords

Anti-Inflammatory Agents, Non-Steroidal, Antibodies, Antineutrophil Cytoplasmic, Antibodies, Monoclonal, Autoimmune Diseases, C-Reactive Protein, Churg-Strauss Syndrome, Cohort Studies, Cyclophosphamide, Drug Therapy, Combination, Endothelium, Vascular, Enzyme Inhibitors, Female, Forearm, Granulomatosis with Polyangiitis, Humans, Immunosuppressive Agents, Infliximab, Interleukin-6, Male, Middle Aged, Mycophenolic Acid, Nitric Oxide, Nitric Oxide Synthase, Nitric Oxide Synthase Type III, Pilot Projects, Plethysmography, Prednisolone, Regional Blood Flow, Tumor Necrosis Factor-alpha, Vasculitis, omega-N-Methylarginine