title: Diffuse endothelial dysfunction is common to ANCA associated systemic vasculitis and polyarteritis nodosa.
abstract: BACKGROUND
  Excess cardiovascular mortality complicates systemic rheumatic disease, suggesting an accelerated atheromatous process, which it has been proposed relates to the vascular inflammation common in such diseases. Impaired endothelium dependent vasodilatation is an early marker of atheromatous disease. It has previously been shown that such endothelial cell dysfunction (ECD) occurring in the brachial artery can complicate primary systemic necrotising vasculitis (SNV).
  
  
  OBJECTIVE
  To determine if ECD occurs in a wider spectrum of primary SNV, if it is restricted to the major arteries, and whether vasculitis subgroup, ANCA status, or renal involvement influenced the endothelial responses.
  
  
  METHODS
  Fifty four patients attending the Birmingham vasculitis clinic, including patients with a range of ANCA and non-ANCA associated primary vasculitides, and a group of age matched controls were recruited. The length of patient follow up and disease activity was variable. Disease activity, damage scores, and cardiovascular risk factors were recorded before assessment of flow mediated brachial artery vasodilatation by high resolution ultrasound. Dermal microvascular responses to acetylcholine were also measured in 32 patients and 21 controls by laser Doppler flowmetry.
  
  
  RESULTS
  ECD was demonstrated in all primary SNV subgroups of patients with ANCA associated vasculitis and in polyarteritis nodosa, compared with controls. Significant impairment occurred in both vascular beds, regardless of vessel size targeted in the inflammatory vasculitis, ANCA association and titre, or renal involvement.
  
  
  CONCLUSIONS
  Diffuse endothelial dysfunction, a predictor of atherosclerotic disease, is found extensively in primary systemic vasculitis. Involvement of different vascular beds is independent of target vessel size or ANCA association, and is unrelated to local disease expression. It is suggested that this results from a systemic response that may be a consequence of primary vasculitis, but is distinct from the local inflammatory vasculitic process.
authors.affiliation: Department of Rheumatology, University of Birmingham, UK. a.filer@bham.ac.uk
authors.forename: A D
authors.initials: AD
authors.lastname: Filer
authors.forename: J M
authors.initials: JM
authors.lastname: Gardner-Medwin
authors.forename: J
authors.initials: J
authors.lastname: Thambyrajah
authors.forename: K
authors.initials: K
authors.lastname: Raza
authors.forename: D M
authors.initials: DM
authors.lastname: Carruthers
authors.forename: R J
authors.initials: RJ
authors.lastname: Stevens
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: S E
authors.initials: SE
authors.lastname: Lowe
authors.forename: J N
authors.initials: JN
authors.lastname: Townend
authors.forename: P A
authors.initials: PA
authors.lastname: Bacon
mesh_terms: D000328:Adult; D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000503:physiopathology; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000276:immunology / Q000503:physiopathology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010488:Polyarteritis Nodosa / Q000276:immunology / Q000503:physiopathology*; D012307:Risk Factors; D012867:Skin / Q000098:blood supply; D014463:Ultrasonography; D014657:Vasculitis / Q000503:physiopathology*; D014664:Vasodilation
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D015415:Biomarkers