title: Non-invasive assessment of coronary flow reserve and ADMA levels: a case-control study of early rheumatoid arthritis patients.
abstract: OBJECTIVE
  Plasma concentration of asymmetric dimethylarginine (ADMA), a major endogenous inhibitor of nitric oxide synthase, is considered a novel risk factor for endothelial dysfunction associated with enhanced atherosclerosis. Coronary microcirculation abnormalities have been demonstrated in patients with early rheumatoid arthritis (ERA) without any signs or symptoms of coronary artery disease (CAD). The aim of the study was to compare the ERA and control groups with ADMA, intima-media thickness (IMT) and coronary flow reserve (CFR) levels. It assessed whether ERA patients have more cardiovascular risk (endothelial dysfunction and coronary microvascular abnormalities), and evaluated whether any difference in IMT/CFR between ERA and controls can be explained by any difference in ADMA levels between the groups.
  
  
  METHODS
  The study involved 25 ERA patients (female/male 21/4; mean age 52.04 +/- 14.05 years; disease duration <or=12 months) and 25 healthy volunteers with no history or current signs of CAD or other traditional risk factors. Dipyridamole trans-thoracic stress echocardiography was preformed to evaluate CFR, and carotid ultrasound to measure the IMT of the common carotid arteries. Blood samples were obtained in order to assess ADMA levels before the patients had received any biological or non-biological DMARDs, or steroid therapy.
  
  
  RESULTS
  CFR was significantly reduced in the ERA patients (2.5 +/- 0.5 vs 3.5 +/- 0.8; P <0.01). In particular, 6/25 (24%) had a CFR of <2 consistent with potentially dangerous coronary flow impairment. Common carotid IMT was significantly greater in the ERA patients, although still within the normal range (0.68 +/- 0.1 vs 0.56 +/- 0.11 mm; P <0.01). There was a significant correlation between CFR and plasma ADMA levels in the ERA population (r = -0.53; P <0.01). IMT was negatively associated with CFR (P <0.05).
  
  
  CONCLUSIONS
  Plasma ADMA levels were significantly higher in the ERA patients. A statistically significant negative effect of ADMA levels on CFR value was observed. The effect of ADMA levels on IMT is not significant.
authors.affiliation: Department of Health Technologies, Cardiology Unit, IRCCS Orthopedic Galeazzi Institute, University of Milan, Milano, Italy. maurizio.turiel@unimi.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Turiel
authors.forename: Fabiola
authors.initials: F
authors.lastname: Atzeni
authors.forename: Livio
authors.initials: L
authors.lastname: Tomasoni
authors.forename: Simona
authors.initials: S
authors.lastname: de Portu
authors.forename: Luigi
authors.initials: L
authors.lastname: Delfino
authors.forename: Bruno Dino
authors.initials: BD
authors.lastname: Bodini
authors.forename: Matteo
authors.initials: M
authors.lastname: Longhi
authors.forename: Simona
authors.initials: S
authors.lastname: Sitia
authors.forename: Mauro
authors.initials: M
authors.lastname: Bianchi
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferrario
authors.forename: Andrea
authors.initials: A
authors.lastname: Doria
authors.forename: Vito
authors.initials: V
authors.lastname: De Gennaro Colonna
authors.forename: Piercarlo
authors.initials: P
authors.lastname: Sarzi-Puttini
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D017536:Carotid Artery, Common / Q000000981:diagnostic imaging; D016022:Case-Control Studies; D003326:Coronary Circulation / Q000502:physiology*; D004176:Dipyridamole; D025401:Echocardiography, Stress; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow; D017540:Tunica Media / Q000000981:diagnostic imaging; D014665:Vasodilator Agents
chemical_list: D015415:Biomarkers; D014665:Vasodilator Agents; C018524:N,N-dimethylarginine; D004176:Dipyridamole; D001120:Arginine; D019001:Nitric Oxide Synthase