title: Assessment of flow-mediated dilation reproducibility:  a nationwide multicenter study.
abstract: OBJECTIVE
  Impaired flow-mediated dilation (FMD) is associated with cardiovascular risk factors and provides prognostic information. Despite the noninvasive nature of this technique, a major limitation to its widespread use is low reproducibility. The aim of this study was to evaluate impact of methodological standardization among different investigation sites on brachial artery FMD reproducibility.
  
  
  METHODS
  Seven Italian centers recruited 135 healthy volunteers, aged 20-60 years. FMD was assessed by high-resolution ultrasound equipped with a stereotactic probe-holding device. Certified sonographers recorded brachial artery scans at baseline (day 1a), 1 h after (day 1b), and 1 month later (day 30). Endothelium-independent vasodilation (EIVD) to sublingual glyceril-trinitrate was recorded at day 1 and day 30. FMD and EIVD were blindly evaluated at the coordinating center by an automated edge detection system. The intra-session (day 1a versus 1b) and inter-session (day 1a versus 30) coefficients of variation were calculated.
  
  
  RESULTS
  FMD was not significantly (P = 0.91) different at day 1a, day 1b and day 30 (6.52 ± 2.9, 6.42 ± 3.1, 6.57 ± 2.8%, respectively). The FMD intra-session coefficient of variation was 9.9 ± 8.4% (from 7.6 to 11.9% across centers). The FMD inter-session coefficient of variation was 12.9 ± 11.6% (from 11.6 to 16.1% across centers). Inter-session coefficient of variation for EIDV was 19.7 ± 16.8%.
  
  
  CONCLUSIONS
  This study shows a homogeneous coefficient of variation for FMD among different centers. The inter-session coefficient of variation was similar to the intra-session coefficient of variation, representing the intrinsic FMD variability. We demonstrate for the first time that rigorous and standardized procedure may provide reproducible FMD assessment to study endothelial function in multicenter clinical trials.
authors.affiliation: Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Ghiadoni
authors.forename: Francesco
authors.initials: F
authors.lastname: Faita
authors.forename: Massimo
authors.initials: M
authors.lastname: Salvetti
authors.forename: Carlo
authors.initials: C
authors.lastname: Cordiano
authors.forename: Almerina
authors.initials: A
authors.lastname: Biggi
authors.forename: Massimo
authors.initials: M
authors.lastname: Puato
authors.forename: Antonio
authors.initials: A
authors.lastname: Di Monaco
authors.forename: Luca
authors.initials: L
authors.lastname: De Siati
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Ambrosio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Gemignani
authors.forename: Maria L
authors.initials: ML
authors.lastname: Muiesan
authors.forename: Stefano
authors.initials: S
authors.lastname: Taddei
authors.forename: Gaetano A
authors.initials: GA
authors.lastname: Lanza
authors.forename: Francesco
authors.initials: F
authors.lastname: Cosentino
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D012016:Reference Values; D015203:Reproducibility of Results; D014664:Vasodilation