Variability and reproducibility of flow-mediated dilatation in a multicentre clinical trial

Eur Heart J. 2013 Dec;34(45):3501-7. doi: 10.1093/eurheartj/eht223. Epub 2013 Jul 2.


Aims: The aim of this study was to assess the reproducibility of flow-mediated dilatation (FMD) in a multicentre setting.

Methods and results: This study was performed as part of the dal-VESSEL trial in which FMD was measured in 19 vascular imaging centres in six European countries. A subgroup of patients who were allocated in the placebo group and scanned twice at each trial time point (substudy) was analysed. Intra-sonographer variability was calculated from FMD measurements 48 h apart. Centre variability and short-, medium-, and long-term reproducibility of FMD were calculated at 48 h and at 3 and 9 months intervals, respectively. Intra- and inter-reader variability was assessed by re-analysing the FMD images by three certified readers at two time intervals, 7 days apart. Sixty-seven patients were included. Variability between centres was comparable at 48 h and 3 months interval but almost doubled at 9 months. The mean absolute difference in %FMD was 1.04, 0.99, and 1.45% at the three time intervals, respectively. Curves were generated to indicate the number of patients required for adequate power in crossover and parallel study designs.

Conclusion: This study demonstrates for the first time that in a multicentre setting reproducible FMD measurements can be achieved for short- and medium-term evaluation, which are comparable with those reported from specialized laboratories. These findings justify the use of FMD as an outcome measure for short- and medium-term assessment of pharmacological interventions.

Keywords: Coronary artery disease; FMD; Power curve; Reproducibility.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Flow Velocity
  • Brachial Artery / diagnostic imaging
  • Brachial Artery / physiology*
  • Endothelium, Vascular / physiology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Observer Variation
  • Reproducibility of Results
  • Ultrasonography
  • Vasodilation / physiology*