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Updated: May 10, 2026
Ultrasound Assessment of Endothelial-Dependent Flow-Mediated Vasodilation of the Brachial Artery in Clinical Research
Published on: October 22, 2014
Variability and reproducibility of flow-mediated dilatation in a multicentre clinical trial
Marietta Charakida1, Eric de Groot, Stavros P Loukogeorgakis
1National Institute for Cardiovascular Outcome Research, UCL, 170 Tottenham Court Road, London W1T 7HA, UK.
Insights
Reproducible flow-mediated dilatation (FMD) measurements are achievable in multicentre settings for short- and medium-term evaluations. This validates FMD as an outcome measure for assessing drug effectiveness over these periods.
Area of Science:
- Vascular biology
- Clinical trials
- Medical imaging
Background:
- Flow-mediated dilatation (FMD) is a key indicator of endothelial function.
- Assessing FMD reproducibility in multicentre settings is crucial for its clinical application.
- Previous studies have primarily focused on single-centre reproducibility.
Purpose of the Study:
- To evaluate the reproducibility of FMD measurements across multiple European vascular imaging centres.
- To determine short-, medium-, and long-term reproducibility of FMD in a multicentre trial setting.
- To provide data supporting the use of FMD as an outcome measure in clinical pharmacology.
Main Methods:
- FMD was measured in 19 centres across six European countries as part of the dal-VESSEL trial.
- Intra-sonographer, centre, and reader variability were assessed at 48-hour, 3-month, and 9-month intervals.
- A subgroup of 67 patients underwent repeated FMD measurements for reproducibility analysis.
Main Results:
- Centre variability for FMD was comparable at 48 hours and 3 months but increased significantly at 9 months.
- Mean absolute differences in %FMD were 1.04% (48h), 0.99% (3m), and 1.45% (9m).
- Intra- and inter-reader variability analyses confirmed measurement consistency.
Conclusions:
- Reproducible FMD measurements can be achieved in multicentre settings for short- and medium-term assessments.
- These multicentre FMD results are comparable to those from specialized laboratories.
- The findings support the use of FMD as a reliable outcome measure for pharmacological intervention studies.
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.
