Within-subject variability of flow-mediated vasodilation of the brachial artery in healthy men and women: implications for experimental studies.
Flow-mediated vasodilation (FMD) of the brachial artery is used as a marker of cardiovascular disease risk. It is defined as the percentage dilation from the baseline diameter in response to a provoked increase in blood flow. The within-subject variability, crucial in the design of trials with FMD as an endpoint, appears to vary widely between studies. We assessed the analytical and within-subject variability of FMD in healthy subjects and estimated the number of subjects needed to detect various treatment effects in intervention trials and observational studies. FMD was assessed with B-mode high-resolution ultrasound (US). A total of 13 volunteers were measured on six occasions, after they had fasted overnight. Within-subject variability was assessed from all six scans per subject. Analytical variation or reading variation was assessed by reading one scan of each subject twice by one observer. The mean (+/-SD) FMD was 5.60 +/- 2.15 FMD% of the baseline diameter. The within-subject SD was 2.8 FMD%, resulting in a coefficient of variation (CV) of 2.8/5.6 x 100% = 50.3%. The CVs for the baseline and maximum diameter were much smaller: 4.8% (SD 0.193 mm at a mean of 4.060 mm) for the baseline and 5.2% (SD 0.222 mm at a mean of 4.285 mm) for the maximum. The CV for reading variation was 34%. The number of subjects needed to detect a treatment difference of 2 FMD% with a probability of 0.05 and a power of 0.80 would be 31 in a crossover design and 62 per group in a parallel design for comparison of group changes. We conclude that the within-subject variability of FMD is large, about 50% of the mean response. This includes biologic and reading variation. Repeated measurements and repeated readings of recorded measurements are recommended to reduce variability.
De Roos
Nicole M
NM
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands. nroos@azu.nl
Bots
Michiel L
ML
Schouten
Evert G
EG
Katan
Martijn B
MB
D000293:Adolescent; D000328:Adult; D001916:Brachial Artery / Q000000981:diagnostic imaging / Q000502:physiology*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D008297:Male; D015588:Observer Variation; D012016:Reference Values; D012039:Regional Blood Flow; D015203:Reproducibility of Results; D012107:Research Design; D018401:Sample Size; D014463:Ultrasonography; D014664:Vasodilation