Methodological approaches to optimize reproducibility and power in clinical studies of flow-mediated dilation

Objectives Our aim was to determine reproducibility of the flow-mediated dilation (FMD) response profile, and discriminatory ability of the components. Background Brachial FMD is widely used to study conduit artery endothelial function. Automated B-mode image edge detection (B-ED) provides a full response profile. Reproducibility and biological relevance of these additional components have not been fully explored. Methods Forty-two healthy adults underwent FMD using B-ED repeated at fixed time intervals up to 3 months. The FMD profile was assessed for diameter changes, area under the curve, and time course. Measures were compared in 25 adults with hypercholesterolemia, 25 subjects with diabetes, and 50 matched control subjects. Results The maximum change in FMD was the most reproducible (coefficient of variation = 9.8%, 10.6%, 6.6%, and 9.2% at 4 to 6 h, 1 week, 1 month, and 3 months, respectively). Most of the variability occurred between subjects rather than within. All FMD measures except time course were significantly reduced in hypercholesterolemia and diabetes. Power curves were generated to indicate the appropriate number of subjects for parallel and crossover study designs. Conclusions Maximum FMD percentage change from baseline is the most reproducible of the response curve measures and best identifies those with risk factors. Flow-mediated dilation measured by B-ED is robust and practical to assess the effect of interventions on endothelial function in clinical trials.