Adherence to guidelines strongly improves reproducibility of brachial artery flow-mediated dilation

Background: Brachial artery FMD is widely used as a non-invasive measure of endothelial function. Adherence to expert guidelines is believed to be of vital importance to obtain reproducible measurements. We conducted a systematic review of studies reporting on the reproducibility of the FMD in order to determine the relation between adherence to current expert guidelines for FMD measurement and its reproducibility. Methods: Medline-database was searched through July 2015 and 458 records were screened for FMD reproducibility studies reporting the mean difference and variance of repeated FMD measurements. An adherence score was assigned to each of the included studies based on reported adherence to published guidelines on the assessment of brachial artery FMD. A Typical Error Estimate (TEE) of the FMD was calculated for each included study. The relation between the FMD TEE and the adherence score was investigated by means of Pearson correlation coefficients and multiple linear regression analysis. Results: Twenty-seven studies involving 48 study groups and 1537 subjects were included in the analyses. The adherence score ranged from 2.4 to 9.2 (out of a maximum of 10) and was strongly and inversely correlated with FMD TEE (adjusted R2 = 0.36, P < 0.01). Use of automated edge-detection software, continuous diameter measurement, true peak diameter for %FMD calculation, a stereostatic probe holder, and higher age emerged as factors associated with a lower FMD TEE. Conclusions: These data demonstrate that adherence to current expert consensus guidelines and applying contemporary techniques for measuring brachial artery FMD decreases its measurement error.