Objective: Impaired flow-mediated dilation (FMD) is associated with cardiovascular risk factors and provides prognostic information. Despite the noninvasive nature of this technique, a major limitation to its widespread use is low reproducibility. The aim of this study was to evaluate impact of methodological standardization among different investigation sites on brachial artery FMD reproducibility.
Methods: Seven Italian centers recruited 135 healthy volunteers, aged 20–60 years. FMD was assessed by high-resolution ultrasound equipped with a stereotactic probe-holding device. Certified sonographers recorded brachial artery scans at baseline (day 1a), 1 h after (day 1b), and 1 month later (day 30). Endothelium-independent vasodilation (EIVD) to sublingual glyceril-trinitrate was recorded at day 1 and day 30. FMD and EIVD were blindly evaluated at the coordinating center by an automated edge detection system. The intra-session (day 1a versus 1b) and inter-session (day 1a versus 30) coefficients of variation were calculated.
Results: FMD was not significantly (P = 0.91) different at day 1a, day 1b and day 30 (6.52 ± 2.9, 6.42 ± 3.1, 6.57 ± 2.8%, respectively). The FMD intra-session coefficient of variation was 9.9 ± 8.4% (from 7.6 to 11.9% across centers). The FMD inter-session coefficient of variation was 12.9 ± 11.6% (from 11.6 to 16.1% across centers). Inter-session coefficient of variation for EIDV was 19.7 ± 16.8%.
Conclusions: This study shows a homogeneous coefficient of variation for FMD among different centers. The inter-session coefficient of variation was similar to the intra-session coefficient of variation, representing the intrinsic FMD variability. We demonstrate for the first time that rigorous and standardized procedure may provide reproducible FMD assessment to study endothelial function in multicenter clinical trials.
aInternal Medicine, University of Pisa
bInstitute of Clinical Physiology, National Research Council, Pisa
cInternal Medicine, University of Brescia
dCardiology, University of Perugia
eClinical Sciences, University of Parma
fExperimental and Clinical Medicine, University of Padua
gCardiology Institute, Università Cattolica del Sacro Cuore, Rome
hCardiology, Department of Clinical & Molecular Medicine, University ‘Sapienza’, Rome
iIRCCS Neuromed, Pozzilli, Italy
Correspondence to Francesco Cosentino, MD, PhD, FESC, Cardiology, Department of Clinical & Molecular Medicine, University ‘Sapienza’, Ospedale Sant’Andrea, 00189 Rome, Italy. Tel: +39 06 3377 5561; fax: +39 06 3377 5061; e-mail: firstname.lastname@example.org
Abbreviations: ANOVA, analysis of variance; BP, blood pressure; CI, confidence intervals; EIDV, endothelium-independent vasodilation; FMD, flow mediated dilation; GTN, glyceril trinitrate; SD, standard deviation
Received 15 November, 2011
Revised 9 February, 2012
Accepted 21 March, 2012