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A new approach to improve the specificity of flow-mediated dilation for indicating endothelial function in cardiovascular research

Atkinson, Grega; Batterham, Alan M.a; Thijssen, Dick H.J.b,c; Green, Daniel J.b,d

Journal of Hypertension:
doi: 10.1097/HJH.0b013e32835b8164

Flow-mediated dilation (FMD) is a noninvasive indicator of endothelial function and is routinely expressed as the percentage change in arterial diameter (FMD%) from a resting baseline (Dbase) to a postischemic peak (Dpeak). This expression is equivalent to the ratio of Dpeak/Dbase and is, therefore, dependent on important statistical assumptions, which have never been analysed in the context of FMD%. We aimed to investigate these assumptions, via a comparison of FMD between samples of children and adults, as well as to explore other approaches to scaling diameter change for Dbase. We found that FMD% did not scale accurately for interindividual differences in Dbase but, as expected, overestimated endothelial function for low Dbase and vice versa. We argue that this imprecise scaling of FMD% is predictable, not explained by physiology and is probably common. This problem is resolved by applying scaling principles, whereby the difference in diameter is the outcome and Dbase is a covariate in a logarithmic-linked generalized linear model. A specific allometric expression of FMD can be derived and we found this to be Dpeak/Dbase0.89 rather than a simple ratio in our particular dataset. We found that sample differences in endothelial function were inaccurate with FMD% versus our new allometric approach, and that FMD% misclassified participants into ‘high’ and ‘low’cohorts, which has implications for prognostic-type studies. We conclude that the general use of FMD% could have led to biased comparisons of different conditions and/or populations in past studies. Our new approach to scaling FMD is flexible for different datasets and is not based on the current assumption that a percentage change is appropriate in all circumstances.

Author Information

aHealth and Social Care Institute, School of Health and Social Care, Teesside University, Middlesbrough

bResearch Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK

cDepartment of Physiology, Nijmegen Medical Centre Radboud University, The Netherlands

dSchool of Sport Science, Exercise and Health, The University of Western Australia, Australia

Correspondence to Professor Greg Atkinson, Health and Social Care Institute, School of Health and Social Care, Parkside West, Teesside University, Middlesbrough, Tees Valley TS1 3BA, UK. Tel: +44 (0) 1642 342758; e-mail:

Abbreviations: Dbase, the recorded baseline diameter in the FMD test;Dpeak, the recorded peak diameter in the FMD test; FMD, flow-mediated dilation

Received 4 July, 2012

Revised 23 September, 2012

Accepted 15 October, 2012

© 2013 Lippincott Williams & Wilkins, Inc.