Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus

Jaume Padilla,Timothy D Mickleborough,Daniel P Wilhite,Blair D Johnson,Sean C Newcomer,Janet P Wallace,Kieren J Mather,Alyce D Fly

doi:10.1186/1476-7120-6-44

Abstract

BackgroundNormalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; however, the adoption of this approach among researchers has been slow. The present study was designed to further examine the efficacy of FMD normalization to shear stress in reducing measurement variability.MethodsFive different magnitudes of reactive hyperemia-induced shear stress were applied to 20 healthy, physically active young adults (25.3 ± 0. 6 yrs; 10 men, 10 women) by manipulating forearm cuff occlusion duration: 1, 2, 3, 4, and 5 min, in a randomized order. A venous blood draw was performed for determination of baseline whole blood viscosity and hematocrit. The magnitude of occlusion-induced forearm ischemia was quantified by dual-wavelength near-infrared spectrometry (NIRS). Brachial artery diameters and velocities were obtained via high-resolution ultrasound. The SSAUC was individually calculated for the duration of time-to-peak dilation.ResultsOne-way repeated measures ANOVA demonstrated distinct magnitudes of occlusion-induced ischemia (volume and peak), hyperemic shear stress, and peak FMD responses (all p < 0.0001) across forearm occlusion durations. Differences in peak FMD were abolished when normalizing FMD to SSAUC (p = 0.785).ConclusionOur data confirm that normalization of FMD to SSAUC eliminates the influences of variable shear stress and solidifies the utility of FMD:SSAUC ratio as an index of endothelial function.

Highlights

Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; the adoption of this approach among researchers has been slow
No effect of sex was found in any of the main outcome variables (SS60secAUC, peak FMD response, FMD:SSAUC ratio), data were pooled across sex
Given that reactive hyperemia varies among individuals and populations [15], the FMD outcome is reflective of both conduit artery endothelial function and magnitude of the hyperemic stimulus

Summary

Introduction

Normalization of brachial artery flow-mediated dilation (FMD) to individual shear stress area under the curve (peak FMD:SSAUC ratio) has recently been proposed as an approach to control for the large inter-subject variability in reactive hyperemia-induced shear stress; the adoption of this approach among researchers has been slow. Following publication of this paper, a radical change in clinical practice within the FMD community was expected; to our surprise, since the time of Pyke and Tschakovsky's publication (April 2007), only two [17,18] out of 92 FMD studies (PubMed search) have incorporated normalization of FMD to SSAUC Reasons for this slow adoption of the recently proposed method to express FMD data may include 1) insufficient lead time after publication of the article for dissemination and implementation; 2) inability to simultaneously capture arterial diameter and velocity; 3) lack of clinical evidence supporting the utility of this approach; and 4) complicated comparison with the large body of evidence collected using the traditional FMD approach

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Discussion

Conclusion