Endothelium function dependence of acute changes in pulse wave velocity and flow-mediated slowing

Abstract

Flow-mediated slowing (FMS), defined as the minimum pulse wave velocity (PWV_min) during reactive hyperemia, is potentially a simple, user-objective test for examining endothelial function. The purpose of the current study was to determine the effects of a known endothelial dysfunction protocol on arm PWV and PWV_min. Complete data were successfully collected in 22 out of 23 healthy adults (23.8 years [SD 4.1], 16 F, 22.8 kg/m² [SD 2.8]). Local endothelial dysfunction was induced by increasing retrograde shear stress in the upper arm, through inflation of a distal (forearm) tourniquet to 75 mmHg, for 30 min. Pre- and post-endothelial dysfunction, PWV was measured followed by simultaneous assessment of PWV_min and flow-mediated dilation (FMD). PWV was measured between the upper arm and wrist using an oscillometric device, and brachial FMD using ultrasound. FMD (%) and PWV_min (m/s) were calculated as the maximum increase in diameter and minimum PWV during reactive hyperemia, respectively. Endothelial dysfunction resulted in a large effect size (ES) decrease in FMD (∆ = -3.10%; 95% CI: -4.15, -2.05; ES = -1.3), and a moderate increase in PWV (∆ = 0.38 m/s; 95% CI: 0.07, 0.69; ES = 0.5) and PWV_min (∆ = 0.16 m/s; 95% CI: 0.05, 0.28; ES = 0.6). There was a large intra-individual (pre- vs post-endothelial dysfunction) association between FMD and PWV_min (r = -0.61; 95% CI: -0.82, -0.24). In conclusion, acute change in PWV and PWV_min are at least partially driven by changes in endothelial function.

Keywords: arterial stiffness; endothelial dysfunction; flow-mediated dilation; measurement validity; retrograde shear stress.

Figure 1.

Experimental set-up. To measure PWV at baseline, and then the minimum PWV during reactive hyperemia (FMS), arterial pressure waveforms were simultaneously captured at proximal (A) and distal (B) sites using an oscillometric device. Duplex Doppler ultrasound was used to measure brachial artery FMD, and to capture pulsed Doppler waveforms (C) at baseline (0 mmHg) and during the ED protocol (75 mmHg). Ante, antegrade; ED, endothelial dysfunction; FMD, flow-mediated dilation; FMS, flow-mediated slowing; Osc, oscillatory; PWV, pulse wave velocity; Retro, retrograde.

Figure 2.

Example traces of FMD (A) and FMS (B) data recorded before and after the ED protocol. (A) Diameters were recorded at 30 Hz for 2 min at baseline, during the 5 min of occlusion, and for 3 min following occlusion release. The diameters were analyzed offline using specialized image analysis software. FMD was calculated as (D_max – D_base)/D_base * 100. (B) PWV was automatically recorded every 3.5 s by the Vicorder device. For PWV_base, PWV was recorded continuously for 2 min and then averaged. For PWV_min, the minimum PWV following occlusion release was automatically detected and then manually confirmed. D_base, baseline brachial diameter; D_max, maximum brachial diameter during reactive hyperemia r; ED, endothelial dysfunction; FMD, flow-mediated dilation; FMS, flow-mediated slowing; PWV, pulse wave velocity; PWV_base, PWV at baseline; PWV_min, minimum PWV during reactive hyperemia.

Figure 3.

Intra-individual (pre- vs post-endothelial dysfunction) associations between FMD with PWV (A) and PWV_min (B) (n = 22 repeated measures). FMD, flow-mediated dilation; PWV, pulse wave velocity; PWV_min, minimum pulse wave velocity.