Adjusting Flow-Mediated Dilation for Shear Stress Stimulus Allows Demonstration of Endothelial Dysfunction in a Population with Moderate Cardiovascular Risk

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

doi:10.1159/000226227

Cited by 68 publications

(77 citation statements)

References 62 publications

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“…This is consistent with previous findings using graded levels of shear stress (22,29,37,43). The slope of the SR-%FMD relationship was significantly steeper in the RA whether the stimulus was expressed as the absolute SR or the increase in SR from baseline (deltaSR).…”

Section: Between-artery Differences: Stimulus-response Relationshipsupporting

confidence: 92%

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress

Jazuli

Pyke

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Jazuli F, Pyke KE. The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress. Am J Physiol Heart Circ Physiol 301: H1667-H1677, 2011. First published July 22, 2011; doi:10.1152/ajpheart.00487.2011.-An inverse relationship between baseline artery diameter (BAD) and flow-mediated vasodilation (FMD) has been identified using reactive hyperemia (RH) to create a shear stress (SS) stimulus in human conduit arteries. However, RH creates a SS stimulus that is inversely related to BAD. The purpose of this study was to compare FMD in response to matched levels of SS in two differently sized upper limb arteries [brachial (BA) and radial (RA) artery]. With the use of exercise, three distinct, shear rate (SR) stimuli were created (SR ϭ blood velocity/vessel diameter; estimate of SS) in the RA and BA. Artery diameter and mean blood velocity were assessed with echo and Doppler ultrasound in 15 healthy male subjects (19 -25 yr). Data are means Ϯ SE. Subjects performed 6 min of adductor pollicis and handgrip exercise to increase SR in the RA and BA, respectively. Exercise intensity was modulated to achieve uniformity in SR between arteries. The three distinct SR levels were as follows: steady-state exercise 39.8 Ϯ 0.6, 57.3 Ϯ 0.7, and 72.4 Ϯ 1.2 s Ϫ1 (P Ͻ 0.001). %FMD and AbsFMD (mm) at the end of exercise were greater in the RA vs. the BA at each shear level [at the highest level: RA ϭ 15.7 Ϯ 1.5%, BA ϭ 5.4 Ϯ 0.8% (P Ͻ 0.001)]. The mean slope of the within-subject SR-%FMD regression line was greater in the RA (RA ϭ 0.33 Ϯ 0.04, BA ϭ 0.13 Ϯ 0.02, P Ͻ 0.001), and a strong within-subjects relationship between %FMD and SR was observed in both arteries (RA: r 2 ϭ 0.92 Ϯ 0.02; BA: r 2 ϭ 0.90 Ϯ 0.03). Within the RA, there was a significant relationship between baseline diameter and %FMD; however, this relationship was not present in the BA (RA: r 2 ϭ 0.76, P Ͻ 0.001; BA: r 2 ϭ 0.03, P ϭ 0.541). These findings suggest that the response to SS is not uniform across differently sized vessels, which is in agreement with previous studies. endothelial function; doppler ultrasound; shear stress; handgrip exercise; baseline diameter THE ENDOTHELIAL CELLS THAT line the arteries are critically involved in the maintenance of vascular homeostasis. In healthy arteries, increases in blood flow-associated shear stress lead to the release of vasodilators [e.g., nitric oxide (NO), endothelial-derived hyperpolarizing factor (EDHF), and prostacyclin] by the endothelium, resulting in an endotheliumdependent vasodilation [flow-mediated vasodilation (FMD)] (1, 3, 28, 35). An inverse relationship between baseline vessel diameter and the magnitude of the conduit artery FMD response in the arm has been reported by several studies (19,42,49,52). As a result, it can be difficult to use FMD to compare endothelial function in groups with varying baseline artery sizes (for example, the young vs. the elderly and men vs. women) because it may be unclear whether a small...

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Section: Between-artery Differences: Stimulus-response Relationshipsupporting

confidence: 92%

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress

Jazuli

Pyke

2011

American Journal of Physiology-Heart and Circulatory Physiology

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“…A recent observation by Padilla et al (27) supports our findings. Internal data from their laboratory showed that continuous assessment of diameter at 5 frames/s yields the same FMD results as R-wave-gated images (n ϭ 10, FMD ϭ 7.58 Ϯ 0.9 vs. 7.62 Ϯ 0.9%, P ϭ 0.655, intraclass correlation ϭ 0.998).…”

Section: Discussionsupporting

confidence: 92%

Measuring FMD in the brachial artery: how important is QRS gating?

Kizhakekuttu

Gutterman

Phillips

et al. 2010

Journal of Applied Physiology

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Recommendations for the measurement of brachial flow-mediated dilation (FMD) typically suggest images be obtained at identical times in the cardiac cycle, usually end diastole (QRS complex onset). This recommendation presumes that inter-individual differences in arterial compliance are minimized. However, published evidence is conflicting. Furthermore, ECG gating is not available on many ultrasound systems; it requires an expensive software upgrade or increased image processing time. We tested whether analysis of images acquired with QRS gating or with the more simplified method of image averaging would yield similar results. We analyzed FMD and nitroglycerinmediated dilation (NMD) in 29 adults with type 2 diabetes mellitus and in 31 older adults and 12 young adults without diabetes, yielding a range of brachial artery distensibility. FMD and NMD were measured using recommended QRS-gated brachial artery diameter measurements and, alternatively, the average brachial diameters over the entire R-R interval. We found strong agreement between both methods for FMD and NMD (intraclass correlation coefficients ϭ 0.88 -0.99). Measuring FMD and NMD using average diameter measurements significantly reduced post-image-processing time (658.9 Ϯ 71.6 vs. 1,024.1 Ϯ 167.6 s for QRS-gated analysis, P Ͻ 0.001). FMD and NMD measurements based on average diameter measurements can be performed without reducing accuracy. This finding may allow for simplification of FMD measurement and aid in the development of FMD as a potentially useful clinical tool. endothelium; shear stress; flow-mediated dilation; method ENDOTHELIAL DYSFUNCTION is characterized by a proinflammatory, prothrombotic, and vasoconstrictive phenotype (16). Maintenance of nitric oxide (NO) bioavailability through activation of endothelial NO synthase is of central importance in maintaining vascular homeostasis.Substantial evidence supports the concept that detection of endothelial dysfunction in the brachial artery is an indicator of systemic endothelial dysfunction (32). Brachial artery reactivity [flow-mediated dilation (FMD)], as measured by highresolution vascular ultrasound prior to and following a hyperemic flow stimulus, is highly dependent on NO bioavailability (9,20). Furthermore, endothelial dysfunction as detected by FMD predicts future cardiovascular risk in those with and without diagnosed coronary artery disease (4,5,11,15,25,26,28,30,35). FMD's ability to stratify individuals into low-, intermediate-, and high-risk categories for future cardiovascular events (35, 36) not only yields potentially clinically relevant information but also identifies the efficacy of medical interventions that enhance endothelial function (23,25).The potential of brachial FMD to be used as a barometer of cardiovascular risk at a population level has led to efforts to standardize the technique with the hope of maximizing the validity and reproducibility of the measurement (7). Recent reviews suggest further refinements to these recommendations (8,18,29). These publications recom...

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“…Due to the variability in SR after ischaemia among subjects, we also calculated FMD to shear rate ratio (FMD:SR AUC ) in order to normalise the FMD for the stimulus. 13,14 To measure the reproducibility and precision of the method we have studied 15 subjects twice (data not published). Within method reproducibility, expressed as the percentage of the coefficient of variation [(SD of the paired differences/the overall mean)√2] × 100, was 5.4% for brachial artery diameter, 7.4% for FMD and 24.8% for mean blood velocity.…”

Section: Methodsmentioning

confidence: 99%

Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: Results from an observational research

Irace

Luca

Shehaj

et al. 2012

Diabetes and Vascular Disease Research

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The GLP-1 receptor agonist exenatide has been approved for adjunctive treatment of type 2 diabetes. Continuous GLP-1 infusion improves endothelial function in vivo; no evidence about a beneficial effect of exenatide on vascular function has been published. The aim of our observational study was to evaluate whether exenatide would improve brachial artery function evaluated by the flow mediated dilation (FMD) technique, compared with glimepiride, in subjects with type 2 diabetes. FMD time course was assessed by ultrasound, after 5 min forearm ischaemia, at baseline and after 16-week treatment. At the end of the study FMD was significantly higher in subjects who assumed exenatide compared with glimepiride (9.1 ± 3.6 vs. 5.6 ± 1.0, p = 0.01). Even if limited by the small number of studied subjects, who were not matched in the two treatment groups, this research study represents the first FMD evidence suggesting that chronic administration of exenatide improves arterial dilation.

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Adjusting Flow-Mediated Dilation for Shear Stress Stimulus Allows Demonstration of Endothelial Dysfunction in a Population with Moderate Cardiovascular Risk

Cited by 68 publications

References 62 publications

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress

The impact of baseline artery diameter on flow-mediated vasodilation: a comparison of brachial and radial artery responses to matched levels of shear stress

Measuring FMD in the brachial artery: how important is QRS gating?

Exenatide improves endothelial function assessed by flow mediated dilation technique in subjects with type 2 diabetes: Results from an observational research

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