Elsevier

Atherosclerosis

Volume 217, Issue 2, August 2011, Pages 415-419
Atherosclerosis

Impact of wall thickness on conduit artery function in humans: Is there a “Folkow” effect?

https://doi.org/10.1016/j.atherosclerosis.2011.03.003Get rights and content

Abstract

Regional heterogeneity in wall architecture and thickness may be present between conduit arteries in the upper and lower limbs in humans. These differences in wall architecture may, in turn, influence vascular responsiveness. Folkow proposed in the 1950s that heterogeneity in wall-to-lumen ratio (W:L) could contribute to differences in vascular responsiveness, but this hypothesis has never been directly confirmed in vivo. Our first aim was to examine wall thickness and W:L across arteries in the lower (common and superficial femoral) and upper limbs (brachial and radial) of healthy men (n = 35) using high resolution ultrasound. In a subgroup (n = 20) we examined the relationship between W:L of these arteries, physiological (flow-mediated dilation, FMD) and pharmacological vasodilation (glyceryl trinitrate, GTN). Diameter and wall thickness differed significantly across all arteries (ANOVA P < 0.001), with smaller arteries having a relatively larger wall thickness. Moreover, we found a significant correlation between W:L and the FMD-response (r = 0.55, P < 0.001), which remained significant after correcting for the eliciting shear stress (r = 0.47, P < 0.001), indicating that W:L/FMD relationship was not primarily related to the impact of diameter on the shear rate stimulus to FMD. W:L also correlated strongly with the GTN-response (r = 0.56, P < 0.001) across all arteries studied. These results indicate that regional heterogeneity exists in W:L within, but also between, limbs. More importantly, differences in W:L contribute to differences in vascular functional responses, reinforcing the conceptual proposal of Folkow, who suggested that arteries with larger W:L exhibit exaggerated responses to vasoactive stimuli.

Introduction

Measures of arterial wall thickness predict cardiovascular events [1], [2], [3] and are frequently used as surrogate markers of atherosclerosis [4]. However, conduit artery wall thickening may also reflect non-atherosclerotic adaptive responses to changes in shear and cyclic stress [5]. Regional heterogeneity between, and within, arterial beds in wall architecture and thickness likely influence functional responses [6]. In the 1950s, Folkow proposed that heterogeneity in wall-to-lumen ratio could explain differences in vascular responsiveness [7], [8]. He provided indirect evidence that enlarged wall-to-lumen ratios induce generalised hyper-responsiveness to vasoactive stimuli, regardless of their distinct biochemical pathways. These findings raise the possibility that conduit arteries of different size and structure may exhibit differences in function which relate to their wall-to-lumen ratio.

Previous studies have reported that smaller vessels react with a relatively larger dilation when exposed to ischemic stimuli (e.g., flow-mediated dilation, FMD) [9], [10], [11] and that one of the major determinants of the dilator response to ischemia is artery size. We recently demonstrated that larger responses in smaller vessels cannot solely be explained by differences in the eliciting shear stress [9]. An alternate explanation relates to the proposal of Folkow that regional differences in conduit arterial responsiveness may be due to differences in their wall-to-lumen ratio. Therefore, we examined the relationship between arterial diameter and wall thickness across different sized conduit arteries in the upper and lower limb of healthy men. Subsequently, we examined whether the magnitude of the conduit artery dilation in response to a physiological shear stress stimulus (FMD) or a pharmacological stimulus (glyceryl trinitrate (GTN)) relates to their wall-to-lumen ratio. We hypothesized that smaller conduit arteries, which possess a larger wall-to-lumen ratio, exhibit exaggerated dilator responses.

Section snippets

Subjects

Thirty-five healthy recreationally active men (28 ± 7 years, 24.1 ± 3.2 kg/m2) were recruited. No subject reported having been diagnosed with cardiovascular disease, diabetes, insulin resistance, cardiovascular risk factors (such as hypercholesterolemia or hypertension) and family history of premature (<50 years) cardiovascular death. Subjects who smoked or were on medications of any type were excluded. The study procedures were approved by the Ethics Committee of Liverpool John Moores University,

Wall-to-lumen ratio between arteries

Baseline resting diameter differed significantly between all four arteries (Fig. 1A). Apart from the comparison between the radial and brachial artery, wall thickness differed significantly between arteries (Fig. 1B). A strong and significant correlation was found between wall thickness and baseline diameter (r = 0.82, P < 0.001). When correcting wall thickness for the lumen, we found significant differences in the wall-to-lumen ratio between the femoral and superficial femoral artery, between the

Discussion

This is the first study to describe regional variation in wall thickness between different sized arteries in the upper and lower limbs within subjects in vivo. Smaller arteries, despite the significantly smaller absolute wall thickness, demonstrate a larger wall-to-lumen ratio than large-sized arteries. This indicates that smaller arteries demonstrate a relatively larger wall thickness than large conduit arteries. We extended these novel findings to examine whether regional heterogeneity in

Acknowledgements

We thank Mr. Christopher Reed for the development and provision of the analysis software for the wall thickness and flow-mediated dilation.

D.H.J.T. is recipient of the E. Dekker post-doc stipend (Netherlands Heart Foundation).

Professor Green is supported by a grant from the Australian Research Council and the National Heart Foundation of Australia.

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