Segment-specific associations between local haemodynamic and imaging markers of early atherosclerosis at the carotid artery: an in vivo human study

Abstract

Low and oscillatory wall shear stress (WSS) has long been hypothesized as a risk factor for atherosclerosis; however, evidence has been inferred primarily from model and post-mortem studies, or clinical studies of patients with already-developed plaques. This study aimed to identify associations between local haemodynamic and imaging markers of early atherosclerosis. Comprehensive magnetic resonance imaging allowed quantification of contrast enhancement (CE) (a marker of endothelial dysfunction) and vessel wall thickness at two distinct segments: the internal carotid artery bulb and the common carotid artery (CCA). Strict criteria were applied to a large dataset to exclude inward remodelling, resulting in 41 cases for which personalized computational fluid dynamic simulations were performed. After controlling for cardiovascular risk factors, bulb wall thickening was found to be weakly, but not significantly, associated with oscillatory WSS. CE at the bulb was significantly associated with low WSS ( p < 0.001) and low flow helicity ( p < 0.05). No significant associations were found for the CCA segment. Local haemodynamics at the bulb were significantly correlated with blood flow rates and heart rates, but not carotid bifurcation geometry (flare and curvature). Therefore low, but not oscillatory, WSS is an early independent marker of atherosclerotic changes preceding intimal thickening at the carotid bulb.

Carotid geometry is an independent predictor of wall thickness – a 3D cardiovascular magnetic resonance study in patients with high cardiovascular risk

“…Similarly, in case series of moderate to high-grade ICA stenosis, the typical WSS and OSI distribution disappeared and was restored after carotid surgery, respectively [ 8 , 25 ]. Thus, our results support the hypothesis that low WSS and high OSI could influence the initiation of atherosclerosis, whereas in manifest stenosis other mechanisms, such as high maximum shear or mechanical stress may trigger plaque progression [ 16 , 24 , 26 – 28 ]. This concept is underlined by previous studies [ 13 , 14 ] showing an association of high maximum shear stress with intra-plaque hemorrhage and conversion into a vulnerable plaque.…”

“…Previous studies [ 7 , 8 , 10 , 22 ] demonstrated the concentration of low absolute WSS or high OSI at the posterior wall of the ICA bulb in normal arteries, suggesting a causal connection of WSS and atherosclerosis, as this is the predilection site of carotid atheroma [ 7 , 23 , 24 ]. Consistently, we observed the same distribution in high-risk patients with carotid plaques.…”

Wall Shear Stress Topological Skeleton Independently Predicts Long-Term Restenosis After Carotid Bifurcation Endarterectomy

“…For all three cohorts LSA was not associated to either wFPA or TSVA ( Table 2), indicating that those WSS topological skeleton descriptors represent statistically independent variables with respect to the commonly adopted exposure to low TAWSS as a main indicator of disturbed shear in arteries. 11,15,27 Wall Shear Stress vs. Clinical Outcome Linear regressions revealed significant associations between the WSS topological skeleton descriptors and IMT at 60 months follow up. In detail, a significant association emerged between maximum IMT and both TSVA (R 2 = 0.505, p < 0.05) and wFPA (R 2 = 0.534, p < 0.05), as reported in Table 3.…”

“…However, the specificity of the currently considered hemodynamic features based on low and oscillatory WSS, which are significant but only moderate predictors of disease localization, 15,29 and their clinical added value, hampered by the practical challenges of including hemodynamic information from computational modelling in large prospective clinical studies, 31 have been questioned. 15,29 To improve, refine and extend our current understanding of the association between local hemodynamics and vascular disease, an increasing interest has been recently dedicated to the analysis of WSS vector field topological skeleton, 5,6,25 composed by fixed points and the stable/unstable manifolds connecting them. At a fixed point, the WSS vector field focally vanishes, and manifolds identify regions where the WSS vector field exerts a contraction/expansion action on the endothelial cells lining the luminal surface.…”

Improving Assessments of Hemodynamics and Vascular Disease

“…These findings are similar to the study by Van Ooij et al [106] that used the same methodology as Paper V, and found weak correlations among these parameters in their cohort of 20 elderly subjects. Gallo et al [107] used CFD simulations to estimate WSS in 41 cases, and did not find correlations between their more specialized geometric parameters like flare and curvature and low or oscillatory shear stress.…”