High wall shear stress and high-risk plaque: an emerging concept

Abstract

In recent years, there has been a significant effort to identify high-risk plaques in vivo prior to acute events. While number of imaging modalities have been developed to identify morphologic characteristics of high-risk plaques, prospective natural-history observational studies suggest that vulnerability is not solely dependent on plaque morphology and likely involves additional contributing mechanisms. High wall shear stress (WSS) has recently been proposed as one possible causative factor, promoting the development of high-risk plaques. High WSS has been shown to induce specific changes in endothelial cell behavior, exacerbating inflammation and stimulating progression of the atherosclerotic lipid core. In line with experimental and autopsy studies, several human studies have shown associations between high WSS and known morphological features of high-risk plaques. However, despite increasing evidence, there is still no longitudinal data linking high WSS to clinical events. As the interplay between atherosclerotic plaque, artery, and WSS is highly dynamic, large natural history studies of atherosclerosis that include WSS measurements are now warranted. This review will summarize the available clinical evidence on high WSS as a possible etiological mechanism underlying high-risk plaque development.

Keywords: Acute coronary syndrome; Computational fluid dynamics; Coronary artery disease; High-risk plaque; Wall shear stress.

Figure 1

Possible mechanism for rapid plaque progression before myocardial infarction (from Ahmadi et al. [24] with permission)

Figure 2

A) Change in plaque composition in low, intermediate, and high WSS segments over 6 months. WSS: wall shear stress (from Samady et al. [35]). B) Change in plaque strain in tertiles of WSS over 6 months. (# denotes that change is significantly different from zero at a p <0.05 level) (Reprinted from EuroIntervention 7/1, Gijsen et al., High shear stress induces a strain increase in human coronary plaques over a 6-month period, 121–127 [45], Copyright (2011), with permission from Europa Digital & Publishing).

Figure 3

A) Percent of segments with low WSS (<10 dynes/cm²) within the lesions and proximal to and distal to lesions. B) Percent of segments with high WSS (≥25 dynes/cm²) within the lesions and proximal to and distal to lesions (*P value: the GLIMMIX procedure in SAS did not converge when fitting the statistical model for Figure 3B. Convergence was achieved when lesion and distal were consolidated into one category). C) Association between WSS and quartiles of plaque burden. The range of plaque burden in each quartile is shown in brackets (Error bars are 1 standard error). WSS: wall shear stress (from Eshtehardi et al. [34]).

Figure 4

Baseline WSS patterns along the course of a coronary artery obstruction. The 3 WSS categories (low <10 dynes/cm²; moderate, 10–17 dynes/cm²; high >17 dynes/cm²) in the bar graph were derived from the terciles of the WSS frequency distribution in 3-mm segments. NC: necrotic core; WSS: wall shear stress (modified from Stone et al. [36] with permission).