Regions of low endothelial shear stress are the sites where coronary plaque progresses and vascular remodelling occurs in humans: an in vivo serial study

Abstract

We performed serial intracoronary studies of patients with stable coronary artery disease (CAD) to investigate the relationships among baseline endothelial shear stress (ESS), CAD progression, and vascular remodelling. Local haemodynamic factors are critical determinants of plaque progression, vascular remodelling, and clinical CAD manifestations. The 3-D anatomy of coronary arteries with lumen obstruction <50% was determined by fusing intracoronary ultrasound and angiographic images in 13 patients at baseline and 8 +/- 2 months later. Cross-sectional area of plaque, lumen, and external elastic membrane (EEM), and coronary flow were measured. Local ESS was calculated. Subsegments with similar ESS were categorized based on low (<12 dynes/cm(2)) and moderate/higher ESS (> or =12 dynes/cm(2)). There were 47 subsegments of similar baseline ESS: nine with low ESS and 38 with moderate/higher ESS. Median subsegment length was 6.9 mm (25th-75th percentiles = 4.2-12.0), and median area of similar ESS of 52.6 mm(2) (25th-75th percentiles = 26.9-88.0). Subsegments with low ESS exhibited plaque progression when compared with subsegments with moderate/higher ESS (33.3% vs. 7.9%, respectively, P = 0.009 adjusted for clustering of lesions within patients) and constrictive remodelling (44.0% vs. 5.3%, respectively, P = 0.16 adjusted for clustering of lesions within patients). Expansive remodelling occurred with similar frequency in subsegments with low vs. moderate/higher baseline ESS. Plaque progresses in subsegments with low ESS, associated with either constrictive or expansive remodelling. Different mechanisms are likely responsible for expansive remodelling in different local vascular environments. Early in vivo identification of arterial subsegments likely to develop high-risk plaque characteristics may allow for selective interventions to avoid adverse cardiac outcomes.