Heterogeneity of plaque burden natural history within individual human coronary atherosclerotic plaques is based on local endothelial shear stress: insights for culprit areas and clinical events

Abstract

Abstract Background Patterns of local endothelial shear stress (ESS) are heterogeneous along the course of individual coronary artery plaques. It is unknown how this heterogeneity affects the local natural history of plaque burden (PB) over time. Objectives To determine the effect of local ESS patterns along the course of coronary plaques at baseline on the heterogeneity of subsequent PB progression, regression, and quiescence in human coronary arteries and its link to clinical events. Methods 302 patients from the PREDICTION study were included in the study. The PREDICTION study was an anatomic natural history followup study of patients treated for an acute coronary syndrome (ACS) performed in 15 Japanese clinical sites, as previously published [1]. Invasive imaging was performed at baseline and, per protocol, at 6-10 months follow-up. Arterial geometry and ESS were derived from angiography/intravascular ultrasound-based vascular profiling. Plaques were identified as regions with plaque thickness > 0.5 mm in at least 3 consecutive 3-mm segments. Plaque progression was defined as change in PB (plaque area/total vessel area*100%) PB >+5% increase, regression as <-5% decrease, and quiescence as no change. The location of each sequential 3-mm segment along the plaque was related to the minimum lumen area (MLA). Performance of PCI in followup was assessed relative to the magnitude of PB change over time. Results 661 plaques (5,658 3-mm segments) from 591 coronary arteries were identified. 56% of 3-mm segments per plaque manifested PB progression, 60% PB regression, and 96% quiescence, and the presence and number of these PB changes were significantly related to plaque length (p<0.002). PB change >20% was associated with low ESS (0.75±0.31 Pa) and marked regression (PB change <-20%) with high ESS (3.94±0.04 Pa) (p<0.001, Figure 1 right panel). 3-mm segments exhibiting substantial PB progression were located along the full length of the plaque, and seldom at the MLA (p=0.874, (Figure 1 left panel), while substantial PB regression was significantly located at the MLA (p<0.001). With increasing ∆PB progression in individual 3-mm segments, a significant increase in performance of PCI was observed (p=0.012, Figure 2). Conclusions PB natural history of 3-mm segments within an individual plaque is heterogeneous, driven by local ESS, with substantial plaque progression/luminal encroachment developing along the entire course of the plaque, and typically not near the MLA. PCI was associated with the magnitude of PB progression/luminal encroachment, regardless of where the progression occurred.Figure 1Figure 2