Abstract 17615: The Extent of Plaque-Free Arterial Wall Influences the Atherogenic Effect of Endothelial Shear Stress: An in vivo 3D Coronary Artery Reconstruction and Computational Fluid Dynamics Study in Humans
Introduction: The response of the endothelium to biomechanical stimuli in the local hemodynamic lumen environment mediates the powerful pro-atherogenic effect of endothelial shear stress (ESS). However, in advanced atherosclerosis, which is associated with a highly dysfunctional and often eroded endothelial layer, the endothelial response is not well known. We assessed the hypothesis that the extent of plaque-free arterial wall (PFAW) influences the pro-atherogenic effect of ESS in human coronary regions.
Methods: 3-dimensional coronary artery reconstruction by angiography & intravascular ultrasound was performed in 374 pts at baseline (BL) and 6-10 months later (FU) to assess plaque natural history as part of the PREDICTION Study. Each artery was divided into consecutive 3-mm segments resulting in 8,137 segments for serial analysis. BL ESS was assessed using computational fluid dynamics. The extent of PFAW at BL was defined as the percentage of the wall with minimal disease (plaque thickness ≤ 0.5 mm) within the segment. Plaque growth was determined according to the relative change in max plaque thickness (%▵maxPT) defined as: (▵maxPT/BL maxPT)×100.
Results: Plaque growth was significantly augmented in regions with BL low ESS (<1 Pa) and preservation of PFAW (extent ≥10%) at BL compared to regions with BL low ESS and minimal PFAW (p<0.01; Figure). After adjusting for baseline plaque characteristics, BL ESS (beta= −0.5% per 10% increase in ESS; p<0.01) was negatively related to %▵maxPT, and the interaction between BL ESS and the extent of PFAW at BL was also independently related to %▵maxPT (beta= −0.8% per 10% increase in PFAW; p<0.01).
Conclusion: An increased extent of PFAW significantly augments the pro-atherogenic effect of ESS, underscoring the response of the normal endothelium to the hemodynamic stimulus. This finding suggests that in advanced stages of atherosclerosis the endothelium is highly dysfunctional and thus, the response to ESS is diminished.
- © 2012 by American Heart Association, Inc.