TY - JOUR TI - Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis AU - Siasos, G. AU - Sara, J.D. AU - Zaromytidou, M. AU - Park, K.H. AU - Coskun, A.U. AU - Lerman, L.O. AU - Oikonomou, E. AU - Maynard, C.C. AU - Fotiadis, D. AU - Stefanou, K. AU - Papafaklis, M. AU - Michalis, L. AU - Feldman, C. AU - Lerman, A. AU - Stone, P.H. JO - Journal of the American College of Cardiology PY - 2018 VL - 71 TODO - 19 SP - 2092-2102 PB - ELSEVIER SCIENCE INC 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN - 0735-1097, 1558-3597 TODO - 10.1016/j.jacc.2018.02.073 TODO - acetylcholine, adult; Article; atherosclerotic plaque; cardiovascular parameters; computational fluid dynamics; coronary angiography; coronary artery atherosclerosis; disease association; disease course; early diagnosis; endothelial dysfunction; endothelial sheer stress; epicardial endothelial dysfunction; female; functional anatomy; human; image segmentation; intermethod comparison; intravascular ultrasound; left anterior descending coronary artery; major clinical study; male; microvascular endothelial dysfunction; middle aged; nonobstructive coronary artery atherosclerosis; plaque area; plaque burden; plaque thickness; priority journal; retrospective study; shear stress; three dimensional echocardiography; coronary artery disease; diagnostic imaging; mechanical stress; pathophysiology; physiology; prospective study; randomization; shear strength; vascular endothelium, Adult; Coronary Artery Disease; Endothelium, Vascular; Female; Humans; Male; Middle Aged; Prospective Studies; Random Allocation; Retrospective Studies; Shear Strength; Stress, Mechanical TODO - Background: Local hemodynamic factors are important determinants of atherosclerotic plaque development and progression. Objectives: The goal of this study was to determine the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis. Methods: Sixty-five patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%) were included. Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using 2-plane coronary angiography and intravascular ultrasound, was used to reconstruct the three-dimensional anatomy of the left anterior descending artery. Each reconstructed artery was divided into sequential 3-mm segments and analyzed for local ESS with computational fluid dynamics; that is, lower ESS levels at both a 3-mm regional level (average ESS and low ESS) and at a vessel level (lowest ESS per artery) and for plaque characteristics (plaque area, plaque thickness, and plaque burden). Results: Coronary segments in arteries with abnormal microvascular function exhibited lower ESS compared with segments in arteries with normal microvascular function (average ESS: 1.67 ± 1.04 Pa vs. 2.03 ± 1.72 Pa [p = 0.050]; lowest ESS: 0.54 ± 0.25 Pa vs. 0.72 ± 0.32 Pa [p = 0.014]). Coronary segments in arteries with abnormal epicardial endothelial function also exhibited significantly lower ESS compared with segments in arteries with normal epicardial function (average ESS: 1.49 ± 0.89 Pa vs. 1.93 ± 1.50 Pa [p < 0.0001]; low ESS: 1.26 ± 0.81 Pa vs. 1.56 ± 1.30 Pa [p = 0.001]; lowest ESS: 0.51 ± 0.27 Pa vs. 0.65 ± 0.29 Pa [p = 0.080]). Patients with abnormal microvascular endothelial function exhibited a progressive decrease in average and low ESS, starting from patients with normal epicardial endothelial function to those with both microvascular and epicardial endothelial dysfunction (p < 0.0001 and p = 0.004, respectively). Conclusions: These data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans. © 2018 American College of Cardiology Foundation ER -