Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis

Gerasimos Siasos, Jaskanwal D. Sara, Marina Zaromytidou, Kyoung H. Park, Ahmet Umit Coskun, Lilach O Lerman, Evangelos Oikonomou, Charles C. Maynard, Dimitris Fotiadis, Kostas Stefanou, Michail Papafaklis, Lampros Michalis, Charles Feldman, Amir Lerman, Peter H. Stone

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2092-2102
Number of pages11
JournalJournal of the American College of Cardiology
Volume71
Issue number19
DOIs
StatePublished - May 15 2018

    Fingerprint

Keywords

  • atherosclerosis
  • coronary artery disease
  • endothelial function
  • endothelial shear stress
  • endothelium
  • microvascular disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Siasos, G., Sara, J. D., Zaromytidou, M., Park, K. H., Coskun, A. U., Lerman, L. O., Oikonomou, E., Maynard, C. C., Fotiadis, D., Stefanou, K., Papafaklis, M., Michalis, L., Feldman, C., Lerman, A., & Stone, P. H. (2018). Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis. Journal of the American College of Cardiology, 71(19), 2092-2102. https://doi.org/10.1016/j.jacc.2018.02.073