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

13 Citations (Scopus)

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

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Coronary Artery Disease
Arteries
Atherosclerotic Plaques
Hydrodynamics
Coronary Angiography
Acetylcholine
Endothelium
Blood Vessels
Anatomy
Atherosclerosis
Pathologic Constriction
Hemodynamics

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis. / Siasos, Gerasimos; Sara, Jaskanwal D.; Zaromytidou, Marina; Park, Kyoung H.; Coskun, Ahmet Umit; Lerman, Lilach O; Oikonomou, Evangelos; Maynard, Charles C.; Fotiadis, Dimitris; Stefanou, Kostas; Papafaklis, Michail; Michalis, Lampros; Feldman, Charles; Lerman, Amir; Stone, Peter H.

In: Journal of the American College of Cardiology, Vol. 71, No. 19, 15.05.2018, p. 2092-2102.

Research output: Contribution to journalArticle

Siasos, G, Sara, JD, Zaromytidou, M, Park, KH, Coskun, AU, Lerman, LO, Oikonomou, E, Maynard, CC, Fotiadis, D, Stefanou, K, Papafaklis, M, Michalis, L, Feldman, C, Lerman, A & Stone, PH 2018, 'Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis', Journal of the American College of Cardiology, vol. 71, no. 19, pp. 2092-2102. https://doi.org/10.1016/j.jacc.2018.02.073
Siasos, Gerasimos ; Sara, Jaskanwal D. ; Zaromytidou, Marina ; Park, Kyoung H. ; Coskun, Ahmet Umit ; Lerman, Lilach O ; Oikonomou, Evangelos ; Maynard, Charles C. ; Fotiadis, Dimitris ; Stefanou, Kostas ; Papafaklis, Michail ; Michalis, Lampros ; Feldman, Charles ; Lerman, Amir ; Stone, Peter H. / Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis. In: Journal of the American College of Cardiology. 2018 ; Vol. 71, No. 19. pp. 2092-2102.
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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.",
keywords = "atherosclerosis, coronary artery disease, endothelial function, endothelial shear stress, endothelium, microvascular disease",
author = "Gerasimos Siasos and Sara, {Jaskanwal D.} and Marina Zaromytidou and Park, {Kyoung H.} and Coskun, {Ahmet Umit} and Lerman, {Lilach O} and Evangelos Oikonomou and Maynard, {Charles C.} and Dimitris Fotiadis and Kostas Stefanou and Michail Papafaklis and Lampros Michalis and Charles Feldman and Amir Lerman and Stone, {Peter H.}",
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T1 - Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis

AU - Siasos, Gerasimos

AU - Sara, Jaskanwal D.

AU - Zaromytidou, Marina

AU - Park, Kyoung H.

AU - Coskun, Ahmet Umit

AU - Lerman, Lilach O

AU - Oikonomou, Evangelos

AU - Maynard, Charles C.

AU - Fotiadis, Dimitris

AU - Stefanou, Kostas

AU - Papafaklis, Michail

AU - Michalis, Lampros

AU - Feldman, Charles

AU - Lerman, Amir

AU - Stone, Peter H.

PY - 2018/5/15

Y1 - 2018/5/15

N2 - 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.

AB - 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.

KW - atherosclerosis

KW - coronary artery disease

KW - endothelial function

KW - endothelial shear stress

KW - endothelium

KW - microvascular disease

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