Author + information
- Received November 27, 2017
- Revision received February 21, 2018
- Accepted February 25, 2018
- Published online May 7, 2018.
- Gerasimos Siasos, MD, PhDa,
- Jaskanwal D. Sara, MBChBb,
- Marina Zaromytidou, MD, PhDa,
- Kyoung H. Park, MD, PhDb,
- Ahmet Umit Coskun, PhDa,
- Lilach O. Lerman, MD, PhDb,
- Evangelos Oikonomou, MD, PhDc,
- Charles C. Maynard, PhDd,
- Dimitris Fotiadis, PhDe,
- Kostas Stefanou, PhDe,
- Michail Papafaklis, MD, PhDe,
- Lampros Michalis, MD, PhDe,
- Charles Feldman, ScDa,∗,
- Amir Lerman, MDb,† and
- Peter H. Stone, MDa,†∗ ()
- aBrigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- bDivision of Cardiovascular Disease, Mayo Clinic, Rochester, Minnesota
- c1st Department of Cardiology, National and Kapodistrian University of Athens Medical School, Hippokration Hospital, Athens, Greece
- dUniversity of Washington, Seattle, Washington
- eMedical School, University of Ioannina, Ioannina, Greece
- ↵∗Address for correspondence:
Dr. Peter H. Stone, Cardiovascular Division, Brigham & Women’s Hospital, 75 Francis Street, Boston, Massachusetts 02115.
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.
- coronary artery disease
- endothelial function
- endothelial shear stress
- microvascular disease
↵† Drs. Lerman and Stone contributed equally to this work and are joint senior authors.
This work was supported by the National Institutes of Health (grants HL-92954 and AG-31750) and the Mayo Foundation. Dr. Stone’s laboratory was supported by the generosity of the Schaubert Family and the George Behrakis Research Foundation, as well as a St. Jude Medical Fellowship. Dr. Lerman has received a consulting fee from Volcano Corporation. All other authors have reported that they have no other relationships relevant to the contents of this paper to disclose.
- Received November 27, 2017.
- Revision received February 21, 2018.
- Accepted February 25, 2018.
- 2018 American College of Cardiology Foundation
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