Endothelial Shear Stress and Coronary Endothelial Dysfunction

Study Questions:

What is the association between low endothelial shear stress (ESS) and microvascular and epicardial endothelial dysfunction in patients with early atherosclerosis?

Methods:

The investigators included 65 patients (mean age 52 ± 11 years) with nonobstructive coronary atherosclerosis (luminal diameter stenosis <30%). Microvascular and epicardial coronary endothelial function was assessed by using intracoronary acetylcholine infusion. Vascular profiling, using two-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:

The authors concluded that data indicate an association between dysfunction of the microvascular and epicardial endothelium and local ESS at the early stages of coronary atherosclerosis in humans.

Perspective:

This study reports significant association of microvascular and epicardial endothelial dysfunction with ESS patterns in patients with nonobstructive coronary artery disease. Furthermore, patients with abnormal microvascular endothelial function exhibited a decrease in local ESS, and there was a progressive decrease in ESS from those with concomitant normal epicardial endothelial function to those with microvascular and epicardial endothelial function that were both abnormal. These data provide a link between local hemodynamic factors and initiation and progression of coronary artery disease, and underscore the need to target the microcirculation early with lifestyle changes and preventive therapies to protect the entire coronary vascular tree.

Clinical Topics: Diabetes and Cardiometabolic Disease, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Acetylcholine, Atherosclerosis, Coronary Angiography, Coronary Artery Disease, Endothelium, Hemodynamics, Hydrodynamics, Life Style, Metabolic Syndrome X, Microcirculation, Plaque, Atherosclerotic, Primary Prevention, Ultrasonography


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