Low Coronary Wall Shear Stress Is Associated With Severe Endothelial Dysfunction in Patients With Nonobstructive Coronary Artery Disease

Abstract

Objectives: We investigated the relationship between low wall shear stress (WSS) and severe endothelial dysfunction (EDFx). Background: Local hemodynamic forces, such as WSS play an important role in atherogenesis through their effect on endothelial cells. We hypothesized that low WSS independently predicts severe EDFx in patients with coronary artery disease (CAD). Methods: Forty-four patients with CAD underwent coronary angiography, fractional flow reserve (FFR) and endothelial function testing. Segments with >10% vasoconstriction after acetylcholine (Ach) infusion were defined as having severe EDFx. WSS, calculated using 3D angiography, velocity measurements and computational fluid dynamics, was defined as low (< 1 Pa), intermediate (1–2.5 Pa) or high (> 2.5 Pa). Results: Median age was 52 years, 73% were females. Mean FFR was 0.94 ± 0.06. In 4,510 coronary segments, median WSS was 3.67 Pa. 24% had severe EDFx. A higher proportion of segments with low WSS had severe EDFx (71%) compared to intermediate WSS (22%) or high WSS (23%) (p < 0.001). Segments with low WSS demonstrated greater vasoconstriction in response to ACh than intermediate or high WSS segments (−10.7% vs. −2.5% vs. +1.3%, respectively, p < 0.001). In a multivariable logistic regression analysis, female sex (OR: 2.44, p = 0.04), diabetes (OR: 5.01, p = 0.007) and low WSS (OR: 9.14, p < 0.001) were independent predictors of severe EDFx. Conclusion: In patients with non-obstructive CAD, segments with low WSS demonstrated more vasoconstriction in response to ACh than intermediate or high WSS segments. Low WSS was independently associated with severe endothelial dysfunction.

Effect of Hemodynamic Parameters on Physiological Blood Flow through Cardiovascular Disease (CVD) – The Perspective Review

“…Newtonian and non-Newtonian blood models are also compared in Thanapong Chaicana et al, [12] paper, where there are almost similar values for WSS in both blood models, representing huge similarities in WSS values although having different blood models. Based on the [11,12,8,18,19,21] papers, we can find a mutual agreement of the authors regarding hemodynamic parameters related significantly to the physiological blood flow. Details of the studies can be observed in Table 1 and Table 2.…”

“…CFD is a tool that has been used for decades in simulation and fluid flow processes. Many researchers consider this method while underwent experimental and simulation investigation for their research as it is time-consuming and low in cost [8,11,12,[18][19][20]. This CFD method not only limited to the selective field such as the mechanical and fluid field but also brings a great contribution to medical fields.…”

“…From the research analysis, it was found that low WSS regions' values are less than or equal to 0.4 Pa while high WSS values were more than or equal to 40 Pa, which occurs at the inner wall and bifurcation angles respectively. Arnav Kumar et al, [19] studying the relationship between severe endothelial dysfunction (EDFx) found that low WSS was greatly contributed with severe EDFx with 71% compared to intermediate WSS (22%) and high WSS (23%). All 44 patients from the research conducted coronary angiography, fractional flow reserve (FFR) and endothelial function testing.…”

“…, is the solute permeability through the pathway, , and , are the osmotic and solvent reflection coefficients, respectively. The is the width, is the radius of leaky junctions, is the length of the leaky junctions, is the velocity vector of transmural flow, is the pressure within the wall, is constant (1. refer to the fluid velocity vector, P is fluid pressure, is blood density, is velocity,∇ 2 is Laplacian operator, is dynamic viscosity, is the gravity constant The authors used the ratio of WSS and ̅̅̅̅̅̅ , the ratio parameter of pressure drop between the proximal inlet with peak systole of the distal outlet to the identified surface response curve Arnav Kumar et al, [19], 2018…”

Low shear stress induces endothelial cell apoptosis and monocyte adhesion by upregulating PECAM‑1 expression

“…increasing evidence has demonstrated that the endothelial dysfunction process is directly influenced by various factors, including nitric oxide dysfunction, epigenetic factors, oxidative stress, inflammatory factors and low shear stress (LSS) (5)(6)(7)(8)(9)(10)(11). among these, lSS, tangential stress produced by endothelial surface blood flow friction, which is observed at bifurcations, branching points and inside areas of curved segments of the coronary artery, induces inflammation and apoptosis, and subsequently disrupts the endothelial barrier, eventually leading to atherosclerosis (11)(12)(13)(14)(15).…”