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

Siasos, Gerasimos; Sara, Jaskanwal D.; Zaromitidou, Marina; Park, Kyoung H.; Coskun, Ahmet U.; Lerman, Lilach O.; Oikonomou, Evangelos; Maynard, Charles; Fotiadis, Dimitris; Stefanou, Kostas; Papafaklis, Michail I.; Michalis, Lampros K.; Feldman, Charles L.; Lerman, Amir; Stone, Peter H.

doi:10.1016/j.jacc.2018.02.073

Cited by 112 publications

(61 citation statements)

References 28 publications

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“…Similarly, our CE wall variable was a surrogate for endothelial dysfunction, albeit a biologically plausible one, as previously outlined. This is also supported by recent reports in coronary artery segments that showed CFD-derived low WSS was independently associated with epicardial and microvascular endothelial dysfunction after acetylcholine infusion [44].…”

Section: Limitationssupporting

confidence: 88%

Segment-specific associations between local haemodynamic and imaging markers of early atherosclerosis at the carotid artery: an in vivo human study

Gallo

Bijari

Morbiducci

et al. 2018

J. R. Soc. Interface.

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Low and oscillatory wall shear stress (WSS) has long been hypothesized as a risk factor for atherosclerosis; however, evidence has been inferred primarily from model and post-mortem studies, or clinical studies of patients with already-developed plaques. This study aimed to identify associations between local haemodynamic and imaging markers of early atherosclerosis. Comprehensive magnetic resonance imaging allowed quantification of contrast enhancement (CE) (a marker of endothelial dysfunction) and vessel wall thickness at two distinct segments: the internal carotid artery bulb and the common carotid artery (CCA). Strict criteria were applied to a large dataset to exclude inward remodelling, resulting in 41 cases for which personalized computational fluid dynamic simulations were performed. After controlling for cardiovascular risk factors, bulb wall thickening was found to be weakly, but not significantly, associated with oscillatory WSS. CE at the bulb was significantly associated with low WSS ( p < 0.001) and low flow helicity ( p < 0.05). No significant associations were found for the CCA segment. Local haemodynamics at the bulb were significantly correlated with blood flow rates and heart rates, but not carotid bifurcation geometry (flare and curvature). Therefore low, but not oscillatory, WSS is an early independent marker of atherosclerotic changes preceding intimal thickening at the carotid bulb.

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Section: Limitationssupporting

confidence: 88%

Segment-specific associations between local haemodynamic and imaging markers of early atherosclerosis at the carotid artery: an in vivo human study

Gallo

Bijari

Morbiducci

et al. 2018

J. R. Soc. Interface.

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“…19 Coronary artery diameter was measured at baseline and with acetylcholine infusion by an independent investigator blinded to Doppler velocity data using a previously described computer-based image analysis system. 20,21 CBF was then calculated as = (average peak velocity) (coronary artery diameter/2) 2 . 16 Coronary vascular resistance was calculated as mean arterial pressure divided by CBF.…”

Section: Coronary Microvascular Function Assessmentmentioning

confidence: 99%

“…22 Endothelium-dependent CMD was defined as an increase in CBF ≤ 0% in response to acetylcholine. 21 Impaired endotheliumindependent microvascular function was defined as CFR ≤ 2. 5.…”

Section: Coronary Microvascular Function Assessmentmentioning

confidence: 99%

Endothelium‐dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction

Yang

Obokata

Reddy

et al. 2019

European J of Heart Fail

Self Cite

116

103

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Background Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium‐dependent and independent coronary microvascular function in HFpEF. Methods and results Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10−6–10−4 mol/L) using a Doppler flow wire with quantitative angiography. Endothelium‐independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium‐dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium‐independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co‐morbidities or other clinical characteristics. As compared to patients with normal endothelium‐independent function, HFpEF patients with endothelium‐independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0 ± 1.8 vs. 8.4 ± 2.9 cm/s, P = 0.002) and higher estimated filling pressures (E/e' 13.1 ± 4.1 vs. 9.6 ± 3.4, P < 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium‐dependent coronary vasodilatation. Endothelium‐independent microvascular dysfunction was associated with increased mortality. Conclusions Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium‐dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co‐morbidities alone. Patients with HFpEF and endothelium‐independent microvascular dysfunction display worse diastolic dysfunction and outcomes.

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“…To date, with a growing trend, prediabetes affects .38% of people in the adult population, and it is associated with an increased risk of developing diabetes (3). Although some prospective studies have shown that prediabetes is associated with an increased risk of cardiovascular disease (4,5), other studies have not found a similar association (6)(7)(8). However, several previous metaanalyses have led to conflicting conclusions (3,9,10), due to differences in end point assessments and study inclusion criteria.…”

mentioning

confidence: 99%

Effects of Metformin Therapy on Coronary Endothelial Dysfunction in Patients With Prediabetes With Stable Angina and Nonobstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study

Sardu

Paolisso

Sacra³

et al. 2019

Diabetes Care

134

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To evaluate the effect of metformin therapy on coronary endothelial function and major adverse cardiac events (MACE) in patients with prediabetes with stable angina and nonobstructive coronary stenosis (NOCS). RESEARCH DESIGN AND METHODS Metformin therapy may be needed to reduce coronary heart disease risk in patients with prediabetes. A total of 258 propensity score-matched (PSM) patients with stable angina undergoing coronary angiography were enrolled in the study. Data from 86 PSM subjects with normoglycemia (NG), 86 PSM subjects with prediabetes (pre-DM), and 86 PSM subjects with prediabetes treated with metformin (pre-DM metformin) were analyzed. During coronary angiography, NOCS was categorized by luminal stenosis <40% and fractional flow reserve >0.80. In addition, we assessed the endothelial function, measuring coronary artery diameter of left anterior descending coronary (LAD) at baseline and after the infusion of acetylcholine, by means of an intracoronary Doppler guide wire. MACE, as cardiac death, myocardial infarction, and heart failure, was evaluated at 24 months of follow-up. RESULTS At baseline, NG patients had a lower percentage of LAD endothelial dysfunction compared with pre-DM patients (P < 0.05). The pre-DM patients had a higher percentage of endothelial LAD dysfunction as compared with the pre-DM metformin patients (P < 0.05). At the 24th month of follow-up, MACE was higher in pre-DM versus NG (P < 0.05). In pre-DM metformin patients, MACE was lower compared with pre-DM patients (P < 0.05). CONCLUSIONS Metformin therapy may reduce the high risk of cardiovascular events in pre-DM patients by reducing coronary endothelial dysfunction.

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

Cited by 112 publications

References 28 publications

Segment-specific associations between local haemodynamic and imaging markers of early atherosclerosis at the carotid artery: an in vivo human study

Segment-specific associations between local haemodynamic and imaging markers of early atherosclerosis at the carotid artery: an in vivo human study

Endothelium‐dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction

Effects of Metformin Therapy on Coronary Endothelial Dysfunction in Patients With Prediabetes With Stable Angina and Nonobstructive Coronary Artery Stenosis: The CODYCE Multicenter Prospective Study

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