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Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study Coronary Microcirculation in Ischemic Heart Disease Low shear stress induces vascular eNOS uncoupling via autophagy-mediated eNOS phosphorylation Angiographic derived endothelial shear stress: a new predictor of atherosclerotic disease progression Low Endothelial Shear Stress Predicts Evolution to High-Risk Coronary Plaque Phenotype in the Future: A Serial Optical Coherence Tomography and Computational Fluid Dynamics Study Local Low Shear Stress and Endothelial Dysfunction in Patients With Nonobstructive Coronary Atherosclerosis Evolving understanding of the heterogeneous natural history of individual coronary artery plaques and the role of local endothelial shear stress Flow-Regulated Endothelial S1P Receptor-1 Signaling Sustains Vascular Development
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Clinical Trial2018 Mar;11(3):462-471.

JOURNAL：JACC Cardiovasc Imaging. Article Link

Role of Low Endothelial Shear Stress and Plaque Characteristics in the Prediction of Nonculprit Major Adverse Cardiac Events: The PROSPECT Study

Stone PH, Maehara A, Coskun AU et al. Keywords: atherosclerosis; coronary artery disease; inflammation; prediction; shear stress

ABSTRACT


OBJECTIVES - This study sought to determine whether low endothelial shear stress (ESS) adds independent prognostication for future major adverse cardiac events (MACE) in coronary lesions in patients with high-risk acute coronary syndrome (ACS) from the United States and Europe.


BACKGROUND - Low ESS is a proinflammatory, proatherogenic stimulus associated with coronary plaque development, progression, and destabilization in human-like animal models and in humans. Previous natural history studies including baseline ESS characterization investigated low-risk patients.

METHODS - In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with ACS underwent 3-vessel intracoronary imaging. Independent predictors of MACE attributable to untreated nonculprit (nc) coronary lesions during 3.4-year follow-up were large plaque burden (PB), small minimum lumen area (MLA), and thin-cap fibroatheroma (TCFA) morphology. In this analysis, baseline ESS of nc lesions leading to new MACE (nc-MACE lesions) and randomly selected control nc lesions without MACE (nc-non-MACE lesions) were calculated. A propensity score for ESS was constructed for each lesion, and the relationship between ESS and subsequent nc-MACE was examined.

RESULTS - A total of 145 lesions were analyzed in 97 patients: 23 nc-MACE lesions (13 TCFAs, 10 thick-cap fibroatheromas [ThCFAs]), and 122 nc-non-MACE lesions (63 TCFAs, 59 ThCFAs). Low local ESS (<1.3 Pa) was strongly associated with subsequent nc-MACE compared with physiological/high ESS (≥1.3 Pa) (23 of 101 [22.8%]) versus (0 of 44 [0%]). In propensity-adjusted Cox regression, low ESS was strongly associated with MACE (hazard ratio: 4.34; 95% confidence interval: 1.89 to 10.00; p < 0.001). Categorizing plaques by anatomic risk (high risk: ≥2 high-risk characteristics PB ≥70%, MLA ≤4 mm2, or TCFA), high anatomic risk, and low ESS were prognostically synergistic: 3-year nc-MACE rates were 52.1% versus 14.4% versus 0.0% in high-anatomic risk/low-ESS, low-anatomic risk/low-ESS, and physiological/high-ESS lesions, respectively (p < 0.0001). No lesion without low ESS led to nc-MACE during follow-up, regardless of PB, MLA, or lesion phenotype at baseline.

CONCLUSIONS - Local low ESS provides incremental risk stratification of untreated coronary lesions in high-risk patients, beyond measures of PB, MLA, and morphology.

Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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