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      Association of endothelial function with thin-cap fibroatheroma as assessed by optical coherence tomography in patients with acute coronary syndromes


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          Thinning of the fibrous cap of atherosclerotic plaque is a major component of plaque vulnerability. The high resolution of optical coherence tomography (OCT) provides an accurate measurement of fibrous-cap thickness. Endothelial dysfunction is associated with inflammation and enhanced local expression of matrix metalloproteinases. We investigated the association between endothelial dysfunction and OCT-derived thin-cap fibroatheroma (TCFA) in patients with acute coronary syndromes (ACS).


          Seventy-four patients with ACS, who underwent both OCT examinations of the culprit lesion before percutaneous coronary intervention and peripheral endothelial function assessment as assessed by logarithmic value of reactive hyperemia index (Ln_RHI), were enrolled. Age-, sex-, hypertension-, and diabetes-matched non-coronary artery disease (non-CAD) patients were also enrolled (n=15).


          Ln_RHI levels were significantly lower in ACS patients compared with non-CAD patients (0.56±0.26 vs 0.74±0.22, P=0.01). Furthermore, the Ln_RHIs of ACS patients with TCFA (n=44) were significantly lower than those of ACS patients without TCFA (n=30) (0.50±0.24 vs 0.65±0.26, P=0.01). There was a weak but significant positive correlation between Ln_RHI and fibrous-cap thickness (Spearman’s ρ=0.25, P=0.03). Multivariate logistic regression analysis identified lower Ln_RHI as an independent factor associated with TCFA in ACS patients (OR per 0.1 increase in Ln_RHI: 0.78 [95% CI: 0.62–0.98], P=0.03).


          Advanced endothelial dysfunction significantly correlates with a thin fibrous cap of coronary plaques in patients with ACS.

          Most cited references16

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          From vulnerable plaque to vulnerable patient: a call for new definitions and risk assessment strategies: Part I.

          Atherosclerotic cardiovascular disease results in >19 million deaths annually, and coronary heart disease accounts for the majority of this toll. Despite major advances in treatment of coronary heart disease patients, a large number of victims of the disease who are apparently healthy die suddenly without prior symptoms. Available screening and diagnostic methods are insufficient to identify the victims before the event occurs. The recognition of the role of the vulnerable plaque has opened new avenues of opportunity in the field of cardiovascular medicine. This consensus document concludes the following. (1) Rupture-prone plaques are not the only vulnerable plaques. All types of atherosclerotic plaques with high likelihood of thrombotic complications and rapid progression should be considered as vulnerable plaques. We propose a classification for clinical as well as pathological evaluation of vulnerable plaques. (2) Vulnerable plaques are not the only culprit factors for the development of acute coronary syndromes, myocardial infarction, and sudden cardiac death. Vulnerable blood (prone to thrombosis) and vulnerable myocardium (prone to fatal arrhythmia) play an important role in the outcome. Therefore, the term "vulnerable patient" may be more appropriate and is proposed now for the identification of subjects with high likelihood of developing cardiac events in the near future. (3) A quantitative method for cumulative risk assessment of vulnerable patients needs to be developed that may include variables based on plaque, blood, and myocardial vulnerability. In Part I of this consensus document, we cover the new definition of vulnerable plaque and its relationship with vulnerable patients. Part II of this consensus document focuses on vulnerable blood and vulnerable myocardium and provide an outline of overall risk assessment of vulnerable patients. Parts I and II are meant to provide a general consensus and overviews the new field of vulnerable patient. Recently developed assays (eg, C-reactive protein), imaging techniques (eg, CT and MRI), noninvasive electrophysiological tests (for vulnerable myocardium), and emerging catheters (to localize and characterize vulnerable plaque) in combination with future genomic and proteomic techniques will guide us in the search for vulnerable patients. It will also lead to the development and deployment of new therapies and ultimately to reduce the incidence of acute coronary syndromes and sudden cardiac death. We encourage healthcare policy makers to promote translational research for screening and treatment of vulnerable patients.
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            Prognostic value of coronary vascular endothelial dysfunction.

            Whether patients at increased risk can be identified from a relatively low-risk population by coronary vascular function testing remains unknown. We investigated the relationship between coronary endothelial function and the occurrence of acute unpredictable cardiovascular events (cardiovascular death, myocardial infarction, stroke, and unstable angina) in patients with and without coronary atherosclerosis (CAD). We measured the change in coronary vascular resistance (DeltaCVR) and epicardial diameter with intracoronary acetylcholine (ACh, 15 micro g/min) to test endothelium-dependent function and sodium nitroprusside (20 micro g/min) and adenosine (2.2 mg/min) to test endothelium-independent vascular function in 308 patients undergoing cardiac catheterization (132 with and 176 without CAD). Patients underwent clinical follow-up for a mean of 46+/-3 months. Acute vascular events occurred in 35 patients. After multivariate analysis that included CAD and conventional risk factors for atherosclerosis, DeltaCVR with ACh (P=0.02) and epicardial constriction with ACh (P=0.003), together with increasing age, CAD, and body mass index, were independent predictors of adverse events. Thus, patients in the tertile with the best microvascular responses with ACh and those with epicardial dilation with ACh had improved survival by Kaplan-Meier analyses in the total population, as did those in the subset without CAD. Similar improvement in survival was also observed when all adverse events, including revascularization, were considered. Endothelium-independent responses were not predictive of outcome. Epicardial and microvascular coronary endothelial dysfunction independently predict acute cardiovascular events in patients with and without CAD, providing both functional and prognostic information that complements angiographic and risk factor assessment.
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              Characterization of human atherosclerosis by optical coherence tomography.

              High-resolution visualization of atherosclerotic plaque morphology may be essential for identifying coronary plaques that cause acute coronary events. Optical coherence tomography (OCT) is an intravascular imaging modality capable of providing cross-sectional images of tissue with a resolution of 10 micro m. To date, OCT imaging has not been investigated in sufficient detail to assess its accuracy for characterizing atherosclerotic plaques. The aim of this study was to establish objective OCT image criteria for atherosclerotic plaque characterization in vitro. OCT images of 357 (diseased) atherosclerotic arterial segments obtained at autopsy were correlated with histology. OCT image criteria for 3 types of plaque were formulated by analysis of a subset (n=50) of arterial segments. OCT images of fibrous plaques were characterized by homogeneous, signal-rich regions; fibrocalcific plaques by well-delineated, signal-poor regions with sharp borders; and lipid-rich plaques by signal-poor regions with diffuse borders. Independent validation of these criteria by 2 OCT readers for the remaining segments (n=307) demonstrated a sensitivity and specificity ranging from 71% to 79% and 97% to 98% for fibrous plaques, 95% to 96% and 97% for fibrocalcific plaques, and 90% to 94% and 90% to 92% for lipid-rich plaques, respectively (overall agreement, kappa=0.83 to 0.84). The interobserver and intraobserver reliabilities of OCT assessment were high (kappa values of 0.88 and 0.91, respectively). Objective OCT criteria are highly sensitive and specific for characterizing different types of atherosclerotic plaques. These results represent an important step in validating this new intravascular imaging modality and will provide a basis for the interpretation of intracoronary OCT images obtained from patients.

                Author and article information

                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                15 February 2019
                : 15
                : 285-291
                [1 ]Division of Cardiology, Yokohama City University Medical Center, Yokohama, Japan, matsu@ 123456yokohama-cu.ac.jp ; hibikiyo@ 123456yokohama-cu.ac.jp
                [2 ]Department of Medical Science and Cardiorenal Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
                Author notes
                Correspondence: Yasushi Matsuzawa; Kiyoshi Hibi, Division of Cardiology, Yokohama City University Medical Center, 4-57 Urafune-cho, Minami-ku, Yokohama 232-0024, Japan, Tel +81 45 261 5656, Fax +81 45 261 9162, Email matsu@ 123456yokohama-cu.ac.jp ; hibikiyo@ 123456yokohama-cu.ac.jp
                © 2019 Matsuzawa et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Clinical Trial Report

                peripheral endothelial function,optical coherence tomography,thin-cap fibroatheroma,plaque vulnerability


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