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Recent reports show that plaque erosion can be diagnosed in vivo using optical coherence tomography in patients with acute coronary syndrome. However, quantitative optical coherence tomographic image criteria for computer-aided diagnosis of plaque erosion have not been established.A total of 42 patients with acute coronary syndrome caused by plaque erosion were included. Plaque erosion was identified according to the previously established optical coherence tomography criteria. Both optical properties and morphological features of the focal-eroded region as well as erosion-adjacent region were analyzed using a custom-designed computer algorithm. Noneroded fibrous plaques remote from the erosion site within the same vessel were used as controls. Eroded plaques have significantly lower surface intensity (P<0.001), lower region of interest intensity (P<0.001), lower surface normalized SD (P<0.001), lower region of interest normalized SD (P<0.001), higher optical attenuation (P<0.001), larger tissue protrusion area (P<0.001), and greater surface roughness (P<0.001) when compared with control plaques. Erosion-adjacent regions also have lower region of interest normalized SD (P=0.008), higher attenuation (P<0.001), and greater surface roughness (P=0.005). Using a logistic regression model built on the quantitative features, plaque erosion can be accurately classified against intact fibrous plaques. There was low inter- and intraobserver variability associated with the algorithm-assisted quantitative assessment.Plaque erosion has distinctive optical properties and morphological features when compared with noneroded fibrous plaques. Quantitative image analysis may enhance diagnostic accuracy for plaque erosion in vivo. [ABSTRACT FROM AUTHOR]

The pathophysiological basis for the association between metabolic syndrome (MetS) and coronary artery disease is not well understood. We sought to characterize coronary plaques in patients with MetS by using optical coherence tomography.We identified 451 coronary plaques from 171 subjects who underwent optical coherence tomographic imaging in 3 coronary arteries. Subjects were divided into 3 groups: diabetes mellitus (DM, n=77), MetS (n=35), and a control group (C group, n=59) without DM or MetS. Optical coherence tomographic analysis included the presence of lipid-rich plaque, maximum lipid arc, lipid-core length, lipid index (LI), fibrous cap thickness, and thin-cap fibroatheroma. We defined LI as mean lipid arc multiplied by lipid-core length. Lipid-core length and LI were significantly greater in DM and MetS than in C group (lipid-core length: 7.7±4.0 and 7.0±3.8 versus 5.5±2.4 mm; P<0.001 and P=0.012, and LI: 1164±716 and 1086±693 versus 796±417 mm; P<0.001 and P=0.008). Maximum lipid arc was significantly greater in DM than in C group, whereas no significant difference was observed between MetS and C group (196±45°, 187±42° versus 176±52°; P=0.002 and P=0.182). Fibrous cap thickness and thin-cap fibroatheroma showed no significant difference among the 3 groups. In multivariate analysis, DM and MetS were independently associated with LI, whereas only acute coronary syndrome was the independent predictor for thin-cap fibroatheroma.Compared with control subjects, coronary plaques in MetS contain larger lipid. However, the MetS criteria used in this study could not distinguish the vulnerable features such as thin-cap fibroatheroma, suggesting the necessity of complementary information to identify patients at high risk for cardiovascular events. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) promotes the development of atherosclerosis and increases the risk of cardiovascular disease. The aim of the present study was to compare the coronary plaque characteristics of patients with and without CKD using optical coherence tomography.We identified 463 nonculprit plaques from 287 patients from the Massachusetts General Hospital (MGH) optical coherence tomography registry. CKD was defined as estimated glomerular filtration rate <60 mL/min per 1.73 m2. A total of 402 plaques (250 patients) were in the non-CKD group and 61 plaques (37 patients) were in the CKD group. Compared with non-CKD plaques, plaques with CKD had a larger lipid index (mean lipid arc×lipid length, 1248.4±782.8 mm° [non-CKD] versus 1716.1±1116.2 mm° [CKD]; P=0.003). Fibrous cap thickness was not significantly different between the groups. Calcification (34.8% [non-CKD] versus 50.8% [CKD]; P=0.041), cholesterol crystals (11.2% [non-CKD] versus 23.0% [CKD]; P=0.048), and plaque disruption (5.5% [non-CKD] versus 13.1% [CKD]; P=0.049) were more frequently observed in the CKD group. In the multivariate linear regression model, a lower estimated glomerular filtration rate and diabetes mellitus were independent risk factors for a larger lipid index.Compared with non-CKD patients, the patients with CKD had a larger lipid index with a higher prevalence of calcium, cholesterol crystals, and plaque disruption. The multivariate linear regression model demonstrated that a lower estimated glomerular filtration rate was an independent risk factor for a larger lipid index.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538. [ABSTRACT FROM AUTHOR]

Background: Current therapies cannot completely reverse advanced atherosclerosis. High levels of amino acids, induced by Western diet, stimulate mTORC1 (mammalian target of rapamycin complex 1)-autophagy defects in macrophages, accelerating atherosclerotic plaque progression. In addition, autophagy-lysosomal dysfunction contributes to plaque necrotic core enlargement and lipid accumulation. Therefore, it is essential to investigate the novel mechanism and molecules to reverse amino acid-mTORC1-autophagy signaling dysfunction in macrophages of patients with advanced atherosclerosis., Methods: We observed that Gpr137b-ps (G-protein-coupled receptor 137B, pseudogene) was upregulated in advanced atherosclerotic plaques. The effect of Gpr137b-ps on the progression of atherosclerosis was studied by generating advanced plaques in ApoE -/- mice with cardiac-specific knockout of Gpr137b-ps. Bone marrow-derived macrophages and mouse mononuclear macrophage cell line RAW264.7 cells were subjected to starvation or amino acid stimulation to study amino acid-mTORC1-autophagy signaling. Using both gain- and loss-of-function approaches, we explored the mechanism of Gpr137b-ps-regulated autophagy., Results: Our results demonstrated that Gpr137b-ps deficiency led to enhanced autophagy in macrophages and reduced atherosclerotic lesions, characterized by fewer necrotic cores and less lipid accumulation. Knockdown of Gpr137b-ps increased autophagy and prevented amino acid-induced mTORC1 signaling activation. As the downstream binding protein of Gpr137b-ps, HSC70 (heat shock cognate 70) rescued the impaired autophagy induced by Gpr137b-ps. Furthermore, Gpr137b-ps interfered with the HSC70 binding to G3BP (Ras GTPase-activating protein-binding protein), which tethers the TSC (tuberous sclerosis complex) complex to lysosomes and suppresses mTORC1 signaling. In addition to verifying that the NTF2 (nuclear transport factor 2) domain of G3BP binds to HSC70 by in vitro protein synthesis, we further demonstrated that HSC70 binds to the NTF2 domain of G3BP through its W90-F92 motif by using computational modeling., Conclusions: These findings reveal that Gpr137b-ps plays an essential role in the regulation of macrophage autophagy, which is crucial for the progression of advanced atherosclerosis. Gpr137b-ps impairs the interaction of HSC70 with G3BP to regulate amino acid-mTORC1-autophagy signaling, and these results provide a new potential therapeutic direction for the treatment of advanced atherosclerosis., Competing Interests: Disclosures None.

Objective: The addition of cystatin C to creatinine in calculating the estimated glomerular filtration rate (eGFR) is known to improve the risk prediction for cardiovascular events. We sought to investigate the associations between eGFRs calculated by three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and coronary plaque phenotype by optical coherence tomography., Patients and Methods: We analyzed 181 nonculprit plaques from 116 coronary artery disease patients. For each patient, the eGFR was calculated using the CKD-EPIcreatinine, CKD-EPIcystatin C, and CKD-EPIcombination equations. Patients were divided into three categories according to the eGFR calculated by each equation (≥90, 60-89, and <60 ml/min/1.73 m)., Results: The prevalence of thin-cap fibroatheroma (TCFA) was correlated inversely with eGFR calculated using CKD-EPIcystatin C and CKD-EPIcombination equations, but not using the CKD-EPIcreatinine equation. The best cut-off values of eGFR calculated by these two equations for differentiating TCFA were 83 and 84 ml/min/1.73 m, respectively. Compared with the CKD-EPIcreatinine equation, patients who were reclassified upward or downward categories by the CKD-EPIcystatin C equation were associated with consistently lower [adjusted odds ratio=0.27, 95% confidence interval (CI), 0.08-0.86] and higher (adjusted odds ratio=2.41, 95% CI, 1.08-5.41) prevalence for TCFA, respectively. The net reclassification improvement with cystatin C, compared with creatinine, was 0.45 (95% CI, 0.20-0.69) for TCFA, 0.38 (95% CI, 0.09-0.67) for thrombus, and 0.21 (95% CI, 0.00-0.42) for cholesterol crystals. Results were generally similar for the CKD-EPIcombination equation., Conclusion: The use of cystatin C alone or in combination with creatinine, compared with creatinine alone, for GFR estimation strengthens the associations between the eGFR and prevalence of vulnerable plaque characteristics.

Objectives: The aim of this study was to investigate the spatial location of vulnerable plaques at coronary artery bifurcations using frequency domain-optical coherence tomography., Background: In-vivo data on geometric location of vulnerable plaques in relation to coronary bifurcation are limited., Materials and Methods: A total of 40 patients with left anterior descending artery bifurcation were studied. Plaque characteristics in five regions in relation to a side branch were compared: opposite flow divider (OFD); bifurcation site (BF); main branch side proximal (MBP); side branch side proximal (SBP); and flow divider (FD). Frequency domain-optical coherence tomography was used for plaque characterization., Results: Seventy-two lipid-rich plaques and 15 thin-cap fibroatheroma (TCFA) were detected in 220 regions of 44 bifurcations. Overall, the main branch side had more vulnerable characteristics compared with the side branch side. The FD was rarely affected by lipid accumulation. The OFD showed the highest prevalence of lipid-rich plaques [47.7% (OFD) vs. 45.5% (MBP), 43.2% (BF), 18.2% (SBP), and 9.1% (FD), P<0.0001] and TCFA [20.5% (OFD) vs. 6.8% (MBP), 6.8% (BF), 2.2% (SBP), and 0.0% (FD), P<0.001] and the thinnest fibrous cap [88.7±43.7 μm (OFD) vs. 123.5±62.7 μm (MBP), 149.6±77.0 μm (BF), 157.4±65.4 μm (SBP), and 163.6±76.9 μm (FD), P=0.002] compared with other regions., Conclusion: Lipid accumulation tends to develop in the zone opposite the side branch. TCFA was localized predominantly in the region OFD, whereas FD was rarely affected.