Coronary Plaque Vulnerability Research Articles

Cardiovascular Imaging Techniques for Detection of Vulnerable Plaques

Abstract Various cardiovascular imaging techniques were developed for the detection of vulnerable atherosclerotic plaques, hoping to be able to predict a cardiovascular event. Plaque vulnerability results from compound pathophysiological mechanisms that lead to structural and morphological changes in lesions. The aim of this review is to present the most recent techniques for the assessment of vulnerable coronary plaques such as cardiac computed tomography angiography (CCTA), optical coherence tomography, or virtual histology intravascular ultra-sound, based on literature data from the last 3 years. CCTA permits direct visualization of the intravascular lumen, together with characterization of the arterial wall. Recent studies maintain that low-attenuation plaques, spotty calcifications, positive vessel remodeling, and the napkin-ring sign are considered main markers of plaque vulnerability and instability. Emerging analytical techniques, such as machine learning or radiomics, will probably demonstrate useful as an auxiliary diagnostic tool for vulnerable plaque detection. The data from the two imaging techniques together provide useful information, especially in patients undergoing a PCI procedure for an acute coronary syndrome. Invasive and noninvasive imaging techniques are able to deliver a large amount of scientific data to assess vulnerable coronary atheromatous plaques. Recent studies demonstrated that information defined by the two techniques is complementary, and using both methods is essential for adequate diagnosis, therapeutic strategy, and prognostic assessment.

The Role of Matrix Metalloproteinases in the Progression and Vulnerabilization of Coronary Atherosclerotic Plaques

Abstract Extracellular matrix (ECM) plays an important role in the development and progression of atherosclerotic lesions. Changes in the ECM are involved in the pathophysiology of many cardiovascular diseases, including atherosclerosis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases, also known as matrixins, with proteolytic activity in the ECM, being responsible for the process of tissue remodeling in various systemic pathologies, including cardiac and vascular diseases. MMPs play an important role in maintaining normal vascular structure, but also in secondary cardiovascular remodeling, in the formation of atherosclerotic plaques and in their vulnerabilization process. In addition to the assigned effect of MMPs in vulnerable plaques, they have a well-defined role in post-infarction ventricular remodeling and in various types of cardiomyopathies, followed by onset of congestive heart failure, with repeated hospitalizations and death. The aim of this manuscript was to provide a summary on the role of serum matrix metalloproteinases in the process of initiation, progression and complication of atherosclerotic lesions, from a molecular level to clinical applicability and risk prediction in patients with vulnerable coronary plaques.

Potential of an Approach Based on the Identification and Treatment of Vulnerable Coronary Plaques.

In this viewpoint paper, the authors are tackling criticism to the limits of invasive imaging modalities for identification and treatment of vulnerable plaques. They believe in the clinical usefulness of invasive imaging modalities for identification of vulnerable plaques, and are suggesting an explanation for the suboptimal results of past studies, that failed to demonstrate a correlation between interventional treatment of vulnerable plaques, and reduction of hard clinical endpoints. Vulnerability studies have been based, so far, on the detection and measurement of plaques lipid content, because of its ease. However, the search for lipid "lakes" as a single common causal feature of acute coronary syndromes does not seem sufficient to identify patients at risk of adverse events. New imaging studies provided the rationale for improving clinical outcomes, adopting a more comprehensive assessment of target plaque morphology. There is little rationale in pursuing a functional assessment of coronary lesions to predict myocardial infarction. Recent studies are further confirming this hypothesis, suggesting that the clinical benefit of the fractional flow reserve-guided strategy is simply due to a significant reduction in the rate of repeated revascularizations, with no significant differences in the incidence of hard endpoints. There is a need to develop new randomized studies, requiring a feasible number of patients, to test the superiority of an approach based on vulnerable plaque sealing and treatment.

Autoantibodies Against ApoB-100 as a New Marker of Coronary Vulnerable Plaque.

Autoantibodies Against ApoB-100 as a New Marker of Coronary Vulnerable Plaque.

Using optical coherence tomography and intravascular ultrasound imaging to quantify coronary plaque cap thickness and vulnerability: a pilot study

BackgroundDetecting coronary vulnerable plaques in vivo and assessing their vulnerability have been great challenges for clinicians and the research community. Intravascular ultrasound (IVUS) is commonly used in clinical practice for diagnosis and treatment decisions. However, due to IVUS limited resolution (about 150–200 µm), it is not sufficient to detect vulnerable plaques with a threshold cap thickness of 65 µm. Optical Coherence Tomography (OCT) has a resolution of 15–20 µm and can measure fibrous cap thickness more accurately. The aim of this study was to use OCT as the benchmark to obtain patient-specific coronary plaque cap thickness and evaluate the differences between OCT and IVUS fibrous cap quantifications. A cap index with integer values 0–4 was also introduced as a quantitative measure of plaque vulnerability to study plaque vulnerability.MethodsData from 10 patients (mean age: 70.4; m: 6; f: 4) with coronary heart disease who underwent IVUS, OCT, and angiography were collected at Cardiovascular Research Foundation (CRF) using approved protocol with informed consent obtained. 348 slices with lipid core and fibrous caps were selected for study. Convolutional Neural Network (CNN)-based and expert-based data segmentation were performed using established methods previously published. Cap thickness data were extracted to quantify differences between IVUS and OCT measurements.ResultsFor the 348 slices analyzed, the mean value difference between OCT and IVUS cap thickness measurements was 1.83% (p = 0.031). However, mean value of point-to-point differences was 35.76%. Comparing minimum cap thickness for each plaque, the mean value of the 20 plaque IVUS-OCT differences was 44.46%, ranging from 2.36% to 91.15%. For cap index values assigned to the 348 slices, the disagreement between OCT and IVUS assignments was 25%. However, for the OCT cap index = 2 and 3 groups, the disagreement rates were 91% and 80%, respectively. Furthermore, the observation of cap index changes from baseline to follow-up indicated that IVUS results differed from OCT by 80%.ConclusionsThese preliminary results demonstrated that there were significant differences between IVUS and OCT plaque cap thickness measurements. Large-scale patient studies are needed to confirm our findings.

Comparison of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol and total cholesterol/high-density lipoprotein cholesterol for the prediction of thin-cap fibroatheroma determined by intravascular optical coherence tomography.

BackgroundThe correlation among the ratios of low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/ HDL-C), total cholesterol/high-density lipoprotein cholesterol (TC/HDL-C) and thin-cap fibroatheroma has not yet been established.MethodsIt was a single center, retrospective observational study. In total, we recruited 421 patients (82.4% men; mean age 65.73 ± 10.44 years) with one culprit vessel which determined by intravascular optical coherence tomography (OCT). The thinnest-capped fibroatheroma (TCFA) group was defined as lipid contents in > 2 quadrants, with the thinnest fibrous cap measuring less than 65 μm. Univariate and multivariate logistic regression were carried out to explore the relationship between lipoprotein ratios, TCFA and other characteristics of plaque. To compare different ratios, the area under curve (AUC) of receiver-operating characteristic (ROC) curve was assessed.ResultsOCT was performed in 421 patients (TCFA group (n = 109), non-TCFA group (n = 312)). LDL-C/HDL-C in the TCFA group was significantly higher than in the non-TCFA group (2.95 ± 1.20 vs. 2.43 ± 0.92, P < 0.05), as was TC/LDL in TCFA and non-TCFA group (4.57 ± 1.58 vs. 4.04 ± 1.13, P < 0.05). Both LDL-C/HDL-C (OR: 1.002 (1.002-1.003), P < 0.05) and TC/HDL-C (OR: 1.001 (1.001-1.004), P < 0.05) were considered independent factors for the prediction of TCFA according to the logistic regression. Based on the AUC comparison, LDL-C/ HDL-C and TC/HDL-C had no significant difference statistically (LDL-C/HDL-C AUC: 0.63; TC/HDL-C AUC: 0.61; P = 0.10) for the prediction of TCFA.ConclusionsLDL-C/HDL-C and TC/HDL-C could be the independent factors for predicting the presence of TCFA, indicating coronary plaque vulnerability in CAD patients. Moreover, TC/HDL-C also showed a comparative performance for the prediction of TCFA as LDL-C/HDL-C.

Abstract 14318: Long Noncoding RNA Differentiation Antagonizing Non-protein Coding RNA 201 Ameliorates Endothelial Dysfunction via Sponging MicroRNA-216a

Background: Endothelial dysfunction contributes to the initiation of atherosclerosis, which has been associated with the long noncoding RNAs (lncRNAs). However, the role of lncRNAs in endothelial function remains largely unknown. This study aimed to investigate whether the differentiation antagonizing non-protein coding RNA 201 (DANCR201) regulated the endothelial function. Methods and Results: The whole transcriptome sequencing was conducted to identify differentially expressed lncRNAs in the peripheral blood from patients with coronary artery diseases who had coronary calcified plaques (n=10), vulnerable plaques (n=5), and control subjects without coronary plaques (n=10). The characteristics of plaques were determined by the coronary computed tomography angiography. The results showed that DANCR201 was significantly downregulated in patients with vulnerable plaques compared to those with calcified plaques and control subjects. The RNA fluorescence in situ hybridization showed that DANCR201 was localized in both cytoplasm and nuclei. Next, we assessed the role of DANCR201 in endothelial function. In the replicative aging model of human umbilical vein endothelial cells (HUVECs), DANCR201 was found to decrease in senescent passage 20 cells compared with young passage 3 cells. Furthermore, DANCR201 overexpression in HUVECs significantly repressed monocytes adhesion to endothelium, inhibited the expression of pro-inflammatory cytokines interleukin 1β, intercellular cell adhesion molecule 1, tumor necrosis factor α, and promoted the abilities of endothelial proliferation and migration, indicating that DANCR201 was a protective factor for endothelial function. Bioinformatics analysis of miRNA-lncRNA interactions indicated that DANCR201 contained a candidate binding sequence of miR-216a which had been reported to promote the endothelial dysfunction through NF-κB pathway. The luciferase assay further showed that DANCR201 specifically combined with miR-216a. Conclusions: Our data indicated that DANCR201 can improve endothelial function via sponging miR-216a, ultimately maintaining vascular normalization. DANCR201 maybe a potential therapeutic target for atherosclerotic plaque progression and instability.

Abstract 12976: Higher Triglyceride Level is Associated With Higher Frequency of Macrophage Accumulation in Coronary Plaques

Introduction: The impact of high triglyceride (TG) level on the characteristics of coronary plaque remains to be elucidated. Hypothesis: Higher TG level is associated with higher prevalence of vulnerable coronary plaque in patients with coronary artery disease (CAD). Methods: A total of 865 consecutive patients who underwent optical coherence tomography (OCT) imaging of the culprit lesion were included. Patients were classified into either the higher TG group (non-fasting TG ≥ 200 mg/dL, n=150) or the lower TG group (non-fasting TG &lt; 200 mg/dL, n=715). The morphologies of culprit plaque assessed by OCT were compared between the two groups. Results: The median (interquartile range) of TG in the 2 groups was 265.5 (221.5 – 314.8) mg/dL and 115.0 (84.0 – 152.0) mg/dL, respectively. The frequency of macrophage accumulation was significantly higher in the higher TG group than the lower TG group (41 vs. 33%, p=0.043) (Panel A), whereas the prevalence of other plaque components including thin-cap fibroatheroma (22 vs. 19%, p=0.386), microchannel (24 vs. 25%, p=0.907) and cholesterol crystal (23 vs. 23%, p=0.862) was comparable between the two groups. The incremental frequency of macrophage accumulation according to TG levels was observed (p=0.015, Panel B). Although the frequency of macrophage accumulation was comparable between the 2 groups among patients with a higher HDL cholesterol (HDL-C) level (&gt;35 mg/dL), macrophage accumulation was significantly more frequent in the higher TG group than in the lower TG group (71 vs. 41%, p=0.032) among patients with a lower HDL-C level (≤35 mg/dL). Conclusions: Higher TG level was associated with higher frequency of macrophage accumulation in culprit plaques in patients with CAD. The present results may partly explain the role of TG on the development of culprit plaque in coronary artery.

Impact of clinical presentations on lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI4mm). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI4mm in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI4mm in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.

Predictors of Coronary Plaque Vulnerability in Patients with Stable Coronary Artery Disease

Aim To identify new predictors for vulnerability of atherosclerotic coronary plaques in patients with stable ischemic heart disease (sIHD).Material and methods This prospective, single-center study included 58 patients with sIHD. Unstable plaques were detected with virtual histology intravascular ultrasound of proximal and medium segments of a coronary artery without significant lesions according to coronarography data. Indexes of inflammation, dyslipidemia and carbohydrate metabolism were considered as candidate predictors for coronary plaque vulnerability.Results In 56 coronary arteries, 58 plaques were detected, 12 of which (20.7 %) were unstable. Vulnerable plaques differed morphologically from stable ones by a greater size of the necrotic core (35.1±8.5 % vs. 24.0±13.2 %; р=0.008), calcified nodules (2.0 [1.0; 5.0] % vs. 1.0 [0; 2.0] %; р=0.006), and a lower content of fibrous components (54.9±10.2 % vs. 66.4±15.8 %; р=0.02). In addition, vulnerable plaques more frequently narrowed the arterial lumen by &gt;70 % of the lumen area (33.3 % vs. 2.2 %; р=0.0006). Correlation analysis showed a negative correlation between the level of high-density lipoproteins (HDL) and calcium volume (r= -0.4104; р=0.023); a positive correlation between the blood glucose level as determined by the oral glucose tolerance test and the lipid component (r=0.48198; р=0.033); and a negative correlation between the apolipoprotein A level and the calcium volume (r= -0.4297; р=0.008).Conclusion The study demonstrated a high prevalence of vulnerable plaques in nontarget coronary arteries in patients with sIHD. In this process, dyslipidemia indexes (LDL, apolipoproteins A) correlate with the calcium volume whereas blood glucose, as measured in the oral glucose tolerance test, correlates with the lipid component of coronary plaque.

Inhibition of PFKFB3 Hampers the Progression of Atherosclerosis and Promotes Plaque Stability.

Aims6-phosphofructo-2-kinase/fructose-2,6-biphosphatase (PFKFB)3-mediated glycolysis is pivotal in driving macrophage- and endothelial cell activation and thereby inflammation. Once activated, these cells play a crucial role in the progression of atherosclerosis. Here, we analyzed the expression of PFKFB3 in human atherosclerotic lesions and investigated the therapeutic potential of pharmacological inhibition of PFKFB3 in experimental atherosclerosis by using the glycolytic inhibitor PFK158.Methods and ResultsPFKFB3 expression was higher in vulnerable human atheromatous carotid plaques when compared to stable fibrous plaques and predominantly expressed in plaque macrophages and endothelial cells. Analysis of advanced plaques of human coronary arteries revealed a positive correlation of PFKFB3 expression with necrotic core area. To further investigate the role of PFKFB3 in atherosclerotic disease progression, we treated 6–8 weeks old male Ldlr–/– mice. These mice were fed a high cholesterol diet for 13 weeks, of which they were treated for 5 weeks with the glycolytic inhibitor PFK158 to block PFKFB3 activity. The incidence of fibrous cap atheroma (advanced plaques) was reduced in PFK158-treated mice. Plaque phenotype altered markedly as both necrotic core area and intraplaque apoptosis decreased. This coincided with thickening of the fibrous cap and increased plaque stability after PFK158 treatment. Concomitantly, we observed a decrease in glycolysis in peripheral blood mononuclear cells compared to the untreated group, which alludes that changes in the intracellular metabolism of monocyte and macrophages is advantageous for plaque stabilization.ConclusionHigh PFKFB3 expression is associated with vulnerable atheromatous human carotid and coronary plaques. In mice, high PFKFB3 expression is also associated with a vulnerable plaque phenotype, whereas inhibition of PFKFB3 activity leads to plaque stabilization. This data implies that inhibition of inducible glycolysis may reduce inflammation, which has the ability to subsequently attenuate atherogenesis.

The association between statin pre-treatment and LDL Levels on the rate of STEMI presentation: data from the ACS Israeli Survey (ACSIS) 2008–2018

Abstract Background ST-elevation myocardial infarction (STEMI) mostly occurs as a result of vulnerable coronary artery plaque rupture. Constituting hypolipidemic and pleiotropic effects, statins stabilize coronary artery plaque and may prevent STEMI events. Purpose To determine the association between statin pre-treatment and its intensity, low-density-lipoprotein cholesterol (LDL-C) levels and presentation of patients with an ACS (STEMI vs. NSTEMI/unstable angina [UAP]). Methods Data was drawn from the Acute Coronary Syndrome Israeli Survey (ACSIS), a biennial prospective survey of ACS patients hospitalized in all CCU/Cardiology departments during 2008–2018. The rate of STEMI vs NSTEMI/UAP at the time of presentation was calculated by LDL-C levels on admission, stratified to 5 subgroups (&amp;lt;50, 50–69, 70–100, 101–130 and &amp;gt;130 mg/dl) and the use of statins, including statin intensity prior to the index ACS event. Results Among 5,103 patients, 875 (17%) were pre-treated with high intensity statin (HIST), 1,389 (27%) with low intensity statin (LIST), and 2,839 (56%) were statin naive patients. Statin-pre-treated patients were older, more likely to suffer from co-morbidities and cardiovascular diseases and were more often pre-treated with anti-platelets. The proportion of patients presenting with STEMI vs. NSTEMI/UAP was significantly lower among HIST vs. LIST vs. statin naive patients (31.0%, 37.8%, 54.0%, respectively, p for trend &amp;lt;0.001). At each LDL-C level, the proportion of STEMI was significantly lower among HIST vs. LIST vs. statin naive patients. Multivariate analysis adjusting for pertinent variables including propensity score for statin use, revealed that HIST was independently associated with lower STEMI presentation, but LDL-C&amp;lt;70 and LIST were not. Conclusions Among patients admitted with ACS, pre-treatment with high intensity statin but not LDL-C level, was independently associated with a lower probability of presenting with STEMI. Funding Acknowledgement Type of funding source: None

Intracoronary polarimetry for characterizing coronary plaque vulnerability in patients with coronary artery disease

Abstract Background Intracoronary polarimetry with polarization-sensitive (PS-) optical frequency domain imaging (OFDI) measures polarization properties, including birefringence and depolarization, in parallel with structural features of conventional OFDI (Figure 1A). Collagen, which imparts mechanical integrity to fibrous caps, and collagen-synthesizing smooth muscle cells exhibit elevated birefringence. Depolarization is increased by the presence of macrophages and lipid/necrotic cores. Purpose This study aimed to compare conventional OFDI and polarimetric signatures of coronary lesions between patients with acute coronary syndrome (ACS) and chronic coronary syndrome (CCS). Furthermore, we aimed to determine a birefringence cut-off value for identifying which fibrous caps belong to ACS culprit lesions. Methods This study consisted of 37 patients with ACS (n=23) or CCS (n=14). ACS culprit lesions (ACS-lesions) and CCS stenotic lesions (CCS-lesions) were included in the analysis (820 mm). Qualitative and quantitative conventional OFDI analysis included the presence of plaque rupture, macrophage infiltration, micro-vessels, thrombus, stenosis severity, fibrous cap thickness (FCT), lipid arc, lipid-burden and calcium-burden index. Birefringence and depolarization of the coronary lesions and fibrous caps were measured in the cross-sectional images showing the minimum FCT or minimum luminal area. Predictors of ACS-lesions were investigated by multivariate regression analysis. Receiver operating characteristic (ROC) analysis was used to determine the birefringence cut-off value identifying ACS fibrous caps (ACS-caps). Results There were no significant differences in clinical characteristics between the two groups, except for previous history of coronary artery disease. Compared to CCS-lesions, ACS-lesions featured higher lipid-burden index and maximum lipid arc (both p&amp;lt;0.05). ACS-lesions featured lower birefringence and higher depolarization than CCS-lesions (p&amp;lt;0.05). Multivariable regression demonstrated an independent association of birefringence with ACS-lesions (p&amp;lt;0.05), even after adjusting for the conventional OFDI findings. Limiting the analysis to the fibrous caps, ACS-caps exhibited significantly lower birefringence (p&amp;lt;0.05) and higher depolarization (p&amp;lt;0.05) that CCS-caps. ROC analysis for differentiating ACS-caps from CCS-caps found that a birefringence value of 0.0004 results in a sensitivity and specificity of 88% and 82%, respectively (Figure 1B, AUC = 0.82). Conclusions Intracoronary polarimetry provides quantitative assessment of coronary lesions related to their composition. Birefringence was an independent robust predictor of ACS-lesions. Decreased birefringence and pronounced depolarization within the ACS-caps may indicate increased collagenolytic activity and macrophage infiltration, respectively. These results suggest that polarization properties may serve as quantitative imaging markers for assessing plaque vulnerability. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): This work was supported by the National Institutes of Health and by Terumo Corporation.

Intensive statin versus low-dose statin + ezetimibe treatment for fibrous cap thickness of coronary vulnerable plaques.

BackgroundAcute coronary syndromes mainly result from abrupt thrombotic occlusion caused by atherosclerotic vulnerable plaques (VPs) that suddenly rupture or erosion. Fibrous cap thickness (FCT) is a major determinant of the propensity of a VP to rupture and is recognized as a key factor. The intensive use of statins is known to have the ability to increase FCT; however, there is a risk of additional adverse effects. However, lower dose statin with ezetimibe is known to be tolerable by patients. The present study aimed to investigate the effect of intensive statin vs. low-dose stain + ezetimibe therapy on FCT, as evaluated using optical coherence tomography.MethodPatients who had VPs (minimum FCT <65 μm and lipid core >90°) and deferred from intervention in our single center from January 2014 to December 2018 were included in the trial. They were divided into the following two groups: intensive statin group (rosuvastatin 15–20 mg or atorvastatin 30–40 mg) and combination therapy group (rosuvastatin 5–10 mg or atorvastatin 10–20 mg + ezetimibe 10 mg). At the 12-month follow-up, we compared the change in the FCT (ΔFCT%) between the two groups and analyzed the association of ΔFCT% with risk factors. Fisher exact test was used for all categorical variables. Student's t test or Mann-Whitney U-test was used for analyzing the continuous data. The relationship between ΔFCT% and risk factors was analyzed using linear regression analysis.ResultTotal 53 patients were finally enrolled, including 26 patients who were in the intensive statin group and 27 who were in the combination therapy group. At the 12-month follow-up, the serum levels of total cholesterol (TC), total triglyceride, low-density lipoprotein (LDL-C), hypersensitive C-reactive protein (hs-CRP), and lipoprotein-associated phospholipase A2 (Lp-PLA2) levels were reduced in both the groups. The ΔTC%, ΔLDL-C%, and ΔLp-PLA2% were decreased further in the combination therapy group. FCT was increased in both the groups (combination treatment group vs. intensive statin group: 128.89 ± 7.64 vs. 110.19 ± 7.00 μm, t = −9.282, P < 0.001) at the 12-month follow-up. The increase in ΔFCT% was more in the combination therapy group (123.46% ± 14.05% vs. 91.14% ± 11.68%, t = −9.085, P < 0.001). Based on the multivariate linear regression analysis, only the serum Lp-PLA2 at the 12-month follow-up (B = −0.203, t = −2.701, P = 0.010), ΔTC% (B = −0.573, t = −2.048, P = 0.046), and Δhs-CRP% (B = −0.302, t = −2.963, P = 0.005) showed an independent association with ΔFCT%.ConclusionsLow-dose statin combined with ezetimibe therapy maybe provide a profound and significant increase in FCT as compared to intensive statin monotherapy. The reductions in Lp-PLA2, ΔTC%, and Δhs-CRP% are independently associated with an increase in FCT.

Effect of Evolocumab on Vulnerable Coronary Plaques: A Serial Coronary Computed Tomography Angiography Study

This study investigated the effects of evolocumab on vulnerable coronary plaques and factors associated with the change in stability and size of plaques in patients taking statins. Vulnerable coronary plaques were defined using coronary computed tomography (CT) angiography as having a density of <50 HU within the region of interest and a remodeling index ≥1.1. The changes in minimum CT density, remodeling index, and percent stenosis of vulnerable coronary plaques after six months of evolocumab administration were retrospectively analyzed in 136 vulnerable coronary plaques from 98 patients (68 men and 30 women; mean age: 72.9 ± 8.7 years) treated with a statin. The administration of evolocumab significantly increased the minimum CT density (39.1 ± 8.1 HU to 84.9 ± 31.4 HU, p < 0.001), reduced the remodeling index (1.29 ± 0.11 to 1.19 ± 0.10, p < 0.001), and decreased the percent stenosis (27.0 ± 10.4% to 21.2 ± 9.8%, p < 0.001). Multiple linear regression analysis revealed that baseline percent stenosis (standard coefficient (β) = −0.391, p = 0.002) independently correlated with the change in minimum CT density, whereas the baseline remodeling index (β = −0.368, p < 0.001) independently correlated with a change in the remodeling index. Evolocumab stabilized vulnerable coronary plaques and reduced their size. These results suggest that evolocumab protects against coronary artery disease progression in patients taking statins.

Relationship between monocyte/lymphocyte ratio and non-culprit plaque vulnerability in patients with acute coronary syndrome: An optical coherence tomography study.

The importance of monocyte/lymphocyte ratio (MLR) has been indicated in the initiation and progression of coronary artery disease. However, few previous researches demonstrated the relationship between MLR and plaque vulnerability. We aimed to investigate coronary non-culprit plaque vulnerability in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT).A total of 72 ACS patients who underwent coronary angiography and OCT test in Beijing Anzhen Hospital were included in this retrospective study. The plaque vulnerability and plaque morphology were assessed by OCT.The non-culprit plaque in high MLR group exhibited more vulnerable features, characterizing as thinner thickness of fibrous cap (P = .013), greater maximum lipid core angle (P = .010) and longer lipid plaque length (P = .041). A prominently negative liner relation was found between MLR and thickness of fibrous cap (R = –0.225, P = .005). Meanwhile, the proportion of OCT-detected thin cap fibro-atheroma (TCFA) (P = .014) and plaque rupture (P = .017) were higher in high MLR group. Most importantly, multivariable logistic regression analysis showed MLR level was identified as an independent contributor to the presence of TCFA (OR:3.316, 95%: 1.448–7.593, P = .005). MLR could differentiate TCFA with a sensitivity of 60.0% and a specificity of 85.1%.Circulating MLR level has potential value in identifying the presence of vulnerable plaque in patients with ACS. MLR, as a non- invasive biomarker of inflammation, may be valuable in revealing plaque vulnerability.

Association between food and nutrients intakes and coronary plaque vulnerability in patients with coronary heart disease: An optical coherence tomography study

Background and aimsDietary intakes play important roles in the prevention and treatment of coronary heart disease (CHD). Coronary plaque vulnerability is the key mechanism leading to CHD progression. We aimed to explore the association between dietary intakes and plaque vulnerability via optical coherence tomography (OCT). Methods and resultsA total of 314 CHD patients were included in this study. Dietary intake status was assessed by semi-quantitative food frequency questionnaire and plaque vulnerability was measured by OCT. The results showed that vegetables were negatively associated with macrophage infiltration, thin cap fibroatheroma (TCFA) and thrombus [odds ratio (OR) = 0.48, 0.38, 0.38, 95% confidence interval (95% CI) = 0.24–0.93, 0.17–0.84, 0.15–0.94, all P < 0.05]; fruits were negatively associated with lipid plaque, TCFA, rupture and thrombus (OR = 0.17, 0.11, 0.12, 0.20, 95% CI = 0.07–0.39, 0.04–0.29, 0.05–0.28, 0.08–0.55, all P < 0.05); salt was positively associated with lipid plaque and TCFA (OR = 2.59, 2.83, 95% CI = 1.14–5.90, 1.23–6.51, all P < 0.05). Regarding nutrients intakes, dietary fiber was negatively associated with macrophage infiltration (OR = 0.34, 95% CI = 0.14–0.85, P = 0.021); folate was negatively associated with lipid plaque, TCFA and rupture (OR = 0.22, 0.16, 0.20, 95% CI = 0.09–0.58, 0.06–0.41, 0.08–0.51, all P < 0.05); vitamin C was negatively associated with TCFA, rupture and thrombus (OR = 0.26, 0.22, 0.05, 95% CI = 0.07–0.95, 0.07–0.65, 0.01–0.25, all P < 0.05); sodium was positively associated with lipid plaque, TCFA, rupture and thrombus (OR = 3.43, 3.96, 2.73, 4.84, 95% CI = 1.51–7.80, 1.66–9.45, 1.18–6.27, 1.76–9.28, all P < 0.05). ConclusionSalt and sodium were dietary risk factors for plaque vulnerability, whereas vegetables, fruits, dietary fiber, folate and vitamin C were dietary protective factors for plaque vulnerability.

Automated classification of coronary plaque calcification in OCT pullbacks with 3D deep neural networks.

.Significance: Detection and characterization of coronary atherosclerotic plaques often need reviews of a large number of optical coherence tomography (OCT) imaging slices to make a clinical decision. However, it is a challenge to manually review all the slices and consider the interrelationship between adjacent slices.Approach: Inspired by the recent success of deep convolutional network on the classification of medical images, we proposed a ResNet-3D network for classification of coronary plaque calcification in OCT pullbacks. The ResNet-3D network was initialized with a trained ResNet-50 network and a three-dimensional convolution filter filled with zeros padding and non-zeros padding with a convolutional filter. To retrain ResNet-50, we used a dataset of OCT images, derived by 18 entire pullbacks from different patients. In addition, we investigated a two-phase training method to address the data imbalance. For an improved performance, we evaluated different input sizes for the ResNet-3D network, such as 3, 5, and 7 OCT slices. Furthermore, we integrated all ResNet-3D results by majority voting.Results: A comparative analysis proved the effectiveness of the proposed ResNet-3D networks against ResNet-2D network in the OCT dataset. The classification performance ( for non-zeros padding and for zeros padding) demonstrated the potential of convolutional neural networks (CNNs) in classifying plaque calcification.Conclusions: This work may provide a foundation for further work in extending the CNN to voxel segmentation, which may lead to a supportive diagnostic tool for assessment of coronary plaque vulnerability.

The investigation and prognosis in patients with non-alcoholic fatty liver disease and coronary vulnerable plaque

Objective: To investigate the prevalence and prognosis of non-alcoholic fatty liver disease (NAFLD) complicated with coronary vulnerable plaque (VP). Method: Consecutive patients were included who had undergone coronary artery CT angiography (CCTA) from January 1, 2011 to January 30, 2015 at the First People's Hospital of Neijiang. NAFLD was diagnosed according to the liver imaging findings (liver/spleen CT ratio≤1.0) and clinical data. Baseline data, diagnosis, vulnerable plaque were recorded and followed up. The end points included all-cause death rate, cardiac death rate, non-fatal myocardial infarction rate, and elective coronary revascularization rate. Result: A total of 1 069 patients were eventually recruited in this study, including 316 (29.6%) cases diagnosed as NAFLD. In patients with NAFLD, 130 (41.1%) cases had vulnerable plaque, which was significantly higher than 217 of 753 non-NAFLD patients (28.8%) (P<0.01). The percentages of spotty calcification, low attenuation plaque, positive remodeling and napkin ring sign in NAFLD cohort were 36.5%, 14.2%, 17.6% and 6.8% respectively, while those corresponding in non-NAFLD cohort were 18.4%, 6.3%, 5.8% and 3.2% respectively. The proportion of each vulnerable feature in NAFLD cohort was significantly higher than that in the non-NAFLD cohort, with P values of 0.016, 0.028, 0.019 and 0.042, respectively. The cardiac mortality rate in NAFLD group was significantly higher than and that of non-NAFLD group (7.0% vs. 3.6%, P=0.044). Multivariate Cox analysis suggested that NAFLD was not an independent risk factor for cardiac death. NAFLD subgroup (n=316) was divided into VP positive group (NAFLD+VP+, n=130) and VP negative group (NAFLD+VP-, n=186). The mean follow-up time was 4.6±1.3 years. All-cause mortality rate, cardiac death rate, elective coronary artery reconstruction rate, non-fatal myocardial infarction rate in NAFLD+VP+group were 20.8%, 12.3%, 25.4%, 13.8% respectively, which were significantly higher than those corresponding rates in NAFLD+VP-group (5.9%, 3.2%, 8.6%, 6.5%) (P<0.01, 0.002,<0.01, and 0.032 respectively). Conclusion: The incidences of cardiac mortality, elective coronary revascularization, and non-fatal myocardial infarction are significantly higher in patients with NAFLD than those without. NAFLD combined with vulnerable plaque of coronary arteries predicts worse prognosis.

Using intravascular ultrasound image-based fluid-structure interaction models and machine learning methods to predict human coronary plaque vulnerability change

Plaque vulnerability prediction is of great importance in cardiovascular research. In vivo follow-up intravascular ultrasound (IVUS) coronary plaque data were acquired from nine patients to construct fluid-structure interaction models to obtain plaque biomechanical conditions. Morphological plaque vulnerability index (MPVI) was defined to measure plaque vulnerability. The generalized linear mixed regression model (GLMM), support vector machine (SVM) and random forest (RF) were introduced to predict MPVI change (ΔMPVI = MPVIfollow-up‒MPVIbaseline) using ten risk factors at baseline. The combination of mean wall thickness, lumen area, plaque area, critical plaque wall stress, and MPVI was the best predictor using RF with the highest prediction accuracy 91.47%, compared to 90.78% from SVM, and 85.56% from GLMM. Machine learning method (RF) improved the prediction accuracy by 5.91% over that from GLMM. MPVI was the best single risk factor using both GLMM (82.09%) and RF (78.53%) while plaque area was the best using SVM (81.29%).