Plaque Vulnerability In Patients Research Articles

A novel radiomics-based technique for identifying vulnerable coronary plaques: a follow-up study.

Previous reports have suggested that coronary computed tomography angiography (CCTA)-based radiomics analysis is a potentially helpful tool for assessing vulnerable plaques. We aimed to investigate whether coronary radiomic analysis of CCTA images could identify vulnerable plaques in patients with stable angina pectoris. This retrospective study included patients initially diagnosed with stable angina pectoris. Patients were randomly divided into either the training or test dataset at an 8 : 2 ratio. Radiomics features were extracted from CCTA images. Radiomics models for predicting vulnerable plaques were developed using the support vector machine (SVM) algorithm. The model performance was assessed using the area under the curve (AUC); the accuracy, sensitivity, and specificity were calculated to compare the diagnostic performance using the two cohorts. A total of 158 patients were included in the analysis. The SVM radiomics model performed well in predicting vulnerable plaques, with AUC values of 0.977 and 0.875 for the training and test cohorts, respectively. With optimal cutoff values, the radiomics model showed accuracies of 0.91 and 0.882 in the training and test cohorts, respectively. Although further larger population studies are necessary, this novel CCTA radiomics model may identify vulnerable plaques in patients with stable angina pectoris.

Serum secreted phosphoprotein 1 level is associated with plaque vulnerability in patients with coronary artery disease.

Vulnerable plaque was associated with recurrent cardiovascular events. This study was designed to explore predictive biomarkers of vulnerable plaque in patients with coronary artery disease. To reveal the phenotype-associated cell type in the development of vulnerable plaque and to identify hub gene for pathological process, we combined single-cell RNA and bulk RNA sequencing datasets of human atherosclerotic plaques using Single-Cell Identification of Subpopulations with Bulk Sample Phenotype Correlation (Scissor) and Weighted gene co-expression network analysis (WGCNA). We also validated our results in an independent cohort of patients by using intravascular ultrasound during coronary angiography. Macrophages were found to be strongly correlated with plaque vulnerability while vascular smooth muscle cell (VSMC), fibrochondrocyte (FC) and intermediate cell state (ICS) clusters were negatively associated with unstable plaque. Weighted gene co-expression network analysis showed that Secreted Phosphoprotein 1 (SPP1) in the turquoise module was highly correlated with both the gene module and the clinical traits. In a total of 593 patients, serum levels of SPP1 were significantly higher in patients with vulnerable plaques than those with stable plaque (113.21 [73.65 - 147.70] ng/ml versus 71.08 [20.64 - 135.68] ng/ml; P < 0.001). Adjusted multivariate regression analysis revealed that serum SPP1 was an independent determinant of the presence of vulnerable plaque. Receiver operating characteristic curve analysis indicated that the area under the curve was 0.737 (95% CI 0.697 - 0.773; P < 0.001) for adding serum SPP1 in predicting of vulnerable plaques. Elevated serum SPP1 levels confer an increased risk for plaque vulnerability in patients with coronary artery disease.

Protruding Aortic Plaque and Coronary Plaque Vulnerability.

Protruding aortic plaque is known to be associated with an increased risk for future cardiac and cerebrovascular events. However, the relationship between protruding aortic plaque and coronary plaque characteristics has not been systematically investigated. A total of 615 patients who underwent computed tomography angiography, and preintervention optical coherence tomography imaging were included. Coronary plaque characteristics were compared to evaluate coronary plaque vulnerability in patients with protruding aortic plaque on computed tomography angiography. 615 patients, the 186 (30.2%) patients with protruding aortic plaque were older and had more comorbidities such as hypertension, chronic kidney disease, and a prior myocardial infarction than those without. They also had a higher prevalence of coronary plaques with vulnerable features such as thin-cap fibroatheroma (85 [45.7%] versus 120 [28.0%], P<0.001), lipid-rich plaque (165 [88.7%] versus 346 [80.7%], P=0.014), macrophages (147 [79.0%] versus 294 [68.5%], P=0.008), layered plaque (117 [62.9%] versus 213 [49.7%], P=0.002), and plaque rupture (96 [51.6%] versus 111 [25.9%], P<0.001). Patients with protruding aortic plaque experienced more major adverse cardiac and cerebrovascular events, including all-cause mortality, nonfatal acute coronary syndromes, and stroke (27 [14.7%] versus 21 [4.9%], P<0.001; 8 [4.3%] versus 1 [0.2%], P<0.001; 5 [2.7%] versus 3 [0.7%], P=0.030; and 5 [2.7%] versus 2 [0.5%], P=0.013, respectively). The current study demonstrates that patients with protruding aortic plaque have more features of coronary plaque vulnerability and are at increased risk of future adverse events.

Anti-Lipoprotein Lipase Antibody as a Useful Marker for Plaque Vulnerability in Patients with Stable Angina.

Identifying patients with vulnerable plaque who have poor prognosis among those with coronary artery disease (CAD) is crucial to deciding future therapeutic interventions. We previously reported that male CAD patients with low anti-apolipoprotein B-100 autoantibody (anti-apoB-100 Ab) levels were at an increased risk of developing unstable plaque lesions. This study focused on the autoantibodies against lipoprotein lipase (LPL), a key enzyme in triglyceride metabolism, which is another risk factor for atherosclerosis, and investigated their association with plaque characteristics. We measured serum anti-LPL Ab levels using a homemade enzyme-linked immunosorbent assay in 80 male CAD patients. Coronary plaque properties were evaluated using iMAP®-intravascular ultrasound. Serum anti-LPL Ab levels were not correlated with plaque burden but were significantly negatively and positively correlated with fibrotic and necrotic plaques, respectively. High-risk patients with low anti-apoB-100 Ab levels were divided into groups according to their anti-LPL Ab levels. The group with high anti-LPL Ab levels exhibited more necrotic plaques and fewer fibrotic plaques as well as higher remnant-like lipoprotein particle levels than the group with low anti-LPL Ab levels. Serum anti-LPL Ab levels can serve as a marker of plaque instability in CAD patients and can help identify higher-risk cases when combined with anti-apoB-100 Ab levels.

Abstract 15654: Layered Plaques and Plaque Vulnerability in Patients With Stable Angina Pectoris

Backgrounds: Layered plaque, a signature of previous plaque destabilization and healing, is one of the predictors for rapid plaque progression, the mechanism of which is unknown. Aims: To investigate the level of vascular inflammation and plaque vulnerability in layered plaques to elucidate possible mechanisms of rapid plaque progression. Methods: Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) were selected. Plaques were defined as any tissue (noncalcified, calcified, or mixed) within or adjacent to the lumen. Pericoronary adipose tissue (PCAT) attenuation was measured at the plaque level on CTA. OCT features of plaque vulnerability were assessed at the corresponding site. Results: A total of 475 plaques from 195 patients presented with stable angina pectoris were included. Layered plaques (n=241), compared to non-layered plaques (n=234), had a higher level of vascular inflammation (-70.94 [-77.86, -64.66] HU vs. -73.52 [-80.83, -67.66] HU, P=0.014, Figure 1). Layered plaques also had a higher prevalence of the features of plaque vulnerability (Figure 2), including lipid-rich plaque (83.8% vs. 66.7%, P&lt;0.001), thin-cap fibroatheroma (TCFA) (26.1% vs. 17.5%, P=0.026), microchannel (61.8% vs. 34.6%, P&lt;0.001), and cholesterol crystal (38.6% vs. 25.6%, P=0.003). Conclusions: Layered plaque was associated with higher levels of vascular inflammation and plaque vulnerability, which might play an important role in plaque progression.

Abstract 16132: Cardiometabolic Risk Factors and Non-Culprit Plaque Characteristics in Patients With STEMI in REAL-TIMI 63B

Introduction: Greater non-calcified plaque volume (NCPV) measured by coronary CT angiography (CCTA) is associated with higher risk of future myocardial infarction in stable patients. However, NCPV and associations with clinical characteristics in patients presenting with a first acute STEMI are not well described. Methods: The REAL-TIMI 63B trial randomized 593 patients with no prior MI presenting with acute STEMI to intravenous recombinant human lecithin-cholesterol acyltransferase (MEDI6012) or placebo; a subset were to undergo CCTA 48-72h after STEMI. Global NCPV, low-attenuation PV (LAPV), and calcified PV (CPV) were measured by a centralized core laboratory blinded to treatment arm. Revascularized segments were excluded from coronary plaque quantification. Results: 188 patients had a CCTA performed at baseline. Of these, 80.3% had NCPV and 77.4% had LAPV outside of the revascularized segments. Median NCPV was 28.4mm 3 [IQR 1.4-92.1], LAPV 3.8mm 3 [0.1-14.9], and CPV 92.4mm 3 [22.6-201.8]. Among the characteristics examined, male vs. female sex (51.3 mm 3 [3.47-100.3] vs 5.6 mm 3 [0.0-17.3]; p=0.0003), BMI &gt;25 kg/m 2 (overweight or obese) (41.20 mm 3 [2.01-104.50] vs 10.98 mm 3 (0.0-61.5); p=0.01) and diabetes (82.6 mm 3 [59.0-123.4] vs 24.2 mm 3 [1.21-85.2]; p=0.038) were associated with greater NCPV (Figure). Conclusions: Among patients with no prior MI undergoing primary PCI for STEMI, we found that most patients had NCPV and LAPV outside the culprit lesion. Male sex and markers of cardiometabolic disease including higher BMI and diabetes were associated with a greater burden of NCPV. These observations underscore the need for intensive medical therapies that may stabilize vulnerable plaque in patients presenting with acute myocardial infarction.

Association of LDL-C level with neoatherosclerosis and plaque vulnerability in patients with late restenosis: an optical coherence tomography study

Neoatherosclerosis (NA) is a significant contributor to late stent failure; however, predictors of late in-stent restenosis (ISR) with NA have not been systematically reported. This study aimed to identify predictors of NA incidence and plaque vulnerability in patients with late ISR and the role of low-density lipoprotein cholesterol (LDL-C) levels in this process. A total of 216 patients with 216 lesions who underwent optical coherence tomography (OCT) before interventional procedure for late drug-eluting stent ISR were enrolled and divided into NA and non-NA groups based on OCT findings. Results showed that higher LDL-C levels were associated with NA, thin-cap fibroatheroma (TCFA), intimal disruption, plaque erosion, and thrombosis. Multivariate regression analysis revealed that the LDL-C level was an independent risk factor for NA and TCFA. The LDL-C levels exhibited a significant predictive value for NA and TCFA, surpassing other factors such as stent age and other lipid types. In conclusion, a high LDL-C level is an independent predictor of NA incidence and plaque vulnerability in patients with late ISR.

Comparison of Atherosclerotic Plaque Compositions in Diabetic and Non-diabetic Patients.

Diabetes mellitus is one of the major risk factors for coronary artery disease. Intravascular ultrasound(IVUS)imaging has an important role in the evaluation of atherosclerotic coronary artery disease. The aim of the study was to investigate the potential link between diabetes mellitus and plaque vulnerability in patients with coronary artery disease. In total, 26 patients with acute coronary syndrome (eight with diabetes mellitus) and 34 with stable angina pectoris (16 with diabetes mellitus) constituted the study population. Patients underwent IVUS ultrasound and virtual histology (VH)-IVUS imaging during routine diagnostic catheterization procedures. A total of 70 plaques in 60 patients were examined. Patients with diabetes mellitus had a significantly greater percentage of fibrofatty components in the minimal lumen area (MLA) (17± 12 in diabetics; 12± 6 in non-diabetics; p=0.06). Thin-cap fibroatheromaswere more frequent in patients with diabetes mellitus (72% versus 45%; p=0.012). There was a positive correlation between the presence of attenuated plaque and hemoglobin A1C (HbA1c) levels as well (7.09 ± 1.66 versus 6.02 ± 1.00; p=0.011). Patients with HbA1C ≥7.5% also had the highest prevalence of attenuated plaque. As shown by VH-IVUS, the prevalence of vulnerable plaques in patients with diabetes mellitus was much higher than that in non-diabetic patients. The presence of attenuated plaque detected in grayscale intravascular ultrasonography was associated with high HbA1C levels in diabetic patients. Diabetes mellitus may cause cardiovascular vulnerability by changing the plaque morphology.

Assessment of vasa vasorum on coronary plaques in patients with acute coronary syndromes using intravascular ultrasound and iMap analysis: A retrospective cohort study.

Studies have revealed that vasa vasorum (VV) neovascularization is vital for the progression and vulnerability of coronary atherosclerotic plaques. The correlation between VV, plaque constituents, and the no-reflow phenomenon (NRP) in percutaneous coronary intervention (PCI) remains elusive. We explored plaque constituents in iMap-intravascular ultrasound (iMap-IVUS) and NRP during PCI for VV lesions. We studied 166 coronary lesions in 166 patients with acute coronary syndromes (ACS) (118 lesions with VV) undergoing pre-intervention intravascular ultrasound (IVUS). We evaluated the diversity in plaque morphological status and post-PCI results based on the presence or absence of VV. The lesions with VV group had significantly higher high-sensitivity C-reactive protein (hs-CRP) levels than the lesions without VV group (8.41 ± 4.98 vs 4.19 ± 3.69 mg/L, P < .001). The frequency of after-stent deployment thrombolysis in myocardial infarction (TIMI) flow grades 0, 1, and 2 was remarkably greater in lesions with VV than in those without VV (22.9% vs 10.4%, P < .001). Plaques at the minimum lumen, necrotic core (1.26 ± 0.64 vs 0.92 ± 0.61 mm2, P < .001; 20.95 ± 7.19 vs 13.34% ± 6.54%, P < .001), and fibrous areas (4.23 ± 1.32 vs 3.92 ± 1.01 mm2, P = .006; 61.01 ± 9.41 vs 56.92% ± 11.42%, P = .001) were considerably larger in the lesions with VV than in those without VV. In addition, densely calcified plaques (0.41 ± 0.26 vs 0.81 ± 0.59 mm2, P < .001; 3.63 ± 2.19 vs 7.18% ± 2.01%, P < .001) were considerably smaller in the lesions with VV than in those without VV. Multivariate analyses revealed that VV and plaque volume were independent predictors of NRP after stent deployment (odds ratio [OR]: 5.13, 95% confidence interval [CI]: 1.19-15.32, P = .002; OR: 4.79, 95% CI: 1.08-9.01, P = .005). Lesions with VV exhibited considerable plaque vulnerability in patients with ACS, and they displayed more NRP during PCI. VV and plaque volume were independent predictors of NRP after stent deployment.

Potential circulating biomarkers of atherosclerotic plaque vulnerability in patients in the early recovery period of atherothrombotic stroke

Despite the informative value of ultrasound examination of atherosclerotic vascular lesions, predicting­ the plaque vulnerabili­ty remains difficult. Circulating blood biomarkers could provide additional criteria that would allow better determination of the risk of recurrent stroke. The aim of our study was to estimate the level of C-reactive protein (CRP), low-density lipoproteins (LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) in the blood of patients in the early recovery period of atherothrombotic stroke depending on the density of atherosclerotic plaque according to duplex scanning of cerebral vessels. Clinical and laboratory analysis of 69 men and 61 women aged (60.42 ± 7.40) years in the early recovery period of atherothrombotic stroke was conducted. Depending on the structure of the atherosclerotic plaque the examinees were divided into two groups with stable (n = 80) and unstable (n = 50) atherosclerotic layers. The blood lipid spectrum was examined on a biochemical analyzer Screen master, the level of CRP was determined with a diagnostic kit and that of Lp-PLA2 by ELISA. Significantly higher levels of LDL, CRP and Lp-PLA2 were observed in patients with unstable atherosclerotic plaque compared to patients with stable atherosclerotic plaque in the early recovery period of atherothrombotic stroke. The increased level of LDL, CRP, and Lp-PLA2 in patients with cerebral atherosclerosis can be considered as an indicator of the vulnerability of atherosclerotic plaques, prone to rupture, and as a prognostic marker of repeated acute ischemic events. Keywords: atherosclerotic plaque, C-reactive protein, lipoprotein-associated phospholipase A2, low density lipoproteins, recovery period of ischemic stroke

Assessment of myocardial bridging and the pericoronary fat attenuation index on coronary computed tomography angiography: predicting coronary artery disease risk

BackgroundThe fat attenuation index (FAI) is a radiological parameter that represents pericoronary adipose tissue (PCAT) inflammation, along with myocardial bridging (MB), which leads to pathological shear stress in the coronary vessels; both are associated with coronary atherosclerosis. In the present study, we assessed the predictive value of FAI values and MB parameters through coronary computed tomography angiography (CCTA) for predicting the risk of coronary atherosclerosis and vulnerable plaque in patients with MB.MethodsWe included 428 patients who underwent CCTA and were diagnosed with MB. FAI values, MB parameters, and high-risk coronary plaque (HRP) characteristics were recorded. The subjects were classified into two groups (A and B) according to the absence or presence of coronary plaque in the segment proximal to the MB. Group B was further divided into Groups B1 (HRP-positive) and B2 (HRP-negative) according to the HRP characteristic classification method. The differences among the groups were analysed. Multiple logistic regression analysis was performed to determine the independent correlation between FAI values and MB parameters and coronary atherosclerosis and vulnerable plaque risk.ResultsCompared to the subjects in Group A, those in Group B presented greater MB lengths, MB depths and muscle index values, more severe MB systolic stenosis and higher FAIlesion values (all P < 0.05). In multivariate logistic analysis, age (OR 1.076, P < 0.001), MB systolic stenosis (OR 1.102, P < 0.001) and FAIlesion values (OR 1.502, P < 0.001) were independent risk factors for the occurrence of coronary atherosclerosis. Compared to subjects in Group B2, those in Group B1 presented greater MB lengths and higher FAI values (both P < 0.05). However, only the FAIlesion value was an independent factor for predicting HRP (OR 1.641, P < 0.001).ConclusionIn patients with MB, MB systolic stenosis was associated with coronary plaque occurrence in the segment proximal to the MB. The FAI value was not only closely related to coronary atherosclerosis occurrence but also associated with plaque vulnerability. FAI values may provide more significant value in the prediction of coronary atherosclerosis than MB parameters in CCTA.

Inflammation, Microcalcification, and Increased Expression of Osteopontin Are Histological Hallmarks of Plaque Vulnerability in Patients with Advanced Carotid Artery Stenosis

severe carotid artery stenosis is a major cause of ischemic stroke and consequent neurological deficits. The most important steps of atherosclerotic plaque development, leading to carotid stenosis, are well-known; however, their exact timeline and intricate causal relationships need to be more characterized. in a cohort of 119 patients, who underwent carotid endarterectomy, we studied the histological correlations between arterial calcification patterns and localization, the presence of the inflammatory infiltrate and osteopontin expression, with ulceration, thrombosis, and intra-plaque hemorrhage, as direct signs of vulnerability. in patients with an inflammatory infiltrate, aphasia was more prevalent, and microcalcification, superficial calcification, and high-grade osteopontin expression were characteristic. Higher osteopontin expression was also correlated with the presence of a lipid core. Inflammation and microcalcification were significantly associated with plaque ulceration in logistic regression models; furthermore, ulceration and the inflammatory infiltrate were significant determinants of atherothrombosis. our results bring histological evidence for the critically important role of microcalcification and inflammatory cell invasion in the formation and destabilization of advanced carotid plaques. In addition, as a calcification organizer, high-grade osteopontin expression is associated with ulceration, the presence of a large lipid core, and may also have an intrinsic role in plaque progression.

Electronegative LDL Is Associated with Plaque Vulnerability in Patients with Ischemic Stroke and Carotid Atherosclerosis

Owing to the high risk of recurrence, identifying indicators of carotid plaque vulnerability in atherothrombotic ischemic stroke is essential. In this study, we aimed to identify modified LDLs and antioxidant enzymes associated with plaque vulnerability in plasma from patients with a recent ischemic stroke and carotid atherosclerosis. Patients underwent an ultrasound, a CT-angiography, and an 18F-FDG PET. A blood sample was obtained from patients (n = 64, 57.8% with stenosis ≥50%) and healthy controls (n = 24). Compared to the controls, patients showed lower levels of total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B (apoB), apoA-I, apoA-II, and apoE, and higher levels of apoJ. Patients showed lower platelet-activating factor acetylhydrolase (PAF-AH) and paraoxonase-1 (PON-1) enzymatic activities in HDL, and higher plasma levels of oxidized LDL (oxLDL) and electronegative LDL (LDL(-)). The only difference between patients with stenosis ≥50% and <50% was the proportion of LDL(-). In a multivariable logistic regression analysis, the levels of LDL(-), but not of oxLDL, were independently associated with the degree of carotid stenosis (OR: 5.40, CI: 1.15-25.44, p < 0.033), the presence of hypoechoic plaque (OR: 7.52, CI: 1.26-44.83, p < 0.027), and of diffuse neovessels (OR: 10.77, CI: 1.21-95.93, p < 0.033), indicating that an increased proportion of LDL(-) is associated with vulnerable atherosclerotic plaque.

Differences in left and right carotid plaque vulnerability in patients with bilateral carotid plaques: a CARE-II study

Background and purposeAtherosclerosis is a very complex process influenced by various systemic and local factors. Therefore, in patients with bilateral carotid plaques (BCPs), there may be differences in carotid plaque...

Radial wall strain: a novel angiographic measure of plaque composition and vulnerability.

The lipid-to-cap ratio (LCR) and thin-cap fibroatheroma (TCFA) derived from optical coherence tomography (OCT) are indicative of plaque vulnerability. We aimed to explore the association of a novel method to estimate radial wall strain (RWS) from angiography with plaque composition and features of vulnerability assessed by OCT. Anonymised data from patients with intermediate stenosis who underwent coronary angiography (CAG) and OCT were analysed in a core laboratory. Angiography-derived RWSmax was computed as the maximum deformation of lumen diameter throughout the cardiac cycle, expressed as a percentage of the largest lumen diameter. The LCR and TCFA were automatically determined on OCT images by a recently validated algorithm based on artificial intelligence. OCT and CAG images from 114 patients (124 vessels) were analysed. The average time for the analysis of RWSmax was 57 (39-82) seconds. The RWSmax in the interrogated plaques was 12% (10-15%) and correlated positively with the LCR (r=0.584; p<0.001) and lipidic plaque burden (r=0.411; p<0.001), and negatively with fibrous cap thickness (r= -0.439; p<0.001). An RWSmax >12% was an angiographic predictor for an LCR >0.33 (area under the curve [AUC]=0.86, 95% confidence interval [CI]: 0.78-0.91; p<0.001) and TCFA (AUC=0.72, 95% CI: 0.63-0.80; p<0.001). Lesions with RWSmax >12% had a higher prevalence of TCFA (22.0% versus 1.5%; p<0.001), thinner fibrous cap thickness (71 μm versus 101 μm; p<0.001), larger lipidic plaque burden (23.3% versus 15.4%; p<0.001), and higher maximum LCR (0.41 versus 0.18; p<0.001) compared to lesions with RWSmax ≤12%. Angiography-derived RWS was significantly correlated with plaque composition and known OCT features of plaque vulnerability in patients with intermediate coronary stenosis.

Elevated EMMPRIN Serum Levels Indicate Plaque Vulnerability in Patients With Asymptomatic High Grade Carotid Stenosis

Carotid atherosclerosis is an important cause of cerebral ischaemic stroke. Sonographic plaque characteristics are inappropriate for exact prediction of possible future ischaemic events. Additional markers are needed to predict the clinical outcome in high grade carotid stenosis. This study aimed to test extracellular matrix metalloproteinase inducer (EMMPRIN), due to its involvement in plaque formation and destabilisation, as a potential marker of high risk vulnerable plaques. EMMPRIN was analysed in pre-operative serum samples from patients with symptomatic and asymptomatic carotid artery stenosis by a specific ELISA. Pre-operative duplex sonography classified the atherosclerotic plaque due to echogenicity. Histopathological analysis of vulnerable and non-vulnerable plaques was based on the American Heart Association (AHA) classification. The study included 265 patients undergoing carotid endarterectomy: 90 (m:f, 69:21) patients with symptomatic and 175 (m:f, 118:57) with asymptomatic disease. Analysis of circulating EMMPRIN revealed significantly higher levels in patients with echolucent plaques (4 480; IQR 3 745, 6 144 pg/mL) compared with echogenic plaques (4 159; IQR 3 418, 5 402 pg/mL; p= .025). Asymptomatic patients with vulnerable plaques had significantly higher levels of EMMPRIN (4 875; IQR 3 850, 7 016 pg/mL) compared with non-vulnerable plaques (4 109; IQR 3 433, 5 402 pg/mL; p < .001). In logistic regression analysis, duplex sonography combined with age, gender, and clinical risk factors predicted vulnerable plaques in asymptomatic patients with an AUC of 0.71 (95% CI 0.61 - 0.80). EMMPRIN significantly improved the AUC in asymptomatic patients (AUC 0.79; 95% CI 0.71 - 0.87; p= .014). Patients with high risk plaques according to ultrasound and histopathological characteristics demonstrated increased serum EMMPRIN levels. EMMPRIN on top of clinical risk factors, including age, gender, and duplex sonography may be used for pre-operative risk stratification in asymptomatic patients.

Effect of combined lipid-lowering therapy on atherosclerotic plaque vulnerability in patients with acute coronary syndrome (Combi-LLT ACS): randomized trial protocol

Aim. To study the effect of high-dose combined lipid-lowering therapy (statins + ezetimibe vs statins + PCSK9 inhibitors) on plaque vulnerability assessed using multimodal imaging (coronary computed tomography angiography (CCTA) and optical coherence tomography, as well as biomarkers in patients with acute coronary syndrome (ACS).Material and methods. This open, prospective, randomized, single-center study will include 120 patients admitted urgently with an ACS. All patients will undergo percutaneous coronary intervention of the infarct-related artery, as well as intracoronary imaging using optical coherence tomography of one or two noninfarct-related arteries. During hospitalization, patients will receive standard therapy for ACS according to clinical guidelines, while statins will initially be prescribed at a maximum dosage of atorvastatin 80 mg/rosuvastatin 40 mg.Patients who showed high compliance and did not reach the target low-density lipoprotein cholesterol (LDL-C) values (≤1,4 mmol/l) 1 month after myocardial infarction/unstable angina at the second visit will be randomized into two groups. Patients of group 1 will receive PCSK9 inhibitors (alirocumab 150 mg by subcutaneous injection once every 2 weeks or evolocumab 140 mg by subcutaneous injection once every 2 weeks) in addition to maximum statin therapy (atorvastatin 80 mg/rosuvastatin 40 mg), while group 2 participants will take ezetimibe at a dose of 10 mg in combination with the maximum dose of statins. In addition, at the second visit, patients will undergo CCTA, assess the cardio-ankle vascular index (CAVI) index and laboratory tests (complete blood count (neutrophil-to-lymphocyte ratio NLR), lipid profile, alanine aminotransferase (ALT), aspartate aminotransferase (AST), Troponin I, Galectin-3, high-sensitivity C-reactive protein (hs-CRP), metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), neutrophil gelatinase-associated lipocalin (NGAL). Total follow-up will last 52 weeks. At the final visit, patients will undergo CCTA, assessment of the CAVI index and laboratory status (NLR, lipid profile, ALT, AST), Troponin I, Galectin-3, hs-CRP, MMP-9, TIMP-1, NGAL).Primary endpoint: reduction in plaque vulnerability according CCTA in non-infarct-related coronary arteries Secondary endpoints: death, stent thrombosis/restenosis, non-fatal myocardial infarction, readmissions with progressive angina, repeat revascularization; changes of the lipid profile (total cholesterol, LDL-C, high-density lipoprotein cholesterol, triglycerides) against the background of maximum combination therapy with statin + PCSK9 inhibitors or statin + ezetimibe; changes of the biomarkers of cardiac injury (Troponin I), inflammation (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).Conclusion. Our study will allow for the first time to compare and evaluate the effect of both PCSK9 inhibitors and ezetimibe in combination with high-dose statin therapy on reducing the plaque vulnerability according to CCTA in non-infarction-related coronary arteries in patients with ACS undergoing percutaneous coronary intervention, as well as to evaluate the diagnostic value of inflammatory biomarkers (NLR, hs-CRP, NGAL, Galectin-3) and matrix remodeling (MMP-9, TIMP-1).

Abstract 10040: Impact of Periaortic Adipose Tissue Detected by Computed Tomography on Aortic Vulnerable Plaques Identified by Non-Obstructive General Angioscopy

Introduction: Periaortic adipose tissue (PAAT) is related to the development of cardiovascular disease. However, the relationship between periaortic adipose tissue (PAAT) and aortic plaque instability has not been elucidated. Hypothesis: We hypothesized that PAAT would be associated with aortic vulnerable plaques derived non-obstructive general angioscopy (NOGA) in patients with cardiovascular disease. Methods: We investigated 117 patients who underwent NOGA of the aorta and CT. PAAT volume was measured using the volume-rendering method by extracting the area from -30 to -190 HU within the thoracic aorta. PAAT volume index (PAAT-I) was defined as PAAT volume divided by the body surface area. We evaluated the number of vulnerable plaques including ruptured plaques, ulcerations, thrombi, intense yellow plaques by NOGA in the whole aorta. All patients were divided into the median value of PAAT-I (16.9 [13.0 - 21.6] ml/m2) Results: The high PAAT-I patients had significantly greater number of vulnerable plaques in the thoracic aorta than the low PAAT-I patients (2 [1-4] vs 1 [0-3], p&lt;0.05). The PAAT-I had a correlation with the number of vulnerable plaques in the thoracic and whole aorta (r=0.44, p&lt;0.001, r=0.35, p&lt;0.01, respectively) Conclusions: PAAT in the thoracic aorta was related to the number of NOGA derived-aortic vulnerable plaques in patients with cardiovascular disease. PAAT may play an important role in the development of aortic plaque instability.

Non-traditional lipid parameters as potential predictors of carotid plaque vulnerability and stenosis in patients with acute ischemic stroke.

Lipid abnormalities are important risk factors in patients with large atherosclerotic strokes. Recent studies have shown that non-traditional lipid parameters are crucial to the development of atherosclerosis and are closely related to the clinical outcome of acute ischemic stroke (AIS). Therefore, we aimed to investigate the relationship between non-traditional lipid parameters and carotid plaque stability and stenosis degree in patients with large atherosclerotic stroke. We retrospectively analyzed 336 patients with AIS. All patients were divided into the non-plaque group, stable plaque group, and vulnerable plaque group according to ultrasound examination. At the same time, the patients were divided into non-stenosis, mild stenosis, moderate stenosis, and severe stenosis groups according to the degree of stenosis. Non-traditional lipid parameters, including residual lipoprotein cholesterol (RLP-C), non-high-density lipoprotein cholesterol (non-HDL-C), non-HDL-C to high-density lipoprotein cholesterol ratio (non-HDL-C/HDL-C), triglyceride to HDL-C ratio (TG/HDL-C), Castelli's risk index (CRI), and the atherogenic index of plasma (AIP). Receiver operating characteristic (ROC) curves and multivariate logistic regression analyses were used to investigate the associations between the non-traditional lipid parameters and carotid plaque vulnerability. Spearman linear correlation analysis was used to test the correlation between variables and the degree of carotid plaque stenosis. This study population included 336 patients with AIS, of whom 294 had a carotid plaque. Multivariate logistic regression model showed that RLP-C (OR, 3.361; 95%CI, 1.311-8.617), non-HDL-C/HDL-C (OR, 1.699; 95%CI, 1.279-2.258), non-HDL-C (OR, 1.704; 95%CI, 1.143-2.540), CRI-I (OR, 1.573; 95%CI, 1.196-2.068), and CRI-II (OR, 2.022; 95%CI, 1.369-2.985) were independent risk factors for carotid plaque vulnerability. In addition, Spearman correlation analysis showed that the values of RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP on admission were positively correlated with the degree of carotid plaque stenosis (all P < 0.001). This study provides evidence that non-traditional lipid parameters (LP-C, non-HDL-C/HDL-C, non-HDL-C, CRI-I, and CRI-II) were potential predictors of carotid plaque vulnerability in patients with AIS. However, no significant correlation was observed between TG/HDL-C and AIP. RLP-C, non-HDL-C/HDL-C, non-HDL-C, TG/HDL-C, CRI-I, CRI-II, and AIP were closely related to the degree of carotid plaque stenosis. Non-traditional lipid parameters can be used as novel biomarkers of carotid plaque vulnerability and stenosis.

The relationships between cholesterol crystals, NLRP3 inflammasome, and coronary atherosclerotic plaque vulnerability in acute coronary syndrome: An optical coherence tomography study.

Cholesterol crystals (CCs) in lesions are the hallmark of advanced atherosclerotic plaque. Previous studies have demonstrated that CCs could activate NLRP3 inflammasome, which played an important role in atherosclerotic lesion progression. However, the relationship between CCs, NLRP3 inflammasome pathway, and plaque vulnerability in patients with ACS is still not elucidated. Two hundred sixty-nine consecutive acute coronary syndrome (ACS) patients with 269 culprit lesions were included in this study. CCs and other plaque characteristics within the culprit lesion segment were evaluated by optical coherence tomography (OCT) before percutaneous coronary intervention (PCI). The NLRP3 mRNA expression in peripheral blood mononuclear cells (PBMCs) and the serum levels of interleukin (IL)-1β, IL-18, and other biological indices were measured. Cholesterol crystals were observed in 105 (39%) patients with 105 culprit lesions. There were no significant differences in baseline clinical characteristics between the patients with CCs (CCs group, n = 105) and the patients without CCs (non-CCs group, n = 164) within the culprit lesion segment except for lipoprotein(a) [Lp(a)]. The CCs group had a higher level of NLRP3 mRNA expression in PBMCs and higher levels of serum cytokine IL-1β and IL-18. OCT showed that the CCs group had longer lesion length, more severe diameter stenosis, and less minimum luminal area (MLA) than the non-CCs group (all p < 0.05). The frequency of thin-cap fibroatheroma (TCFA), thrombus, accumulation of macrophages, plaque rupture, micro-channel, calcification, spotty calcification, and layered plaque was higher in the CCs group than in the non-CCs groups (all p < 0.05). Multivariate logistic analysis revealed that the level of NLRP3 expression (OR = 10.204), IL-1β levels (OR = 3.523), IL-18 levels (OR = 1.006), TCFA (OR = 3.593), layered plaque (OR = 5.287), MLA (OR = 1.475), macrophage accumulation (OR = 2.881), and micro-channel (OR = 3.185) were independently associated with CCs. Acute coronary syndrome patients with CCs in culprit lesions had a higher expression of NLRP3, IL-1β, and IL-18, and had more vulnerable plaque characteristics than patients without CCs. CCs might have interacted with NLRP3 inflammasome activation in patients with ACS, which could contribute to plaque vulnerability in culprit lesions.