Plaque Vulnerability In Patients Research Articles

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.

Circulating long non-coding RNA Coromarker expression correlated with inflammation, coronary artery stenosis, and plaque vulnerability in patients with coronary artery disease.

The aim of the study was to assess the correlation between circulating long non-coding RNA (lncRNA) OTTHUMT00000387022 (named Coromarker) expression and disease severity, inflammatory cytokine levels, and plaque vulnerability in patients with coronary artery disease (CAD). A total of 134 participants who received coronary angiography were enrolled and classified them as CAD patients (N=89) and controls (N=45). Blood samples were obtained from all subjects. Quantitative polymerase chain reaction was used to evaluate Coromarker expression. The enzyme-linked immunosorbent test was used to measure inflammatory cytokines including high sensitivity C reactive protein (hsCRP), interleukin (IL)-1β (IL-1β), IL-6, NOD-like receptor protein 3 (NLRP3), and markers of coronary plaque stability including matrix metallopeptidase 9 (MMP-9) and soluble CD40 ligand (sCD40L). The severity of coronary stenosis was determined from the Gensini Score. LncRNA Coromarker expression was elevated to a greater extent in CAD patients than in control subjects before and after adjustments for age/gender (both p < 0.001); it was an independent predictor of CAD risk (area under curve: 0.824, 95% CI: 0.732-0.915). Additionally, Coromarker expression was significantly associated with Gensini Score (r=0.574, p < 0.001), hsCRP (r=0.221, p=0.015), IL-1β (r=0.351, p < 0.001), IL-6 (r=0.286, p < 0.01), and NLRP3 levels (r=0.312, p < 0.001). Coromarker expression was found to be linked with MMP-9 (r=0.260, p < 0.01) and sCD40L (r=0.441, p < 0.001). Circulating lncRNA Coromarker expression correlates with increased disease severity and inflammation as well as plaque vulnerability in patients with CAD.

Analysis of Risk Factors for Vulnerable Plaque Formation and Pathogenic in Carotid Artery.

The formation of vulnerable carotid artery plaque may be closely related to a single factor or caused by multiple factors. This paper discusses the pathogenic risk factors for vulnerable plaque in patients with severe internal carotid artery (ICA) stenosis who received endarterectomy through regression analysis. A total of 98 patients with a complete clinical and laboratory assessment underwent carotid endarterectomy. Metabolic syndrome (MetS) and MetS components, ICA plaque thickness and ICA peak systolic velocity, previous ischemic stroke or transient ischemic attack (TIA), and other risk factors were included in the pathogenic risk factor for vulnerable plaque. Univariate logistic regression analysis was used to determine vulnerable carotid plaque risk factors. If P <0.2, it was considered potential confounders. Binary logistic regression model was controlled for potential confounders. Among the 98 patients, stable carotid plaques 38 (39%) and unstable carotid plaques 60 (61%), male 76 (77.6%) and female 22 (22.4%), and Han Chinese 68 (68.4%) and Mongols 30 (30.6%). Univariate logistic regression to P <0.2 has 6 risk factors, which are previous ischemic stroke or TIA, ICA peak systolic velocity, ICA plaque thickness, body mass index, total cholesterol, and alcohol consumption. The significant result of the binary logistic regression analysis was the previous ischemic stroke or TIA (OR=4.52; 95% CI, 1.67-12.09), P =0.003 and ICA peak systolic velocity (OR=1.01; 95% CI, 1.00-1.02), P =0.014. The patients with previous ischemic stroke or TIA and higher ICA peak systolic velocity are associated with vulnerable plaque pathogenic features. There is no obligatory association between MetS and formation of carotid plaque vulnerability.

Impact of in-hospital versus ambulatory glucose variability on coronary plaque vulnerability in patients with coronary artery disease

AimThe impact of in-hospital and ambulatory glucose variability (GV) on lipid core plaques (LCP) is unclear. We evaluated the relation of GV during hospitalization and after discharge to LCPs. MethodsA total of 35 patients undergoing percutaneous coronary intervention (PCI) under near-infrared spectroscopy intravascular ultrasound (NIRS-IVUS) guidance for acute myocardial infarction (MI) and stable coronary artery disease were prospectively included. LCP was evaluated with a lipid core burden index (LCBI) and a maximum LCBI in 4 mm (max LCBI4mm) in the non-target vessel using NIRS-IVUS. GV was measured by a flush glucose monitoring system. ResultsIn-hospital mean amplitude of glucose excursion (MAGE) was significantly higher than that after discharge (73.4±26.8 vs. 66.0±22.8 mg/dl, p=0.03). In the entire study population, LCBI and maxLCBI4mm in the non-target vessel were correlated with MAGE after discharge (r=0.51, p=0.002 and r=0.39, p=0.02), but not significantly correlated with in-hospital MAGE. The relations of MAGE to higher LCBI and maxLCBI4mm were more evident in patients with acute MI. ConclusionsGV was greater during hospitalization than after discharge in patients undergoing PCI. Greater GV after discharge was significantly associated with higher LCBI and maxLCBI4mm, suggesting that ambulatory GV may be closely link to coronary atherosclerosis.

Impact of Alirocumab on Release Markers of Atherosclerotic Plaque Vulnerability in Patients with Mixed Hyperlipidemia and Vulnerable Atherosclerotic Plaque.

Background and Objectives: Atherosclerosis is a disease in the pathogenesis of which plasma factors apart from elevated cholesterol levels play a keyrole. Such factors include osteopontin (OPN), osteoprotegerin (OPG), and metalloproteinases (MMPs), which are factors that may be responsible for the stabilization of atherosclerotic plaque. The aim of this study was to assess the effect of modern lipid-lowering therapy by using proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitor on the concentrations of these factors. Materials and Methods: The study included people suffering from dyslipidemia who were eligible to start alirocumab therapy. In this group, the concentrations of OPN, OPG, and MMPs were assessed before the initiation of therapy and after three months of its duration. Results: In the study, we observed a statistically significant reduction in the concentrations of OPN, OPG (p < 0.001), and metalloproteinase 2 (MMP-2) (p < 0.05) after the applied therapy. Moreover, we noticed that in the group of patients soon to start alirocumab therapy, the concentrations of these factors were higher compared to the control group (p < 0.001). Conclusions: The results of our study show that therapy with alirocumab significantly reduces the concentration of factors that affect atherosclerotic plaque vulnerability, which may explain their important role in reducing cardiovascular risk in patients undergoing this therapy.

Predictive Value of Non-high-Density Lipoprotein Cholesterol and Neutrophil-Lymphocyte Ratio for Coronary Artery Vulnerable Plaques in Type 2 Diabetes Mellitus.

BackgroundPatients with diabetes have an increased risk of developing vulnerable plaques (VPs), in which dyslipidemia and chronic inflammation play important roles. Non-high-density lipoprotein cholesterol (non-HDL-C) and neutrophil-lymphocyte ratio (NLR) have emerged as potential markers of both coronary artery VPs and cardiovascular prognosis. This study aimed to investigate the predictive value of non-HDL-C and NLR for coronary artery VPs in patients with type 2 diabetes mellitus (T2DM).MethodsWe retrospectively enrolled 204 patients with T2DM who underwent coronary computed tomography angiography between January 2018 and June 2020. Clinical data including age, sex, hypertension, smoking, total cholesterol, low-density lipoprotein cholesterol, HDL-C, triglyceride, non-HDL-C, glycated hemoglobin, neutrophil count, lymphocyte count, NLR, and platelet count were analyzed. Multivariate logistic regression was used to estimate the association between non-HDL-C, NLR, and coronary artery VPs. Receiver operating curve analysis was performed to evaluate the value of non-HDL-C, NLR, and their combination in predicting coronary artery VPs.ResultsIn our study, 67 patients (32.84%) were diagnosed with VPs, 75 (36.77%) with non-VP, and 62 (30.39%) with no plaque. Non-HDL-C and NLR were independent risk factors for coronary artery VPs in patients with T2DM. The areas under the ROC curve of non-HDL-C, NLR, and their combination were 0.748 [95% confidence interval (CI): 0.676–0.818], 0.729 (95% CI: 0.650–0.800), and 0.825 (95% CI: 0.757–0.887), respectively.ConclusionEither non-HDL-C or NLR could be used as a predictor of coronary artery VPs in patients with T2DM, but the predictive efficiency and sensitivity of their combination would be better.

Cholesterol crystals in non-culprit plaques of STEMI patients: A 3-vessel OCT study

BackgroundCholesterol crystals (CCs) are regular microstructures found within the necrotic core of atherosclerotic plaques and have been hypothesized to be related to plaque destabilization. We attempted to investigate the potential association between CCs and non-culprit plaque vulnerability in patients with ST-segment elevated myocardial infarction (STEMI) and study morphological features of CCs in ruptured non-culprit plaques. MethodsA total of 261 patients with ST-segment elevation myocardial infarction who underwent 3-vessel optical coherence tomography (OCT) imaging were included. Non-culprit plaques were divided into two groups according to the presence or absence of CCs in the plaque to compare the morphological characteristics of the plaques. The differences in parameters of the non-culprit plaque CCs were explored between ruptured plaques and unruptured plaques. ResultsTotally, 530 non-culprit plaques (29 ruptured plaques and 501 unruptured plaques) were identified by OCT. The incidence of CCs was 21.1%. Compared with non-culprit plaques without CCs, those with CCs had a larger lipid burden. Macrophages (p < 0.001) and spotty calcification (p = 0.002) were more frequently observed in non-culprit plaques with CCs. The frequency of CCs was significantly higher (p = 0.001) and the CCs were larger (p = 0.046) and more superficial (p = 0.005) in ruptured non-culprit plaques than in unruptured non-culprit plaques. The maximum lipid arc and fibrous cap thickness were independent predictors of plaque rupture, but the presence of CCs was not. ConclusionsNon-culprit plaques with CCs have more vulnerable features. CCs are more frequently found in ruptured non-culprit plaques and larger and more superficial CCs are associated with plaque rupture.

Clinical Parameters and Epigenetic Biomarkers of Plaque Vulnerability in Patients with Carotid Stenosis.

Atheromatous disease is the first cause of death and dependency in developed countries and carotid artery atherosclerosis is one of the main causes of severe ischaemic strokes. Current management strategies are mainly based on the degree of stenosis and patient selection has limited accuracy. This information could be complemented by the identification of biomarkers of plaque vulnerability, which would permit patients at greater and lesser risk of stroke to be distinguished, thus enabling a better selection of patients for surgical or intensive medical treatment. Although several circulating protein-based biomarkers with significance for both the diagnosis of carotid artery disease and its prognosis have been identified, at present, none have been clinically implemented. This review focuses especially on the most relevant clinical parameters to take into account in routine clinical practice and summarises the most up-to-date data on epigenetic biomarkers of carotid atherosclerosis and plaque vulnerability.

Abstract 290: Ccr2 Expression Is Increased In Patients With Symptomatic Carotid Arterial Occlusive Disease

Objectives: Chemokines and their receptors play critical roles in the progression of atherosclerosis. The chemokine receptor, C-C chemokine receptor type 2 (CCR2), mediates an essential role in the differentiation of pro-inflammatory monocytes into macrophages. Recent studies suggest that proinflamatory macrophages in plaques predict plaque progression. While there is no clinical consensus on which patient with asymptomatic carotid artery stenosis would benefit from carotid endarterectomy (CEA), we hypothesized that CCR2 plaque content may predict plaque progression. Methods: Carotid plaque of ten patients undergoing elective CEA were harvested from the operating room, paraffin-embedded, sectioned into 5μm segments, immuno-stained for CCR2 and CD68, and imaged. Three 200х500μm regions-of-interest (ROIs) were randomly selected within 200μm of the lumen (superficial intima), outside 200μm of the lumen (deep intima), and the arterial media. Two independent observers evaluated the number of CCR2 and/or CD68 positive cells. Counts in each ROI were averaged and analyzed with Student’s t-test. Results: Patients with symptomatic carotid artery stenosis (6/10) demonstrated higher CCR2 and CCR2-CD68 double positive cells within the superficial intima of carotid artery plaques (A, p&lt;0.05, n=10). Similarly, patients with symptomatic disease also showed increased CCR2 in the plaque media (B, p&lt;0.05, n=10). Interestingly, we also observed a higher number of CCR2 positive cells in the media layer of smokers (6/10) compared to non-smokers (C, p&lt;0.05, n=10). Conclusions: Our study demonstrates the close association between CCR2 cellular content and the incidence of symptomatic carotid artery disease. Additionally, CCR2 plaque content appears to correlate with risk-factors such as smoking. These studies have important implications regarding the impact of immune modulation on carotid plaque vulnerability in patients with asymptomatic carotid artery stenosis.

Coronary Computed Tomography Angiography Analysis of Calcium Content to Identify Non-culprit Vulnerable Plaques in Patients With Acute Coronary Syndrome.

BackgroundAside from the culprit plaque, the presence of vulnerable plaques in patients with acute coronary syndrome (ACS) may be associated with future cardiac events. A link between calcification and plaque rupture has been previously described.AimTo assess whether analysis of the calcium component of coronary plaques using CT angiography, coronary computed tomographic angiography (CCTA) can help to detect additional vulnerable plaques in patients with non-ST elevation myocardial infarction (NSTEMI).Materials And MethodsCross sectional study of consecutive patients referred for NSTEMI from 30 July to 30 August 2018 with CCTA performed before coronary angiography with systematic optical coherence tomography (OCT) analysis of all coronary arteries within 24 h of clinical onset of NSTEMI. Three types of plaques were defined: culprit plaques defined by angiography (vulnerable culprit plaques–VCP) – plaques with a fibrous cap thickness < 65 microns or thrombus in OCT (vulnerable non-culprit plaque–VNCP) – plaques with a fibrous cap thickness ≥ 65 microns in OCT (stable plaque–SP).ResultsA total of 134 calcified plaques were identified in 29 patients (73% male, 59 ± 14 years) with 29(22%) VCP, 28(21%) VNCP and 77(57%) SP. Using CCTA analysis of the calcium component, factors associated with vulnerable plaques were longer calcification length, larger calcification volume, lower calcium mass, higher Agatston score plaque-specific (ASp), presence of spotty calcifications and an intimal position in the wall. In multivariate analysis, ASp, calcification length and spotty calcifications were independently associated to vulnerable plaques. There was no difference between VCP and VNCP.ConclusionsCCTA analysis of calcium component of the plaque could help to identify additional vulnerable plaques in NSTEMI patients.

Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity.

Approximately 12% of patients with acute myocardial infarction (AMI) experience a recurrent major adverse cardiovascular event within 1 year of their primary event, with most occurring within the first 90 days. Thus, there is a need for new therapeutic approaches that address this 90‐day post‐AMI high‐risk period. The formation and eventual rupture of atherosclerotic plaque that leads to AMI is elicited by the accumulation of cholesterol within the arterial intima. Cholesterol efflux, a mechanism by which cholesterol is removed from plaque, is predominantly mediated by apolipoprotein A‐I, which is rapidly lipidated to form high‐density lipoprotein in the circulation and has atheroprotective properties. In this review, we outline how cholesterol efflux dysfunction leads to atherosclerosis and vulnerable plaque formation, including inflammatory cell recruitment, foam cell formation, the development of a lipid/necrotic core, and degradation of the fibrous cap. CSL112, a human plasma‐derived apolipoprotein A‐I, is in phase 3 of clinical development and aims to reduce the risk of recurrent cardiovascular events in patients with AMI in the first 90 days after the index event by increasing cholesterol efflux. We summarize evidence from preclinical and clinical studies suggesting that restoration of cholesterol efflux by CSL112 can stabilize plaque by several anti‐inflammatory/immune‐regulatory processes. These effects occur rapidly and could stabilize vulnerable plaques in patients who have recently experienced an AMI, thereby reducing the risk of recurrent major adverse cardiovascular events in the high‐risk early post‐AMI period.

Elevated Lipoprotein(a) as a potential residual risk factor associated with lipid-rich coronary atheroma in patients with type 2 diabetes and coronary artery disease on statin treatment: Insights from the REASSURE-NIRS registry

Background and aimsThe residual risk of atherosclerotic cardiovascular disease (ASCVD) in patients with diabetes on statin therapy warrants identification of other pro-atherogenic drivers. Lipoprotein(a) [Lp(a)] promotes the formation of necrotic cores within vessel walls. Given that patients with diabetes have an Lp(a)-associated ASCVD risk, Lp(a) might lead to plaque vulnerability in patients with diabetes on statin therapy. MethodsWe analyzed target lesions that underwent PCI in 312 patients with coronary artery disease (CAD) on statin treatment from the REASSURE-NIRS registry (NCT04864171). Maximum 4-mm lipid-core-burden index (maxLCBI4mm) in target lesions was measured with near-infrared spectroscopy (NIRS) imaging. The relationship between Lp(a) levels and maxLCBI4mm was investigated in patients with and without diabetes. ResultsHigh-intensity statin use (p = 0.49) and on-treatment low-density lipoprotein cholesterol (LDL-C) (p = 0.32) and Lp(a) levels (p = 0.09) were comparable between patients with and without diabetes. Lp(a) levels were significantly associated with maxLCBI4mm in patients with diabetes (p = 0.01) but not in patients without diabetes (p = 0.96). Multivariate analysis showed that LDL-C levels (p = 0.03) predict maxLCBI4mm in patients without diabetes, but not Lp(a) levels (p = 0.91). Both LDL-C (p = 0.01) and Lp(a) (p = 0.04) levels were independent predictors of maxLCBI4mm in patients with diabetes. Even in patients with diabetes achieving LDL-C <1.8 mmol/L (70 mg/dL), Lp(a) levels remained associated with maxLCBI4mm (p = 0.04). ConclusionsA significant relationship between Lp(a) and maxLCBI4mm exists in patients with diabetes and CAD on statin treatment, even with LDL-C <1.8 mmol/L (70 mg/dL). Lp(a) might be associated with more vulnerable coronary atheroma in patients with diabetes despite receiving statin therapy.

Relationship of the Low-Density Lipoprotein Cholesterol/High-Density Lipoprotein Cholesterol Ratio with a Vulnerable Plaque in Patients with Severe Carotid Artery Stenosis: A Case-Control Study in the Han Chinese Population.

Carotid plaque is often an important factor in ischemic stroke after it changes from stable to vulnerable, and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) are associated with plaque vulnerability. We aimed to investigate whether the LDL-c/HDL-c ratio, an easily available and novel biomarker, is associated with vulnerable plaques and enhances the warning effect on vulnerability compared to LDL-c or HDL-c alone. We conducted a retrospective study of 187 patients with severe CAS admitted to the Department of Vascular Surgery at the Nanjing Drum Tower Hospital from January 2019 to July 2021. They were divided into a stable plaque group and a vulnerable plaque group according to carotid ultrasonography, carotid angiography (CTA), and plaque pathology. Baseline information was collected and compared between the two groups. Correlation analysis was used to determine the degree of correlation between clinical variables. Univariate and multifactor logistic regression analyses were used to examine independent risk factors for vulnerable plaque in patients with severe CAS. Receiver operating characteristic (ROC) curves were used to assess the capacity of LDL-c/HDL-c to predict the occurrence of vulnerable plaque. The age of the vulnerable plaque group was 68.12 ± 8.90 years, with 85 males (89.91%); the age of the stable plaque group was 68.77 ± 8.43 years, with 70 males (89.74%). Multivariate logistic regression analysis showed that LDL-c/HDL-c, smoking and diabetes were independent risk factors for vulnerable plaque (all P <0.05). The risk of vulnerable plaque was 4.78-fold greater in the highest LDL-c/HDL-c quartile (≥ 2.63) than in the lowest quartile (≤ 1.31) (P-trend <0.001), and the area under the ROC curve for LDL-c/HDL-c (AUC=0.681, P <0.001) was higher than that for LDL-c and HDL-c. LDL-c/HDL-c, smoking and diabetes were independent risk factors for vulnerable plaque in patients with severe CAS, and LDL-c/HDL-c had a higher predictive value for the presence of vulnerable plaque compared with other lipid parameters.

The Potential Mediating Effects of Inflammation on the Association Between Type D Personality and Coronary Plaque Vulnerability in Patients With Coronary Artery Disease: An Optical Coherence Tomography Study.

Type D personality involves the interaction between negative affectivity with social inhibition and has been associated with an increased risk of coronary artery disease (CAD) progression and coronary plaque vulnerability. However, the underlying mechanisms in the relationship between type D personality and coronary plaque vulnerability remain indeterminate. The present study examined the potential mediating effects of inflammation biomarkers on the association between type D personality and coronary plaque vulnerability in patients with CAD. A total of 347 patients (mean [standard deviation] age = 56.6 [11.2] years; 29.3% women) with CAD who had culprit coronary plaques were examined for type D personality. The inflammation biomarkers (high-sensitivity C-reactive protein, interleukin 6 [IL-6], and tumor necrosis factor α [TNF-α]) were evaluated. Each individual inflammation biomarker was standardized using z scores to calculate inflammation standardized sumscores. Plaque vulnerability of culprit lesions was measured in vivo using optical coherence tomography. The presence of type D personality (38%) was associated with TNF-α, IL-6, and inflammation standardized sumscores (t = 2.74, Cohen d = 0.32, p = .006; t = 4.03, Cohen d = 0.44, p ≤. 001; t = 4.16, Cohen d = 0.11, p = .001, respectively). In addition, the standardized inflammation sumscore was a mediator of the relationship between type D personality and lipid-rich plaques (effect sizes = 0.12, 95% confidence interval = 0.007-0.286, p = .064) and plaque rupture vulnerability (effect sizes = 0.16, 95% confidence interval = 0.043-0.365, p = .024). Analysis of continuous type D scores revealed that TNF-α, IL-6, and inflammation standardized sumscores also mediate the relationship between the primary effect of negative affectivity and plaque vulnerability. Inflammation activation is a potential mediator of the association between type D personality and plaque vulnerability. The negative affectivity component of type D personality might be particularly relevant to the inflammatory aspects of plaque vulnerability.

Vulnerable Plaque in Patients with Acute Coronary Syndrome: Identification, Importance, and Management

MI is a leading cause of morbidity and mortality worldwide. Coronary artery thrombosis is the final pathologic feature of the most cases of acute MI primarily caused by atherosclerotic coronary artery disease. The concept of vulnerable plaque has evolved over the years but originated from early pioneering work unveiling the crucial role of plaque rupture and subsequent coronary thrombosis as the dominant cause of MI. Along with systemic cardiovascular risk factors, developments of intravascular and non-invasive imaging modalities have allowed us to identify coronary plaques thought to be at high risk for rupture. However, morphological features alone may only be one of many factors which promote plaque progression. The current vulnerable-plaque-oriented approaches to accomplish personalized risk assessment and treatment have significant room for improvement. In this review, the authors discuss recent advances in the understanding of vulnerable plaque and its management strategy from pathology and clinical perspectives.