Plaque Instability In Patients Research Articles

CircSKA3 is Associated With the Risk of Extracranial Artery Stenosis and Plaque Instability Among Ischemic Stroke Patients.

Circular RNA circSKA3 (spindle and kinetochore-related complex subunit 3) has been identified as a prognostic factor in ischemic stroke. The objective of this study was to investigate the association of circSKA3 with the risk of extracranial artery stenosis (ECAS) and plaque instability in patients with ischemic stroke. We constructed a competing endogenous RNA (ceRNA) network regulated by circSKA3 based on differentially expressed circRNAs and mRNAs between five patients and five controls. Gene Ontology (GO) analysis was performed on the 65 mRNAs within the network, revealing their primary involvement in inflammatory biological processes. A total of 284 ischemic stroke patients who underwent various imaging examinations were included for further analyses. Each 1 standard deviation increase in the log-transformed blood circSKA3 level was associated with a 56.3% increased risk of ECAS (P = 0.005) and a 142.1% increased risk of plaque instability (P = 0.005). Patients in the top tertile of circSKA3 had a 2.418-fold (P < 0.05) risk of ECAS compared to the reference group (P for trend = 0.02). CircSKA3 demonstrated a significant but limited ability to discriminate the presence of ECAS (AUC = 0.594, P = 0.015) and unstable carotid plaques (AUC = 0.647, P = 0.034). CircSKA3 improved the reclassification power for ECAS (NRI: 9.86%, P = 0.012; IDI: 2.97%, P = 0.007) and plaque instability (NRI: 36.73%, P = 0.008; IDI: 7.05%, P = 0.04) beyond conventional risk factors. CircSKA3 played an important role in the pathogenesis of ischemic stroke by influencing inflammatory biological processes. Increased circSKA3 was positively associated with the risk of ECAS and plaque instability among ischemic stroke patients.

Elevated FAI Index of Pericoronary Inflammation on Coronary CT Identifies Increased Risk of Coronary Plaque Vulnerability after COVID-19 Infection.

Inflammation is a key factor in the development of atherosclerosis, a disease characterized by the buildup of plaque in the arteries. COVID-19 infection is known to cause systemic inflammation, but its impact on local plaque vulnerability is unclear. Our study aimed to investigate the impact of COVID-19 infection on coronary artery disease (CAD) in patients who underwent computed tomography angiography (CCTA) for chest pain in the early stages after infection, using an AI-powered solution called CaRi-Heart®. The study included 158 patients (mean age was 61.63 ± 10.14 years) with angina and low to intermediate clinical likelihood of CAD, with 75 having a previous COVID-19 infection and 83 without infection. The results showed that patients who had a previous COVID-19 infection had higher levels of pericoronary inflammation than those who did not have a COVID-19 infection, suggesting that COVID-19 may increase the risk of coronary plaque destabilization. This study highlights the potential long-term impact of COVID-19 on cardiovascular health, and the importance of monitoring and managing cardiovascular risk factors in patients recovering from COVID-19 infection. The AI-powered CaRi-Heart® technology may offer a non-invasive way to detect coronary artery inflammation and plaque instability in patients with COVID-19.

695 Upregulated monocyte expression of PLIN2 is associated with plaque instability in coronary artery disease

Abstract Aims Perilipin 2 (PLIN2), a protein associated with intracellular lipid droplets (LDs), is involved in lipid metabolism of macrophages resident in atherosclerotic plaques and its up-regulation leads to LDs accumulation. LDs enlargement results in the macrophage transformation into foam cells, a key step for the onset of atherosclerosis. In the present study, we investigated the role of PLIN2 and its regulation mechanisms in atherosclerosis and plaque instability in patients with a diagnosis of ST-elevation myocardial infarction (STEMI) and stable chronic angina (SA). Methods and results We enrolled 120 patients with a diagnosis of STEMI and 42 SA patients with symptoms of stable effort angina lasting more than 12 months. Peripheral blood mononuclear cells (PBMCs) were isolated from EDTA whole blood samples through standard gradient centrifugation over Ficoll-Hypaque. Monocytes were purified through indirect magnetic labelling of PBMCs. PLIN2 mRNA expression was investigated by Real Time-PCR and PLIN2 protein level was analysed in CD14+ monocytes by flow cytometry. Proteasome activity was assayed using AMC-tagged peptide substrate (Succ-LLVY-AMC), which releases free highly fluorescent AMC (Ex/Em 350/440 nm) in the presence of proteolytic activity. In CD14+ monocyte, PLIN2 protein expression was significantly increased in STEMI as compared to SA patients (P &amp;lt; 0.001), while PLIN2 mRNA level was not different in the two groups (P = n.s.). Despite proteasome activity was higher in STEMI as compared to SA patients (P &amp;lt; 0.001), significant inverse correlations were evident between PLIN2 levels and proteasome activity in the two groups (P = 0.05). Conclusions CD14+ monocyte PLIN2 protein expression was higher in STEMI as compared to SA patients suggesting an involvement in plaque instability. Despite proteasome activity was higher in STEMI patients, probably due to the elevated inflammatory burden, PLIN2 could escape proteasome degradation in a more efficient manner in STEMI as compared to SA patients.

The risk of carotid plaque instability in patients with metabolic syndrome is higher in women with hypertriglyceridemia

BackgroundMetabolic syndrome certainly favors growth of carotid plaque; however, it is uncertain if it determines plaque destabilization. Furthermore, it is likely that only some components of metabolic syndrome are associated with increased risk of plaque destabilization. Therefore, we evaluated the effect of different elements of metabolic syndrome, individually and in association, on carotid plaques destabilization.MethodsA total of 186 carotid endarterectomies from symptomatic and asymptomatic patients were histologically analysed and correlated with major cardiovascular risk factors.ResultsMetabolic syndrome, regardless of the cluster of its components, is not associated with a significant increase in risk of plaque destabilization, rather with the presence of stable plaques. The incidence of unstable plaques in patients with metabolic syndrome is quite low (43.9 %), when compared with that seen in the presence of some risk factors, but significantly increases in the subgroup of female patients with hypertriglyceridemia, showing an odds ratio of 3.01 (95% CI, 0.25–36.30).ConclusionsOur data may help to identify patients with real increased risk of acute cerebrovascular diseases thus supporting the hypothesis that the control of hypertriglyceridemia should be a key point on prevention of carotid atherosclerotic plaque destabilization, especially in post-menopausal female patients.

Analysis of risk factors for carotid plaque instability in patients with coronary heart disease

Objective To study the risk factors influencing the characteristics of carotid artery plaque in patients with coronary heart disease (CHD). Methods Data of patients admitted to our hospital from March 2018 to August 2019 who were diagnosed with coronary artery disease by coronary angiography were collected. A total of 127 patients with cervical vascular plaques were detected by carotid artery color Doppler ultrasonography. According to the morphology and acoustic characteristics of the plaques, they were divided into the unstable plaque group (78 cases) and the stable plaque group (49 cases). The general data and blood indicators of the two groups were compared, including blood lipid level, fasting blood glucose, uric acid and homocysteine, etc. Meanwhile, the correlation degree between the characteristics of carotid artery plaque and risk factors was evaluated, so as to analyze the influence of the above hematological indicators on the characteristics of carotid artery plaque in patients with coronary heart disease combined with carotid artery plaque. Results Among the 127 patients, the serum uric acid and homocysteine levels in the carotid artery unstable plaque group were higher than those in the stable plaque group (p< 0.05), and there was a correlation between serum uric acid and plaque instability (OR=1.020, p< 0.05), indicating that high uric acid level increased the risk of unstable plaque in patients with coronary heart disease. Conclusion The elevated serum uric acid level in CHD population is closely related to the instability of carotid plaque. The instability of carotid plaque can be used as one of the indicators to predict and evaluate the severity of coronary heart disease.

Peptidylarginine Deiminase 4 as a Possible Biomarker of Plaque Instability in Carotid Artery Stenosis

Background and purposeNeutrophil extracellular traps (NETs) exhibit pro-inflammatory and pro-thrombotic properties. However, they have only been reported as important regulators in atherosclerosis, especially in atherothrombosis. We investigated the presence of NETs and plaque instability in patients with carotid artery stenosis. Material and methodsA total of 39 consecutive patients with carotid artery stenosis were evaluated. All patients underwent carotid artery stenting (CAS) with dual protection (simultaneous flow reversal + distal filter) and blood aspiration as a method of distal embolism prevention. Local arterial blood was aspirated at the stent site and peptidylarginine deiminase 4 (PAD4), which is essential for the formation of NETs, was measured. The relationships between PAD4 and the patient profile, blood examination and plaque data were investigated. ResultsThe mean value of PAD4 in local arterial blood in CAS was 0.5 ng/ml. Bivariate analysis demonstrated that PAD4 was associated with the neutrophil to lymphocyte ratio (p = 0.007), high-density lipoprotein (p = 0.02), triglycerides to high-density lipoprotein ratio (p = 0.007), ulceration (p = 0.02) and plaque contrast enhancement on T1 black blood imaging (p = 0.03). In multiple linear regression analyses, PAD4 was correlated with the neutrophil to lymphocyte ratio (p = 0.01) and ulceration (p = 0.01, cut-off value: 0.49 odds ratio: 19.3). ConclusionsPAD4, representative of the presence of NETs, was high in carotid plaques with unstable features. The neutrophil to lymphocyte ratio in peripheral blood was suggested to be a biomarker of vulnerable plaques. Elucidating the role of NETs may aid in clarifying factors that promote the instability of carotid plaques.

Macrophage infiltrates in coronary plaque erosion portend a worse cardiovascular outcome in patients with acute coronary syndrome

Abstract Background Plaque erosion (PE) is responsible for at least one-third of acute coronary syndrome (ACS). Inflammatory activation is considered a key mechanism of plaque instability in patients with plaque rupture through the release of metalloproteinases and the inhibition of collagen synthesis that in turns lead to fibrous cap degradation. However, the clinical relevance of macrophage infiltration has never been investigated in patients with PE. Purpose In our study, we aimed at assessing the presence of optical coherence tomography (OCT)-defined macrophage infiltrates (MØI) at the culprit site in ACS patients with PE, evaluating their clinical and OCT correlates, along with their prognostic value. Methods ACS patients undergoing OCT imaging and presenting PE as culprit lesion were retrospectively selected. Presence of MØI at culprit site and in non-culprit segments along the culprit vessel was assessed. The incidence of major adverse cardiac events (MACEs), defined as the composite of cardiac death, recurrent myocardial infarction and target vessel revascularization (TVR), was assessed [follow-up median (interquartile range, IQR) time 2.5 (2.03–2.58) years]. Results We included 153 patients [median age (IQR) 64 (53–75) years, 99 (64.7%) males]. Fifty-one (33.3%) patients presented PE with MØI and 102 (66.7%) PE without MØI. Patients having PE with MØI compared with PE patients without MØI had more vulnerable plaque features both at culprit site and at non-culprit segments. In particular, culprit lesion analysis demonstrated that patients with PE with MØI had a significantly thinner fibrous cap [median (IQR) 100 (60–120) μm vs. 160 (95–190) μm, p&amp;lt;0.001], higher prevalence of thrombus [41 (80.4%) vs. 64 (62.7%), p=0.028], lipid plaque [39 (76.5%) vs. 50 (49.0%), p&amp;lt;0.001], TCFA [20 (39.2%) vs. 14 (13.7%), p=0.001], and a higher maximum lipid arc [median [IQR] 250.0° (177.5°-290.0°) vs. 190.0° (150.0°-260.0°), p=0.018) at the culprit lesion compared with PE without MØI. MACEs were significantly more frequent in PE with MØI patients compared with PE without MØI [11 (21.6%) vs. 6 (5.9%), p=0.008], mainly driven by a higher risk of cardiac death and TVR. At multivariable Cox regression model, PE with MØI [HR=2.95, 95% CI (1.09–8.02), p=0.034] was an independent predictor of MACEs. Conclusion Our study demonstrates that among ACS patients with PE the presence of MØI at culprit lesion is associated with a more aggressive phenotype of coronary atherosclerosis with more vulnerable plaque features, along with a worse prognosis at a long-term follow-up. These findings are of the utmost importance in the era of precision medicine because clearly show that macrophage infiltrates may identify patients with a higher cardiovascular risk requiring more aggressive secondary prevention therapies and a closer clinical follow-up. Prognosis Funding Acknowledgement Type of funding source: None

Association between periodontal disease and vulnerable plaque morphology in patients undergoing carotid endarterectomy.

Periodontal disease (PD) is a chronic inflammatory oral condition with potentially important systemic sequelae. We sought to determine whether the presence of PD in patients with severe carotid disease was associated with morphological features consistent with carotid plaque instability. A total of 52 dentate patients hospitalized for carotid endarterectomy (CEA) had standardized assessments of their periodontal status, including measurements of probing pocket depth (PPD), clinical attachment level (CAL) and bleeding on probing (BoP). Carotid plaque morphology was assessed by ultrasound using the gray scale median (GSM) score and by immunohistochemistry using anti-CD68 and anti-alpha-actin antibodies, markers for macrophages and smooth muscle cells (SMCs) respectively. In total 30/52 patients (58%) had PD. Significant associations were noted between low GSM on ultrasound and each mm in PPD (p=0.001), each mm in CAL (p=0.002) and with a 10% increase in BoP (p=0.009). Using the standardized PERIO definition the association remained robust (aOR=10.4 [95% CI:2.3-46.3], p=.002). Significant associations were also observed with high macrophage accumulation and each individual PD measure (p<0.01 for PPD, CAL and BoP) and with the PERIO definition (aOR=15 [95% CI:1.8-127.8], p=.01). Similarly, low SMC density was also significantly associated with individual measures of PD (p<0.05 for PPD, CAL and BoP), but not with the PERIO definition (aOR 3.4 [95% CI:0.9-12.8], p=.07). The presence of PD was significantly associated with both ultrasound and immunohistochemistry features of carotid plaque instability in patients undergoing CEA.

Association between abdominal fat distribution and coronary plaque instability in patients with acute coronary syndrome

Background and aimsThis study aimed to assess possible association of detailed abdominal fat profiles with coronary plaque characteristics in patients with acute coronary syndrome (ACS). Methods and resultsIn 60 patients with ACS, culprit arteries were evaluated at 1-mm intervals (length analyzed: 66 ± 28 mm) by grayscale and integrated backscatter intravascular ultrasound (IB-IVUS) before percutaneous coronary intervention. Standard IVUS indexes (as a volume index: volume/length), plaque components (as percent tissue volume) and fibrous cap thickness (FCT) were assessed by IB-IVUS. Plain abdominal computed tomography was performed to evaluate subcutaneous adipose tissue (SAT) area, visceral adipose tissue (VAT) area, and VAT/SAT ratio. While SAT area only correlated with vessel volume (r = 0.27, p = 0.04), VAT area correlated positively with vessel (r = 0.30, p = 0.02) and plaque (r = 0.33, p = 0.01) volumes and negatively with FCT (r = −0.26, p = 0.049), but not with percent plaque volume and plaque tissue components. In contrast, higher VAT/SAT ratio significantly correlated with higher percent lipid (r = 0.34, p = 0.008) and lower percent fibrous (r = −0.34, p = 0.007) volumes with a trend toward larger percent plaque volume (r = 0.19, p = 0.15), as well as thinner FCT (r = −0.53, p < 0.0001). In the multiple regression analysis, higher VAT/SAT ratio was independently associated with higher percent lipid with lower percent fibrous volumes (p = 0.03 for both) and thinner fibrous cap thickness (p = 0.0001). ConclusionCoronary plaque vulnerability, defined as increased lipid content with thinner fibrous cap thickness, appears to be more related to abnormal abdominal fat distribution, or so-called hidden obesity, compared with visceral or subcutaneous fat amount alone in patients with ACS.

CD4+/CD8+ ratio positively correlates with coronary plaque instability in unstable angina pectoris patients but fails to predict major adverse cardiovascular events.

Background:The association between CD4+/CD8+ ratio and coronary plaque instability in patients with unstable angina pectoris (UAP) has not been investigated. We sought to elucidate the correlation between CD4+/CD8+ ratio and plaque instability in this patient population.Methods:We enrolled 266 UAP patients who underwent pre-intervention optical coherence tomography (OCT) examination and percutaneous coronary intervention in our center from January 2016 to January 2018. Features of coronary plaques in the culprit arteries were classified as unstable plaque and stable plaque. Primary endpoint was occurrence of a major adverse cardiovascular event (MACE). Receiver operating characteristic (ROC) analyses were used to determine the predictive efficacy of the CD4+/CD8+ ratio for a group of unstable plaque patients, and binary logistic regression analysis was performed to evaluate potential independent predictors of plaque instability. All-cause mortality and MACE between the two groups were analyzed.Results:UAP patients with unstable plaque had a higher CD4/CD8 ratio compared with stable plaque patients (p < 0.05). Results of binary logistic regression analyses showed that CD4+/CD8+ ratio ⩾1.725 and prior stroke were predictors and risk factors of plaque instability (p < 0.05). ROC analyses showed that CD4+/CD8+ ratio ⩾1.725 was predictive of plaque instability in UAP patients. However, the Kaplan–Meier estimate for MACE and all-cause mortality showed no statistical significance.Conclusions:Higher CD4+/CD8+ ratio is associated with higher risk of plaque instability in our cohort of UAP patients. However, CD4+/CD8+ ratio was not an independent predictor of 1-year MACE or all-cause mortality.

Association of Plasma Marker of Oxidized Lipid with Histologic Plaque Instability in Patients with Peripheral Artery Disease

The association between oxidized low-density lipoprotein (OxLDL) and plaque instability in coronary and carotid artery disease is well established. However, the association between OxLDL and the histologic changes of plaque in peripheral artery disease has not been clearly elucidated. This study aims to investigate the association between plasma OxLDL and histologic plaque instability in patients with peripheral artery disease. Prospectively obtained plaques from 48 patients who underwent endovascular atherectomy (n=20), surgical endarterectomy (n=9), or bypass surgery (n=19) for treatment of atherosclerotic femoropopliteal artery disease were evaluated for histologic fibrosis, sclerosis, calcification, necrosis, cholesterol cleft, and foamy macrophages using hematoxylin and eosin, oil red O, and immunohistochemical staining. Unstable plaques were defined as plaques that were positive for foamy macrophages and with lipid content of more than 10% of the total plaque area. Plasma OxLDL levels were measured using an enzyme-linked immunosorbent assay (Mercodia AB, Uppsala, Sweden). Of the 48 patients, 26 (54%) had unstable plaques. The unstable plaque group was younger, had fewer angiographic total occlusions, less calcification, and more CD68-positive and LOX-1-positive cells than the stable plaque group. Plasma OxLDL levels were significantly higher in the unstable plaque group than in the stable plaque group (57.4±13.9 vs. 47.2±13.6 U/L, P=0.014). Multivariate analysis revealed that plasma OxLDL level, smoking, angiographic nontotal occlusion, and statin nonuse were independent predictors of unstable plaque. Among patients with peripheral artery disease, the histologic instability of femoropopliteal plaque was independently associated with high plasma OxLDL, smoking, nontotal occlusion, and statin nonuse. Further large-scale studies are necessary to evaluate the role of noninvasive OxLDL measurement for predicting plaque instability and future adverse vascular event.

P5366Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging

Abstract Background The relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described. Hypothesis EPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI. Methods Data on coronary artery plaques from 121 patients presenting with acute coronary syndrome or stable angina who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no-EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI. Results We used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low-density lipoprotein cholesterol concentration, triglyceride concentration, and high-density lipoprotein cholesterol concentration). The EPA group had significantly lower mean lipid index (818±806 vs. 1,574±891) and macrophage grade (13.5±5.9 vs. 19.3±7.4) but higher mean minimum fibrous cap thickness (109.2±55.7 vs. 81.6±36.4 μm) than the no-EPA group (P=0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P=0.043 and 0.024, respectively). Conclusion This OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI. Acknowledgement/Funding None

Eicosapentaenoic acid therapy is associated with decreased coronary plaque instability assessed using optical frequency domain imaging.

BackgroundThe relationship between eicosapentaenoic acid (EPA) therapy and coronary plaque stability assessed by optical frequency domain imaging (OFDI) has not been thoroughly described.HypothesisEPA therapy is associated with decreased plaque instability in patients undergoing percutaneous coronary intervention (PCI) using OFDI.MethodsData on coronary artery plaques from 121 patients who consecutively underwent PCI between October 2015 and July 2018 were retrospectively analyzed. Of these patients, 109 were untreated (no‐EPA group), whereas 12 were treated with EPA (EPA group). Each plaque's morphological characteristics were analyzed using OFDI.ResultsWe used 1:4 propensity score matching for patients who received or did not receive EPA therapy before PCI. Baseline characteristics were balanced between both groups (age, sex, body mass index, diabetes mellitus, hypertension, dyslipidemia, chronic kidney disease, smoking, previous PCI or coronary artery bypass grafting, previous myocardial infarction, prior statin use, acute coronary syndrome, hemoglobin A1c level, low‐density lipoprotein cholesterol concentration, triglyceride concentration, and high‐density lipoprotein cholesterol concentration). OFDI data from 60 patients were analyzed in this study. The EPA group had significantly lower mean lipid index (818 ± 806 vs 1574 ± 891) and macrophage grade (13.5 ± 5.9 vs 19.3 ± 7.4) but higher mean minimum fibrous cap thickness (109.2 ± 55.7 vs 81.6 ± 36.4 μm) than the no‐EPA group (P = 0.010, 0.019, and 0.040, respectively). Multiple logistic regression analyses showed that prior EPA use was independently associated with lower lipid index and macrophage grade (P = 0.043 and 0.024, respectively).ConclusionThis OFDI analysis suggests that EPA therapy is associated with decreased plaque instability in patients undergoing PCI.

Correlation of Serum Uric Acid Levels with Nonculprit Plaque Instability in Patients with Acute Coronary Syndromes: A 3-Vessel Optical Coherence Tomography Study.

Elevated serum uric acid (SUA) level is known to be a prognostic factor in patients with acute coronary syndrome (ACS). However, the correlation between SUA level and coronary plaque instability has not been fully evaluated. The aim of this study was to investigate the association between SUA level and plaque instability of nonculprit lesions in patients with ACS using optical coherence tomography. A total of 150 patients with ACS who underwent 3-vessel optical coherence tomography were selected. Patients were classified into 3 groups according to tertiles of SUA level. There was a trend towards a thinner fibrous cap (0.15 ± 0.06 versus 0.07 ± 0.01 versus 0.04 ± 0.01 mm2, p < 0.001) and a wider mean lipid arc (169.41 ± 33.16 versus 177.22 ± 37.76 versus 222.43 ± 47.65°, p < 0.001) with increasing SUA tertile. The plaques of the high and intermediate tertile groups had a smaller minimum lumen area than the low tertile group (6.02 ± 1.11 versus 5.38 ± 1.28 mm2, p < 0.001). In addition, thin-cap fibroatheromas, microvessels, macrophages, and cholesterol crystals were more frequent in the high tertile group than the low and intermediate groups. Multivariate analysis showed SUA level to be a predictor of plaque instability.

Pathological Quantification of Carotid Artery Plaque Instability in Patients Undergoing Carotid Endarterectomy.

Unstable atherosclerotic carotid plaques cause cerebral thromboemboli and ischemic events. However, this instability has not been pathologically quantified, so we sought to quantify it in patients undergoing carotid endarterectomy (CEA).Methods and Results:Carotid plaques were collected during CEA from 67 symptomatic and 15 asymptomatic patients between May 2015 and August 2016. The specimens were stained with hematoxylin-eosin and elastica-Masson. Immunohistochemistry was performed using an endothelial-specific antibody to CD31, CD34 and PDGFRβ. The histopathological characteristics of the plaques were studied. By multiple-variable logistic regression analysis, plaque instability correlated with the presence of plaque rupture [odds ratio (OR), 9.75; P=0.013], minimum fibrous cap thickness (OR per 10 μm 0.70; P=0.025), presence of microcalcifications in the fibrous cap (OR 7.82; P=0.022) and intraplaque microvessels (OR 1.91; P=0.043). Receiver-operating characteristics analyses showed that these factors combined into a single score diagnosed symptomatic carotid plaques in patients with carotid artery stenosis with a high level of accuracy (area under the curve 0.92; 95% confidence interval 0.85-0.99 vs. asymptomatic). This analysis of carotid plaque instability strongly suggested that the diagnostic scoring of carotid plaque instability improves the understanding and treatment of carotid artery disease in patients undergoing CEA.

Abstract 324: Pathological Quantitative Assessment of Plaque Instability in Patients Undergoing Carotid Endarterectomy

Introduction: Instability of carotid atherosclerotic plaques leads to cerebral thromboemboli and ischemic symptoms. However, there has been no specific pathological quantification for the instability of carotid atherosclerotic plaque. The purpose of this study was to quantify atherosclerotic plaque instability in patients undergoing carotid endarterectomy (CEA). Methods: Carotid plaques were collected after CEA from 67 symptomatic and 15 asymptomatic patients between May 2015 and August 2016. Samples were stained with hematoxylin/eosin and Elastica-Masson (E-Masson). Immunohistochemistry was performed by using an endothelial specific antibody to CD31, CD 34 and PDGFRβ. Plaques were assessed for histopathological characteristics. Results: Multivariable logistic regression analysis demonstrated that plaque instability was independently associated with the presence of plaque rupture (odds ratio [OR], 9.75, 95% confidence interval [CI]: 1.62 to 58.6, p = 0.013), the minimal fibrous cap thickness (FCT) (OR per 10 μm 0.70, 95% CI: 0.51 to 0.96, p = 0.025), the presence of microcalcification in the fibrous cap (OR 7.82, 95% CI: 1.35 to 45.4, p = 0.022) and the intraplaque microvessels (OR 1.91, 95% CI: 1.02 to 3.57, p = 0.043). If these four independent parameters were combined to a score using the equation derived from the multivariable logistic regression model (Logit(Score) = 0.179 + 2.277 * (insert 1 if plaque rupture present; else 0) - 0.355 * (insert minimal FCT in multiples of 10 μm) + 2.057 * (insert 1 if microcalcification in the fibrous cap present; else 0) + 0.646 * (insert intraplaque microvessels /mm 2 ), the diagnostic efficiency could be improved to an AUC 0.92 (95% CI: 0.85-0.99, optimal cut-off value 0.814, sensitivity 89.6%, specificity 86.7%, PPV 96.8%, NPV 65.0%, diagnostic accuracy 89.0%). Conclusions: This study suggested the diagnostic scoring was useful for the quantification of carotid plaque instability in patients undergoing CEA.

INTERLEUKIN-6 AND THE RISK OF ADVERSE OUTCOMES IN PATIENTS AFTER AN ACUTE CORONARY SYNDROME: OBSERVATIONS FROM THE SOLID-TIMI 52 TRIAL

Interleukin-6 (IL-6) is an inflammatory marker implicated in plaque instability in patients with ACS. The prognostic value of IL-6 after ACS is not well described. IL-6 concentration (Singulex Erenna) was assessed at baseline in 4,939 subjects in SOLID-TIMI 52, a randomized trial of darapladib in

Is plasma-soluble CD36 associated with density of atheromatous plaque and ankle–brachial index in early-onset coronary artery disease patients?

CD36 is a major macrophage scavenger receptor for oxidised low-density lipoprotein particles. Soluble CD36 (sCD36) is circulating as a ligand-bound complex and may be present in microparticles shed from cells such as platelets, monocytes/macrophages, or adipocytes. Positive association of plasma sCD36 with insulin resistance has been reported, and it has been proposed that sCD36 might represent a marker of macrophage activation and inflammation leading to atherosclerosis. Recently we have identified an association between CD36 polymorphism and low thickness of atheromatous plaque, suggesting its protective effect against atherosclerosis development. To obtain insight into the relationship between plasma concentration of sCD36 and radiological parameters of atherosclerosis in patients with early-onset coronary artery disease (CAD). The study group comprised 70 clinically stable patients (18 women and 52 men) with early CAD (aged no more than 50 years for men and 55 years for women). Fasting blood sample was taken for serum glucose, lipid profile, ApoA1, ApoB, Lp(a), and plasma sCD36 protein measurements. Each subject's weight, height, waist and hip circumference, and systolic and diastolic blood pressure were measured, and the body mass index, waist-to-hip ratio, and mean arterial pressure were calculated. Doppler ultrasound examinations of carotid and peripheral arteries were performed in all patients. Thickness of intima-media complex (IMC) of common carotid (CCA) and brachial arteries, as well as density and thickness of atheromatous plaque at CCA bifurcation, were measured with M'Ath programme. Plasma concentrations of CD36 antigen were measured by ELISA. Correlations between quantitative variables and sCD36 plasma concentration were assessed with the Spearman rank correlation coefficient (Rs). Associations between qualitative variables and sCD36 plasma concentration were tested with the Mann-Whitney U test. We observed no significant correlations between sCD36 concentration and radiological parameters of atherosclerosis. We found only borderline significant negative correlation of sCD36 concentration with thickness of IMC of left brachial artery. We also observed a significantly negative correlation with CCA plaque density, but only in the female subgroup and on the right side. Borderline higher sCD36 plasma concentrations were observed in patients with lower ankle-brachial index value (< 0.9). The results of the study show no strong associations and do not prove either detrimental or beneficial influence of sCD36 on radiological parameters of atherosclerosis. Further research is necessary to assess the association of high plasma sCD36 concentrations with the risk of plaque instability in patients with early-onset CAD.

Association between blood glucose variability and coronary plaque instability in patients with acute coronary syndromes.

BackgroundBlood glucose variability is receiving considerable attention as a new risk factor for coronary artery disease. This study aimed to investigate the association between blood glucose variability and coronary plaque tissue characteristics.MethodsIn 57 patients with acute coronary syndrome, integrated backscatter intravascular ultrasound (IB-IVUS) and gray-scale IVUS were performed before balloon dilatation or stent implantation in the culprit vessels. Standard IVUS indices were evaluated for volume index (volume/length), and plaque components were measured by IB-IVUS for percent tissue volume. In addition to conventional glucose indicators, blood glucose variability in a stable state was determined by calculating the mean amplitude of glycemic excursions (MAGE) using a continuous glucose monitoring system.ResultsHigher MAGE values were significantly correlated with larger percent plaque volumes (r = 0.32, p = 0.015), and increased lipid (r = 0.44, p = 0.0006) and decreased fibrous (r = −0.45, p = 0.0005) plaque components. In contrast, HbA1c or fasting plasma glucose values were not significantly correlated with plaque volumes and percent plaque components. Homeostasis model assessment of insulin resistance values were positively correlated with vessel (r = 0.35, p = 0.007) and plaque (r = 0.27, p = 0.046) volumes, but not with percent plaque components. In multiple regression analysis, higher MAGE values were independently associated with increased lipid (β = 0.80, p = 0.0035) and decreased fibrous (β = -0.79, p = 0.0034) contents in coronary plaques.ConclusionsAmong all glucose indicators studied, only higher blood glucose variability was an independent determinant of increased lipid and decreased fibrous contents with larger plaque burden, suggesting blood glucose variability as one of the important factors related to coronary plaque vulnerability.

Upregulation of miR-155 in CD4(+) T Cells Promoted Th1 Bias in Patients With Unstable Angina.

An imbalance between T helper 1 (Th1) and T helper 2 (Th2) cells has been reported to increase plaque instability in patients with unstable angina (UA). MicroRNAs play a vital role in the differentiation of CD4(+) T cells. However, the role of microRNAs in regulation of Th1/Th2 balance in UA remains unclear. In this study, we aimed to elucidate microRNA expression profiles of circulating CD4(+) T cells in UA and to explore the function of microRNAs in the Th1/Th2 balance. A total of 53 patients with UA and 31 control subjects without coronary artery disease were enrolled. Microarray analysis of the microRNA expression profiles of CD4(+) T cells revealed that miR-155 was the most significantly upregulated microRNA of the 451 differentially expressed microRNAs. The upregulation of miR-155 expression was positively correlated with the percentage of Th1 cells and interferon-gamma (IFN-γ) levels in patients with UA. In addition, overexpression of miR-155 in human circulating CD4(+) T cells promoted Th1 differentiation. Further studies identified IFN-γ receptor alpha chain (IFN-γ Rα) mRNA as a direct and functional target of miR-155. A luciferase reporter assay verified that miR-155 directly targeted IFN-γ Rα mRNA. Small-interfering RNA-mediated knockdown of IFN-γ Rα mRNA showed effects similar to those of ectopic miR-155 expression. Thus, our study indicated that upregulation of miR-155 in circulating CD4(+) T cells in patients with UA promoted a shift in the Th1/Th2 balance toward Th1 dominance by repressing IFN-γ Rα, which may subsequently enhance plaque instability.