Calcified Plaque Research Articles

Abstract 15473: A New Metabolic Phenotype in a Mouse Model of Chronic Kidney Disease and Atherosclerosis

Introduction: Patients with chronic kidney disease (CKD) experience significant cardiovascular morbidity and mortality. Vascular calcification is a hallmark of CKD and a strong predictor of atherosclerotic cardiovascular disease. Hypothesis: We hypothesize that CKD-induced vascular calcification potentiates atherosclerosis. Methods: First, wished to conduct a pilot study to confirm that a co-treatment of the low-density protein receptor mutant mice (Ldlr whc ) with a 0.2% adenine in a western diet will produce accelerated atherosclerosis, consistent with a well-known phenotype in the 5/6 nephrectomy model on an ApoE or Ldlr knockout background. Then we developed a two-step non-surgical mouse model in which the induction of calcification by a 0.2% adenine treatment was followed by western diet-induced hyperlipidemia. Results: Contrary to expected, the adenine and western diet (W+A) co-treatment resulted in a striking reduction of plasma triglycerides (TG), aortic root atherosclerosis, and liver lipids despite a fully penetrant CKD phenotype with tubulointerstitial damage, increased blood urea nitrogen, hyperphosphatemia, polyuria, vascular calcification, and osteoporosis. The two-step induction of CKD and atherosclerosis demonstrated partially normalized but reduced plasma triglycerides and liver lipid content, polyurea, and polydipsia in CKD mice, and there was no difference in atherosclerotic burden or plaque calcification between the groups. Interestingly we observed an increase in food and calorie intake and 24-hour glucose excretion in the urine in the pre-treated group compared with mice on a western diet without pre-treatment, while plasma glucose levels were not different between the groups. Conclusion: The paradoxical lack of dyslipidemia in mice treated with adenine provides an insight into the potential effects of tubulointerstitial kidney disease and nephrogenic diabetes incipits on lipid metabolism and atherosclerosis. 1

Abstract 13441: Transcriptomic Analysis of Endothelial Colony Forming Cells From the BioHEART-CT Study to Unravel New Biomarkers for Coronary Artery Disease

Coronary artery disease (CAD) remains the leading cause of death worldwide. There are unmet needs for the diagnosis and treatment for patients with CAD, especially those without modifiable risk factors who are suspected to be at low risk for CAD. Endothelial function has predictive value for future cardiovascular events. We previously showed that endothelial colony forming cells (ECFCs) derived from the BioHEART-CT (The BioHEART Study: Assessing Patients with Suspected Cardiovascular Disease for New Biomarkers and Risk Factors) cohort can be used as a viable tool to evaluate endothelial function in patients as these cells retain the memory of their host. Here, we aimed to characterize the transcriptomic profiles of ECFCs in non-CAD and CAD patients. Based upon our previous findings on the positive correlation between mitochondrial superoxide level and the severity of CAD, we hypothesize that the transcriptomic and functional analyses of the mitochondrial pathways are dysregulated in the ECFCs in CAD patients. RNA-sequencing was performed in ECFCs cultured from the peripheral blood of 44 patients from the BioHEART-CT cohort who had computed tomography coronary angiograms scored for coronary artery calcium (CAC) and Gensini to measure CAD severity. The cohort included 45.5% women and 54.5% men with an average age of 61.6 years. Non-CAD group was determined by a Gensini score of zero, whereas CAD group was determined by a Gensini score of greater than 5. These CAD patients had median CAC score of 266.8, with significant presence of calcified and soft plaques in their coronary arteries. Transcriptomic analysis of ECFCs showed that a total of 37 genes were upregulated and 77 genes were downregulated in the CAD patients. To investigate the functional relevance of the pathways altered in the CAD cohort, dysregulation of genes was analyzed using gene set enrichment analysis. We found that the metabolic processes, those associated with mitochondrial biogenesis, were significantly altered in the ECFCs. Our approach of using RNA-sequencing to determine the gene characteristics of CAD patients and their functional relevance to disease has the potential to unravel previously un-identified genes or biomarkers that are distinct to CAD patients.

Abstract 13995: Relationships Between Neighborhood Disadvantage and Cardiovascular Findings at Autopsy in Subjects With Sudden Death

Introduction: Neighborhood disadvantage is associated with a higher risk of sudden cardiac death. However, autopsy findings have never been investigated in this context. Here, we sought to explore associations between neighborhood disadvantage and cardiovascular findings at autopsy in cases of sudden death in the State of Maryland. Methods: State of Maryland investigation reports from 2,278 subjects within the CVPath Sudden Death Registry were screened for street addresses and 9-digit zip-codes. Area Deprivation Index (ADI), used as metric for neighborhood disadvantage, was available for 1,464 subjects; 650 of whom self-identified as Black and 814 as White. The primary study outcome measurements were causes of death and gross and histopathologic findings of the heart. Results: Subjects from most disadvantaged neighborhoods ( i.e. , ADI ≥ 8; n = 607) died at younger age compared with subjects from less disadvantaged neighborhoods ( i.e. , ADI ≤ 7; n = 857; 46.07 ± 14.10 versus 47.78 ± 13.86 years; p = 0.02) and were more likely Black or women. They were, however, less likely to die from cardiac causes of death (61.8% versus 67.7%; p = 0.02) and had less severe atherosclerotic plaque features, including plaque burden, calcification, intraplaque hemorrhage, and thin-cap fibroatheromas. In addition, subjects from most disadvantaged neighborhoods had lower frequencies of plaque rupture (18.8% versus 25.1%, p = 0.004). However, these associations were omitted after adjustment for traditional risk factors and race. Conclusion: Neighborhood disadvantage did not associate with cause of death or coronary histopathology after adjustment for cardiovascular risk factors and race, implying that social determinants of health other than neighborhood disadvantage play a more prominent role in cardiovascular pathology.

Abstract 12773: Computed Tomography Angiography Evaluation of Coronary Plaque Burden in South Asians and Non-Hispanic Whites Over 65 Years of Age

Introduction: South Asians (SA) have greater atherosclerotic cardiovascular disease (ASCVD) rates than non-Hispanic whites (NHW). SA ethnicity is a risk factor for cardiovascular disease, according to ACC/AHA guidelines. However, data on pattern of atherosclerosis in SA is limited. This study examines plaque burden in SA using quantitative plaque analysis from coronary CT angiography (CCTA). Methods: This is a cross-sectional study comparing the prevalence of atherosclerosis in SA to that of NHW. We identified 104 South Asians who underwent CCTA and quantitative plaque analysis. We then matched 1:1 with 104 non-Hispanic whites. Age, gender, diabetes, hypertension and smoking were utilized to perform a 1: 1 covariate match. Quantification of coronary plaque was conducted using automated plaque analysis software (Cleerly, NY, NY). Percentage atheroma volume (PAV), which is a measure of total plaque divided by total vessel volume, was calculated for each plaque subtypes. Results: A total of 208 subjects formed the study population. The mean age was 71.2±4.9, 66% being male, 38% had DM, 72% reported hypertension, and 10% were past smokers in each group. The SA cohort had significantly higher calcified plaque PAV compared to NHW cohort, median (IQR), 7.6(1.9, 15.5) versus 3.9(1.3, 9.6), (p=0.027). Noncalcified plaque PAV was higher in SA 5.2 (3.0, 7.9) versus 4.5 (2.6,7.2), but not statistically significant (p=0.35). The number of subjects with obstructive disease (&gt50% stenosis) trended higher in the SA cohort (71% of SA versus 60% of NHW) (p=0.08). Conclusions: South Asians had significantly higher calcified plaque PAV and a higher prevalence of obstructive disease compared to the NHW cohort. These results are suggestive of a unique plaque burden and distinctive characteristics in the SA population, which may explain the greater incidence of cardiovascular events and supports the current guidelines.

Abstract 13889: Effect of Eicosapentaenoic and Docosahexaenoic Acid Supplementation on Noncalcified Coronary Plaque and Coronary Artery Calcium Score in Subjects With Coronary Artery Disease According to Hypertension Status

Introduction: Higher amounts of noncalcified plaque and higher coronary artery calcium (CAC) scores are associated with increased cardiovascular events and mortality. The effect of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on noncalcified coronary plaque and more advanced calcified plaque as measured by the CAC score according to hypertensive (HTN) status is unknown. Methods: A total of 242 subjects with coronary artery disease (CAD) on statin were randomized to 3.36 g of EPA+DHA or none (control) for 30 months. Coronary plaque composition and CAC scores were measured with computed tomographic coronary angiography at baseline and 30-month follow-up. Results: Mean (SD) age was 63.1 years (7.7); mean (SD) LDL-C: 77.8 mg/dL (27.3) and median [IQR] triglyceride (TG): 117.5 mg/dL [81.3,166.8]. Despite a significantly higher CAC score at baseline in HTN subjects, both HTN and normotensive (NTN) subjects had similar CAC progression over 30 months with no difference between EPA+DHA and control groups (Figure B). NTN subjects on EPA+DHA had a 20.7% reduction in TG level and 36.6% lower neutrophil count, a marker of inflammation, and lack of progression of noncalcified plaque compared to control who had progression (median % change: -7.6 vs 13.2 mm 3 /mm, P=0.008) (Figure A). In contrast, HTN subjects on EPA+DHA and control had progression of noncalcified coronary plaque with no significant difference between the two groups (Figure A) Conclusions: EPA+DHA prevented progression of noncalcified plaque in NTN subjects but not HTN subjects with no effect on more advanced plaque which has calcified in the setting of low LDL-C and TG levels. The benefit of EPA+DHA in CAD patients on statin therapy appears limited to noncalcified coronary plaque in NTN subjects. Whether this benefit is related to more favorable effects on inflammation based on blood pressure status should be examined further.

Carotid plaque components and other carotid artery features associated with risk of stroke: A systematic review and meta-analysis

ObjectiveTo compare the difference in the risk of stroke for four kinds of carotid artery plaque and carotid artery stenosis. MethodsLiterature was collected by searching the PubMed, Embase, Cochrane library and Ovid databases up to June 2022, using the free search terms "carotid plaque" and "stroke". Meta-analysis was performed on the selected articles using Stata16 to analyse the relationship of stroke risk factors. ResultsA total of 11 studies including 6661 participants were included. Meta-analysis results showed that the incidence of stroke was statistically significantly different between IPH (intraplaque haemorrhage) plaques and LRNC (lipid-rich necrotic core) plaques (RR: 1.27, 95% CI: 1.04–1.55, P < 0.05) and IPH plaques and calcification plaques (RR: 2.99, 95% CI: 1.74–5.14, P < 0.0001). Furthermore, there was a statistically significant difference between TRFC (thinned or ruptured fibrous caps) plaques and carotid artery stenosis (RR: 10.84, 95% CI: 5.60–20.98, P < 0.0001) and calcification plaques and carotid artery stenosis (RR: 0.83, 95% CI: 0.75–0.92, P < 0.0001). However, there was no statistically significant difference between the IPH and carotid artery stenosis (RR: 1.55, 95% CI: 0.68–3.52, P > 0.05), LRNC and TRFC (RR: 0.80, 95% CI: 0.11–5.82, P > 0.05), LRNC and calcification (RR: 1.81, 95% CI: 0.90–3.66, P > 0.05) and LRNC and carotid artery stenosis (RR: 1.40, 95% CI: 0.69–2.81, P > 0.05). ConclusionIPH was associated with a higher incidence of stroke compared to LRNC and calcification plaques and TRFC has a higher risk of stroke than calcification plaques and carotid stenosis. This evidence suggests that IPH and TRFC may play an important role in predicting stroke.

Differentiating malignant pleural mesothelioma and metastatic pleural disease based on a machine learning model with primary CT signs: A multicentre study

Rationale and ObjectivesIt is still a challenge to make confirming diagnosis of malignant pleural mesothelioma (MPM), especially differentiating from metastatic pleural disease (MPD). The aim of this study was to develop a model to distinguish MPM with MPD based on primary CT signs. Materials and methodsWe retrospectively recruited 150 MPM patients and 147 MPD patients from two centers and assigned them to training (115 MPM patients and 113 MPD patients) and testing (35 MPM patients and 34 MPD patients) cohorts. The images were analyzed for pleural thickening, hydrothorax, lymphadenopathy, thoracic volume and calcified pleural plaque (CPP). The selected clinical characteristics and primary CT signs comprised the model by multivariate logistic regression in the training cohort. Then the model was tested on the external testing cohort. ROC curve and F1 score were used to validate the capability of the model in both two cohorts. ResultsThere were significant differences between two groups: (1) carcinoembryonic antigen (CEA); (2) nodular and mass pleural thickening; (3) the enhancement of pleura; (4) focal, diffuse and circumferential pleural thickening; (5) the thickest pleura; (6) thickening of diaphragmatic pleura; (7) multiple nodules and effusion of interlobar pleura; (8) hilar LN and ring enhancement of LN; (9) punctate and stipe CPP. The AUC and F1 score of the model were 0.970 and 0.857 in the training cohort, 0.955 and 0.818 in the testing cohort. ConclusionThe model holds promise for use as a diagnostic tool to distinguish MPM from MPD.

Intravascular Lithotripsy in Peripheral Artery Disease.

Peripheral artery disease affects millions of people worldwide, and it is associated with significantly higher morbidity and mortality. In addition, it represents a significant challenge for the interventional operators to appropriately and successfully revascularize heavily calcified stenoses. There are several established atherectomy devices with the risk of procedural complications including dissection and perforation, among others. Intravascular lithotripsy (IVL) is a novel tool with relatively less procedural risk compared to the existing modalities. It is a device that emits high-energy ultrasound waves mounted on a balloon catheter that causes fractures on the calcium plaques allowing balloon expansion and luminal gain. Five trials have been published showing the safety and effectiveness of IVL, including one trial evaluating the device in common femoral artery and infrapopliteal arteries. The available data from the limited number of trials are very encouraging and demonstrates minimal risk. Additional studies on a larger scale are needed further to understand the its long-term effects and possible risks.

Atherogenic Indices as a Predictor of Aortic Calcification in Prostate Cancer Patients Assessed Using 18F-Sodium Fluoride PET/CT.

A major pathophysiological cause of cardiovascular disease is vascular plaque calcification. Fluorine 18−Sodium Fluoride (18F-NaF) PET/CT can be used as a sensitive imaging modality for detection of vascular calcification. The aim of this study was to find a non-invasive, cost-efficient, and readily available metric for predicting vascular calcification severity. This retrospective study was performed on 36 participants who underwent 18F-NaF fused PET/CT scans. The mean standard uptake values (SUVs) were calculated from manually sectioned axial sections over the aortic arch and thoracic aorta. Correlation analyses were performed between SUVs and calculated atherogenic indices (AIs). Castelli’s Risk Index I (r = 0.63, p < 0.0001), Castelli’s Risk Index II (r = 0.64, p < 0.0001), Atherogenic Coefficient (r = 0.63, p < 0.0001), Atherogenic Index of Plasma (r = 0.51, p = 0.00152), and standalone high-density lipoprotein (HDL) cholesterol (r = −0.53, p = 0.000786) were associated with aortic calcification. AIs show strong association with aortic arch and thoracic aorta calcifications. AIs are better predictors of vascular calcification compared to standalone lipid metrics, with the exception of HDL cholesterol. Clinical application of AIs provides a holistic metric beneficial for enhancing screening and treatment protocols.

The Role of Inflammation in Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1β, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

Effect of balloon pre-dilation on performance of self-expandable nitinol stent in femoropopliteal artery

Balloon pre-dilation is usually performed before implantation of a nitinol stent in a femoropopliteal artery in a case of severe blockage or calcified plaque. However, its effect on performance of the nitinol stent in a diseased femoropopliteal artery has not been studied yet. This study compares the outcomes of stenting with pre-dilation and without it by modelling the entire processes of stent deployment. Fatigue deformation of the implanted stent is also modelled under diastolic–systolic blood pressure, repetitive bending, torsion, axial compression and their combination. Reduced level of stress in the stent occurs after stenting with pre-dilation, but causing the increased damage in the media layer, i.e. the middle layer of the arterial wall. Generally, pre-dilation increases the risk of nitinol stent’s fatigue failure. Additionally, the development of in-stent restenosis is predicted based on the stenting-induced tissue damage in the media layer, and no severe mechanical irritation is induced to the media layer by pre-dilation, stent deployment or fatigue loading.

Associations of non-HDL-C and triglyceride/HDL-C ratio with coronary plaque burden and plaque characteristics in young adults.

Coronary artery disease (CAD) is uncommon in young adult patients. However, these patients have different risk factor profiles and high-risk coronary plaques are more common. The aim of this study was to examine the relations between the coronary plaque burden, plaque composition, serum non-high-density lipoprotein cholesterol (non-HDL-C) levels, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio in young adults. We analyzed a total of 551 patients under age 45 who had undergone coronary computed tomography angiography (CCTA). Coronary plaque characteristics were analyzed using CCTA. Multivariate linear regression analysis was used to assess the predictors of non-calcified plaque (NCB) and calcified plaque (CB) burdens. Serum non-HDL-C levels and TG/HDL-C ratio were higher in the coronary atherosclerosis patient group. Serum non-HDL-C levels and the TG/HDL-C ratio were higher in the obstructive CAD patient group. The plaque burden was positively correlated with non-HDL-C (r = 0.30; p < 0.001), and TG/HDL-C ratio (r = 0.18; p < 0.001). NCB was positively correlated with age, gender, smoking status, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, serum triglycerides, hbA1c, non-HDL-C, and TG/HDL-C ratio. Non-HDL-C (β coefficient = 0.13; p = 0.023) and TG/HDL-C ratio (β = 0.10; p = 0.042) were independent predictors of NCB. Serum non-HDL-C levels and TG/HDL-C were significantly associated with the presence and burden of coronary plaques. Serum non-HDL-C and TG/HDL-C ratios were independently associated with NCB, suggesting their use as easy-to-compute markers for identifying high-risk groups in young adults.

Plaque composition on ultra-high-resolution coronary computed tomography angiography with optical coherence tomography correlation.

A 68-year-old man presented to our chest pain unit with angina and a low pre-test probability for coronary artery disease (CAD). Troponin levels were normal, and echocardiography showed an intact left ventricular function. Coronary computed tomography angiography (CCTA) was performed using a first-generation dual-source photon-counting detector computed tomography (PCD-CT, NAEOTOM Alpha®, Siemens Healthineers) in a novel ultra-high resolution (UHR) mode. Data were reconstructed at 0.6 and 0.2 mm to reflect the typical appearance on standard and PCD-CT scanners (Panels A/D and B/E, respectively). The RCX presented with a mixed plaque and moderate-to-severe stenosis, right coronary artery (RCA) with a soft plaque and moderate-to-severe stenosis (Panels A and B), and LAD with a mostly a calcified plaque and mild stenosis (Figure 1D). UHR reconstructions revealed a fibrous cap on the calcified plaque (Panel E). Subsequent invasive coronary angiography including optical coherence tomography (OCT) confirmed a significant stenosis in the RCA [Panel C, fibrous plaque with micro-calcifications (arrowhead)] and left circumflex coronary artery (LCX) (mostly fibrotic components). Both were successfully treated with drug-eluting stents [thrombolysis in myocardial infarction (TIMI) coronary grade flow 3 (TIMI 3)]. Further, OCT confirmed the mild stenosis of the LAD caused by lesion with a fibrous cap over the calcification (Panel F).

The influence of overweight and obesity in the oral health of a sample of portuguese adults

Abstract Background Overweight and obesity may lead to different problems in various body systems and in the oral cavity. Dental caries and periodontal disease have been related with overweight. The aim of this study was to assess how overweight and obesity have impact on the lifestyle, oral habits and oral pathologies. Methods We conducted an observational cross-sectional study where we applied a questionnaire to 140 individuals from Lisbon and Viseu, Portugal., which 70 had a normal Body Mass Index (BMI) (control group) and 70 had an excessive BMI. We also made an oral observation in each individual to record the permanent teeth decayed, missing and filled index (DMFT), the Community Periodontal Index and the oral hygiene status. Results From the final sample, 30% of the subjects with overweight brushed their teeth once a day or less, while the majority (62.9%) of the control group brushed twice a day. In the oral examination, 70% had calculus, while in the control group only 22.5% presented calcified plaque. The DMFT was higher among the obesity group in comparison with the control group. Regarding periodontal disease, the participants with overweight need more dental intervention (81.4%) in contrast with the control group (14%). Conclusions Most overweight and obese individuals present precarious oral hygiene habits, higher prevalence of dental caries, and worse periods of periodontal health. They are not aware of the repercussions of the association between their cariogenic diet, oral health and overweight. Key messages • Oral health behaviors are related with other health conditions, namely obesity and this is a fundamental public health issue. • Primary preventive strategies should be established having in consideration the oral health status of adults in treatment for obesity and in weight control programs.

Collagenase Clostridium histolyticum Treatment Improves Degree of Curvature in Peyronie’s Disease with Calcified Plaques

BackgroundPeyronie’s disease (PD) is a fibrotic condition of the penis characterized by abnormal plaque formation. Intralesional collagenase Clostridium histolyticum (CCh) is effective in noncalcified PD; however, its effectiveness in calcified PD is not well characterized. ObjectiveTo assess curvature improvement in calcified PD plaques treated with CCh. Design, setting, and participantsWe prospectively evaluated men with calcified PD electing CCh treatment at our institution from October 2018 to November 2020. We assessed curvature with artificial erection and goniometer before and at least 3 mo after treatment. We classified the type of plaque calcification based on ultrasound. InterventionIntralesional CCh. Each treatment cycle consisted of two CCh injections (0.58 mg) into the plaque at the point of maximal penile curvature. The second injection was performed 72 h to 1 wk later, after which participants began modeling. All men were intended to receive a total of eight injections in four cycles, each 6 wk apart. Outcome measurements and statistical analysisChange in penile curvature after CCh was measured. We assessed for differences in outcomes based on the number of injections and type of calcification. Unless otherwise specified, data are presented as medians (interquartile range). Results and limitationsSixty men with calcified PD elected CCh; 47 had complete follow-up data. Thirty-nine men completed treatments with eight injections, while the remaining discontinued after a median of five (four to six) injections. There was no difference in response between type 2 and type 3 plaques. Curvature significantly improved by 17.5° (37.5–10.0°) in patients who completed treatment and by 15.0° (20.0–0.0°) in those who discontinued. Limitations include a small sample. ConclusionsMen with calcified PD plaques improve with CCh treatment and show similar improvements regardless of calcification type. Patient summaryIn this study, we evaluated the efficacy of collagenase Clostridium histolyticum (CCh) treatment in calcified Peyronie’s disease (PD) plaques. We found that treatment in calcified plaques demonstrated significant improvement in curvature and the grading of calcification did not impact the degree of curvature improvement. We conclude that participants with calcified PD plaques can benefit from nonsurgical CCh treatment.

Automatic Segmentation of Calcified Plaques and Vessel Borders from Abdominal Aorta CTA Images Using a 2D Spatial Convolutional Multilayer Machine Vision Classifier

The aorta, including the thoracic and abdominal aortas, distributes blood from the heart to the upper and lower circulatory systems. Abdominal aortic sclerosis can cause abdominal aortic aneurysm. When the diameter of the aorta increases by more than 1.5 times its normal size (e.g., ≥4−5 cm, mean diameter in an adult is 2−3 cm), the risk of aneurysm rupture gradually increases. Aneurysm rupture and its associated bleeding have high mortality rates. Hence, the prediction of large diameter aortic aneurysms is an important issue with great clinical implications. In computed tomography angiography (CTA) imaging examination, an assistive tool for automatic image segmentation must be developed to help cardiologists and radiologists evaluate the risk of rupture progression and make appropriate treatment decisions. In this study, two‐dimensional (2D) spatial convolution operations (corner detection) and a multilayer machine vision classifier enabled the automatic segmentation of the luminal region, vascular intima, and calcified plaques in the abdominal aorta. The 2D spatial convolution operations can efficiently increase focus, remove unwanted noise in the convolutional layer, and segment calcified plaques and the vessel border by using a general regression neural network (GRNN)‐based classifier. The classifier's outputs can also be visualized in color presentation (red, green, and blue color series) to identify vessel borders and calcified plaques. Luminal change rate (LCR), calcified plaque rate (CPR), and ellipse ratio (ER) can be defined as criteria for evaluating changes in the luminal region and locating calcified plaques, which can be used to identify the locations of cross‐sectional shape changes and calcified plaques. Based on the collected CTA images from the clinical case studies, the proposed multilayer classifier has promising results for the intended medical purpose. With the LCR index, the correlation coefficients (R2) for manual image segmentation and automatic image segmentation is &gt;0.90 in positive correlation for vessel borders segmentation. The proposed method is an adaptive learning scheme with potential clinical applications in automatic CTA image segmentation for further abdominal aortic aneurysm (AAA) risk evaluation. © 2022 Institute of Electrical Engineers of Japan. Published by Wiley Periodicals LLC.

Additive effects of ezetimibe, evolocumab, and alirocumab on plaque burden and lipid content as assessed by intravascular ultrasound: A PRISMA-compliant meta-analysis.

Background:The additive effects of ezetimibe, evolocumab or alirocumab on lipid level, plaque volume, and plaque composition using intravascular ultrasound (IVUS) remain unclear.Methods:According to the Preferred Reporting Items for Systematic reviews and Meta-Analyses statement, we performed a systematic review and meta-analysis of trials assessing the effects of ezetimibe, evolocumab, and alirocumab on coronary atherosclerosis using IVUS. The primary outcome was change in total atheroma volume (TAV), and the secondary outcomes were changes and differences in plaque composition and lipid content.Results:Data were collected from 9 trials, involving 917 patients who received ezetimibe, evolocumab or alirocumab in addition to a statin and 919 patients who received statins alone. The pooled estimate demonstrated a significant reduction in TAV with the addition of ezetimibe and favorable effects of evolocumab and alirocumab on TAV. Subgroup analysis also supported favorable effects of evolocumab and alirocumab on TAV, according to baseline TAV, gender, type 2 diabetes mellitus, and prior stain use. Addition of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to statin therapy resulted in significant reductions in low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG), but not in high-density lipoprotein cholesterol (HDL-C). The pooled estimate also showed significant favorable effects of ezetimibe on LDL-C, TC, and TG, but an insignificant effect on HDL-C. Patients who received ezetimibe showed similar changes in the necrotic core, fibro-fatty plaque, fibrous plaque, and dense calcification compared with patients not treated with ezetimibe.Conclusions:The addition of ezetimibe to statin therapy may further reduce plaque and lipid burdens but may not modify plaque composition. Although current evidence supports a similar impact from the addition of PCSK9 inhibitors to statin therapy, more evidence is needed to confirm such an effect.

Decoding the transcriptome of calcified atherosclerotic plaque at single-cell resolution

Atherogenesis involves an interplay of inflammation, tissue remodeling and cellular transdifferentiation (CTD), making it especially difficult to precisely delineate its pathophysiology. Here we use single-cell RNA sequencing and systems-biology approaches to analyze the transcriptional profiles of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) in calcified atherosclerotic core (AC) plaques and patient-matched proximal adjacent (PA) portions of carotid artery tissue from patients undergoing carotid endarterectomy. Our results reveal an anatomic distinction whereby PA cells express inflammatory mediators, while cells expressing matrix-secreting genes occupy a majority of the AC region. Systems biology analysis indicates that inflammation in PA ECs and VSMCs may be driven by TNFa signaling. Furthermore, we identify POSTN, SPP1 and IBSP in AC VSMCs, and ITLN1, SCX and S100A4 in AC ECs as possible candidate drivers of CTD in the atherosclerotic core. These results establish an anatomic framework for atherogenesis which forms the basis for exploration of a site-specific strategy for disruption of disease progression.

Association between Arousals during Sleep and Subclinical Coronary Atherosclerosis in Patients with Obstructive Sleep Apnea.

(1) Aim: We aim to evaluate the association between arousals during sleep and subclinical coronary atherosclerosis detected by coronary computed tomography angiography (CTA) in patients with obstructive sleep apnea (OSA). (2) Methods: This was a cross-sectional study. Consecutive newly diagnosed OSA patients, who underwent coronary CTA examinations within 3 months of the sleep study, were eligible. We used the arousal index (ArI) derived from polysomnography to assess arousals during sleep and a semi-automated plaque quantification software to characterize and quantify the subclinical coronary atherosclerosis. Multiple regression models were used to evaluate the associations of the ArI with the coronary atherosclerotic plaque presence, volume, and composition. (3) Results: A total of 99 patients with OSA were included in the study. In the multivariable models, patients with a high ArI (ArI > 32.2 events/h) were more likely to have coronary plaques compared to those with a low ArI (ArI ≤ 32.2 events/h) (OR: 3.29 [95% CI: 1.284 to 8.427], p = 0.013). Furthermore, the ArI exhibited significant associations with total (β = 0.015), noncalcified (β = 0.015), and low-attenuation (β = 0.012) coronary plaque volume after accounting for established risk factors (p = 0.008, 0.004, and 0.002, respectively). However, no association between the ArI and calcified plaque volume was found. (4) Conclusion: Repetitive arousals during sleep are associated with an increased coronary plaque burden in patients with OSA, which remained robust after adjusting for multiple established cardiovascular risk factors.

Identification of non-calcified coronary plaque characteristics using machine learning radiomic analysis of non-contrast high-resolution CT

Abstract Objective To explore whether machine learning (ML) radiomic analysis of low-dose, high-resolution, non-contrast, ECG gated cardiac CT scan allows identification of non-calcified coronary plaque characteristics. Background Novel imaging and analysis techniques may provide the ability to detect non-calcified or high risk coronary plaques on a non-contrast CT scan, advancing cardiovascular diagnostics. Methods We prospectively enrolled 125 patients with a non-calcified plaque and an adverse plaque characteristic (APC), and 25 controls without visible atherosclerosis on coronary CT angiography (CCTA). All patients underwent the non-contrast CT exam prior to CCTA. 419 radiomic features were calculated to identify: presence of any CAD, obstructive CAD (stenosis&amp;gt;50%), plaque with ≥2 APC, degree of calcification and specific APCs. ML models were trained on a training set (917 segmentations) and tested on a separate (validation) set (292 segmentations). Results Among the radiomic features 88.3% was associated with any plaque, 0.9% with obstructive CAD and 76.4% with presence of at least two APCs. Overall, 80.2%, 88.5% and 36.5%, of features were associated with calcified, partially calcified, and noncalcified plaques, respectively. Regarding APCs, 61.1%, 61.8%, 84.2%, and 61.3%, of features were associated with low attenuation (LAP), napkin-ring sign (NRS), spotty calcification (SC), and positive remodeling (PR), respectively. ML models outperformed conventional methods for the presence of plaque, obstructive stenosis, presence of 2 APC, as well as for noncalcified plaque and partially calcified plaque, but not for calcified plaque. ML models also significantly outperformed identification of LAP and PR, but neither NRS nor SC. Conclusions Radiomic analysis of non-contrast CT heart exams may allow identification of specific non-calcified coronary plaque characteristics which could aid cardiovascular risk stratification or pre-screening of individuals prior to contrast enhanced CCTA exam. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Science Center