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Coronary computed tomography angiography (CTA) allows for the assessment of atherosclerotic plaque burden across the entire coronary vasculature. No studies have examined the relationship between the underlying pathology of the culprit lesion and total plaque burden in patients with acute coronary syndromes. The aim of this study was to compare the total plaque burden between patients with plaque rupture versus plaque erosion. A total of 232 patients who presented with their first non-ST-segment elevation acute coronary syndrome and underwent both CTA and optical coherence tomography imaging before intervention were selected. Quantitative analysis was performed using semi-automated software (Autoplaque version 3.0, Cedars-Sinai Medical Center). An attenuation of <30 Hounsfield units defined low-density non-calcified plaque (LDNCP). All 3 vessels were assessed using the modified 17-segment American Heart Association model for coronary segment classification. Among 232 patients, 125 (53.9%) had plaque rupture and 107 (46.1%) had plaque erosion. Total plaque burden (48.2 [39.8–54.9] % vs. 44.1 [38.6–50.0] %, P ​= ​0.006), total non-calcified plaque (NCP) burden (46.6 [39.1–53.3] % vs. 43.0 [37.6–49.2] %, P ​= ​0.013), total LDNCP burden (2.3 [1.4–3.0] % vs. 1.7 [1.2–2.6] %, P ​= ​0.016), and total calcified plaque (CP) burden (0.8 [0.1–1.6] % vs. 0.4 [0.0–1.4] %, P ​= ​0.047) were significantly greater in patients with culprit plaque rupture than in those with culprit plaque erosion. Patients with plaque rupture, compared with those with plaque erosion, had a greater total plaque burden, NCP burden, LDNCP burden, and CP burden. URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04523194. Patients with plaque rupture had a greater total plaque burden than those with plaque erosion. LAD ​= ​left anterior descending artery; LCX ​= ​left circumflex artery; RCA ​= ​right coronary artery. [Display omitted] [ABSTRACT FROM AUTHOR]

The relationship between plaque burden and microscopic characterization of plaque features as it pertains to clinical presentation has not been fully investigated. The aim of this study was to compare the relationship between plaque burden and plaque vulnerability in patients with acute coronary syndromes (ACS) versus chronic coronary syndrome (CCS). Patients who underwent both coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) before coronary intervention were enrolled. All plaques were detected in culprit vessels using CTA, and total plaque volume (TPV) and OCT features were assessed at the corresponding sites. All plaques were divided into three groups according to the tertile levels of TPV (low TPV: <96.5 ​mm3, moderate TPV: 96.5–164.7 ​mm3, high TPV: ≥164.8 ​mm3). A total of 990 plaques were imaged by OCT in 419 patients: 445 plaques in 190 (45.3%) patients with ACS and 545 in 229 (54.7%) with CCS. Macrophage was more prevalent in plaques with greater TPV in patients who presented with ACS but not in those who presented with CCS (low vs. moderate vs. high TPV group: macrophage 57.4% vs. 71.8% vs. 82.4% in ACS; 63.4% vs. 67.8% vs. 66.7% in CCS; interaction P ​= ​0.004). Lipid arc increased as TPV increased, especially in patients who presented with ACS. Conversely, the layer index increased as TPV increased in patients with CCS. Greater plaque burden was closely related to higher levels of plaque vulnerability in ACS and greater volume of layered plaque in CCS. clinicaltrials.gov Identifier: NCT04523194. Plaque burden has been demonstrated to be associated with plaque vulnerability. The relationship between plaque burden and vulnerability could differ between acute coronary syndromes (ACS) and chronic coronary syndrome (CCS). However, no study systematically compared the relationship. This study demonstrated that as total plaque volume increased, the levels of plaque vulnerability increased in ACS, whereas microscopic features related to the plaque healing process, such as calcification and layered plaque formation, became more prevalent in CCS. The results suggest that patients presenting with either ACS or CCS may require distinct management strategies. [ABSTRACT FROM AUTHOR]

Objective: Lipids play key role in coronary atherosclerosis. The role of non-high-density lipoprotein cholesterol (non-HDL-C) in atherosclerotic plaques using intravascular imaging remains unclear. This study aimed to assess its relationship with coronary plaque features using intravascular ultrasound (IVUS) in acute coronary syndrome (ACS). Methods: A total of 601 patients divided into two groups: normal non-HDL-C≤130 mg/dl (n = 410) and high non-HDL cholesterol >130 mg/dl (n = 191). IVUS performed before coronary intervention. Results: Mean age 53.18 ± 12.29 years. No significant differences in hypertension, diabetes, and smoking between groups. Plaque burden was significantly higher among normal versus high non-HDL-C groups (79.59 ± 9.98 % vs. 81.61 ± 5.39 %; p = 0.001). At minimal luminal site, fibrofatty percentage was higher in normal non-HDL-C group (p = 0.027), while necrotic core greater in high non-HDL-C group (p = 0.033). Segmental analysis, necrotic core was significantly higher in percentage (p = 0.006) and volumes (p = 0.011) in normal versus high non-HDL-C groups. Total cholesterol (r = 0.099, p = 0.015), LDL-C (r = 0.081, p = 0.046), triglycerides (r = 0.083, p = 0.041),and non-HDL-C (r = 0.099, p = 0.015) positively correlated with plaque burden. Total cholesterol (r = 0.115, p = 0.005), LDL-C (r = 0.107, p = 0.009), and non-HDL-C (r = 0.105, p = 0.010) positively correlated with necrotic core volume. Linear regression analysis showed age and non-HDL-C as predictors of higher plaque burden. Multiple linear regression analysis; age, body mass index, and non-HDL-C were predictors of larger necrotic core volume. Conclusion: Non-HDL-C levels were positively associated with plaque burden, measure of extent of atherosclerosis. It is closely associated with and is a predictor of necrotic core volume; a marker of plaque vulnerability. This IVUS study demonstrates potential role of non-HDL-C in causation of plaque in ACS.

Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles. We evaluated the 8-week effects of FANC in Western-type diet-fed ApoE-deficient mice by either continuous intraperitoneal delivery (20 μM, 50 μl weekly) or via drinking water (300 nM). FANC reduced aortic atheroma burden, serum total cholesterol, and oxidative stress markers malondialdehyde and 4-hydroxynonenal levels. FANC attenuated hepatic lipid deposit, with changed expression of lipid homeostasis-related genes HMGCR, SREBP, PCSK9, and LDLR in a pattern similar to mice treated with ezetimibe. FANC also inhibited intestinal cholesterol absorption, resembling the action of ezetimibe. The lipid-lowering and anti-atherosclerotic effects of FANC reappeared in Western-type diet-fed LDLr-deficient mice. FANC bound insulin receptor β (IRβ) via DHLA, leading to AKT activation. However, unlike insulin, which also bound IRβ to activate AKT to induce HO-1, activation of AKT by FANC was independent of HO-1 expression in human aortic endothelial cells (HAECs). Alternatively, FANC up-regulated NRF2, interfered the binding of KEAP1 to NRF2, and promoted KEAP1 degradation to free NRF2 for nuclear entry to induce HO-1 that suppressed the expression of ICAM-1 and VCAM-1. Consistently, FANC suppressed ox-LDL-induced enhanced attachment of THP-derived macrophages onto HAECs. In macrophages, FANC up-regulated ABCA1, and reversed ox-LDL-induced suppression of cholesterol efflux. FANC effected in vitro at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis.

Background The effect of transcatheter aortic valve replacement (TAVR) on changes of computed tomography-derived fractional flow reserve (CT-FFR) values was controversial. Thus, we aimed to identify the impact of TAVR on changes of CT-FFR values, plaque characteristics, and the associated clinical impact.Methods This single-center observational study included 39 consecutive patients with severe aortic valve disease undergone TAVR between August 2019 and April 2023, whom were performed with preoperative and postoperative coronary CT angiography (CCTA). The computation of CT-FFR and plaque characteristics was performed by an independent central core laboratory.Results Each patient underwent CCTA and CT-FFR assessment without encountering any complications. Notably, both at discharge and six months post-TAVR, there was a significant improvement observed in the New York Heart Association (NYHA) functional classification, left ventricular fractional shortening, and ejection fraction compared to pre-operative levels. The CT-FFR for left anterior descending artery (LAD), left anterior descending artery (LCX), and right coronary artery (RCA) had no obvious change at discharge compared to pre-operation (0.92 ± 0.05 vs. 0.93 ± 0.05, p = 0.109; 0.96 ± 0.03 vs. 0.95 ± 0.03, p = 0.523; 0.97 ± 0.04 vs. 0.97 ± 0.03, p = 0.533; respectively). Furthermore, TAVR did not exert a significant impact on plaque burden during the perioperative period.Conclusions Our report suggested that TAVR did not significantly affect coronary CT-FFR measurements and plaque characteristics in the perioperative period, and furthermore, the patients’ cardiac function showed gradual improvement in the short-term following discharge.

This study assesses the agreement of Artificial Intelligence-Quantitative Computed Tomography (AI-QCT) with qualitative approaches to atherosclerotic disease burden codified in the multisociety 2022 CAD-RADS 2.0 Expert Consensus. 105 patients who underwent cardiac computed tomography angiography (CCTA) for chest pain were evaluated by a blinded core laboratory through FDA-cleared software (Cleerly, Denver, CO) that performs AI-QCT through artificial intelligence, analyzing factors such as % stenosis, plaque volume, and plaque composition. AI-QCT plaque volume was then staged by recently validated prognostic thresholds, and compared with CAD-RADS 2.0 clinical methods of plaque evaluation (segment involvement score (SIS), coronary artery calcium score (CACS), visual assessment, and CAD-RADS percent (%) stenosis) by expert consensus blinded to the AI-QCT core lab reads. Average age of subjects were 59 ± 11 years; 44% women, with 50% of patients at CAD-RADS 1–2 and 21% at CAD-RADS 3 and above by expert consensus. AI-QCT quantitative plaque burden staging had excellent agreement of 93% (k = 0.87 95% CI: 0.79–0.96) with SIS. There was moderate agreement between AI-QCT quantitative plaque volume and categories of visual assessment (64.4%; k = 0.488 [0.38–0.60]), and CACS (66.3%; k = 0.488 [0.36–0.61]). Agreement between AI-QCT plaque volume stage and CAD-RADS % stenosis category was also moderate. There was discordance at small plaque volumes. With ongoing validation, these results demonstrate a potential for AI-QCT as a rapid, reproducible approach to quantify total plaque burden. [ABSTRACT FROM AUTHOR]

Background: The coronary artery disease‐reporting and data system (CAD‐RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results. Artificial intelligence software can quantify the plaque composition, fat attenuation index, and fractional flow reserve. Objective: To analyze plaque features of varying severity in patients with a combination of CAD‐RADS stenosis and plaque burden categorization and establish a random forest classification model. Methods: The data of 100 patients treated between April 2021 and February 2022 were retrospectively collected. The most severe plaque observed in each patient was the target lesion. Patients were categorized into three groups according to CAD‐RADS: CAD‐RADS 1−2 + P0−2, CAD‐RADS 3−4B + P0−2, and CAD‐RADS 3−4B + P3−4. Differences and correlations between variables were assessed between groups. AUC, accuracy, precision, recall, and F1 score were used to evaluate the diagnostic performance. Results: A total of 100 patients and 178 arteries were included. The differences of computed tomography fractional flow reserve (CT‐FFR) (H = 23.921, p < 0.001), the volume of lipid component (H = 12.996, p = 0.002), the volume of fibro‐lipid component (H = 8.692, p = 0.013), the proportion of lipid component volume (H = 22.038, p < 0.001), the proportion of fibro‐lipid component volume (H = 11.731, p = 0.003), the proportion of calcification component volume (H = 11.049, p = 0.004), and plaque type (χ2 = 18.110, p = 0.001) was statistically significant. Conclusion: CT‐FFR, volume and proportion of lipid and fibro‐lipid components of plaques, the proportion of calcified components, and plaque type were valuable for CAD‐RADS stenosis + plaque burden classification, especially CT‐FFR, volume, and proportion of lipid and fibro‐lipid components. The model built using the random forest was better than the clinical model (AUC: 0.874 vs. 0.647). [ABSTRACT FROM AUTHOR]

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤4 mm² demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00-5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA >4 mm². Patients with combination of TCFA, MLA ≤4 mm² and PB =70% showed high risk of MI (HR 5.23, 95% CI 1.05-25.9, p = 0.043). Lesions with MLA ≤4 mm² had 6-fold risk of TVF (HR 6.16, 95% CI 1.24-30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤4 mm² and PB =70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD) risk and plaque scores are often subjective and biased, particularly in mid-age asymptomatic women, whose CAD risk assessment has been historically underestimated. In this study, a new automatic ascending aorta time-to-peak-distention (TPD) analysis was developed for fast screening and as an independent surrogate for subclinical atherosclerosis in asymptomatic women. CCTA was obtained in 50 asymptomatic adults. Plaque burden segment involvement score (SIS) and automatic TPD were obtained from all subjects. Logistic regression analyses were performed to investigate the association between CAD risk scores and TPD with severe coronary plaque burden (SIS>5). TPD, individually, was found to be a significant predictor of SIS>5. Additionally, sex was a significant effect modifier of TPD, with a stronger statistically significant association with women. Four-dimensional aortic time-to-peak distention could supplement conventional CCTA analysis and offer a quick objective screening tool for plaque burden severity and CAD risk stratification, especially in women. [ABSTRACT FROM AUTHOR]

Coronary Artery Disease Reporting and Data System (CAD-RADS) was created to standardize reporting system for patients undergoing coronary CT angiography (CCTA) and to guide possible next steps in patient management. The goal of this updated 2022 CAD-RADS 2.0 is to improve the initial reporting system for CCTA by considering new technical developments in Cardiac CT, including data from recent clinical trials and new clinical guidelines. The updated CAD-RADS classification will follow an established framework of stenosis, plaque burden, and modifiers, which will include assessment of lesion-specific ischemia using CT fractional-flow-reserve (CT-FFR) or myocardial CT perfusion (CTP), when performed. Similar to the method used in the original CAD-RADS version, the determinant for stenosis severity classification will be the most severe coronary artery luminal stenosis on a per-patient basis, ranging from CAD-RADS 0 (zero) for absence of any plaque or stenosis to CAD-RADS 5 indicating the presence of at least one totally occluded coronary artery. Given the increasing data supporting the prognostic relevance of coronary plaque burden, this document will provide various methods to estimate and report total plaque burden. The addition of P1 to P4 descriptors are used to denote increasing categories of plaque burden. The main goal of CAD-RADS, which should always be interpreted together with the impression found in the report, remains to facilitate communication of test results with referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will continue to provide a framework of standardization that may benefit education, research, peer-review, artificial intelligence development, clinical trial design, population health and quality assurance with the ultimate goal of improving patient care. Keywords: Coronary Artery Disease, Coronary CTA, CAD-RADS, Reporting and Data System, Stenosis Severity, Report Standardization Terminology, Plaque Burden, Ischemia Supplemental material is available for this article. This article is published synchronously in Radiology: Cardiothoracic Imaging, Journal of Cardiovascular Computed Tomography, JACC: Cardiovascular Imaging, Journal of the American College of Radiology, and International Journal for Cardiovascular Imaging. © 2022 Society of Cardiovascular Computed Tomography. Published by RSNA with permission.

Background/Aims: The relationship between carotid artery plaque burden, phenotype and serum cystatin C at normal and impaired renal function is still unclear. Methods: Demographic characteristics, carotid ultrasonography and other relevant information of 1,477 patients were collected. The association of carotid artery plaque burden, plaque phenotype with serum cystatin C was evaluated by strategy analysis based on renal function. Results: Serum cystatin C (OR=2.05, 95% CI: 1.83-2.29, P<.01) was a risk factor of stable plaque among patients with normal glomerular filtration rate. However, in the patients with mild impaired renal function, serum cystatin C was not only a risk factor for stable plaque (OR=1.60, 95%CI: 1.43-1.78, P<.001) but also was a risk factor for unstable plaque (OR=1.21, 95%CI: 1.10-1.32, P<.001). The smoothing function curve and a three-piecewise linear regression revealed that a nonlinear relationship was observed between serum cystatin C and plaque burden. When serum cystatin C was in the range of 0.75-1.30 (mg/L), the plaque burden tended to increase. Conclusion: In normal renal function, serum cystatin C may confer stability of plaques. In mildly impaired renal function, serum cystatin C is a risk predictor of plaques. In normal renal function circumstances, serum cystatin C may benefit to the stability of plaques. In mild impaired renal function circumstances, serum cystatin C are a risk predictors of plaques. [ABSTRACT FROM AUTHOR]

With growing adoption of coronary computed tomographic angiography (CTA), there is increasing evidence for and interest in the prognostic importance of atherosclerotic plaque volume. Manual tools for plaque segmentation are cumbersome, and their routine implementation in clinical practice is limited. The aim of this study was to develop nomographic quantitative plaque values from a large consecutive multicenter cohort using coronary CTA. Quantitative assessment of total atherosclerotic plaque and plaque subtype volumes was performed in patients undergoing clinically indicated coronary CTA, using an Artificial Intelligence–Enabled Quantitative Coronary Plaque Analysis tool. A total of 11,808 patients were included in the analysis; their mean age was 62.7 ± 12.2 years, and 5,423 (45.9%) were women. The median total plaque volume was 223 mm3 (IQR: 29-614 mm3) and was significantly higher in male participants (360 mm3; IQR: 78-805 mm3) compared with female participants (108 mm3; IQR: 10-388 mm3) (P < 0.0001). Total plaque increased with age in both male and female patients. Younger patients exhibited a higher prevalence of noncalcified plaque. The distribution of total plaque volume and its components was reported in every decile by age group and sex. The authors developed pragmatic age- and sex-stratified percentile nomograms for atherosclerotic plaque measures using findings from coronary CTA. The impact of age and sex on total plaque and its components should be considered in the risk-benefit analysis when treating patients. Artificial Intelligence–Enabled Quantitative Coronary Plaque Analysis work flows could provide context to better interpret coronary computed tomographic angiographic measures and could be integrated into clinical decision making. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: CT coronary angiography (CTCA) is a guideline-endorsed assessment for patients with stable angina and suspected coronary disease. Although associated with excellent negative predictive value in ruling out obstructive coronary disease, there are limitations in the ability of CTCA to predict hemodynamically significant coronary disease. The CAPTivAte study aims to assess the utility of Aggregated Plaque Burden (APB) in predicting ischemia based on Fractional Flow Reserve (FFR). Methods: In this retrospective study, patients who had a CTCA and invasive FFR of the LAD were included. The entire length of the LAD was analyzed using semi-automated software which characterized total plaque burden and plaque morphological subtype (including Low Attenuation Plaque (LAP), Non-calcific plaque (NCP) and Calcific Plaque (CP). Aggregated Plaque Burden (APB) was calculated. Univariate and multivariate analysis were performed to assess the association between these CT-derived parameters and invasive FFR. Results: There were 145 patients included in this study. 84.8 % of patients were referred with stable angina. There was a significant linear association between APB and FFR in both univariate and multivariate analysis (Adjusted R-squared = 0.0469; p = 0.035). Mean Agatston scores are higher in FFR positive vessels compared to FFR negative vessels (371.6 (±443.8) vs 251.9 (±283.5, p = 0.0493). Conclusion: CTCA-derived APB is a reliable predictor of ischemia assessed using invasive FFR and may aid clinicians in rationalizing invasive vs non-invasive management strategies. Vessel-specific Agatston scores are significantly higher in FFR-positive vessels than in FFR-negative vessels. Associations between HU-derived plaque subtype and invasive FFR were inconclusive in this study.

Abstract Background and Aims Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden. Methods This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk. Results A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P

Abstract Background and purpose Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study combined HR-VWI, hemodynamics, and peripheral blood inflammatory indicators to investigate the role of these factors in symptomatic intracranial atherosclerotic stenosis (sICAS) and their inter-relationships. Methods Patients diagnosed with atherosclerotic middle cerebral artery stenosis were recruited retrospectively from June 2018 to July 2022. Plaque enhancement was qualitatively and quantitatively analyzed, and the degree of plaque enhancement was graded according to the plaque-to-pituitary stalk contrast ratio (CR). Computational fluid dynamics models were constructed, and then hemodynamic parameters, including wall shear stress (WSS) and pressure ratio (PR), were measured and recorded. Univariate and multivariable analyses were performed to identify factors that can predict sICAS. In addition, the correlation analysis between the plaque characteristics on HR-VWI, hemodynamic parameters, and peripheral blood inflammatory indicators was performed to investigate the interrelationships between these factors. Results Thirty-two patients were included. A higher proportion of plaque enhancement, maximum WSS, and WSS ratio (WSSR) were significantly associated with sICAS. The multiple logistic regression analysis showed that only the WSSR was an independent risk factor for sICAS. The correlation analysis revealed that both the CR and plaque burden showed linear positive correlation with the WSSR (R = 0.411, P = 0.022; R = 0.474, P = 0.007, respectively), and showed linear negative correlation with the lymphocyte to monocyte ratio (R = 0.382, P = 0.031; R = 0.716, P

Objectives: Individuals with familial hypercholesterolemia (FH) are at an increased risk for coronary artery disease (CAD). While prior research has shown variability in coronary artery calcification (CAC) among those with FH, studies with small sample sizes and single-center recruitment have been limited in their ability to characterize CAC and plaque burden in subgroups based on age and sex. Understanding the spectrum of atherosclerosis may result in personalized risk assessment and tailored allocation of costly add-on, non-statin lipid-lowering therapies. We aimed to characterize the presence and burden of CAC and coronary plaque on computed tomography angiography (CTA) across age- and sex-stratified subgroups of individuals with FH who were without CAD at baseline. Methods: We pooled 1,011 patients from six cohorts across Brazil, France, the Netherlands, Spain, and Australia. Our main measures of subclinical atherosclerosis included CAC ranges (i.e., 0, 1–100, 101–400, >400) and CTA-derived plaque burden (i.e., no plaque, non-obstructive CAD, obstructive CAD). Results: Ninety-five percent of individuals with FH (mean age: 48 years; 54% female; treated LDL-C: 154 mg/dL) had a molecular diagnosis and 899 (89%) were on statin therapy. Overall, 423 (42%) had CAC=0, 329 (33%) had CAC 1–100, 160 (16%) had CAC 101–400, and 99 (10%) had CAC >400. Compared to males, female patients were more likely to have CAC=0 (48% [n = 262] vs 35% [n = 161]) and no plaque on CTA (39% [n = 215] vs 26% [n = 120]). Among patients with CAC=0, 85 (20%) had non-obstructive CAD. Females also had a lower prevalence of obstructive CAD in CAC 1–100 (8% [n = 15] vs 18% [n = 26]), CAC 101–400 (32% [n = 22] vs 40% [n = 36]), and CAC >400 (52% [n = 16] vs 65% [n = 44]). Female patients aged 50–59 years were less likely to have obstructive CAD in CAC >400 (55% [n = 6] vs 70% [n = 19]). Conclusion: In this large, multi-national study, we found substantial age- and sex-based heterogeneity in CAC and plaque burden in a cohort of predominantly statin-treated individuals with FH, with evidence for a less pronounced increase in atherosclerosis among female patients. Future studies should examine the predictors of resilience to and long-term implications of the differential burden of subclinical coronary atherosclerosis in this higher risk population.

ObjectiveAssessing the impact of lumbar disc herniation (LDH) on the plaque burden of coronary atherosclerosis is our objective.MethodsIn this study, a total of 212 patients (age 46–80 years) with unstable angina (UA) who underwent coronary angiography (CAG) in our hospital from January 2018 to July 2022 due to UA were included. Patients were divided into LDH group (n = 106) and no LDH group (n = 106). Gensini scores were calculated to assess the plaque burden of coronary. Logistic analysis was used to examine potential risk variables linked to the Gensini score. The association between lumbar disc lesions grading and coronary plaque burden was analysed by Spearman's correlation test. LDH patients with higher plaque burden (n = 56) were further divided into evolocumab treatment group (n = 28) and conventional treatment group (n = 28). Cox regression analysis were performed.ResultsPatients with LDH had higher Gensini scores (P

Coronary artery disease is the leading cause of morbidity and mortality worldwide. Despite remarkable advances in the management of coronary artery disease, the prediction of adverse coronary events remains challenging. Over the preceding decades, considerable effort has been made to improve risk stratification using noninvasive imaging. Recently, these efforts have increasingly focused on the direct imaging of coronary atherosclerotic plaque. Modern imaging now allows imaging of coronary plaque burden, plaque type, atherosclerotic plaque activity, and plaque thrombosis, which have major potential to refine patient risk stratification, aid decision making, and advance future clinical practice. [Display omitted] • The prediction of adverse coronary events remains challenging. • Noninvasive imaging in coronary artery disease is increasingly being focused on the atherosclerotic plaque. • The assessment of plaque burden, plaque type, disease activity, and plaque thrombosis hold promise in improving patient risk stratification. [ABSTRACT FROM AUTHOR]

Objectives: Pre-clinical models of human atherosclerosis are extensively used; however, traditional histological methods do not allow for a holistic view of vascular lesions. We describe an ex-vivo, high-resolution MRI method that allows the 3 dimensional imaging of the vessel for aortic plaque visualization and quantification. Materials and methods: Aortas from apolipoprotein-E-deficient (apoE−/−) mice fed an atherogenic diet (group 1) or a control diet (group 2) were subjected to 14 T MR imaging using a 3D gradient echo sequence. The obtained data sets were reconstructed (Matlab), segmented, and analyzed (Avizo). The aortas were further sectioned and subjected to traditional histological analysis (Oil-Red O and hematoxylin staining) for comparison. Results: A resolution up to 15 × 10x10 μm3 revealed that plaque burden (mm3) was significantly (p < 0.05) higher in group 1 (0.41 ± 0.25, n = 4) than in group 2 (0.01 ± 0.01, n = 3). The achieved resolution provided similar detail on the plaque and the vessel wall morphology compared with histology. Digital image segmentation of the aorta's lumen, plaque, and wall offered three-dimensional visualizations of the entire, intact aortas. Discussion: 14 T MR microscopy provided histology-like details of pathologically relevant vascular lesions. This work may provide the path research needs to take to enable plaque characterization in clinical applications. [ABSTRACT FROM AUTHOR]

Coronary artery disease reporting and data system (CAD-RADS) predicts future cardiovascular events in patients with coronary artery disease (CAD). However, information on vascular inflammation and vulnerability remains scarce. Patients who underwent coronary computed tomography angiography (CTA) and optical coherence tomography (OCT) prior to coronary intervention were enrolled. All three coronary arteries were evaluated for CAD-RADS score and pericoronary adipose tissue (PCAT) attenuation, while the culprit vessel was analyzed for plaque vulnerability by OCT. A total of 385 patients with 915 lesions were divided into two groups based on CAD-RADS score: 103 (26.8%) were categorized as CAD-RADS 4b/5 and 282 (73.2%) as CAD-RADS ≤4a. Patients with CAD-RADS 4b/5 had a higher level of PCAT attenuation (mean of 3 coronary arteries) than those with CAD-RADS ≤4a (−68.4 ​± ​6.7 HU vs. −70.1 ​± ​6.5, P ​= ​0.022). The prevalence of macrophage was higher, and lipid index was greater in patients with CAD-RADS 4b/5 than CAD-RADS ≤4a (94.2% vs. 83.0%, P ​= ​0.004, 1845 vs. 1477; P ​= ​0.003). These associations were significant in the culprit vessels of patients with chronic coronary syndrome but not in those with acute coronary syndromes. Higher CAD-RADS score was associated with higher levels of vascular inflammation and plaque vulnerability. [ABSTRACT FROM AUTHOR]

Background and Aims: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. However, the relationship between serum cystatin C level and coronary atherosclerotic plaque burden is limited. We aimed to evaluate the relationship between circulating cystatin C and coronary atherosclerotic plaque burden. Methods: This study was a cross-sectional study based on China community population. Measurements of plaque burden were based on the segment-involvement score (SIS) and segment stenosis score (SSS), which derived from the Coronary Artery Tree Model Depicting Coronary Artery Plaque Scores. Logistic regression model was used to demonstrate the association between cystatin C level and coronary artery plaque burden. Mendelian randomization (MR) analyses were conducted to assess the causal effect of cystatin C level on coronary atherosclerosis risk. Results: A total of 3,043 objects were included in the present study. The odds risks (OR) of severe plaque burden in the highest serum cystatin C levels (OR: 2.50; Cl:1.59–3.91; P < 0.001) and medium-level cystatin C levels (OR: 1.86; 95% Cl: 1.21–2.88; P = 0.005) were significantly higher after fulled adjusted confounders compared with the lowest levels of serum cystatin C by SSS. The MR analysis showed that genetic predicted cystatin C levels was associated with an increased risk of coronary atherosclerosis (OR, 1.004; 95% CI, 1.002–1.006, P < 0.001). Conclusion: Elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. Cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. What is already known on this topic?: Coronary artery disease is currently the most common cardiovascular disease and the leading global cause of mortality. Previous studies reported that higher serum cystatin C levels were associated with an increased risk for future cardiovascular events, independent of the normal creatinine levels or estimated glomerular filtration rate (eGFR) values. The presence of high-risk coronary atherosclerotic plaque burden is associated with increased risk of cardiovascular events. However, the association between serum cystatin C and coronary atherosclerotic plaque burden is not very clear. What this study adds?: Our study demonstrated that the elevated serum cystatin C levels were associated with coronary atherosclerotic plaque burden. In addition, we found that serum cystatin C levels had a causal effect on an increased risk of coronary atherosclerosis at the genetic level. How this study might affect research, practice or policy?: Current research finds that serum cystatin C levels were associated with coronary atherosclerosis. The metabolic pathway of cystatin C could be a target for new therapies against CAD. [ABSTRACT FROM AUTHOR]

Myocardial bridging (MB) is a common congenital cardiovascular anomaly. There are reported associations of MB with different clinical presentations like effort angina, acute coronary syndromes (ACS) and sudden cardiac death. Acceleration of atherosclerosis in proximal vessel is reported in patients with MB, while bridged segments are reported to be free of atherosclerosis We assessed patients who underwent intravascular ultrasound (IVUS) guided percutaneous intervention (PCI) of left anterior descending (LAD) artery. Plaque characteristics derived from IVUS analysis were compared between those who displayed myocardial bridge versus those who did not harbour the anomaly. One hundred and forty-seven (147) patients underwent IVUS guided PCI. Incidence of MB was 44/147 (29.9%). Mean age of patients who had MB {+} was higher (62.1 ± 10.3 vs. 57.8 ± 11.2 (p =.03). 142/147 (96.6%) patients presented with ACS. ST elevation myocardial infarction (STEMI) was the most common presenting diagnosis (110/147 to 74.8%). There were no differences in qualitative plaque characteristics – attenuated plaque, calcification or calcium score between two groups. Plaque burden and length of the lesion in the proximal vessel were not different. Among patients with MB {+}, atheromatous extension to segments underlying the bridge was seen in 31/44 (70.5%) cases. In a series of patients who presented with advanced clinical atherosclerosis, plaque characteristics were not different in patients who harboured myocardial bridge vs. those who did not have the anomaly. Atheromatous involvement was seen extending into bridged segment contrary to previous reports. [ABSTRACT FROM AUTHOR]

Background: Lesions with thin-cap fibroatheroma (TCFA), small luminal area and large plaque burden (PB) have been considered at high risk of cardiovascular events. Older patients were not represented in studies which demonstrated correlation between clinical outcome and plaque characteristics. This study aims to investigate the prognostic role of high-risk plaque characteristics and long-term outcome in older patients presenting with non-ST elevation acute coronary syndrome (NSTEACS). Methods: This study recruited older patients aged ≥75 years with NSTEACS undergoing virtual-histology intravascular ultrasound (VH-IVUS) imaging from the Improve Clinical Outcomes in high-risk patieNts with acute coronary syndrome (ICON-1). Primary endpoint was the composite of major adverse cardiovascular events (MACE) consisting of all-cause mortality, myocardial infarction (MI), and any revascularisation. Every component of MACE and target vessel failure (TVF) including MI and any revascularisation were considered as secondary endpoints. Results: Eighty-six patients with 225 vessels undergoing VH-IVUS at baseline completed 5-year clinical follow-up. Patients with minimal lumen area (MLA) ≤4 mm2 demonstrated increased risk of MACE (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.00–5.59, p = 0.048) with a worse event-free survival (Log Rank 4.17, p = 0.041) than patients with MLA >4 mm2. Patients with combination of TCFA, MLA ≤4 mm2 and PB ≥70% showed high risk of MI (HR 5.23, 95% CI 1.05–25.9, p = 0.043). Lesions with MLA ≤4 mm2 had 6-fold risk of TVF (HR 6.16, 95% CI 1.24–30.5, p = 0.026). Conclusions: Small luminal area appears as the major prognostic factor in older patients with NSTEACS at long-term follow-up. Combination of TCFA, MLA ≤4 mm2 and PB ≥70% was associated with high risk of MI. Clinical Trial Registration: NCT01933581.

Background and purpose: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke, and high-resolution vessel wall imaging (HR-VWI) can be used to assess the plaque characteristics of ICAS. This study combined HR-VWI, hemodynamics, and peripheral blood inflammatory indicators to investigate the role of these factors in symptomatic intracranial atherosclerotic stenosis (sICAS) and their inter-relationships. Methods: Patients diagnosed with atherosclerotic middle cerebral artery stenosis were recruited retrospectively from June 2018 to July 2022. Plaque enhancement was qualitatively and quantitatively analyzed, and the degree of plaque enhancement was graded according to the plaque-to-pituitary stalk contrast ratio (CR). Computational fluid dynamics models were constructed, and then hemodynamic parameters, including wall shear stress (WSS) and pressure ratio (PR), were measured and recorded. Univariate and multivariable analyses were performed to identify factors that can predict sICAS. In addition, the correlation analysis between the plaque characteristics on HR-VWI, hemodynamic parameters, and peripheral blood inflammatory indicators was performed to investigate the interrelationships between these factors. Results: Thirty-two patients were included. A higher proportion of plaque enhancement, maximum WSS, and WSS ratio (WSSR) were significantly associated with sICAS. The multiple logistic regression analysis showed that only the WSSR was an independent risk factor for sICAS. The correlation analysis revealed that both the CR and plaque burden showed linear positive correlation with the WSSR (R = 0.411, P = 0.022; R = 0.474, P = 0.007, respectively), and showed linear negative correlation with the lymphocyte to monocyte ratio (R = 0.382, P = 0.031; R = 0.716, P < 0.001, respectively). Conclusions: The plaque enhancement and WSSR were significantly associated with sICAS, WSSR was an independent risk factor for sICAS. Plaque enhancement and plaque burden showed linear correlation with the WSSR and lymphocyte-to-monocyte ratio (LMR). Hemodynamics and inflammation combined to promote plaque progression. [ABSTRACT FROM AUTHOR]

Atherosclerosis is the major risk factor for cardiovascular disease (CVD), the first cause of death worldwide. Chronic low-grade inflammation and a sustained oxidative milieu are causatively related to atherosclerosis onset and progression, and therefore, dietary patterns rich in bioactive compounds with anti-inflammatory and antioxidant activities might likely contribute to revert or slowing the progression of atherosclerosis. The aim of this study is to analyse the association between fruit and vegetables intake, quantitatively measured through carotene plasma concentrations, and atherosclerotic burden, as a surrogate biomarker of CVD, in free-living subjects from the DIABIMCAP cohort study. The 204 participants of the DIABIMCAP Study cohort (Carotid Atherosclerosis in Newly Diagnosed Type 2 Diabetic Individuals, ClinicalTrials.gov Identifier: NCT01898572), were included in this cross-sectional study. Total, α-, and β-carotenes were quantified by HPLC-MS/MS. Lipoprotein analysis in serum was performed by 2D- 1H NMR- DOSY, and atherosclerosis and intima media thickness (IMT) were measured through standardized bilateral carotid artery ultrasound imaging. Subjects with atherosclerosis (n = 134) had lower levels of large HDL particles than subjects without atherosclerosis. Positive associations were found between α-carotene and both large and medium HDL particles, and inverse associations were found between β- and total carotene, and VLDL and its medium/small particles. Subjects with atherosclerosis presented significantly lower plasma concentrations of total carotene compared with subjects without atherosclerosis. Plasma concentrations of carotene decreased as the number of atherosclerotic plaques increased, although after multivariate adjustment, the inverse association between β- and total carotene with plaque burden remained significant only in women. A diet rich in fruit and vegetables results in higher plasmatic carotene concentrations, which are associated with a lesser atherosclerotic plaque burden. [ABSTRACT FROM AUTHOR]

Background and purpose: Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke (IS), and high‐resolution vessel wall imaging (HR‐VWI) can be used to assess the plaque characteristics of ICAS. This study aimed to qualitatively and quantitatively assess plaque enhancement of ICAS and to investigate the relationship between plaque enhancement, plaque morphological features, and IS. Methods: Data from adult patients with ICAS from April 2018 to July 2022 were retrospectively collected, and all patients underwent HR‐VWI examination. Plaque enhancement was qualitatively and quantitatively assessed, and the plaque‐to‐pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Plaque characteristics, such as plaque burden and area, were quantitatively measured using HR‐VWI. Furthermore, receiver‐operating characteristic (ROC) analysis was performed to assess the ability of CR to discriminate plaque enhancement. The patients were divided into a symptomatic ICAS group and an asymptomatic ICAS group according to the clinical and imaging characteristics. Univariate and multivariate analyses were performed to investigate which factors were significantly associated with plaque enhancement and symptomatic ICAS. The plaque burden and CR were compared using linear regression. Results: A total of 91 patients with ICAS were enrolled in this study. ICAS plaque burden was significantly associated with plaque enhancement (p =.037), and plaque burden was linearly positively correlated with CR (R = 0.357, p =.001). ROC analysis showed that the cutoff value of CR for plaque enhancement was 0.56 (specificity of 81.8%). Both plaque enhancement and plaque burden were significantly associated with symptomatic ICAS, and only plaque enhancement was an independent risk factor after multivariate analysis. Conclusion: Plaque burden was an independent risk factor for plaque enhancement and showed a linear positive correlation with CR. The cutoff value of CR for plaque enhancement was 0.56, and CR ≥ 0.56 was significantly associated with symptomatic ICAS, which was independently associated with plaque enhancement. [ABSTRACT FROM AUTHOR]

Purpose of Review: Imaging of adverse coronary plaque features by coronary computed tomography angiography (CCTA) has advanced greatly and at a fast pace. We aim to describe the evolution, present and future in plaque analysis, and its value in comparison to plaque burden. Recent Findings: Recently, it has been demonstrated that in addition to plaque burden, quantitative and qualitative assessment of coronary plaque by CCTA can improve the prediction of future major adverse cardiovascular events in diverse coronary artery disease scenarios. The detection of high-risk non-obstructive coronary plaque can lead to higher use of preventive medical therapies such as statins and aspirin, help identify culprit plaque, and differentiate between myocardial infarction types. Even more, over traditional plaque burden, plaque analysis including pericoronary inflammation can potentially be useful tools for tracking disease progression and response to medical therapy. Summary: The identification of the higher risk phenotypes with plaque burden, plaque characteristics, or ideally both can allow the allocation of targeted therapies and potentially monitor response. Further observational data are now required to investigate these key issues in diverse populations, followed by rigorous randomized controlled trials. [ABSTRACT FROM AUTHOR]

Mengqi Yang,1 Huachen Jiao,2 Yan Li,2 Lei Zhang,1 Juan Zhang,2 Xia Zhong,1 Yitao Xue2 1First College for Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of China; 2Cardiology Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, People’s Republic of ChinaCorrespondence: Yitao Xue, Cardiology Department, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jing Shi Road, Lixia District, Jinan, 250014, People’s Republic of China, Tel +8613505313455, Email xytsdzydfy@126.comBackground: Atherosclerosis (AS) is the leading cause of cardiovascular diseases, such as myocardial infarction and stroke. Guanmaitong granule (GMTG) is a TCM (Traditional Chinese medicine) prescribed to treat AS. However, its mechanism remains unclear.Methods: We obtained reliable ingredients and targets of GMTG using the HERB database. AS-related targets were obtained from HERB and GeneCards databases. The target database was constructed by intersecting the ingredients of GMTG with the AS-related targets. STRING and Cytoscape were used to create protein-protein interaction (PPI) network and screen core targets. GO enrichment analysis and KEGG pathway analyses were performed using R. Finally, the ApoE−/− mice AS model was induced by a high-fat diet (HFD) for in vivo validation of core pathways and targets.Results: A total of 124 ingredients and 418 potential targets of GMTG for treating AS were obtained. Numerous ingredients and targets were related to Panax notoginseng, Salvia miltiorrhiza, and Astragalus. Most core targets and pathways were involved in the inflammatory immune response. GMTG could decrease serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and oxidized low-density lipoprotein level and increase the serum high-density lipoprotein-cholesterol level. Furthermore, GMTG reduced the plaque burden and promoted plaque remodeling by reducing plaque area, lipid deposition, foam cell content, and collagen fiber content in the plaque in the aortic root of ApoE−/− mice. GMTG inhibited systemic and plaque inflammatory immune response and increased plaque stability by inhibiting the excessive release of the TLR4/MyD88/NF-κB pathway-induced inflammatory cytokines, tumor necrosis factor, interleukin-6, and interleukin-1 beta.Conclusion: Radix notoginseng, Radix salviae liguliobae, and Radix astragali are the main ingredients of GMTG for treating AS. Further, GMTG could regulate the level of serum lipids and inhibit inflammatory immune response, which resulted in anti-AS effects such as plaque stabilization, reduction of plaque burden, and plaque remodeling. GMTG is a promising multi-target treatment for AS.Keywords: Guanmaitong granule, atherosclerosis, inflammatory immune response, plaque burden, plaque remodeling

Abstract Background The S209F variant of Abelson Interactor Protein 3 (ABI3) increases risk for Alzheimer’s disease (AD), but little is known about its function in relation to AD pathogenesis. Methods Here, we use a mouse model that is deficient in Abi3 locus to study how the loss of function of Abi3 impacts two cardinal neuropathological hallmarks of AD—amyloid β plaques and tau pathology. Our study employs extensive neuropathological and transcriptomic characterization using transgenic mouse models and adeno-associated virus-mediated gene targeting strategies. Results Analysis of bulk RNAseq data confirmed age-progressive increase in Abi3 levels in rodent models of AD-type amyloidosis and upregulation in AD patients relative to healthy controls. Using RNAscope in situ hybridization, we localized the cellular distribution of Abi3 in mouse and human brains, finding that Abi3 is expressed in both microglial and non-microglial cells. Next, we evaluated Abi3 −/− mice and document that both Abi3 and its overlapping gene, Gngt2, are disrupted in these mice. Using multiple transcriptomic datasets, we show that expression of Abi3 and Gngt2 are tightly correlated in rodent models of AD and human brains, suggesting a tight co-expression relationship. RNAseq of the Abi3-Gngt2−/− mice revealed upregulation of Trem2, Plcg2, and Tyrobp, concomitant with induction of an AD-associated neurodegenerative signature, even in the absence of AD-typical neuropathology. In APP mice, loss of Abi3-Gngt2 resulted in a gene dose- and age-dependent reduction in Aβ deposition. Additionally, in Abi3-Gngt2 −/− mice, expression of a pro-aggregant form of human tau exacerbated tauopathy and astrocytosis. Further, using in vitro culture assays, we show that the AD-associated S209F mutation alters the extent of ABI3 phosphorylation. Conclusions These data provide an important experimental framework for understanding the role of Abi3-Gngt2 function and early inflammatory gliosis in AD. Our studies also demonstrate that inflammatory gliosis could have opposing effects on amyloid and tau pathology, highlighting the unpredictability of targeting immune pathways in AD.

Abstract Background and purpose Intracranial atherosclerotic stenosis (ICAS) is a major cause of ischemic stroke (IS), and high‐resolution vessel wall imaging (HR‐VWI) can be used to assess the plaque characteristics of ICAS. This study aimed to qualitatively and quantitatively assess plaque enhancement of ICAS and to investigate the relationship between plaque enhancement, plaque morphological features, and IS. Methods Data from adult patients with ICAS from April 2018 to July 2022 were retrospectively collected, and all patients underwent HR‐VWI examination. Plaque enhancement was qualitatively and quantitatively assessed, and the plaque‐to‐pituitary stalk contrast ratio (CR) indicated the degree of plaque enhancement. Plaque characteristics, such as plaque burden and area, were quantitatively measured using HR‐VWI. Furthermore, receiver‐operating characteristic (ROC) analysis was performed to assess the ability of CR to discriminate plaque enhancement. The patients were divided into a symptomatic ICAS group and an asymptomatic ICAS group according to the clinical and imaging characteristics. Univariate and multivariate analyses were performed to investigate which factors were significantly associated with plaque enhancement and symptomatic ICAS. The plaque burden and CR were compared using linear regression. Results A total of 91 patients with ICAS were enrolled in this study. ICAS plaque burden was significantly associated with plaque enhancement (p = .037), and plaque burden was linearly positively correlated with CR (R = 0.357, p = .001). ROC analysis showed that the cutoff value of CR for plaque enhancement was 0.56 (specificity of 81.8%). Both plaque enhancement and plaque burden were significantly associated with symptomatic ICAS, and only plaque enhancement was an independent risk factor after multivariate analysis. Conclusion Plaque burden was an independent risk factor for plaque enhancement and showed a linear positive correlation with CR. The cutoff value of CR for plaque enhancement was 0.56, and CR ≥ 0.56 was significantly associated with symptomatic ICAS, which was independently associated with plaque enhancement.

The Lipid Rich Plaque (LRP) Study established the association between high volume of lipidic content (maximum Lipid Core Burden Index [maxLCBI 4mm ] >400) in the coronary arteries and subsequent non-culprit major adverse cardiac events (NC-MACE). This analysis sought to assess the clinical impact of more than one lipid-rich plaque in the coronary tree. The LRP patient population was divided into four cohorts: 1) patients with all segments with maxLCBI 4mm = 0; 2) patients with all coronary segments maxLCBI 4mm < 400, but >0; 3) patients with 1 segment maxLCBI 4mm > 400; and 4) patients with 2+ coronary segments with maxLCBI 4mm > 400. Baseline characteristics, plaque-level characteristics, and follow-up outcomes were described. Among 1550 patients, only 3.2 % had all segments with maxLCBI 4mm = 0; 65.1 % had segments with maxLCBI 4mm > 0 but <400; 22.5 % had one segment with maxLCBI 4mm > 400; and 9.5 % had 2+ coronary segments with maxLCBI 4mm > 400. Distribution within the coronary tree (one versus multiple arteries) did not differ. Overall, 1269 patients were allocated to follow-up (per study design). The composite of all-cause death, cardiac death, any revascularization, and NC-MACE was statistically higher in patients with 1 segment maxLCBI 4mm > 400 and numerically even higher in patients with 2+ segments with maxLCBI 4mm > 400. Patients with maxLCBI 4mm = 0 had no events within two years. There is a stepwise increased risk of all-cause death, cardiac death, any revascularization, and NC-MACE according to the number of coronary segments with maxLCBI 4mm > 400. In contrast, maxLCBI 4mm = 0 results in a low event rate. The Lipid-Rich Plaque Study (LRP), https://clinicaltrials.gov/ct2/show/NCT02033694 , NCT02033694. • LRP Study established association between maxLCBI 4mm > 400 in coronaries NC-MACE. • This substudy shows increased risk of death, revascularization, and NC-MACE. • Risk increases stepwise with number of coronary segments with maxLCBI 4mm > 400. • In contrast, a maxLCBI 4mm = 0 results in an extremely low event rate. • This concept needs to be investigated further in a large, prospective clinical trial. [ABSTRACT FROM AUTHOR]

Atherosclerotic cardiovascular disease risk (ASCVD) is an ongoing epidemic, and lipid abnormalities are its primordial cause. Most individuals suffering a first ASCVD event are previously asymptomatic and often do not receive preventative therapies. The cornerstone of primary prevention has been the identification of individuals at risk through risk calculators based on clinical and laboratory traditional risk factors plus risk enhancers. However, it is well accepted that a clinical risk calculator misclassifies a significant proportion of individuals leading to the prescription of a lipid-lowering medication with very little yield or a missed opportunity for lipid-lowering agents with a potentially preventable event. The development of coronary artery calcium scoring (CAC) and CT coronary angiography (CCTA) provide complementary tools to directly visualize coronary plaque and other risk-modifying imaging components that can potentially provide individualized lipid management.Understanding patient selection for CAC or potentially CCTA and the risk implications of the different parameters provided, such as CAC score, coronary stenosis, plaque characteristics and burden, epicardial adipose tissue, and pericoronary adipose tissue, have grown more complex as technologies evolve. These parameters directly affect the shared decision with patients to start or withhold lipid-lowering therapies, to adjust statin intensity or LDL cholesterol goals. Emerging lipid lowering studies with non-invasive imaging as a guide to patient selection and treatment efficacy, plus the evolution of lipid lowering therapies from statins to a diverse armament of newer high-cost agents have pushed these two fields forward with a complex interaction. This review will discuss existing risk estimators, and non-invasive imaging techniques for subclinical coronary atherosclerosis, traditionally studied using CAC and more recently CCTA with qualitative and quantitative measurements. We will also explore the current data, gaps of knowledge and future directions on the use of these techniques in the risk-stratification and guidance of lipid management.

Coronary Artery Disease Reporting and Data System (CAD-RADS) was created to standardize reporting system for patients undergoing coronary CT angiography (CCTA) and to guide possible next steps in patient management. The goal of this updated 2022 CAD-RADS 2.0 is to improve the initial reporting system for CCTA by considering new technical developments in cardiac CT, including data from recent clinical trials and new clinical guidelines. The updated CAD-RADS classification will follow an established framework of stenosis, plaque burden, and modifiers, which will include assessment of lesion-specific ischemia using CT fractional-flow-reserve (CT-FFR) or myocardial CT perfusion (CTP), when performed. Similar to the method used in the original CAD-RADS version, the determinant for stenosis severity classification will be the most severe coronary artery luminal stenosis on a per-patient basis, ranging from CAD-RADS 0 (zero) for absence of any plaque or stenosis to CAD-RADS 5 indicating the presence of at least one totally occluded coronary artery. Given the increasing data supporting the prognostic relevance of coronary plaque burden, this document will provide various methods to estimate and report total plaque burden. The addition of P1 to P4 descriptors are used to denote increasing categories of plaque burden. The main goal of CAD-RADS, which should always be interpreted together with the impression found in the report, remains to facilitate communication of test results with referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will continue to provide a framework of standardization that may benefit education, research, peer-review, artificial intelligence development, clinical trial design, population health and quality assurance with the ultimate goal of improving patient care. [ABSTRACT FROM AUTHOR]

Coronary computed tomography (CT) angiography (CCTA) is increasingly recognized for diagnosing obstructive coronary artery disease (CAD) among patients presenting with chest pain. In this review, we summarize the utility of CCTA to determine luminal stenosis and identifying coronary plaques with high-risk features. We review different scoring systems that can quantify total plaque burden including how artificial intelligence can facilitate more detailed plaque assessment. We discuss how CCTA can also be used to detect the hemodynamic significance of CAD lesions (fractional flow reserve CT and CT perfusion) and also local factors outside the vessel wall that may predispose to plaque rupture (fat attenuation index and wall shear stress). We conclude with technological advances in imaging acquisition using photon counting CT and post-image processing techniques especially those that can mitigate blooming artifacts. [ABSTRACT FROM AUTHOR]

Although the presence of severe stenosis in the left main coronary artery (LMCA) is a well-established predictor of mortality, whether this extends to nonobstructive atherosclerosis in the LMCA is unknown. The aim of this study was to evaluate the association between LMCA disease by intravascular ultrasound (IVUS) and long-term mortality. Between 2005 and 2013, 3,239 patients with LMCA IVUS imaging without LMCA revascularization (either before angiography or scheduled based on index angiography or IVUS) were included. The primary and secondary endpoints were all-cause and cardiac mortality at a minimum of 5 years obtained from the National Death Index. The IVUS-measured LMCA minimum lumen area (MLA) and plaque burden were 13.1 ± 5.0 mm2 and 41.7% ± 15.6%, respectively. The median follow-up was 8.2 years. The Kaplan-Meier estimated 12-year all-cause and cardiac death rates were 37.5% and 17.0%, respectively. Greater plaque burden (unadjusted HR per 10%: 1.17; 95% CI: 1.12-1.22; P < 0.0001) and smaller IVUS MLA (unadjusted HR per 1 mm2: 0.98; 95% CI: 0.96-0.99; P = 0.0008) were associated with all-cause death. After adjusting for clinical, angiographic, and IVUS factors, plaque burden (adjusted HR per 10%: 1.12; 95% CI: 1.04-1.21; P = 0.003) but not MLA (adjusted HR per 1 mm2: 1.02; 95% CI: 0.99-1.04; P = 0.18) was associated with long-term all-cause death. These findings were also consistent for long-term cardiac mortality. In the present large-scale study with a 12-year follow-up, increasing LMCA plaque burden was associated with long-term all-cause and cardiac mortality in patients not undergoing LMCA revascularization, even when the lumen area was preserved. [Display omitted] [ABSTRACT FROM AUTHOR]

Coronary Artery Disease Reporting and Data System (CAD-RADS) was created to standardize reporting system for patients undergoing coronary CT angiography (CCTA) and to guide possible next steps in patient management. The goal of this updated 2022 CAD-RADS 2.0 is to improve the initial reporting system for CCTA by considering new technical developments in Cardiac CT, including data from recent clinical trials and new clinical guidelines. The updated CAD-RADS classification will follow an established framework of stenosis, plaque burden, and modifiers, which will include assessment of lesion-specific ischemia using CT fractional-flow-reserve (CT-FFR) or myocardial CT perfusion (CTP), when performed. Similar to the method used in the original CAD-RADS version, the determinant for stenosis severity classification will be the most severe coronary artery luminal stenosis on a per-patient basis, ranging from CAD-RADS 0 (zero) for absence of any plaque or stenosis to CAD-RADS 5 indicating the presence of at least one totally occluded coronary artery. Given the increasing data supporting the prognostic relevance of coronary plaque burden, this document will provide various methods to estimate and report total plaque burden. The addition of P1 to P4 descriptors are used to denote increasing categories of plaque burden. The main goal of CAD-RADS, which should always be interpreted together with the impression found in the report, remains to facilitate communication of test results with referring physicians along with suggestions for subsequent patient management. In addition, CAD-RADS will continue to provide a framework of standardization that may benefit education, research, peer-review, artificial intelligence development, clinical trial design, population health and quality assurance with the ultimate goal of improving patient care. [ABSTRACT FROM AUTHOR]

Background: The aim of the study is to research the relationship between the severity of liver fibrosis and the burden of carotid and systemic atherosclerosis. Methods: The study includes 163 patients 40 to 64 years of age without atherosclerotic CVD or liver disease. All patients underwent duplex scanning of the carotid and lower limb arteries. All patients underwent transient liver elastometry using the FibroScan (Echosens, France). Results: Carotid plaque was detected in 110 (67.5%) patients. Based on the results of linear regression analysis, relationships between liver stiffness and carotid total plaque area (r = 0.21; p = 0.025) were found. Significant relationships were established between liver stiffness and atherosclerosis burden score based on the results of linear regression (r = 0.17; p = 0.029). Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis. An increase in liver stiffness >4.5 kPa was associated with an odds ratio of generalized atherosclerosis of 3.48 (95% CI 1.07–11.3; p = 0.038) after adjusting confounding factors. Conclusion: Among patients 40–64 years of age without established atherosclerotic CVD and liver disease, liver stiffness directly correlates with the burden of carotid and systemic atherosclerosis. Liver stiffness showed moderate diagnostic performance (AUC 0.666; p = 0.01) with regard to generalized atherosclerosis. [ABSTRACT FROM AUTHOR]

Atherosclerosis caused major morbidity and mortality worldwide. Molecules possessing lipid-lowering and/or anti-inflammatory properties are potential druggable targets against atherosclerosis. We examined the anti-atherosclerotic effects of fluorescent gold nanoclusters (FANC), which were dihydrolipoic acid (DHLA)-capped 2-nm gold nanoparticles. We evaluated the 8-week effects of FANC in Western-type diet-fed ApoE-deficient mice by either continuous intraperitoneal delivery (20 μM, 50 μl weekly) or via drinking water (300 nM). FANC reduced aortic atheroma burden, serum total cholesterol, and oxidative stress markers malondialdehyde and 4-hydroxynonenal levels. FANC attenuated hepatic lipid deposit, with changed expression of lipid homeostasis-related genes HMGCR, SREBP, PCSK9, and LDLR in a pattern similar to mice treated with ezetimibe. FANC also inhibited intestinal cholesterol absorption, resembling the action of ezetimibe. The lipid-lowering and anti-atherosclerotic effects of FANC reappeared in Western-type diet-fed LDLr-deficient mice. FANC bound insulin receptor β (IRβ) via DHLA, leading to AKT activation. However, unlike insulin, which also bound IRβ to activate AKT to induce HO-1, activation of AKT by FANC was independent of HO-1 expression in human aortic endothelial cells (HAECs). Alternatively, FANC up-regulated NRF2, interfered the binding of KEAP1 to NRF2, and promoted KEAP1 degradation to free NRF2 for nuclear entry to induce HO-1 that suppressed the expression of ICAM-1 and VCAM-1. Consistently, FANC suppressed ox-LDL-induced enhanced attachment of THP-derived macrophages onto HAECs. In macrophages, FANC up-regulated ABCA1, and reversed ox-LDL-induced suppression of cholesterol efflux. FANC effected in vitro at nano moles. In conclusion, our findings showed novel actions and multiple mechanisms of FANC worked coherently against atherosclerosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The effect of transcatheter aortic valve replacement (TAVR) on changes of computed tomography-derived fractional flow reserve (CT-FFR) values was controversial. Thus, we aimed to identify the impact of TAVR on changes of CT-FFR values, plaque characteristics, and the associated clinical impact., Methods: This single-center observational study included 39 consecutive patients with severe aortic valve disease undergone TAVR between August 2019 and April 2023, whom were performed with preoperative and postoperative coronary CT angiography (CCTA). The computation of CT-FFR and plaque characteristics was performed by an independent central core laboratory., Results: Each patient underwent CCTA and CT-FFR assessment without encountering any complications. Notably, both at discharge and six months post-TAVR, there was a significant improvement observed in the New York Heart Association (NYHA) functional classification, left ventricular fractional shortening, and ejection fraction compared to pre-operative levels. The CT-FFR for left anterior descending artery (LAD), left anterior descending artery (LCX), and right coronary artery (RCA) had no obvious change at discharge compared to pre-operation (0.92 ± 0.05 vs. 0.93 ± 0.05, p  = 0.109; 0.96 ± 0.03 vs. 0.95 ± 0.03, p  = 0.523; 0.97 ± 0.04 vs. 0.97 ± 0.03, p  = 0.533; respectively). Furthermore, TAVR did not exert a significant impact on plaque burden during the perioperative period., Our report suggested that TAVR did not significantly affect coronary CT-FFR measurements and plaque characteristics in the perioperative period, and furthermore, the patients' cardiac function showed gradual improvement in the short-term following discharge.

Background: The S209F variant of Abelson Interactor Protein 3 (ABI3) increases risk for Alzheimer's disease (AD), but little is known about its function in relation to AD pathogenesis. Methods: Here, we use a mouse model that is deficient in Abi3 locus to study how the loss of function of Abi3 impacts two cardinal neuropathological hallmarks of AD—amyloid β plaques and tau pathology. Our study employs extensive neuropathological and transcriptomic characterization using transgenic mouse models and adeno-associated virus-mediated gene targeting strategies. Results: Analysis of bulk RNAseq data confirmed age-progressive increase in Abi3 levels in rodent models of AD-type amyloidosis and upregulation in AD patients relative to healthy controls. Using RNAscope in situ hybridization, we localized the cellular distribution of Abi3 in mouse and human brains, finding that Abi3 is expressed in both microglial and non-microglial cells. Next, we evaluated Abi3−/− mice and document that both Abi3 and its overlapping gene, Gngt2, are disrupted in these mice. Using multiple transcriptomic datasets, we show that expression of Abi3 and Gngt2 are tightly correlated in rodent models of AD and human brains, suggesting a tight co-expression relationship. RNAseq of the Abi3-Gngt2−/− mice revealed upregulation of Trem2, Plcg2, and Tyrobp, concomitant with induction of an AD-associated neurodegenerative signature, even in the absence of AD-typical neuropathology. In APP mice, loss of Abi3-Gngt2 resulted in a gene dose- and age-dependent reduction in Aβ deposition. Additionally, in Abi3-Gngt2−/− mice, expression of a pro-aggregant form of human tau exacerbated tauopathy and astrocytosis. Further, using in vitro culture assays, we show that the AD-associated S209F mutation alters the extent of ABI3 phosphorylation. Conclusions: These data provide an important experimental framework for understanding the role of Abi3-Gngt2 function and early inflammatory gliosis in AD. Our studies also demonstrate that inflammatory gliosis could have opposing effects on amyloid and tau pathology, highlighting the unpredictability of targeting immune pathways in AD. [ABSTRACT FROM AUTHOR]

A better understanding of endothelial dysfunction holds promise for more effective interventions for atherosclerosis prevention and treatment. Endothelial signaling by the non-catalytic region of the tyrosine kinase (NCK) family of adaptors, consisting of NCK1 and NCK2, has been implicated in cardiovascular development and postnatal angiogenesis but its role in vascular disease remains incompletely understood. Here, we report stage- and sex-dependent effects of endothelial NCK2 signaling on arterial wall inflammation and atherosclerosis development. Male and female Nck1-null atheroprone mice enabling inducible, endothelial-specific Nck2 inactivation were fed a high fat diet (HFD) for 8 or 16 weeks to model atherosclerosis initiation and progression, respectively. Analysis of aorta preparations en face during disease progression, but not initiation, showed a significant reduction in plaque burden in males, but not females, lacking endothelial NCK2 relative to controls. Markers of vascular inflammation were reduced by endothelial NCK2 deficiency in both males and females during atherosclerosis progression but not initiation. At advanced stages of disease, plaque size and severity of atherosclerotic lesions were reduced by abrogation of endothelial NCK2 signaling only in males. Collectively, our results demonstrate stage- and sex-dependent modulation of atherosclerosis development by endothelial NCK2 signaling.

Abstract Background Reduced left ventricular function, assessed by global longitudinal strain (GLS), is sometimes observed in asymptomatic patients with diabetes mellitus (DM) and is often present in patients with diabetes-related microvascular complications. Our aim was to assess the association between microvascular complications, coronary artery plaque burden (PB) and GLS in asymptomatic patients with DM and non-obstructive coronary artery disease (CAD). Methods This cross-sectional study included patients with DM without any history, symptoms or objective evidence of obstructive CAD. All patients were identified in the outpatient Clinic of Endocrinology at Odense University Hospital Svendborg. An echocardiography and a coronary computed tomography angiography were performed to assess GLS and the degree of CAD, respectively. A coronary artery stenosis

Coronary artery plaque burden, low attenuation non-calcified plaque (LAP), and pericoronary adipose tissue (PCAT) on coronary CT angiography (CCTA), have been linked to future cardiac events. The purpose of this study was to evaluate intra- and inter reader reproducibility in the quantification of coronary plaque burden and its characteristics using an artificial intelligence-enhanced semi-automated software. A total of 10 women and 6 men, aged 52 (IQR 49-58) underwent CCTA using a Siemens Somatom Force, Somatom Definition AS and Somatom Definition Flash scanners. Two expert readers utilized dedicated semi-automatic software (vascuCAP, Elucid Bioimaging, Wenham, MA) to assess calcified plaque, low attenuation plaque and PCAT. Readers were blinded to all clinical information and repeated their analysis at 6 weeks in random order to minimize recall bias. Data analysis was performed on the right and left coronary arteries. Intra- and inter-reader reproducibility was compared using Pearson correlation coefficient, while absolute values between analyses and readers were compared with paired non-parametric tests. This is a sub-study of the Specialized Center of Research Excellence (SCORE) clinical trial (5U54AG062334). A total of 64 vessels from 16 patients were analyzed. Intra-reader Pearson correlation coefficients for calcified plaque volume, LAP volume and PCAT volumes were 0.96, 0.99 and 0.92 for reader 1 and 0.94, 0.94 and 0.95 for reader 2, respectively, (all p < 0.0001). Inter-reader Pearson correlation coefficients for calcified plaque volume, LAP and PCAT volumes were 0.92, 0.96 and 0.78, and 0.99, 0.99 and 0.93 on the second analyses, all had a p value <0.0001. There was no significant bias on the corresponding Bland–Altman analyses. Volume measurement of coronary plaque burden and PCAT volume can be performed with high intra- and inter-reader agreement. [ABSTRACT FROM AUTHOR]

Aims: To illuminate the pathological synergy between Aβ and tau leading to emergence of neurofibrillary tangles (NFT) in Alzheimer's disease (AD), here, we have performed a comparative neuropathological study utilising three distinctive variants of human tau (WT tau, P301L mutant tau and S320F mutant tau). Previously, in non‐transgenic mice, we showed that WT tau or P301L tau does not form NFT while S320F tau can spontaneously aggregate into NFT, allowing us to test the selective vulnerability of these different tau conformations to the presence of Aβ plaques. Methods: We injected recombinant AAV‐tau constructs into neonatal APP transgenic TgCRND8 mice or into 3‐month‐old TgCRND8 mice; both cohorts were aged 3 months post injection. This allowed us to test how different tau variants synergise with soluble forms of Aβ (pre‐deposit cohort) or with frank Aβ deposits (post‐deposit cohort). Results: Expression of WT tau did not produce NFT or altered Aβ in either cohort. In the pre‐deposit cohort, S320F tau induced Aβ plaque deposition, neuroinflammation and synaptic abnormalities, suggesting that early tau tangles affect the amyloid cascade. In the post‐deposit cohort, contemporaneous expression of S320F tau did not exacerbate amyloid pathology, showing a dichotomy in Aβ‐tau synergy based on the nature of Aβ. P301L tau produced NFT‐type inclusions in the post‐deposit cohort, but not in the pre‐deposit cohort, indicating pathological synergy with pre‐existing Aβ deposits. Conclusions: Our data show that different tau mutations representing specific folding variants of tau synergise with Aβ to different extents, depending on the presence of cerebral deposits. [ABSTRACT FROM AUTHOR]

Objective: Lipids play key role in coronary atherosclerosis. The role of non-high-density lipoprotein cholesterol (non-HDL-C) in atherosclerotic plaques using intravascular imaging remains unclear. This study aimed to assess its relationship with coronary plaque features using intravascular ultrasound (IVUS) in acute coronary syndrome (ACS)., Methods: A total of 601 patients divided into two groups: normal non-HDL-C≤130 mg/dl (n = 410) and high non-HDL cholesterol >130 mg/dl (n = 191). IVUS performed before coronary intervention., Results: Mean age 53.18 ± 12.29 years. No significant differences in hypertension, diabetes, and smoking between groups. Plaque burden was significantly higher among normal versus high non-HDL-C groups (79.59 ± 9.98 % vs. 81.61 ± 5.39 %; p = 0.001). At minimal luminal site, fibrofatty percentage was higher in normal non-HDL-C group (p = 0.027), while necrotic core greater in high non-HDL-C group (p = 0.033). Segmental analysis, necrotic core was significantly higher in percentage (p = 0.006) and volumes (p = 0.011) in normal versus high non-HDL-C groups. Total cholesterol (r = 0.099, p = 0.015), LDL-C (r = 0.081, p = 0.046), triglycerides (r = 0.083, p = 0.041),and non-HDL-C (r = 0.099, p = 0.015) positively correlated with plaque burden. Total cholesterol (r = 0.115, p = 0.005), LDL-C (r = 0.107, p = 0.009), and non-HDL-C (r = 0.105, p = 0.010) positively correlated with necrotic core volume. Linear regression analysis showed age and non-HDL-C as predictors of higher plaque burden. Multiple linear regression analysis; age, body mass index, and non-HDL-C were predictors of larger necrotic core volume., Conclusion: Non-HDL-C levels were positively associated with plaque burden, measure of extent of atherosclerosis. It is closely associated with and is a predictor of necrotic core volume; a marker of plaque vulnerability. This IVUS study demonstrates potential role of non-HDL-C in causation of plaque in ACS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)