UNASSIGNED: Coronary artery calcium score (CACS) is an established marker of coronary artery disease (CAD) and has been extensively used to stratify risk in asymptomatic individuals. However, the value of CACS in predicting plaque morphology in patients with advanced CAD is less established. The present analysis aims to assess the association between CACS and plaque characteristics detected by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) imaging in patients with obstructive CAD.
UNASSIGNED: Seventy patients with obstructive CAD underwent coronary computed tomography angiography (CTA) and 3-vessel NIRS-IVUS imaging were included in the present analysis. The CTA data were used to measure the CACS in the entire coronary tree and the segments assessed by NIRS-IVUS, and these estimations were associated with the NIRS-IVUS measurements at a patient and segment level.
UNASSIGNED: In total, 65 patients (188 segments) completed the study protocol and were included in the analysis. A weak correlation was noted between the CACS, percent atheroma volume (r = 0.271, P = .002), and the calcific burden measured by NIRS-IVUS (r = 0.648, P < .001) at patient-level analysis. Conversely, there was no association between the CACS and the lipid content, or the incidence of high-risk plaques detected by NIRS. Linear regression analysis at the segment level demonstrated an association between the CACS and the total atheroma volume (coefficient, 0.087; 95% CI, 0.024-0.149; P = .008) and the calcific burden (coefficient, 0.117; 95% CI, 0.048-0.186; P = .001), but there was no association between the lipid content or the incidence of high-risk lesions.
UNASSIGNED: In patients with obstructive CAD, the CACS is not associated with the lipid content or plaque phenotypes. These findings indicate that the CACS may have a limited value for screening or stratifying cardiovascular risk in symptomatic patients with a high probability of CAD.

BACKGROUND: Atherosclerotic (AS) plaques require a dense necrotic core and a robust fibrous cap to maintain stability. While previous studies have indicated that the traditional Chinese medicine Huang Lian Jie Du Decoction (HLJDD) possesses the capability to stabilize AS plaques, the underlying mechanisms remain obscure. This study aims to delve deeper into the potential mechanisms by which HLJDD improves AS through an integrated research strategy.
METHODS: Leveraging an AS model in ApoE-/- mice exposed to a high-fat diet (HFD), we scrutinized the therapeutic effects of HLJDD using microscopic observations, oil red O staining, HE staining and Masson staining. Employing comprehensive techniques of network pharmacology, bioinformatics, and molecular docking, we elucidated the mechanism by which HLJDD stabilizes AS plaques. In vitro experiments, utilizing ox-LDL-induced macrophages and apoptotic vascular smooth muscle cells (VSMCs), assessed the impact of HLJDD on efferocytosis and the role of SLC2A1.
RESULTS: In vivo experiments showcased the efficacy of HLJDD in reducing the quantity of aortic plaques, diminishing lipid deposition, and enhancing plaque stability in AS mice. Employing network pharmacology and machine learning, we pinpointed SLC2A1 as a crucial regulatory target. Molecular docking further validated the binding of HLJDD components with SLC2A1. The experiments demonstrated a dose-dependent upregulation in SLC2A1 expression by HLJDD, amplifying efferocytosis. Importantly, this effect was reversed by the SLC2A1 inhibitor STF-31, highlighting the pivotal role of SLC2A1 as a target.
CONCLUSIONS: The HLJDD can modulate macrophage efferocytosis by enhancing the expression levels of SLC2A1, thereby improving the stability of atherosclerotic plaques.

BACKGROUND: The aim of this study was to exploit integrated PET/MRI to simultaneously evaluate the morphological, component, and metabolic features of advanced atherosclerotic plaques and explore their incremental value.
METHODS: In this observational prospective cohort study, patients with advanced plaque in the carotid artery underwent 18F-FDG PET/MRI. Plaque morphological features were measured, and plaque component features were determined via MRI according to AHA lesion-types. Maximum standardized uptake values (SUVmax) and tissue to background ratio (TBR) on PET were calculated. Area under the receiver-operating characteristic curve (AUC) and net reclassification improvement (NRI) were used to compare the incremental contribution of FDG uptake when added to AHA lesion-types for symptomatic plaque classification.
RESULTS: A total of 280 patients with advanced plaque in the carotid artery were recruited. A total of 402 plaques were confirmed, and 87 of 402 (21.6%) were symptomatic plaques. 18F-FDG PET/MRI was performed a mean of 38 days (range 1-90) after the symptom. Increased stenosis degree (61.5% vs. 50.0%, p < 0.001) and TBR (2.96 vs. 2.32, p < 0.001) were observed in symptomatic plaques compared with asymptomatic plaques. The performance of the combined model (AHA lesion type VI + stenosis degree + TBR) for predicting symptomatic plaques was the best among all models (AUC = 0.789). The improvement of the combined model (AHA lesion type VII + stenosis degree + TBR) over AHA lesion type VII model for predicting symptomatic plaques was the highest (AUC = 0.757/0.454, combined model/AHA lesion type VII model), and the NRI was 50.7%.
CONCLUSIONS: Integrated PET/MRI could simultaneously evaluate the morphological component and inflammation features of advanced atherosclerotic plaques and provide supplementary optimization information over AHA lesion-types for identifying vulnerable plaques in atherosclerosis subjects to achieve further stratification of stroke risk.

UNASSIGNED: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis.
UNASSIGNED: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis.
UNASSIGNED: Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant.
UNASSIGNED: This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.

UNASSIGNED: Inflammation is a central driver of atherogenesis and eventual plaque rupture. This study aimed to evaluate the association between residual inflammatory risk (RIR) and vulnerable plaques in the carotid artery in patients with ischemic stroke.
UNASSIGNED: Patients with acute ischemic stroke were enrolled from January 2021 to July 2022. They were divided into four groups: RIR only (LDL-C <2.6 mmol/L and hsCRP ≥2 mg/L), residual cholesterol risk (RCR) only (LDL-C ≥2.6 mmol/L and hsCRP <2 mg/L), both risk or residual cholesterol and inflammatory risk (RCIR) (LDL-C ≥2.6 mmol/L and hsCRP ≥2 mg/L), and neither risk (LDL-C <2.6 mmol/L and hsCRP <2 mg/L). Vulnerable plaques were determined if it had a low attenuated plaque CT value of <35 Hounsfield Units (HU) and a remodeling index of >1.1, which indicated a positive remodeling.
UNASSIGNED: Out of the 468 enrolled patients, 157 (33.5%) were detected to have vulnerable plaques. The proportion of patients with neither risk, RIR, RCR, and RCIR were 32.9%, 28.6%, 18.8%, and 19.7%, respectively. Patients with vulnerable plaques exhibited a higher prevalence of hyperlipidemia (P = 0.026), higher proportion of RIR (P = 0.015), a higher ratio of stroke subtypes of large artery atherosclerosis (P = 0.012), and high leukocyte counts (P < 0.001). The logistic regression analysis detected that RIR was associated with vulnerable plaques after adjusted for major confounding factors (OR 1.98, 95% CI 1.13-3.45, P = 0.016), especially in the large artery atherosclerosis subtype (OR 2.71, 95% CI 1.08-6.77, P = 0.034).
UNASSIGNED: In patients with ischemic stroke, RIR is associated with the vulnerability of carotid plaques, especially for those with the large artery atherosclerosis subtype. Therefore, further studies investigating the interventions to modulate inflammation in these patients may be warranted.

UNASSIGNED: One of the widespread manifestations of cerebral small vessel disease (CSVD) of the brain parenchyma is white matter lesion, which appears as white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI). Previous studies have illustrated that large artery atherosclerosis is related to CSVD, but the precise progress of pathogenesis remains unknown. High-resolution MRI (HR-MRI) has the ability to delineate intracranial vascular walls, enabling a thorough exploration of the structure and composition of unstable plaques. This study aimed to apply HR-MRI to characterize the wall changes and plaque characteristics of middle cerebral arteries in patients with WMHs and to investigate the correlation between plaque vulnerability parameters and different degrees of WMHs.
UNASSIGNED: In this study, 138 patients with acute ischemic stroke at Harbin Medical University\'s First Clinical Hospital (May 2021 to October 2023) were cross-sectionally reviewed and underwent conventional brain and HR-MRI using T1-weighted 3D volumetric isotropic turbo spin echo acquisition (T1W-3D-VISTA) of the unilateral middle cerebral artery (MCA). According to Fazekas grade (0-6), the patients were divided into two groups: Fazekas score 0-2, no-or-mild WMHs; and Fazekas 3-6, moderate-to-severe WMHs. The intraplaque hemorrhage, plaque distribution, plaque enhancement, plaque load, remodeling pattern, and stenosis of the two groups were measured. Binary logistic regression analysis was conducted to evaluate the relationship between vulnerable plaques and WMHs.
UNASSIGNED: Of the participants who were initially considered for inclusion, 71 were deemed eligible, among whom 34 were placed in the no-or-mild WMH group and 37 in the moderate-to-severe WMH group. Between the two groups, there were significant differences in intraplaque hemorrhage (P=0.01), a wide distribution (P=0.02), and plaque enhancement (P=0.02). Univariate analysis showed that WMHs were associated with age [odds ratio (OR) =1.080; 95% confidence interval (CI): 1.020-1.144; P=0.008], hypertension (OR =3.500; 95% CI: 1.276-9.597; P=0.01), intraplaque hemorrhage (OR =3.955; 95% CI: 1.247-12.538; P=0.02), a wide distribution (OR =3.067; 95% CI: 1.159-8.115; P=0.02), and significant plaque enhancement (OR =4.372; 95% CI: 1.101-17.358; P=0.03); however, the multivariate results showed that the only independent factors associated with WMHs were age (OR =1.095; 95% CI: 1.019-1.176; P=0.01) and intraplaque hemorrhage (OR =5.88; 95% CI: 1.466-23.592; P=0.01).
UNASSIGNED: Our findings suggest that age and intraplaque hemorrhage may be associated with more severe WMHs in patients with acute ischemic stroke, which may be helpful for further clinical examination and intervention treatment.

UNASSIGNED: Arterial remodeling is a compensatory mechanism of the vessel wall in response to atherosclerotic plaque growth. However, the clinical significance of vascular remodeling of carotid lesions remains unclear. Through this study, we aimed to evaluate the association between vascular remodeling and ischemic symptoms in patients with an internal carotid artery (ICA) stenosis degree ≥50%, considering the differences in plaque calcification patterns.
UNASSIGNED: This retrospective cross-sectional study included adult patients with moderate-to-severe proximal ICA stenosis associated with atherosclerotic plaques admitted to the Zhejiang Hospital between September 2018 and March 2023. Parameters such as lumen diameter, plaque calcification types, calcium scores, and calcification thickness were assessed using non-contrast and contrast-enhanced computed tomography angiography (CTA). The remodeling ratio (RR) was calculated by dividing the maximum distance of the proximal ICA between the inner border of the arterial lumen at the plaque site and the outer borders of the plaque by the luminal diameter. Atherosclerosis risk factors and medications were recorded. The Mann-Whitney U test or chi-square test was used to compare the differences between groups. Correlations were measured using Pearson\'s correlation coefficient. Predictors of ischemic symptoms were assessed using multivariable logistic regression analysis, with results expressed as odds ratio (ORs) with 95% confidence intervals (CIs). A P value less than 0.05 (two-sided) was considered to indicate statistical significance The differences in RR among plaque calcification types and the association between vascular remodeling and clinical symptoms were analyzed.
UNASSIGNED: A total of 242 ICAs in 196 patients were included in this study, and 84 were symptomatic and 158 were asymptomatic. The RR in symptomatic ICA [median, 1.31 (interquartile range, 1.17-1.68)] was significantly greater than that in asymptomatic group [median, 1.20 (interquartile range, 1.05-1.45)], P=0.006). Significant differences in RR existed among plaque calcification types, among which type 5 and 6 plaques had the highest RR. About 71.5% (173/242) of all ICAs showed positive remodeling. Significant correlations were observed between RR and ischemic symptoms and between positive remodeling and calcification thickness (P<0.05 for all variables). On multivariable logistic regression analysis, calcification thickness remained significantly associated with positive remodeling of carotid arteries (OR 2.30; 95% CI: 1.06-5.01; P=0.036).
UNASSIGNED: Arterial remodeling exists in the ICA. A significant association between arterial positive remodeling and plaque calcification thickness was established. RR helps predict ischemic symptoms. The results of our study suggest that arterial remodeling serves as a novel measure to help ascertain the risk stratification of ischemic events in carotid atherosclerotic disease.

UNASSIGNED: Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification.
UNASSIGNED: We recruited 360 patients with ≥50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer-Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test.
UNASSIGNED: We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666-0.768) and a Hosmer-Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138-0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029-0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617-0.723) increased the C-statistics (p=0.028).
UNASSIGNED: Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥50% carotid stenosis.
We studied whether using contrast-enhanced ultrasound (CEUS) to detect intraplaque neovascularization could help better determine the risk of ischemic stroke. We compared the combined use of color Doppler ultrasound (CDUS) and CEUS with CDUS alone in patients with more than 50% carotid narrowing. Our findings showed that combining clinical details, CDUS, and CEUS was more effective (0.719 vs 0.672). This means that CEUS provides extra insight when gauging ischemic stroke risk compared with CDUS alone. This could help in accurately identifying patients at high risk of stroke. However, more extensive studies are needed to fully understand the role of these tests in the evaluation of stroke risk.

Acute thrombosis secondary to atherosclerotic plaque rupture is the main cause of acute cardiac and cerebral ischemia. An animal model of unstable atherosclerotic plaques is highly important for investigating the mechanism of plaque rupture and thrombosis. However, current animal models involve complex operations, are costly, and have plaque morphologies that are different from those of humans. We aimed to establish a simple animal model of vulnerable plaques similar to those of humans. Rabbits were randomly divided into three groups. Group A was given a normal formula diet for 13 weeks. Group C underwent surgery on the intima of the right carotid artery with - 80 °C cryofluid-induced injury after 1 week of a high-fat diet and further feeding a 12-week high-fat diet. Group B underwent the same procedure as Group C but without the - 80 °C cryofluid. Serum lipid levels were detected via ELISA. The plaque morphology, stability and degree of stenosis were evaluated through hematoxylin-eosin (HE) staining, Masson trichrome staining, Elastica van Gieson staining (EVG), and oil red O staining. Macrophages and inflammatory factors in the plaques were assessed via immunohistochemical analysis. The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels in groups B and C were significantly greater than those in group A. No plaque formation was observed in group A. The plaques in group B were very small. In group C, obvious plaques were observed in the blood vessels, and the plaques exhibited a thin fibrous cap, a large lipid core, and partially visible neovascularization, which is consistent with the characteristics of vulnerable plaques. In the plaques of group C, a large number of macrophages were present, and matrix metalloproteinase 9 (MMP-9) and lectin-like oxidized LDL receptor 1 (LOX-1) were abundantly expressed. We successfully established a rabbit model of vulnerable carotid plaque similar to that of humans through the combination of cryofluid-induced endothelial injury and a high-fat diet, which is feasible and cost effective.

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