Efficacy of Coronary Calcium Score in Predicting Coronary Artery Morphology in Patients With Obstructive Coronary Artery Disease.

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Huanglian Jiedu Decoction enhances the stability of atherosclerotic plaques through SLC2A1-mediated efferocytosis.

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. CONCLUSION: The HLJDD can modulate macrophage efferocytosis by enhancing the expression levels of SLC2A1, thereby improving the stability of atherosclerotic plaques.

Increased Incidence of Adverse Events in Diabetes Mellitus Patients with Combined Multiple Vulnerable Plaque Features. New Insights From the COMBINE OCT-FFR trial.

AIMS: To evaluate the individual as well as combined impact of OCT-detected vulnerability features (OCT-VFs) in the prediction of major adverse cardiovascular events (MACE) in non-ischemic lesions in patients with diabetes mellitus (DM). METHODS AND RESULTS: The COMBINE OCT-FFR (NCT02989740) was a prospective, double-blind, international, natural history study that included patients with DM having ≥1 lesions with a fractional flow reserve >0.80, undergoing systematic OCT assessment. Pre-specified OCT-VFs included TCFA, r-MLA, h-PB, and CP. The primary endpoint (MACE) was a composite of cardiac mortality, target vessel myocardial infarction, clinically driven target lesion revascularization or hospitalization for unstable angina up to 5 years, analyzed according to the presence of these OCT-VFs, both individually and in combination. TCFA, r-MLA, h-PB and CP were identified in 98 (25.1%), 159 (40.8%), 56 (14.4%), and 116 (29.8%) patients, respectively. The primary endpoint rate increased progressively from 6.9% to 50.0% (HR=10.10; 95%CI, 3.37 to 30.25, p<0.001) in patients without OCT-VFs compared to those with concomitant h-PB, r-MLA, CP, and TCFA. Importantly, while TCFA, h-PB, r-MLA and CP were individually associated with the primary endpoint, the presence of two or more OCT-VFs significantly increased the likelihood of adverse events at 5 years. CONCLUSIONS: In patients with DM and non-ischemic lesions, TCFA, h-PB, r-MLA and CP were predictors of adverse events. However, the presence of two or more OCT-VFs significantly increased the likelihood of MACE at 5 years. Further studies are warranted to confirm these findings and their potential clinical implications in a randomized fashion.

Management of Coronary Vulnerable Plaque With Medical Therapy or Local Preventive Percutaneous Coronary Intervention.

Acute coronary syndromes (ACS) often result from the rupture or erosion of high-risk coronary atherosclerotic plaques (ie, vulnerable plaques). Advances in intracoronary imaging such as intravascular ultrasound, optical coherence tomography, or near-infrared spectroscopy have improved the identification of vulnerable plaques, characterized by large plaque burden, small minimal luminal area, thin fibrous cap, and large lipid content. Although pharmacology, including lipid-lowering agents, and intensive risk-factor control are pivotal for management of vulnerable plaques and secondary prevention, recurrent events tend to accrue despite intensive pharmacotherapy. Therefore, it has been hypothesized that local preventive percutaneous coronary intervention may passivate these vulnerable plaques, preventing the occurrence of plaque-related ACS. However, solid evidence is lacking on its use for treatment of non-flow-limiting vulnerable plaques. As such, the optimal management of vulnerable plaques has not been established. Herein, we have reviewed the diagnosis and management of vulnerable plaques, focusing on systematic pharmacology and focal treatments.

Computed Tomography Angiography Identified High-Risk Coronary Plaques: From Diagnosis to Prognosis and Future Management.

CT angiography has become, in recent years, a main evaluating modality for patients with coronary artery disease (CAD). Recent advancements in the field have allowed us to identity not only the presence of obstructive disease but also the characteristics of identified lesions. High-risk coronary atherosclerotic plaques are identified in CT angiographies via a number of specific characteristics and may provide prognostic and therapeutic implications, aiming to prevent future ischemic events via optimizing medical treatment or providing coronary interventions. In light of new evidence evaluating the safety and efficacy of intervening in high-risk plaques, even in non-flow-limiting disease, we aim to provide a comprehensive review of the diagnostic algorithms and implications of plaque vulnerability in CT angiography, identify any differences with invasive imaging, analyze prognostic factors and potential future therapeutic options in such patients, as well as discuss new frontiers, including intervening in non-flow-limiting stenoses and the role of CT angiography in patient stratification.

Syndecan-1 as a predictor of vulnerable atherosclerotic plaques.

Aims: Cardiovascular disease remains a major global health concern, with atherosclerosis (AS) being a significant contributor. Vulnerable plaques play a critical role in acute cardiovascular events. Syndecan-1 (SDC-1), a vital membrane proteoglycan in the vascular endothelial glycocalyx, is believed to be associated with plaque progression. However, its precise relationship with severity and vulnerability of atherosclerotic plaque remains unclear. This study aimed to investigate SDC-1 expression and its potential correlation with plaque vulnerability in ApoE-/- atherosclerosis mouse model. Methods and results: Eight-week-old mice were induced into the AS model using a high-fat diet (HFD) and/or partial ligation of the left common carotid artery (PLCA), with a chow diet (CD) control group. After 16 weeks, plaques in the aortic root showed the following order: HFD + PLCA group > HFD group > CD + PLCA group > CD group. Immunohistochemistry revealed heightened accumulation of lipid/foam cells and CD68-labeled macrophages in the plaques, elevated vascular endothelial growth factor (VEGF), and matrix Metalloproteinase-9 (MMP-9) in the HFD + PLCA group's plaques, along with reduced collagen and α-SMA-labeled smooth muscle cells, resulting in the highest vulnerability index value. Immunohistofluorescence analysis of frozen plaque sections showed significantly higher SDC-1 expression in the AS mice group compared to the CD group, both positively correlated with plaque vulnerability. Serum analysis demonstrated elevated levels of SDC1, sphingosine 1-phosphate (S1P), and VEGF-A in the AS mice, all positively correlated with plaque vulnerability. Multivariate analysis identified SDC1 as an independent predictor of plaque vulnerability. Conclusion: This study enhances our understanding of plaque vulnerability mechanisms and presents SDC1 as a potential biomarker for atherosclerosis. These findings underscore the importance of addressing modifiable risk factors, such as diet and hemodynamics and suggest the utility of serum SDC1 as a valuable clinical marker. Ultimately, these insights may lead to more effective strategies in combating cardiovascular diseases and improving patient outcomes.

Association between Pericarotid Fat Density and Positive Remodeling in Patients with Carotid Artery Stenosis.

Background/Objectives: The underlying mechanism of the potential involvement of inflammatory crosstalk between pericarotid fat and vascular layers in atherosclerosis pathogenesis is unclear. We investigated the association between pericarotid fat density and positive remodeling and inflammatory markers in carotid stenosis. We hypothesized that pericarotid fat density might serve as a marker of plaque inflammation in a clinical setting. Methods: We evaluated the stenosis degree and pericarotid fat density in 258 patients with carotid plaques. Plaque composition was examined, and the correlation between pericarotid fat density and expansive remodeling was investigated. Pearson's product-moment correlation coefficient was used to examine the relationship between pericarotid fat density and the expansive remodeling ratio. We also evaluated the relationship of pericarotid fat density with plaque composition, degree of stenosis, and macrophage and microvessel counts by. The subgroup analysis compared these factors between symptomatic mild carotid stenosis. Results: The pericarotid fat density was -63.0 ± 11.1 HU. The carotid fat densities were -56.8 ± 10.4 HU in symptomatic and -69.2 ± 11.4 HU in asymptomatic lesions. The pericarotid fat density values in intraplaque hemorrhage, lipid-rich necrotic core, and fibrous plaque were -51.6 ± 10.4, -59.4 ± 12.8, and -74.2 ± 8.4 HU, respectively. Therefore, the expansive remodeling ratio was 1.64 ± 0.4. Carotid fat density and expansive remodeling ratio were correlated. Immunohistochemistry showed high macrophage and microvessel levels (143.5 ± 61.3/field and 121.2 ± 27.7/field, respectively). In symptomatic mild carotid stenosis, pericarotid fat density was correlated with other inflammatory factors. The pericarotid fat density and expansive remodeling ratio (2.08 ± 0.21) were high in mild stenosis (-50.1 ± 8.4 HU). Conclusions: Pericarotid fat and intraplaque components were well correlated. Carotid fat density may be a marker of plaque inflammation in carotid plaques.

Management of vulnerable patient phenotypes and acute coronary syndrome mechanisms.

Atherosclerosis is a chronic vascular disease. Its prevalence increases with aging. However, atherosclerosis may also affect young subjects without significant exposure to the classical risk factors. Recent evidence indicates clonal hematopoiesis of indeterminate potential (CHIP) as a novel cardiovascular risk factor that should be suspected in young patients. CHIP represents a link between impaired bone marrow and atherosclerosis. Atherosclerosis may present with an acute symptomatic manifestation or subclinical events that favor plaque growth. The outcome of a plaque relies on a balance of innate and environmental factors. These factors can influence the processes that initiate and propagate acute plaque destabilization leading to intraluminal thrombus formation or subclinical vessel healing. Thirty years ago, the first autopsy study revealed that coronary plaques can undergo rupture even in subjects without a known cardiovascular history. Nowadays, cardiac magnetic resonance studies demonstrate that this phenomenon is not rare. Myocardial infarction is mainly due to plaque rupture and plaque erosion that have different pathophysiological mechanisms. Plaque erosion carries a better prognosis as compared to plaque rupture. Thus, a tailored conservative treatment has been proposed and some studies demonstrated it to be safe. On the contrary, plaque rupture is typically associated with inflammation and anti-inflammatory treatments have been proposed in response to persistently elevate biomarkers of systemic inflammation. In conclusion, atherosclerosis may present in different forms or phenotypes. Vulnerable patient phenotypes, identified by using intravascular imaging techniques, biomarkers, or even genetic analyses, are characterized by distinctive pathophysiological mechanisms. These different phenotypes merit tailored management.

Atherosclerotic Coronary Plaque Features in Patients With Chronic Obstructive Pulmonary Disease and Acute Coronary Syndrome.

Previous studies reported a robust relation between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). Systemic inflammation has been proposed as possible pathogenetic mechanism linking these 2 entities, although data on atherosclerotic coronary features in COPD patients are lacking. We studied atherosclerotic coronary plaque features in COPD patients presenting with acute coronary syndrome (ACS) using optical coherence tomography (OCT). ACS patients who underwent intracoronary OCT imaging of the culprit vessel were enrolled. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into 2 groups according to the presence of an established diagnosis of COPD, and plaque features at the culprit site and along the culprit vessel were compared between the groups. Of 146 ACS patients (mean age:66.1 ± 12.7 years, 109 men), 47 (32.2%) had COPD. Patients with COPD had significantly higher prevalence of MØI (78.7% vs 54.5%, p = 0.005) and thin cap fibroatheroma (TCFA) (48.9% vs 22.2%, p = 0.001) at the culprit site. In the multivariate logistic regression, COPD was independently associated with MØI (odds ratio [OR] 21.209, 95% confidence interval [CI] 1.679 to 267.910, p = 0.018) and TCFA at the culprit site (OR 5.345, 95% CI 1.386 to 20.616, p = 0.015). Similarly, COPD was independently associated with both MØI (OR 3.570, 95% CI 1.472 to 8.658, p = 0.005) and TCFA (OR 4.088, 95% CI 1.584 to 10.554, p = 0.004) along the culprit vessel. In conclusion, in ACS patients who underwent OCT imaging of the culprit vessel, COPD was an independent predictor of plaque inflammation and vulnerability. These results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability.

Diagnostic potential of TSH to HDL cholesterol ratio in vulnerable carotid plaque identification.

Objective: This study aimed to investigate the predictive value of the thyroid-stimulating hormone to high-density lipoprotein cholesterol ratio (THR) in identifying specific vulnerable carotid artery plaques. Methods: In this retrospective analysis, we included 76 patients with carotid plaques who met the criteria for admission to Zhejiang Hospital from July 2019 to June 2021. High-resolution magnetic resonance imaging (HRMRI) and the MRI-PlaqueView vascular plaque imaging diagnostic system were utilized to analyze carotid artery images for the identification of specific plaque components, including the lipid core (LC), fibrous cap (FC), and intraplaque hemorrhage (IPH), and recording of the area percentage of LC and IPH, as well as the thickness of FC. Patients were categorized into stable plaque and vulnerable plaque groups based on diagnostic criteria for vulnerable plaques derived from imaging. Plaques were categorized based on meeting one of the following consensus criteria for vulnerability: lipid core area over 40% of total plaque area, fibrous cap thickness less than 65 um, or the presence of intraplaque hemorrhage. Plaques meeting the above criteria were designated as the LC-associated vulnerable plaque group, the IPH-associated group, and the FC-associated group. Multivariate logistic regression was employed to analyze the factors influencing carotid vulnerable plaques and specific vulnerable plaque components. Receiver operating characteristic (ROC) curves were used to assess the predictive value of serological indices for vulnerable carotid plaques. Results: We found that THR (OR = 1.976; 95% CI = 1.094-3.570; p = 0.024) and TSH (OR = 1.939, 95% CI = 1.122-3.350, p = 0.018) contributed to the formation of vulnerable carotid plaques. THR exhibited an area under the curve (AUC) of 0.704 (95% CI = 0.588-0.803) (p = 0.003), and the AUC for TSH was 0.681 (95% CI = 0.564-0.783) (p = 0.008). THR was identified as an independent predictor of LC-associated vulnerable plaques (OR = 2.117, 95% CI = 1.064-4.212, p = 0.033), yielding an AUC of 0.815. THR also demonstrated diagnostic efficacy for LC-associated vulnerable plaques. Conclusion: This study substantiated that THR and TSH have predictive value for identifying vulnerable carotid plaques, with THR proving to be a more effective diagnostic indicator than TSH. THR also exhibited predictive value and specificity in the context of LC-associated vulnerable plaques. These findings suggest that THR may be a promising clinical indicator, outperforming TSH in detecting specific vulnerable carotid plaques.

Notoginsenoside R1 decreases intraplaque neovascularization by governing pericyte-endothelial cell communication via Ang1/Tie2 axis in atherosclerosis.

Atherosclerosis represents the major cause of mortality worldwide and triggers higher risk of acute cardiovascular events. Pericytes-endothelial cells (ECs) communication is orchestrated by ligand-receptor interaction generating a microenvironment which results in intraplaque neovascularization, that is closely associated with atherosclerotic plaque instability. Notoginsenoside R1 (R1) exhibits anti-atherosclerotic bioactivity, but its effect on angiogenesis in atherosclerotic plaque remains elusive. The aim of our study is to explore the therapeutic effect of R1 on vulnerable plaque and investigate its potential mechanism against intraplaque neovascularization. The impacts of R1 on plaque stability and intraplaque neovascularization were assessed in ApoE-/- mice induced by high-fat diet. Pericytes-ECs direct or non-direct contact co-cultured with VEGF-A stimulation were used as the in vitro angiogenesis models. Overexpressing Ang1 in pericytes was performed to investigate the underlying mechanism. In vivo experiments, R1 treatment reversed atherosclerotic plaque vulnerability and decreased the presence of neovessels in ApoE-/- mice. Additionally, R1 reduced the expression of Ang1 in pericytes. In vitro experiments demonstrated that R1 suppressed pro-angiogenic behavior of ECs induced by pericytes cultured with VEGF-A. Mechanistic studies revealed that the anti-angiogenic effect of R1 was dependent on the inhibition of Ang1 and Tie2 expression, as the effects were partially reversed after Ang1 overexpressing in pericytes. Our study demonstrated that R1 treatment inhibited intraplaque neovascularization by governing pericyte-EC association via suppressing Ang1-Tie2/PI3K-AKT paracrine signaling pathway. R1 represents a novel therapeutic strategy for atherosclerotic vulnerable plaques in clinical application.

Prospective Deep Learning-based Quantitative Assessment of Coronary Plaque by CT Angiography Compared with Intravascular Ultrasound.

AIMS: Coronary computed tomography angiography provides noninvasive assessment of coronary stenosis severity and flow impairment. Automated artificial intelligence analysis may assist in precise quantification and characterization of coronary atherosclerosis, enabling patient-specific risk determination and management strategies. This multicenter international study compared an automated deep-learning-based method for segmenting coronary atherosclerosis in coronary computed tomography angiography (CCTA) against the reference standard of intravascular ultrasound (IVUS). METHODS AND RESULTS: The study included clinically stable patients with known coronary artery disease from 15 centers in the U.S. and Japan. An artificial intelligence (AI)-enabled plaque analysis service was utilized to quantify and characterize total plaque (TPV), vessel, lumen, calcified plaque (CP), non-calcified plaque (NCP), and low attenuation plaque (LAP) volumes derived from CCTA and compared with IVUS measurements in a blinded, core laboratory-adjudicated fashion. In 237 patients, 432 lesions were assessed; mean lesion length was 24.5 mm. Mean IVUS-TPV was 186.0 mm3. AI-enabled plaque analysis on CCTA showed strong correlation and high accuracy when compared with IVUS; correlation coefficient, slope, and Y intercept for TPV were 0.91, 0.99, and 1.87, respectively; for CP volume 0.91, 1.05, and 5.32, respectively; and for NCP volume 0.87, 0.98, and 15.24, respectively. Bland-Altman analysis demonstrated strong agreement with little bias for these measurements. CONCLUSIONS: Artificial intelligence enabled CCTA quantification and characterization of atherosclerosis demonstrated strong agreement with IVUS reference standard measurements. This tool may prove effective for accurate evaluation of coronary atherosclerotic burden and cardiovascular risk assessment.[ClinicalTrails.gov identifier: NCT05138289].

Evaluating the association between vascular remodeling and plaque calcification patterns of the carotid artery and its effects on ischemic symptoms using CT angiography.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Association of vulnerable plaques with white matter hyperintensities on high-resolution magnetic resonance imaging.

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Residual inflammatory risk and vulnerable plaque in the carotid artery in patients with ischemic stroke.

Objective: 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. Methods: 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. Results: 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). Conclusions: 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.

In Vivo Classification and Characterization of Carotid Atherosclerotic Lesions with Integrated 18F-FDG PET/MRI.

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.

Radiomics and artificial intelligence: General notions and applications in the carotid vulnerable plaque.

Carotid atherosclerosis plays a substantial role in cardiovascular morbidity and mortality. Given the multifaceted impact of this disease, there has been increasing interest in harnessing artificial intelligence (AI) and radiomics as complementary tools for the quantitative analysis of medical imaging data. This integrated approach holds promise not only in refining medical imaging data analysis but also in optimizing the utilization of radiologists' expertise. By automating time consuming tasks, AI allows radiologists to focus on more pertinent responsibilities. Simultaneously, the capacity of AI in radiomics to extract nuanced patterns from raw data enhances the exploration of carotid atherosclerosis, advancing efforts in terms of (1) early detection and diagnosis, (2) risk stratification and predictive modeling, (3) improving workflow efficiency, and (4) contributing to advancements in research. This review provides an overview of general concepts related to radiomics and AI, along with their application in the field of carotid vulnerable plaque. It also offers insights into various research studies conducted on this topic across different imaging techniques.

Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.