Plaque Characteristics Research Articles

Machine Learning Constructed Based on Patient Plaque and Clinical Features for Predicting Stent Malapposition: A Retrospective Study.

Stent malapposition (SM) following percutaneous coronary intervention (PCI) for myocardial infarction continues to present significant clinical challenges. In recent years, machine learning (ML) models have demonstrated potential in disease risk stratification and predictive modeling. ML models based on optical coherence tomography (OCT) imaging, laboratory tests, and clinical characteristics can predict the occurrence of SM. We studied 337 patients from the Affiliated Hospital of Zunyi Medical University, China, who had PCI and coronary OCT from May to October 2023. We employed nested cross-validation to partition patients into training and test sets. We developed five ML models: XGBoost, LR, RF, SVM, and NB based on calcification features. Performance was assessed using ROC curves. Lasso regression selected features from 46 clinical and 21 OCT imaging features, which were optimized with the five ML algorithms. In the prediction model based on calcification features, the XGBoost model and SVM model exhibited higher AUC values. Lasso regression identified five key features from clinical and imaging data. After incorporating selected features into the model for optimization, the AUC values of all algorithmic models showed significant improvements. The XGBoost model demonstrated the highest calibration accuracy. SHAP values revealed that the top five ranked features influencing the XGBoost model were calcification length, age, coronary dissection, lipid angle, and troponin. ML models developed using plaque imaging features and clinical characteristics can predict the occurrence of SM. ML models based on clinical and imaging features exhibited better performance.

Polygenic Risk Is Associated With Long-Term Coronary Plaque Progression and High-Risk Plaque.

The longitudinal relation between coronary artery disease (CAD) polygenic risk score (PRS) and long-term plaque progression and high-risk plaque (HRP) features is unknown. The goal of this study was to investigate the impact of CAD PRS on long-term coronary plaque progression and HRP. Patients underwent CAD PRS measurement and prospective serial coronary computed tomography angiography (CTA) imaging. Coronary CTA scans were analyzed with a previously validated artificial intelligence-based algorithm (atherosclerosis imaging-quantitative computed tomography imaging). The relationship between CAD PRS and change in percent atheroma volume (PAV), percent noncalcified plaque progression, and HRP prevalence was investigated in linear mixed-effect models adjusted for baseline plaque volume and conventional risk factors. A total of 288 subjects (mean age 58 ± 7 years; 60% male) were included in this study with a median scan interval of 10.2 years. At baseline, patients with a high CAD PRS had a more than 5-fold higher PAV than those with a low CAD PRS (10.4% vs 1.9%; P< 0.001). Per 10 years of follow-up, a 1 SD increase in CAD PRS was associated with a 0.69% increase in PAV progression in the multivariable adjusted model. CAD PRS provided additional discriminatory benefit for above-median noncalcified plaque progression during follow-up when added to a model with conventional risk factors (AUC: 0.73 vs 0.69; P = 0.039). Patients with high CAD PRS had an OR of 2.85 (95%CI: 1.14-7.14; P = 0.026) and 6.16 (95%CI: 2.55-14.91; P< 0.001) for having HRP at baseline and follow-up compared with those with low CAD PRS. Polygenic risk is strongly associated with future long-term plaque progression and HRP in patients suspected of having CAD.

Radiomics Analysis of CTO Plaques for Predicting Successful Guidewire Crossing Within 30 Minutes of PCI.

Coronary computed tomography angiography provides valuable information for evaluating the difficulty of chronic total occlusion (CTO) percutaneous coronary intervention. This study aimed to investigate the value of CTO plaque characteristics derived from radiomics analysis for predicting the difficulty of percutaneous coronary intervention. Patients with CTO were retrospectively enrolled from a hospital as training and internal test sets and from the other 2 territory hospitals as external test sets. Radiomics characteristics were extracted from the CTO segment on coronary computed tomography angiography. Radiomics and combined models were developed to predict successful guidewire crossing within 30 minutes (guidewire success) of CTO percutaneous coronary intervention. Subgroup analysis was conducted to investigate the influence of potential risk factors on the radiomics model performance. A total of 551 patients (median, 60; interquartile range, 52.00-66.00 years, 460 men) with 565 CTO lesions were finally enrolled. In the training, internal test, and external test sets, 203 of 357, 85 of 149, and 38 of 59 CTO lesions achieved guidewire success, respectively. Six radiomics features were selected for constructing the radiomics model. In the external test set, the area under the receiver operating characteristic curve of the radiomics model was significantly higher than prior prediction models (P<0.05 for all) with the area under the receiver operating characteristic curve, accuracy, sensitivity, and specificity of 0.86, 74.58%, 81.58%, and 61.90%, respectively. The performance of the radiomics model was dependent on calcification, CTO location, adjacent branch(es), and operator caseload. CTO characteristics revealed by radiomics analysis can be used as effective imaging biomarkers for predicting guidewire success. However, the performance of the radiomics model depends on anatomic and operator factors.

Association Between Coronary Artery Spasm and Atherosclerotic Disease.

In at least one-half of the patients with angina or ischemia and nonobstructive coronary arteries undergoing coronary function testing, coronary artery spasm (CAS) is detected. CAS is associated with an adverse prognosis regarding recurrent complaints and ischemic events. Current treatment options are mainly focused on the complaints, not on the underlying pathophysiological process. In this review we discuss available evidence regarding the presence, amount, and morphology of atherosclerosis in CAS patients. The reviewed evidence confirmed that atherosclerosis and vulnerable plaque characteristics are often detected in patients with CAS. The amount of atherosclerosis is higher in patients with focal CAS compared with patients with diffuse CAS. Severity of atherosclerosis is associated with the presence of CAS and the prognosis in CAS patients with atherosclerotic stenosis is worse. Therefore, CAS patients with atherosclerosis might benefit from targeted atherosclerotic treatment. Longitudinal studies are needed to elucidate the exact relation between atherosclerosis and CAS.

Coronary Artery Plaque Characteristics and Calcium Scoring in Patients With Type 2 Diabetes and Coronary Artery Disease

Coronary Artery Plaque Characteristics and Calcium Scoring in Patients With Type 2 Diabetes and Coronary Artery Disease

Coronary Plaque Characterization with T1-weighted MRI and Near-Infrared Spectroscopy to Predict Periprocedural Myocardial Injury.

Purpose To clarify the predominant causative plaque constituent for periprocedural myocardial injury (PMI) following percutaneous coronary intervention: (a) erythrocyte-derived materials, indicated by a high plaque-to-myocardium signal intensity ratio (PMR) at coronary atherosclerosis T1-weighted characterization (CATCH) MRI, or (b) lipids, represented by a high maximum 4-mm lipid core burden index (maxLCBI4 mm) at near-infrared spectroscopy intravascular US (NIRS-IVUS). Materials and Methods This retrospective study included consecutive patients who underwent CATCH MRI before elective NIRS-IVUS-guided percutaneous coronary intervention at two facilities. PMI was defined as post-percutaneous coronary intervention troponin T values greater than five times the upper reference limit. Multivariable analysis was performed to identify predictors of PMI. Finally, the predictive capabilities of MRI, NIRS-IVUS, and their combination were compared. Results A total of 103 lesions from 103 patients (median age, 72 years [IQR, 64-78]; 78 male patients) were included. PMI occurred in 36 lesions. In multivariable analysis, PMR emerged as the strongest predictor (P = .001), whereas maxLCBI4 mm was not a significant predictor (P = .07). When PMR was excluded from the analysis, maxLCBI4 mm emerged as the sole independent predictor (P = .02). The combination of MRI and NIRS-IVUS yielded the largest area under the receiver operating curve (0.86 [95% CI: 0.64, 0.83]), surpassing that of NIRS-IVUS alone (0.75 [95% CI: 0.64, 0.83]; P = .02) or MRI alone (0.80 [95% CI: 0.68, 0.88]; P = .30). Conclusion Erythrocyte-derived materials in plaques, represented by a high PMR at CATCH MRI, were strongly associated with PMI independent of lipids. MRI may play a crucial role in predicting PMI by offering unique pathologic insights into plaques, distinct from those provided by NIRS. Keywords: Coronary Plaque, Periprocedural Myocardial Injury, MRI, Near-Infrared Spectroscopy Intravascular US Supplemental material is available for this article. © RSNA, 2024.

Dilated lenticulostriate artery on whole-brain vessel wall imaging differentiates pathogenesis and predicts clinical outcomes in single subcortical infarction.

This study aimed to investigate the dilation of lenticulostriate artery (LSA) identified by whole-brain vessel wall imaging (WB-VWI) in differentiating the etiologic subtypes of single subcortical infarction (SSI) and to determine whether the appearance of dilated LSA was associated with 90-day clinical outcomes in parental atherosclerotic disease (PAD)-related SSI. Patients with acute SSI were prospectively enrolled and categorized into PAD-related SSI and cerebral small-vessel disease (CSVD)-related SSI groups. The imaging features of LSA morphology (branches, length, dilation, and tortuosity), plaques (burden, remodeling index, enhancement degree, and hyperintense plaque), and CSVD (white matter hyperintensity, lacunes, cerebral microbleed, and enlarged perivascular space) were evaluated. The logistic regression was performed to determine the association of dilated LSA with PAD-related SSI and 90-day clinical outcomes. In total, 131 patients (mean age, 52.2 ± 13.2 years; 99 men) were included. The multivariate logistic regression analysis revealed that the presence of dilated LSAs (odds ratio (OR), 7.40; 95% confidence interval (CI): 1.88-29.17; p = 0.004)) was significantly associated with PAD-related SSI. Moreover, after adjusting for confounding factors, the association of poor outcomes with the total length of LSAs (OR, 0.94; 95% CI: 0.90-0.99; p = 0.011), dilated LSAs (OR, 0.001; 95% CI: 0.0001-0.08; p = 0.002), and plaque burden (OR, 1.35; 95% CI: 1.11-1.63; p = 0.002) remained statistically significant. The dilation of LSA visualized on WB-VWI could differentiate various subtypes of SSI within LSA territory and was a prognostic imaging marker for 90-day clinical outcomes for PAD-related SSI. Evaluation of LSA morphology based on WB-VWI can differentiate the pathogenesis and predict clinical outcomes in SSI, providing crucial insights into the etiologic mechanisms, risk stratification, and tailored therapies for these patients. The prognosis of SSIs within lenticulostriate territory depend on the etiology of the disease. LSA dilation on WB-VWI was associated with parental atherosclerosis and better 90-day outcomes. Accurately identifying the etiology of SSIs in lenticulostriate territory assists in treatment decision-making.

High-resolution MR vessel wall imaging and cardiovascular health for evaluating the occurrence of ischemic stroke

ObjectivesTo explore the value of high-resolution MR vessel wall imaging (HR-VWI) based plaque characteristics combined with cardiovascular health (CVH) metrics in the risk evaluation of ischemic stroke attributed to middle cerebral artery (MCA) atherosclerotic stenosis. MethodsRetrospective analysis of 209 participants with middle cerebral atherosclerosis, 146 patients with high signal in the MCA area on DWI were included in the symptomatic group, and 63 patients were included in the asymptomatic group. The degree of stenosis, enhancement ratio, plaque burden, remodeling index, and intraplaque hemorrhage were measured and compared between groups. Seven CVH metrics and other clinical data were obtained. The association between these factors and ischemic stroke was investigated by univariate and multivariate analysis. ResultsThe degree of stenosis [OR, 1.036 (95 % CI, 1.014–1.058); P = 0.001], plaque burden [OR, 0.958 (95 % CI, 0.928–0.989); P = 0.009], intraplaque hemorrhage [OR, 3.530 (95 % CI, 1.233–10.110); P = 0.019], physical activity [OR, 4.321 (95 % CI, 1.526–12.231); P = 0.006], and diet [OR, 8.986 (95 % CI, 2.747–29.401); P < 0.001] were the independent characteristics associated with the occurrence of ischemic stroke. ROC curve showed that the combination of plaque characteristics, diet, and physical activity achieved the highest AUC of 0.828 (95 % CI 0.770–0.877; P < 0.001), with sensitivity and specificity being 86.30 % and 66.67 %, respectively. ConclusionPlaque characteristics combined with CVH metrics may identify high-risk populations for ischemic stroke and offer novel insights into risk evaluation and stratification.

Association Between Calculated Small Dense Low-Density Lipoprotein Cholesterol (sdLDL-C) and Soft Carotid Plaques on CT Angiogram of the Head and Neck.

Cerebrovascular accident (CVA), also commonly known as stroke, is an acute condition characterized by jeopardized perfusion of the brain tissue. Atherosclerosis is a common converging point for the various risk factors for CVA. It is a chronic, evolving condition of the vessel wall characterized by peculiar lesions known as atheromas. Low-density lipoprotein cholesterol (LDL-C) has been one of the established and traditional risk factors for the development of plaques in atherosclerosis. Small dense LDL-C (sdLDL-C) is a subclass of LDL-C that is considered more atherogenic, and its role in atherosclerotic plaque formation has been very well established. Hence, in this study, we aimed to find the association between calculated sdLDL-C and atherosclerotic carotid plaque (including various plaque characteristics). This retrospective cross-sectional study was conducted at Sri Ramachandra Medical College and Research Institute between December 2022 and December 2023 after getting ethics approval from the Institutional Ethics Committee. Patients who underwent CT angiogram(312) were included in the study, and their lipid profile data were collected from the Laboratory Information System. Participants were divided into groups depending on the presence or absence of carotid plaque, the characteristics of the plaque, and the narrowing caused by the plaque. sdLDL-C was calculated using Sampson formula from the lipid parameters in these groups. Statistical analysis was done using SPSS Statistics version 16.0 (SPSS Inc. Released 2007. SPSS for Windows, Version 16.0. Chicago, SPSS Inc.). A p-value of <0.05 was considered significant. sdLDL-C was significantly higher in the plaque group (37.25 ± 13.69 mg/dL) when compared to the group without plaques on CT angiogram (34.09 ± 11.64 mg/dL) (p<0.05), wherein the LDL-C wasn't significantly different between the two groups. sdLDL-C was also elevated in the soft plaque sub-group (39.46 ± 13.63 mg/dL) when compared to the calcific plaque sub-group (35.41 ± 13.05 mg/dL), which was statistically significant (p<0.05). sdLDL-C is associated with atherosclerotic carotid plaques, especially the soft plaques on CT angiogram, which are considered to be vulnerable plaques. Thus, calculated sdLDL-C can be utilized as a cost-effective tool to assess plaque vulnerability and monitor hypolipidemic treatment in addition to LDL-C.

Evaluation of microcirculatory protection in percutaneous revascularisation: A stent implantation technique and device comparison.

Coronary microvascular dysfunction (CMD) after percutaneous coronary intervention (PCI) is prognostically important and may also be a cause of persistent angina. The stent balloon inflation technique or material properties may influence the degree of CMD post-PCI. Thirty-six patients with stable angina attending for elective PCI were randomized to either slow drug eluting stent (DES) implantation technique (DES slow group): +2 atm. every 5 s., maintained for a further 30 s or a standard stent implantation technique (DES std group): rapid inflation and deflation. PressureWire X with thermodilution at rest and hyperemia and optical coherence tomography (OCT) were performed pre- and post-PCI. Combined primary endpoints were changes in index of microvascular resistance (delta IMR) and coronary flow reserve (delta CFR) following PCI. The secondary endpoints included differences in cardiac troponinI (delta cTnI) at 6 hpost-PCI, Seattle angina questionnaire (SAQ) at 1, 3, 6, and 12 months and OCT measures of stent results immediately post-PCI and at 3 months. Both groups were well matched, with similar baseline characteristics and OCT-defined plaque characteristics. Delta IMR was significantly better in the DES slow PCI arm with a median difference of -4.14 (95%CI -10.49, -0.39, p = 0.04). Delta CFR was also numerically higher with a median difference of 0.47 (95% CI -0.52, 1.31, p = 0.46). This did not translate to improved delta median cTnI(1.5 (34.8) vs. 0 (27.5) ng/L, p = 0.75) or median SAQ scoreat 3 months, (85 (20) vs. 95 (17.5), p = 0.47). Slow stent implantation is associated with less CMD after elective PCI in patients with stable angina.

Beyond Stress Ischemia: Unveiling the Multifaceted Nature of Coronary Vulnerable Plaques Using Cardiac Computed Tomography.

Historically, cardiovascular prevention has been predominantly focused on stress-induced ischemia, but recent trials have challenged this paradigm, highlighting the emerging role of vulnerable, non-flow-limiting coronary plaques, leading to a shift towards integrating plaque morphology with functional data into risk prediction models. Coronary computed tomography angiography (CCTA) represents a high-resolution, low-risk, and largely available non-invasive modality for the precise delineation of plaque composition, morphology, and inflammatory activity, further enhancing our ability to stratify high-risk plaque and predict adverse cardiovascular outcomes. Coronary artery calcium (CAC) scoring, derived from CCTA, has emerged as a promising tool for predicting future cardiovascular events in asymptomatic individuals, demonstrating incremental prognostic value beyond traditional cardiovascular risk factors in terms of myocardial infarction, stroke, and all-cause mortality. Additionally, CCTA-derived information on adverse plaque characteristics, geometric characteristics, and hemodynamic forces provides valuable insights into plaque vulnerability and seems promising in guiding revascularization strategies. Additionally, non-invasive assessments of epicardial and pericoronary adipose tissue (PCAT) further refine risk stratification, adding prognostic significance to coronary artery disease (CAD), correlating with plaque development, vulnerability, and rupture. Moreover, CT imaging not only aids in risk stratification but is now emerging as a screening tool able to monitor CAD progression and treatment efficacy over time. Thus, the integration of CAC scoring and PCAT evaluation into risk stratification algorithms, as well as the identification of high-risk plaque morphology and adverse geometric and hemodynamic characteristics, holds promising results for guiding personalized preventive interventions, helping physicians in identifying high-risk individuals earlier, tailoring lifestyle and pharmacological interventions, and improving clinical outcomes in their patients.

Application of high-resolution MRI in evaluating statin efficacy on symptomatic intracranial atherosclerosis.

To investigate the efficacy of statins on symptomatic intracranial atherosclerotic plaques using high-resolution 3.0 T MR vessel wall imaging (HR-MRI). Patients with symptomatic intracranial atherosclerotic plaques (cerebral ischemic events within the last three months) confirmed by HR-MRI from July 2017 to August 2022 were retrospectively included in this study. The enrolled patients started statin therapy at baseline. All the patients underwent the follow-up HR-MRI examination after statin therapy for at least 3 months. A paired sample t-test and Wilcoxon rank sum test were used to evaluate the changes in plaque characteristics after statin therapy. Multivariate linear regression was further used to investigate the clinical factors associated with statin efficacy. A total of 48 patients (37 males; overall mean age = 60.2 ± 11.7 years) were included in this study. The follow-up time was 7.0 (5.6-12.0) months. In patients treated with statins for > 6 months (n = 31), plaque length, wall thickness, plaque burden, luminal stenosis and plaque enhancement were significantly reduced. Similar results were found in patients with good lipid control (n = 21). Younger age, lower BMI and hypertension were associated with decreased plaque burden. Lower BMI, hypertension and longer duration of statin therapy were associated with decreased plaque enhancement. Younger age and hypertension were associated with decreased luminal stenosis (all p < 0.05). HR-MRI can effectively evaluate plaques changes after statin therapy. Statins can reduce plaque burden and stabilize plaques. The effect of statin may have a relationship with age, BMI, hypertension, and duration of statin therapy. High-resolution MRI can be applied to evaluate the efficacy of statins on symptomatic intracranial atherosclerotic plaques. Long-term statin use and well-controlled blood lipid levels can help reduce plaque burden and stabilize plaques. High-resolution MRI provides great help evaluating the changes of plaque characteristics after statin therapy. Efficacy of statins is associated with duration of use, controlled lipid levels, and clinical factors. High-resolution MRI can serve as an effective method for following-up symptomatic intracranial atherosclerosis.

Exploring the relationship between epicardial fat and coronary plaque burden and characteristics: insights from cardiac ct imaging.

Epicardial adipose tissue (EAT) may enhance the risk of coronary artery disease (CAD). We investigated the relationship between EAT density (a maker of local inflammation) and coronary plaque characteristics in stable CAD patients. This study included 123 individuals who underwent coronary artery calcium scan and coronary CT angiography to evaluate CAD. Plaque characteristics were analyzed by semi-automated software (QAngio, Leiden, Netherlands). Non-contrast CT scans were used to measure EAT density (HU) and volume (cc) (Philips, Cleveland, OH). Multivariate regression models were used to evaluate the association of EAT density and volume with different plaque types. The mean (SD) age was 59.4±10.1 years, 53% were male, the mean (SD) EAT density was -77.2±4.6 HU and the volume was 118.5±41.2 cc. After adjustment for cardiovascular risk factors, EAT density was associated with fibrous fatty (FF) plaque (p<0.03). A 1 unit increase in HU was associated with a 7% higher FF plaque, and lower EAT density is independently associated to FF plaque. The association between EAT density and fibrous (p=0.08), and total noncalcified (p=0.09) plaque trended toward but did not reach significance. There was no association between EAT volume and any plaque type. These results suggest that inflammatory EAT may promote coronary atherosclerosis. Therefore, non-contrast cardiac CT evaluation of EAT quality can help better assess cardiovascular risk.

Factors Associated with High-Risk Plaque Characteristics Among Patients with Medium to Severe Carotid Artery Stenosis

ObjectiveThere has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis (CAS). This study aims to identify potential risk factors associated with high-risk carotid plaques. MethodsThis is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, NASCET criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography (MRA) at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (Types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage (IPH) and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated. ResultsA total of 62 patients (mean age: 68.7+/-9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81%±13.53%. In multivariate regression analysis, CRP > 2mg/l was strongly associated with symptomatic stenosis (OR=9.92 [1.12-88.178]; P=0.039), and low HDL levels (<1200mmol/l) were associated with lipidic/necrotic plaque core (OR=16.88 [1.10-259.30]; P=0.043). Low HDL levels (OR=7.22 [1.00-51.95], P=0.049) and HbA1c >7% (OR=0.08 [0.01-0.93], P=0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR=14.26 [1.21-168.34], P=0.035) was associated with Type V plaques. ConclusionsThis preliminary study has revealed some potential risk factors associated with unstable carotid plaques. This data could help the future development of prognostic models in order to early detect patients that could benefit from further intervention.

Diagnostics Accuracy of Magnetic Resonance Imaging in Detection of Atherosclerotic Plaque Characteristics in Carotid Arteries Compared to Histology: A Systematic Review.

Carotid plaque composition represents one of the main risk factors of future ischemic stroke. MRI provides excellent soft tissue contrast that can distinguish plaque characteristics. Our objective was to analyze the diagnostic accuracy of MRI imaging in the detection of carotid plaque characteristics compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis through a systematic review. After prospective registration in PROSPERO (ID CRD42022329690), Medline Ovid, Embase.com, Cochrane Library, and Web of Science Core were searched without any search limitation up to May 27, 2022 to identify eligible articles. Of the 8168 studies, 53 (37 × 1.5 T MRI, 17 × 3 T MRI) evaluated MRI accuracy in the detection of 13 specific carotid plaque characteristics in 169 comparisons. MRI demonstrated high diagnostic accuracy for detection of calcification (3 T MRI: mean sensitivity 92%/mean specificity 90%; 1.5 T MRI: mean sensitivity 81%/mean specificity 91%), fibrous cap (1.5 T: 89%/87%), unstable plaque (1.5 T: 89%/87%), intraplaque hemorrhage (1.5 T: 86%/88%), and lipid-rich necrotic core (1.5 T: 89%/79%). MRI also proved to have a high level of tissue discrimination for the carotid plaque characteristics investigated, allowing potentially for a better risk assessment and follow-up of patients who may benefit from more aggressive treatments. These results emphasize the role of MRI as the first-line imaging modality for comprehensive assessment of carotid plaque morphology, particularly for unstable plaque. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Melatonin Ameliorates Atherosclerotic Plaque Vulnerability by Regulating PPARδ-Associated Smooth Muscle Cell Phenotypic Switching.

Vulnerable atherosclerotic plaque rupture, the leading cause of fatal atherothrombotic events, is associated with an increased risk of mortality worldwide. Peroxisome proliferator-activated receptor delta (PPARδ) has been shown to modulate vascular smooth muscle cell (SMC) phenotypic switching, and, hence, atherosclerotic plaque stability. Melatonin reportedly plays a beneficial role in cardiovascular diseases; however, the mechanisms underlying improvements in atherosclerotic plaque vulnerability remain unknown. In this study, we assessed the role of melatonin in regulating SMC phenotypic switching and its consequential contribution to the amelioration of atherosclerotic plaque vulnerability and explored the mechanisms underlying this process. We analyzed features of atherosclerotic plaque vulnerability and markers of SMC phenotypic transition in high-cholesterol diet (HCD)-fed apolipoprotein E knockout (ApoE-/-) mice and human aortic SMCs (HASMCs). Melatonin reduced atherosclerotic plaque size and necrotic core area while enhancing collagen content, fibrous cap thickness, and smooth muscle alpha-actin positive cell coverage on the plaque cap, which are all known phenotypic characteristics of vulnerable plaques. In atherosclerotic lesions, melatonin significantly decreased the synthetic SMC phenotype and KLF4 expression and increased the expression of PPARδ, but not PPARα and PPARγ, in HCD-fed ApoE-/- mice. These results were subsequently confirmed in the melatonin-treated HASMCs. Further analysis using PPARδ silencing and immunoprecipitation assays revealed that PPARδ plays a role in the melatonin-induced SMC phenotype switching from synthetic to contractile. Collectively, we provided the first evidence that melatonin mediates its protective effect against plaque destabilization by enhancing PPARδ-mediated SMC phenotypic switching, thereby indicating the potential of melatonin in treating atherosclerosis.

Application of adipose tissue-derived stem cell therapy with a clinically relevant dose does not significantly affect atherosclerotic plaque characteristics in a streptozotocin-induced hyperglycaemia mouse model

AimsDiabetes mellitus (DM) induces increased inflammation of atherosclerotic plaques, resulting in elevated plaque instability. Mesenchymal stem cell (MSC) therapy was shown to decrease plaque size and increase stability in non-DM animal models. We now studied the effect of MSC therapy in a streptozotocin-induced hyperglycaemia mouse model using a clinically relevant dose of adipose tissue-derived MSCs (ASCs). MethodsHyperglycaemia was induced in male C57BL/6 ApoE−/− mice (n=24) via intraperitoneal streptozotocin (STZ) injection (0.05 mg/g bodyweight) for 5 consecutive days. 16 weeks after the first STZ injection, the mice received either 100,000 ASCs (n=9) or vehicle (n=14) intravenously. The effects of ASC treatment on the size and stability of aortic root atherosclerotic plaques were determined 4 weeks post-treatment via (immuno)histochemical analyses. Furthermore, plasma monocyte subsets within 3 days pre- and 3 days post-treatment, and 4 weeks post-treatment, were studied. ResultsASC treatment did not significantly affect atherosclerotic plaque size or intra-plaque inflammation. Although ASC-treated mice had a higher percentage of intra-plaque fibrosis (42.5±3.3%) compared to vehicle-treated mice (37.6±6.8%, p=0.07), this did not reach significance. Additionally, although differences in the percentages of circulating pro- and anti-inflammatory monocytes were observed after ASC treatment compared to pre-treatment (p=0.005), their levels did not differ significantly at any time point compared to vehicle-treated mice. ConclusionsASC treatment with a clinically relevant dose did not significantly affect atherosclerotic plaque size or intra-plaque inflammation in a hyperglycaemia mouse model. Despite a borderline significant improvement in intraplaque fibrotic content, the potential of ASC treatment on atherosclerotic plaque stability in a diabetic environment remains to be determined.

Aggravating effect of abnormal low-density protein cholesterol level on coronary atherosclerotic plaque in type 2 diabetes mellitus patients assessed by coronary computed tomography angiography

BackgroundThe abnormal low-density protein cholesterol (LDL-C) level in the development of atherosclerosis is often comorbid in individuals with type 2 diabetes mellitus(T2DM). This study aimed to investigate the aggravating effect of abnormal LDL-C levels on coronary artery plaques assessed by coronary computed tomography angiography (CCTA) in T2DM.Materials and methodsThis study collected 3439 T2DM patients from September 2011 to February 2022. Comparative analysis of differences in coronary plaque characteristics was performed for the patients between the normal LDL-C level group and the abnormal LDL-C level group. Factors with P < 0.1 in the univariable linear regression analyses were included in the multivariable linear stepwise regression.ResultsA total of 2820 eligible T2DM patients were included and identified as the normal LDL-C level group (n = 973) and the abnormal LDL-C level group (n = 1847). Compared with the normal LDL-C level group, both on a per-patient basis and per-segment basis, patients with abnormal LDL-C level showed more calcified plaques, partially calcified plaques, low attenuation plaques, positive remodellings, and spotty calcifications. Multivessel obstructive disease (MVD), nonobstructive stenosis (NOS), obstructive stenosis (OS), plaque involvement degree (PID), segment stenosis score (SSS), and segment involvement scores (SIS) were likely higher in the abnormal LDL-C level group than that in the normal LDL-C level group (P < 0.001). In multivariable linear stepwise regression, the abnormal LDL-C level was validated as an independent positive correlation with high-risk coronary plaques and the degree and extent of stenosis caused by plaques (low attenuation plaque: β = 0.116; positive remodelling: β = 0.138; spotty calcification: β = 0.091; NOS: β = 0.427; OS: β = 0.659: SIS: β = 1.114; SSS: β = 2.987; PID: β = 2.716, all P value < 0.001).ConclusionsAbnormal LDL-C levels aggravate atherosclerotic cardiovascular disease (ASCVD) in patients with T2DM. Clinical attention deserves to be caught by the tailored identification of cardiovascular risk categories in T2DM individuals and the achievement of the corresponding LDL-C treatment goal.

HR-MRI-based nomogram network calculator to predict stroke recurrence in high-risk non-disabling ischemic cerebrovascular events patients.

To investigate the use of high-resolution magnetic resonance imaging (HR-MRI) to identify the characteristics of culprit plaques in intracranial arteries, and to evaluate the predictive value of the characteristics of culprit plaques combined with the modified Essen score for the recurrence risk of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) patients. A retrospective analysis was conducted on 180 patients with HR-NICE at the First Affiliated Hospital of Xinxiang Medical University, including 128 patients with no recurrence (non-recurrence group) and 52 patients with recurrence (recurrence group). A total of 65 patients with HR-NICE were collected from the Sixth Affiliated Hospital of Shanghai Jiaotong University as a validation group, and their modified Essen scores, high-resolution magnetic resonance vessel wall images, and clinical data were collected. The culprit plaques were analyzed using VesselExplorer2 software. Univariate and multivariate logistic regression analyses were used to identify independent risk factors for recurrence, and a nomogram was constructed using R software to evaluate the discrimination of the model. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) was used to evaluate the model performance. Calibration curves and Decision Curve Analysis (DCA) were used to evaluate the model efficacy. Intra-plaque hemorrhage (OR = 3.592, 95% CI = 1.474-9.104, p = 0.006), homocysteine (OR = 1.098, 95% CI = 1.025-1.179, p = 0.007), and normalized wall index (OR = 1.114, 95% CI = 1.027-1.222, p = 0.015) were significantly higher in the recurrent stroke group than in the non-recurrent stroke group, and were independent risk factors for recurrent stroke. The performance of the nomogram model (AUC = 0.830, 95% CI: 0.769-0.891; PR-AUC = 0.628) was better than that of the modified Essen scoring model (AUC = 0.660, 95% CI: 0.583-0.738) and the independent risk factor combination model (AUC = 0.827, 95% CI: 0.765-0.889). The nomogram model still had good model performance in the validation group (AUC = 0.785, 95% CI: 0.671-0.899), with a well-fitting calibration curve and a DCA curve indicating good net benefit efficacy for patients. High-resolution vessel wall imaging combined with a modified Essen score can effectively assess the recurrence risk of HR-NICE patients, and the nomogram model can provide a reference for identifying high-risk populations with good clinical application prospects.

Plasma C-reactive protein is associated with a pro-inflammatory and adverse plaque phenotype

Background and aimsSystemic low-grade inflammation, measured by plasma high-sensitivity C-reactive protein (hsCRP) levels, is an important risk factor for atherosclerotic cardiovascular disease (ASCVD). To date, however, it is unknown whether plasma hsCRP is associated with adverse histological plaque features. MethodsPlaques were derived during carotid endarterectomy. Patients with hsCRP levels ≥2 mg/L were evaluated for pro-inflammatory and adverse plaque characteristics, as well as future ASCVD events, and compared with patients with low hsCRP levels. Logistic and linear regression analyses in addition to subdistribution hazard ratios were conducted, adjusted for cardiovascular risk factors. ResultsA total of 1096 patients were included, of which 494 (46.2 %) had hsCRP levels ≥2 mg/L. Elevated hsCRP levels 2 mg/L were independently associated with levels of plaque interleukin 6, beta coefficient of 109.8 (95 % confidence interval (CI): 33.4, 186.5; p = 0.005) pg/L, interleukin 8 levels, 194.8 (110.4, 378.2; p = 0.03) pg/L and adiponectin plaque levels, −16.8 (−30.1, −3.6; p = 0.01) μg/L, compared with plaques from patients with low hsCRP levels. Histological analysis revealed increased vessel density in high hsCRP patients, odds ratio (OR) of 1.57 (1.20, 2.09; p = 0.001), larger lipid core, 1.35 (1.02, 1.73; p = 0.04), and increased macrophage content, 1.32 (1.02, 1.73; p = 0.04). Over a 3-year follow-up period, hsCRP levels ≥2 mg/L were associated with a hazard ratio of 1.81 (1.03, 3.16; p = 0.04) for coronary artery disease event risk. ConclusionsThe distinct inflammatory and histological features observed in carotid plaques among individuals with hsCRP levels ≥2 mg/L underscore the utility of plasma hsCRP as a potent identifier for patients harboring high-risk plaques.