-
Diagnostics (Basel, Switzerland) May 2024Atherosclerotic plaque buildup in the coronary and carotid arteries is pivotal in the onset of acute myocardial infarctions or cerebrovascular events, leading to... (Review)
Review
Atherosclerotic plaque buildup in the coronary and carotid arteries is pivotal in the onset of acute myocardial infarctions or cerebrovascular events, leading to heightened levels of illness and death. Atherosclerosis is a complex and multistep disease, beginning with the deposition of low-density lipoproteins in the arterial intima and culminating in plaque rupture. Modern technology favors non-invasive imaging techniques to assess atherosclerotic plaque and offer insights beyond mere artery stenosis. Among these, computed tomography stands out for its widespread clinical adoption and is prized for its speed and accessibility. Nonetheless, some limitations persist. The introduction of photon-counting computed tomography (PCCT), with its multi-energy capabilities, enhanced spatial resolution, and superior soft tissue contrast with minimal electronic noise, brings significant advantages to carotid and coronary artery imaging, enabling a more comprehensive examination of atherosclerotic plaque composition. This narrative review aims to provide a comprehensive overview of the main concepts related to PCCT. Additionally, we aim to explore the existing literature on the clinical application of PCCT in assessing atherosclerotic plaque. Finally, we will examine the advantages and limitations of this recently introduced technology.
PubMed: 38893593
DOI: 10.3390/diagnostics14111065 -
Journal of Clinical Medicine May 2024Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major... (Review)
Review
Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease.
PubMed: 38892807
DOI: 10.3390/jcm13113096 -
International Journal of Molecular... May 2024Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered... (Review)
Review
Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.
Topics: Humans; Plaque, Atherosclerotic; Tomography, Optical Coherence; Coronary Artery Disease; Acute Coronary Syndrome
PubMed: 38891972
DOI: 10.3390/ijms25115786 -
Nutrition, Metabolism, and... May 2024Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the...
BACKGROUND AND AIMS
Systemic inflammation and oxidation are primary contributors to the development of atherosclerosis. Oxidation of low-density lipoprotein (LDL) particles within the vascular endothelium has been hypothesized to be an initial step in the formation of atherosclerotic plaques, with inflammatory cytokines serving as the signaling mechanism for concomitant macrophage activation. Supplementation with the antioxidative macular xanthophylls (lutein [L], zeaxanthin [Z], and meso-zeaxanthin [MZ]) has been shown to aid in the reduction of inflammatory physiologic responses; therefore, we hypothesized that in our study population, supplementation with these xanthophylls would facilitate a systemic reduction in markers of inflammation and cardiovascular lipid oxidation.
METHODS AND RESULTS
In this double-blind placebo-controlled supplementation study, participants were randomly allocated to receive the active intervention containing L (10 mg) + MZ (10 mg) + Z (2 mg) or placebo (containing sunflower oil). Serum concentrations of carotenoids (assessed by HPLC), inflammatory cytokines (IL-6, IL-1β, TNF-α) and oxidized LDL (OxLDL; by solid-phase sandwich ELISA) were measured at baseline and at 6-months. Results showed that over the supplementation period, compared to placebo, the active group demonstrated statistically significant increases in serum concentrations of L, Z, & MZ (p < 0.05), reductions in inflammatory cytokines IL-1β (p < 0.001) and TNF-α (p = 0.003), as well as a corresponding reduction in serum OxLDL (p = 0.009).
CONCLUSIONS
Our data show that L, Z, & MZ supplementation results in decreased serum IL-1β, TNF-α, and OxLDL. This suggests that these carotenoids are acting systemically to attenuate oxidative lipid products and inflammation, thus reducing their contribution to atherosclerotic plaque formation.
PubMed: 38890092
DOI: 10.1016/j.numecd.2024.05.009 -
Circulation. Cardiovascular Imaging Jun 2024This study aimed to develop and validate a computed tomography angiography based machine learning model that uses plaque composition data and degree of carotid stenosis...
BACKGROUND
This study aimed to develop and validate a computed tomography angiography based machine learning model that uses plaque composition data and degree of carotid stenosis to detect symptomatic carotid plaques in patients with carotid atherosclerosis.
METHODS
The machine learning based model was trained using degree of stenosis and the volumes of 13 computed tomography angiography derived intracarotid plaque subcomponents (eg, lipid, intraplaque hemorrhage, calcium) to identify plaques associated with cerebrovascular events. The model was internally validated through repeated 10-fold cross-validation and tested on a dedicated testing cohort according to discrimination and calibration.
RESULTS
This retrospective, single-center study evaluated computed tomography angiography scans of 268 patients with both symptomatic and asymptomatic carotid atherosclerosis (163 for the derivation set and 106 for the testing set) performed between March 2013 and October 2019. The area-under-receiver-operating characteristics curve by machine learning on the testing cohort (0.89) was significantly higher than the areas under the curve of traditional logit analysis based on the degree of stenosis (0.51, <0.001), presence of intraplaque hemorrhage (0.69, <0.001), and plaque composition (0.78, <0.001), respectively. Comparable performance was obtained on internal validation. The identified plaque components and associated cutoff values that were significantly associated with a higher likelihood of symptomatic status after adjustment were the ratio of intraplaque hemorrhage to lipid volume (≥50%, 38.5 [10.1-205.1]; odds ratio, 95% CI) and percentage of intraplaque hemorrhage volume (≥10%, 18.5 [5.7-69.4]; odds ratio, 95% CI).
CONCLUSIONS
This study presented an interpretable machine learning model that accurately identifies symptomatic carotid plaques using computed tomography angiography derived plaque composition features, aiding clinical decision-making.
Topics: Humans; Computed Tomography Angiography; Male; Machine Learning; Female; Retrospective Studies; Plaque, Atherosclerotic; Aged; Middle Aged; Carotid Artery Diseases; Carotid Stenosis; Predictive Value of Tests; Reproducibility of Results; Carotid Arteries; Severity of Illness Index
PubMed: 38889214
DOI: 10.1161/CIRCIMAGING.123.016274 -
Journal of Ethnopharmacology Jun 2024Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease....
ETHNOPHARMACOLOGICAL RELEVANCE
Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease. The decoction has demonstrated its capability to protect arteries and resist atherosclerosis. Its mechanisms for anti-atherosclerosis effect, nevertheless, remain unknown.
AIMS OF THE STUDY
The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis.
MATERIALS AND METHODS
The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms.
RESULTS
In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque.
CONCLUSION
ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.
PubMed: 38885915
DOI: 10.1016/j.jep.2024.118466 -
Clinical Cardiology Jun 2024The coronary artery disease-reporting and data system (CAD-RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results....
The Plaque Analysis Classifies the Coronary Artery Disease-Reporting and Data System (CAD-RADS) Stenosis and Plaque Burden Categories: Association of the Plaque Features, Fat Attenuation Index, Coronary Computed Tomography Fractional Flow Reserve, and the Combination of Stenosis and Calcification.
BACKGROUND
The coronary artery disease-reporting and data system (CAD-RADS) 2.0 is used to standardize the reporting of coronary computed tomography angiography (CCTA) results. Artificial intelligence software can quantify the plaque composition, fat attenuation index, and fractional flow reserve.
OBJECTIVE
To analyze plaque features of varying severity in patients with a combination of CAD-RADS stenosis and plaque burden categorization and establish a random forest classification model.
METHODS
The data of 100 patients treated between April 2021 and February 2022 were retrospectively collected. The most severe plaque observed in each patient was the target lesion. Patients were categorized into three groups according to CAD-RADS: CAD-RADS 1-2 + P0-2, CAD-RADS 3-4B + P0-2, and CAD-RADS 3-4B + P3-4. Differences and correlations between variables were assessed between groups. AUC, accuracy, precision, recall, and F1 score were used to evaluate the diagnostic performance.
RESULTS
A total of 100 patients and 178 arteries were included. The differences of computed tomography fractional flow reserve (CT-FFR) (H = 23.921, p < 0.001), the volume of lipid component (H = 12.996, p = 0.002), the volume of fibro-lipid component (H = 8.692, p = 0.013), the proportion of lipid component volume (H = 22.038, p < 0.001), the proportion of fibro-lipid component volume (H = 11.731, p = 0.003), the proportion of calcification component volume (H = 11.049, p = 0.004), and plaque type (χ = 18.110, p = 0.001) was statistically significant.
CONCLUSION
CT-FFR, volume and proportion of lipid and fibro-lipid components of plaques, the proportion of calcified components, and plaque type were valuable for CAD-RADS stenosis + plaque burden classification, especially CT-FFR, volume, and proportion of lipid and fibro-lipid components. The model built using the random forest was better than the clinical model (AUC: 0.874 vs. 0.647).
Topics: Humans; Male; Female; Fractional Flow Reserve, Myocardial; Plaque, Atherosclerotic; Retrospective Studies; Computed Tomography Angiography; Middle Aged; Coronary Angiography; Coronary Stenosis; Severity of Illness Index; Coronary Artery Disease; Coronary Vessels; Vascular Calcification; Aged
PubMed: 38884449
DOI: 10.1002/clc.24305 -
Frontiers in Endocrinology 2024The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a... (Review)
Review
The global prevalence of cardiovascular diseases (CVD) continues to rise steadily, making it a leading cause of mortality worldwide. Atherosclerosis (AS) serves as a primary driver of these conditions, commencing silently at an early age and culminating in adverse cardiovascular events that severely impact patients' quality of life or lead to fatality. Dyslipidemia, particularly elevated levels of low-density lipoprotein cholesterol (LDL-C), plays a pivotal role in AS pathogenesis as an independent risk factor. Research indicates that abnormal LDL-C accumulation within arterial walls acts as a crucial trigger for atherosclerotic plaque formation. As the disease progresses, plaque accumulation may rupture or dislodge, resulting in thrombus formation and complete blood supply obstruction, ultimately causing myocardial infarction, cerebral infarction, and other common adverse cardiovascular events. Despite adequate pharmacologic therapy targeting LDL-C reduction, patients with cardiometabolic abnormalities remain at high risk for disease recurrence, highlighting the importance of addressing lipid risk factors beyond LDL-C. Recent attention has focused on the causal relationship between triglycerides, triglyceride-rich lipoproteins (TRLs), and their remnants in AS risk. Genetic, epidemiologic, and clinical studies suggest a causal relationship between TRLs and their remnants and the increased risk of AS, and this dyslipidemia may be an independent risk factor for adverse cardiovascular events. Particularly in patients with obesity, metabolic syndrome, diabetes, and chronic kidney disease, disordered TRLs and its remnants levels significantly increase the risk of atherosclerosis and cardiovascular disease development. Accumulation of over-synthesized TRLs in plasma, impaired function of enzymes involved in TRLs lipolysis, and impaired hepatic clearance of cholesterol-rich TRLs remnants can lead to arterial deposition of TRLs and its remnants, promoting foam cell formation and arterial wall inflammation. Therefore, understanding the pathogenesis of TRLs-induced AS and targeting it therapeutically could slow or impede AS progression, thereby reducing cardiovascular disease morbidity and mortality, particularly coronary atherosclerotic heart disease.
Topics: Humans; Cardiovascular Diseases; Lipoproteins; Triglycerides; Atherosclerosis; Animals; Dyslipidemias; Risk Factors
PubMed: 38883601
DOI: 10.3389/fendo.2024.1409653 -
European Journal of Radiology Open Jun 2024To determine the value of an algorithm for reducing stair-step artifacts for advanced coronary analyses in sequential mode coronary CT angiography (CCTA).
Increasing the rate of datasets amenable to CT and quantitative plaque analysis: Value of software for reducing stair-step artifacts demonstrated in photon-counting detector CT.
PURPOSE
To determine the value of an algorithm for reducing stair-step artifacts for advanced coronary analyses in sequential mode coronary CT angiography (CCTA).
METHODS
Forty patients undergoing sequential mode photon-counting detector CCTA with at least one stair-step artifact were included. Twenty patients (14 males; mean age 57±17years) with 45 segments showing stair-step artifacts and without atherosclerosis were included for CT analysis. Twenty patients (20 males; mean age 74±13years) with 22 segments showing stair-step artifacts crossing an atherosclerotic plaque were included for quantitative plaque analysis. Artifacts were graded, and CT and quantitative coronary plaque analyses were performed in standard reconstructions and in those reconstructed with a software (entitled ) for artifact reduction.
RESULTS
Stair-step artifacts were significantly reduced in compared to standard reconstructions (p<0.05). In standard reconstructions, CT was not feasible in 3/45 (7 %) segments but was feasible in all reconstructions. In 9/45 (20 %) segments without atherosclerosis, the algorithm led to a change of CT values from pathologic in standard to physiologic values in reconstructions. In one segment (1/22, 5 %), quantitative plaque analysis was not feasible in standard but only in reconstruction. The mean overall plaque volume (111±60 mm), the calcific (77±47 mm), fibrotic (31±28 mm), and lipidic (4±3 mm) plaque components were higher in standard than in reconstructions (overall 75±50 mm, p<0.001; calcific 51±42 mm, p<0.001; fibrotic 22±19 mm, p<0.05; lipidic 3±3 mm, p=0.055).
CONCLUSION
Despite the lack of reference standard modalities for CT and coronary plaque analysis, initial evidence indicates that an algorithm for reducing stair-step artifacts in sequential mode CCTA increases the rate and quality of datasets amenable to advanced coronary artery analysis, hereby potentially improving patient management.
PubMed: 38882632
DOI: 10.1016/j.ejro.2024.100574 -
Circulation Jun 2024Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of...
BACKGROUND
Thromboembolic events, including myocardial infarction (MI) or stroke, caused by the rupture or erosion of unstable atherosclerotic plaques are the leading cause of death worldwide. Although most mouse models of atherosclerosis develop lesions in the aorta and carotid arteries, they do not develop advanced coronary artery lesions. Moreover, they do not undergo spontaneous plaque rupture with MI and stroke or do so at such a low frequency that they are not viable experimental models to study late-stage thrombotic events or to identify novel therapeutic approaches for treating atherosclerotic disease. This has stymied the development of more effective therapeutic approaches for reducing these events beyond what has been achieved with aggressive lipid lowering. Here, we describe a diet-inducible mouse model that develops widespread advanced atherosclerosis in coronary, brachiocephalic, and carotid arteries with plaque rupture, MI, and stroke.
METHODS
We characterized a novel mouse model with a C-terminal mutation in the scavenger receptor class B, type 1 (SR-BI), combined with knockout (designated SR-BI/). Mice were fed Western diet (WD) for 26 weeks and analyzed for MI and stroke. Coronary, brachiocephalic, and carotid arteries were analyzed for atherosclerotic lesions and indices of plaque stability. To validate the utility of this model, SR-BI/ mice were treated with the drug candidate AZM198, which inhibits myeloperoxidase, an enzyme produced by activated neutrophils that predicts rupture of human atherosclerotic lesions.
RESULTS
SR-BI/ mice show high (>80%) mortality rates after 26 weeks of WD feeding because of major adverse cardiovascular events, including spontaneous plaque rupture with MI and stroke. Moreover, WD-fed SR-BI/ mice displayed elevated circulating high-sensitivity cardiac troponin I and increased neutrophil extracellular trap formation within lesions compared with control mice. Treatment of WD-fed SR-BI/ mice with AZM198 showed remarkable benefits, including >90% improvement in survival and >60% decrease in the incidence of plaque rupture, MI, and stroke, in conjunction with decreased circulating high-sensitivity cardiac troponin I and reduced neutrophil extracellular trap formation within lesions.
CONCLUSIONS
WD-fed SR-BI/ mice more closely replicate late-stage clinical events of advanced human atherosclerotic disease than previous models and can be used to identify and test potential new therapeutic agents to prevent major adverse cardiac events.
PubMed: 38881440
DOI: 10.1161/CIRCULATIONAHA.123.067931