Coronary Atherosclerotic Plaque Research Articles

Automated detection and classification of coronary atherosclerotic plaques on coronary CT angiography using deep learning algorithm

Automated detection and classification of coronary atherosclerotic plaques on coronary CT angiography using deep learning algorithm

Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients

BackgroundLp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator.ObjectivesThis research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition.Materials and methodsSerum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded.ResultsIncreased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients.ConclusionsLevels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

Noninvasive Atherosclerotic Phenotyping: The Next Frontier into Understanding the Pathobiology of Coronary Artery Disease.

Despite recent advances, coronary artery disease remains one of the leading causes of mortality worldwide. Noninvasive imaging allows atherosclerotic phenotyping by measurement of plaque burden, morphology, activity and inflammation, which has the potential to refine patient risk stratification and guide personalized therapy. This review describes the current and emerging roles of advanced noninvasive cardiovascular imaging methods for the assessment of coronary artery disease. Cardiac computed tomography enables comprehensive, noninvasive imaging of the coronary vasculature, and is used to assess luminal stenoses, coronary calcifications, and distinct adverse plaque characteristics, helping to identify patients prone to future events. Novel software tools, implementing artificial intelligence solutions, can automatically quantify and characterize atherosclerotic plaque from standard computed tomography datasets. These quantitative imaging biomarkers have been shown to improve patient risk stratification beyond clinical risk scores and current clinical interpretation of cardiac computed tomography. In addition, noninvasive molecular imaging in higher risk patients can be used to assess plaque activity and plaque thrombosis. Noninvasive imaging allows unique insight into the burden, morphology and activity of atherosclerotic coronary plaques. Such phenotyping of atherosclerosis can potentially improve individual patient risk prediction, and in the near future has the potential for clinical implementation.

Impact of endothelial shear stress on coronary atherosclerotic plaque progression and composition: A meta-analysis and systematic review

Background and aimsIntracoronary pressure gradients and translesional flow patterns have been correlated with coronary plaque progression and lesion destabilization. In this study, we aimed to determine the relationship between endothelial shear stress and plaque progression and to evaluate the effect of shear forces on coronary plaque features. MethodsA systematic review was conducted in medical on-line databases. Selected were studies including human participants who underwent coronary anatomy assessment with computational fluid dynamics (CFD)-based wall shear stress (WSS) calculation at baseline with anatomical evaluation at follow-up. A total of six studies were included for data extraction and analysis. ResultsThe meta-analysis encompassed 31′385 arterial segments from 136 patients. Lower translesional WSS values were significantly associated with a reduction in lumen area (mean difference −0.88, 95% CI −1.13 to −0.62), an increase in plaque burden (mean difference 4.32, 95% CI 1.65 to 6.99), and an increase in necrotic core area (mean difference 0.02, 95% CI 0.02 to 0.03) at follow-up imaging. Elevated WSS values were associated with an increase in lumen area (mean difference 0.78, 95% CI 0.34 to 1.21) and a reduction in both fibrofatty (mean difference −0.02, 95% CI −0.03 to −0.01) and fibrous plaque areas (mean difference −0.03, 95% CI −0.03 to −0.03). ConclusionThis meta-analysis shows that WSS parameters were related to vulnerable plaque features at follow-up. These results emphasize the impact of endothelial shear forces on coronary plaque growth and composition. Future studies are warranted to evaluate the role of WSS in guiding clinical decision-making.

ESR Essentials: imaging in stable chest pain - practice recommendations by ESCR.

Stable chest pain is a common symptom with multiple potential causes. Non-invasive imaging has an important role in diagnosis and guiding management through the assessment of coronary stenoses, atherosclerotic plaque, myocardial ischaemia or infarction, and cardiac function. Computed tomography (CT) provides the anatomical evaluation of coronary artery disease (CAD) with the assessment of stenosis, plaque type and plaque burden, with additional functional information available from CT fractional flow reserve (FFR) or CT myocardial perfusion imaging. Stress magnetic resonance imaging, nuclear stress myocardial perfusion imaging, and stress echocardiography can assess myocardial ischaemia and other cardiac functional parameters. Coronary CT angiography can be used as a first-line test for many patients with stable chest pain, particularly those with low to intermediate pre-test probability. Functional testing may be considered for patients with known CAD, where the clinical significance is uncertain based on anatomical testing, or in patients with high pre-test probability. This practice recommendations document can be used to guide the selection of non-invasive imaging for patients with stable chest pain and provides brief recommendations on how to perform and report these diagnostic tests.

Preventive percutaneous coronary intervention versus optimal medical therapy alone for the treatment of vulnerable atherosclerotic coronary plaques (PREVENT): a multicentre, open-label, randomised controlled trial

Acute coronary syndrome and sudden cardiac death are often caused by rupture and thrombosis of lipid-rich atherosclerotic coronary plaques (known as vulnerable plaques), many of which are non-flow-limiting. The safety and effectiveness of focal preventive therapy with percutaneous coronary intervention of vulnerable plaques in reducing adverse cardiac events are unknown. We aimed to assess whether preventive percutaneous coronary intervention of non-flow-limiting vulnerable plaques improves clinical outcomes compared with optimal medical therapy alone. PREVENT was a multicentre, open-label, randomised controlled trial done at 15 research hospitals in four countries (South Korea, Japan, Taiwan, and New Zealand). Patients aged 18 years or older with non-flow-limiting (fractional flow reserve >0·80) vulnerable coronary plaques identified by intracoronary imaging were randomly assigned (1:1) to either percutaneous coronary intervention plus optimal medical therapy or optimal medical therapy alone, in block sizes of 4 or 6, stratified by diabetes status and the performance of percutaneous coronary intervention in a non-study target vessel. Follow-up continued annually in all enrolled patients until the last enrolled patient reached 2 years after randomisation. The primary outcome was a composite of death from cardiac causes, target-vessel myocardial infarction, ischaemia-driven target-vessel revascularisation, or hospitalisation for unstable or progressive angina, assessed in the intention-to-treat population at 2 years. Time-to-first-event estimates were calculated with the Kaplan-Meier method and were compared with the log-rank test. This report is the principal analysis from the trial and includes all long-term analysed data. The trial is registered at ClinicalTrials.gov, NCT02316886, and is complete. Between Sept 23, 2015, and Sept 29, 2021, 5627 patients were screened for eligibility, 1606 of whom were enrolled and randomly assigned to percutaneous coronary intervention (n=803) or optimal medical therapy alone (n=803). 1177 (73%) patients were men and 429 (27%) were women. 2-year follow-up for the primary outcome assessment was completed in 1556 (97%) patients (percutaneous coronary intervention group n=780; optimal medical therapy group n=776). At 2 years, the primary outcome occurred in three (0·4%) patients in the percutaneous coronary intervention group and in 27 (3·4%) patients in the medical therapy group (absolute difference -3·0 percentage points [95% CI -4·4 to -1·8]; p=0·0003). The effect of preventive percutaneous coronary intervention was directionally consistent for each component of the primary composite outcome. Serious clinical or adverse events did not differ between the percutaneous coronary intervention group and the medical therapy group: at 2 years, four (0·5%) versus ten (1·3%) patients died (absolute difference -0·8 percentage points [95% CI -1·7 to 0·2]) and nine (1·1%) versus 13 (1·7%) patients had myocardial infarction (absolute difference -0·5 percentage points [-1·7 to 0·6]). In patients with non-flow-limiting vulnerable coronary plaques, preventive percutaneous coronary intervention reduced major adverse cardiac events arising from high-risk vulnerable plaques, compared with optimal medical therapy alone. Given that PREVENT is the first large trial to show the potential effect of the focal treatment for vulnerable plaques, these findings support consideration to expand indications for percutaneous coronary intervention to include non-flow-limiting, high-risk vulnerable plaques. The CardioVascular Research Foundation, Abbott, Yuhan Corp, CAH-Cordis, Philips, and Infraredx, a Nipro company.

Chronic Administration of Methamphetamine Aggravates Atherosclerotic Vulnerable Plaques in Apolipoprotein E Knockout Mice Fed with a High-cholesterol Diet.

It has been observed previously that chronic methamphetamine (METH) administration could upregulate neuropeptide Y (NPY) expression and promote atherosclerotic formation in apolipoprotein E knockout (ApoE-/-) mice fed with a normal cholesterol or high diet and NPY might be involved in the pathogenesis of METH-induced atherogenic effects through NPY Y1 receptor pathway. Vulnerable coronary atherosclerotic plaque (VP) is a critical pathological finding responsible for the acute coronary syndrome (ACS). In this study, we explored whether METH abuse could aggravate the formation of VP in ApoE-/- mice fed with high cholesterol diet. The purpose of this study was to observe if chronic METH administration could aggravate vulnerable plaque (VP) formation in ApoE-/- mice fed with a high-cholesterol diet. Male ApoE-/- mice fed with a high-cholesterol diet were intraperitoneally injected with normal saline (NS) or 8 mg/kg/day METH (M8) for 24 weeks. Body weight was monitored from baseline to 24 weeks at 2 weeks intervals. After 24 weeks of treatment, plasma lipid variables were measured. Movat's staining and immunohistochemical staining were performed on frozen sections of the aortic roots to calculate VP percentage and intraplaque hemorrhage (IPH) percentage and detect expression of NPY, vascular endothelial growth factor (VEGF), and CD31. In vitro, the expressions of Y2R, VEGF, and CD31 were detected by immunofluorescence staining in aortic endothelial cells incubated with PBS, 100μM METH, 10nmol NPY, or 100μM METH plus 10nmol NPY for 12 hours. The CD31 positive area, percentage of IPH, VP, and the expressions of NPY and VEGF were significantly increased in the M8 group than in the NS group. In vitro, the expressions of Y2R, VEGF, and CD31 were significantly increased in the METH+NPY group than in the PBS, METH, and NPY groups and these effects could be blunted by treatment with a Y2R antagonist or DPPIV inhibitor. Chronic METH administration could aggravate VP in ApoE-/- mice fed with a high-cholesterol diet, possibly through upregulating vascular NPY and VEGF expression and promoting angiogenesis and vessel rupture in atherosclerotic plaques. Our findings indicated that increased VP formation might contribute to the development of acute coronary syndrome post-chronic METH abuse by activating DPPIV/NPY/Y2R pathway.

Atherosclerotic coronary plaque regression from lipid-lowering therapies: A meta-analysis and meta-regression

BackgroundStudies reporting collective and comprehensive data on plaque regression of different lipid-lowering therapies (LLTs) are limited. ObjectivesWe evaluated plaque regression of LLTs based on multiple markers and performed subgroup analyses based on LLT type and post-treatment LDL-C levels MethodsA literature search was performed to identify studies assessing plaque regression from LLTs. The following LLTs groups were included: High-intensity statin (HIS), HIS+ eicosapentaenoic acid (EPA), HIS + ezetimibe, Low-intensity statin (LIS), LIS + EPA, LIS + Ezetimibe, and PCSK9 inhibitors. Our primary outcomes were change in percent atheroma volume (PAV). Secondary outcomes included mean differences in total atheroma volume (TAV), lumen, plaque, and vessel volumes, fibrous cap thickness (FCT), and lipid arc (LA). Subgroup analyses were performed on LLT type and post-treatment LDL-C levels. Meta-regression was performed to control for covariates. ResultsWe identified 51 studies with 9,113 adults (22 % females). LLTs reduced PAV levels (-1.10 % [-1.63, -0.56], p < 0.01), with significant reduction observed with HIS, LIS + ezetimibe, LIS + EPA, and PCSK9 inhibitors. LLTs reduced TAV levels (-5.84 mm3 [-8.64 to -3.04] p < 0.01), mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). LLTs reduced plaque volume and LA and increased FCT. ConclusionThe plaque regression associated with LLTs is observed to be mainly driven by HIS, reducing both TAV and PAV. This suggest that HIS is the most effective LLT for plaque regression Unstructured abstractWe evaluated plaque regression of LLTs from 51 studies. We found that while reduction of PAV (-1.10 % [-1.63, -0.56], p < 0.01) were present across different LLT types, reduction of TAV (-5.84 mm3 [-8.64 to -3.04] p < 0.01) was mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). These results suggest that HIS is the most effective LLT for plaque regression.

Circulating miR-6821-5p levels and coronary calcification in asymptomatic familial hypercholesterolemia patients

Background and aimsPremature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. MethodsPatients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (−) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups. ResultsmiR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (−). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures. ConclusionsUp-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.

Pathological Characteristics and Classification of Unstable Coronary Atherosclerotic Plaques.

Important forensic diagnostic indicators of sudden death in coronary atherosclerotic heart disease, such as acute or chronic myocardial ischemic changes, sometimes make it difficult to locate the ischemic site due to the short death process, the lack of tissue reaction time. In some cases, the deceased died of sudden death on the first-episode, resulting in difficulty for medical examiners to make an accurate diagnosis. However, clinical studies on coronary instability plaque revealed the key role of coronary spasm and thrombosis caused by their lesions in sudden coronary death process. This paper mainly summarizes the pathological characteristics of unstable coronary plaque based on clinical medical research, including plaque rupture, plaque erosion and calcified nodules, as well as the influencing factors leading to plaque instability, and briefly describes the research progress and technique of the atherosclerotic plaques, in order to improve the study on the mechanism of sudden coronary death and improve the accuracy of the forensic diagnosis of sudden coronary death by diagnosing different pathologic states of coronary atherosclerotic plaques.

Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification.

Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated. Serum was collected from patients with chronic kidney disease and controls, and the levels of 4-HNE and 8-iso-prostaglandin F2α were measured. Sections of coronary atherosclerotic plaques from donors were immunostained to analyze calcium deposition and 4-HNE. A total of 658 patients with coronary artery disease who received coronary computed tomography angiography were recruited to analyze the relationship between coronary calcification and the rs671 mutation in aldehyde dehydrogenase 2 (ALDH2). ALDH2 knockout (ALDH2-/-) mice, smooth muscle cell-specific ALDH2 knockout mice, ALDH2 transgenic mice, and their controls were used to establish vascular calcification models. Primary mouse aortic smooth muscle cells and human aortic smooth muscle cells were exposed to medium containing β-glycerophosphate and CaCl2 to investigate cell calcification and the underlying molecular mechanisms. Elevated 4-HNE levels were observed in the serum of patients with chronic kidney disease and model mice and were detected in calcified artery sections by immunostaining. ALDH2 knockout or smooth muscle cell-specific ALDH2 knockout accelerated the development of vascular calcification in model mice, whereas overexpression or activation prevented mouse vascular calcification and the osteochondrogenic differentiation of vascular smooth muscle cells. In patients with coronary artery disease, patients with ALDH2 rs671 gene mutation developed more severe coronary calcification. 4-HNE promoted calcification of both mouse aortic smooth muscle cells and human aortic smooth muscle cells and their osteochondrogenic differentiation in vitro. 4-HNE increased the level of Runx2 (runt-related transcription factor-2), and the effect of 4-HNE on promoting vascular smooth muscle cell calcification was ablated when Runx2 was knocked down. Mutation of Runx2 at lysine 176 reduced its carbonylation and eliminated the 4-HNE-induced upregulation of Runx2. Our results suggest that 4-HNE increases Runx2 stabilization by directly carbonylating its K176 site and promotes vascular calcification. ALDH2 might be a potential target for the treatment of vascular calcification.

The role of computed tomography angiography in assessing the correlation between properties of coronary atherosclerotic plaque and blood lipids.

Coronary atherosclerotic heart disease (CAHD) is the leading cause of death in developed countries. This study aimed to explore the correlation between the properties of coronary atherosclerotic plaque and blood lipids using computed tomography angiography (CTA). A total of 83 patients with coronary heart disease were included in this study (males: 50; females: 33; average age: [59 ± 8] years old). They were classified into the stable angina group and unstable angina group. Atherosclerotic plaques were classified as fatty plaques (soft plaques), fibrous plaques, and calcified plaques based on the computed tomography (CT) values. SPSS 17.0 statistical software was used to analyze the correlation between the properties of angina and the CT values of atherosclerotic plaques, blood lipids, and plaque properties, and then compared between the stable and unstable angina groups. There were statistically significant differences in plaque properties between the stable and unstable angina groups (P< 0.001). During CTA examination, we found statistically significant differences in the CT density values of atherosclerotic plaques between the stable and unstable angina groups (P< 0.001). There were statistically significant differences between the properties of angina and the level of blood lipids (P< 0.05). Anginal properties negatively correlated with calcified plaques and positively correlated with non-calcified plaques. Calcified plaques negatively correlated with total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), and positively correlated with high-density lipoprotein cholesterol (HDL-C). Non-calcified plaques negatively correlated with HDL-C and positively correlated with TC, LDL-C, and TG.

Prediction of the development of new coronary atherosclerotic plaques with radiomics

BackgroundRadiomics is expected to identify imaging features beyond the human eye. We investigated whether radiomics can identify coronary segments that will develop new atherosclerotic plaques on coronary computed tomography angiography (CCTA). MethodsFrom a prospective multinational registry of patients with serial CCTA studies at ≥ 2-year intervals, segments without identifiable coronary plaque at baseline were selected and radiomic features were extracted. Cox models using clinical risk factors (Model 1), radiomic features (Model 2) and both clinical risk factors and radiomic features (Model 3) were constructed to predict the development of a coronary plaque, defined as total PV ​≥ ​1 ​mm3, at follow-up CCTA in each segment. ResultsIn total, 9583 normal coronary segments were identified from 1162 patients (60.3 ​± ​9.2 years, 55.7% male) and divided 8:2 into training and test sets. At follow-up CCTA, 9.8% of the segments developed new coronary plaque. The predictive power of Models 1 and 2 was not different in both the training and test sets (C-index [95% confidence interval (CI)] of Model 1 vs. Model 2: 0.701 [0.690–0.712] vs. 0.699 [0.0.688–0.710] and 0.696 [0.671–0.725] vs. 0.0.691 [0.667–0.715], respectively, all p ​> ​0.05). The addition of radiomic features to clinical risk factors improved the predictive power of the Cox model in both the training and test sets (C-index [95% CI] of Model 3: 0.772 [0.762–0.781] and 0.767 [0.751–0.787], respectively, all p ​< ​00.0001 compared to Models 1 and 2). ConclusionRadiomic features can improve the identification of segments that would develop new coronary atherosclerotic plaque. Clinical Trial RegistrationClinicalTrials.gov NCT0280341.

The Role of Fluid Mechanics in Coronary Atherosclerotic Plaques: An Up-to-Date Review

The Role of Fluid Mechanics in Coronary Atherosclerotic Plaques: An Up-to-Date Review

Data-driven models for the prediction of coronary atherosclerotic plaque progression/regression

Coronary artery disease is defined by the existence of atherosclerotic plaque on the arterial wall, which can cause blood flow impairment, or plaque rupture, and ultimately lead to myocardial ischemia. Intravascular ultrasound (IVUS) imaging can provide a detailed characterization of lumen and vessel features, and so plaque burden, in coronary vessels. Prediction of the regions in a vascular segment where plaque burden can either increase (progression) or decrease (regression) following a certain therapy, has remained an elusive major milestone in cardiology. Studies like IBIS-4 showed an association between plaque burden regression and high-intensity rosuvastatin therapy over 13 months. Nevertheless, it has not been possible to predict if a patient would respond in a favorable/adverse fashion to such a treatment. This work aims to (i) Develop a framework that processes lumen and vessel cross-sectional contours and extracts geometric descriptors from baseline and follow-up IVUS pullbacks; and to (ii) Develop, train, and validate a machine learning model based on baseline/follow-up IVUS datasets that predicts future percent of atheroma volume changes in coronary vascular segments using only baseline information, i.e. geometric features and clinical data. This is a post hoc analysis, revisiting the IBIS-4 study. We employed 140 arteries, from 81 patients, for which expert delineation of lumen and vessel contours were available at baseline and 13-month follow-up. Contour data from baseline and follow-up pullbacks were co-registered and then processed to extract several frame-wise features, e.g. areas, plaque burden, eccentricity, etc. Each pullback was divided into regions of interest (ROIs), following different criteria. Frame-wise features were condensed into region-wise markers using tools from statistics, signal processing, and information theory. Finally, a stratified 5-fold cross-validation strategy (20 repetitions) was used to train/validate an XGBoost regression models. A feature selection method before the model training was also applied. When the models were trained/validated on ROI defined by the difference between follow-up and baseline plaque burden, the average accuracy and Mathews correlation coefficient were 0.70 and 0.41 respectively. Using a ROI partition criterion based only on the baseline’s plaque burden resulted in averages of 0.60 accuracy and 0.23 Mathews correlation coefficient. An XGBoost model was capable of predicting plaque progression/regression changes in coronary vascular segments of patients treated with rosuvastatin therapy in 13 months. The proposed method, first of its kind, successfully managed to address the problem of stratification of patients at risk of coronary plaque progression, using IVUS images and standard patient clinical data.

Comprehensive biomechanical and anatomical atherosclerotic plaque metrics predict major adverse cardiovascular events: A new tool for clinical decision making

Background and aimsAnatomical imaging alone of coronary atherosclerotic plaques is insufficient to identify risk of future adverse events and guide management of non-culprit lesions. Low endothelial shear stress (ESS) and high plaque structural stress (PSS) are associated with events, but individually their predictive value is insufficient for risk prediction. We determined whether combining multiple complementary, biomechanical and anatomical plaque characteristics improves outcome prediction sufficiently to inform clinical decision-making. MethodsWe examined baseline ESS, ESS gradient (ESSG), PSS, and PSS heterogeneity index (HI), and plaque burden in 22 lesions that developed subsequent events and 64 control lesions that remained quiescent from the PROSPECT study. Results86 fibroatheromas were analysed from 67 patients. Lesions with events showed higher PSS HI (0.32 vs. 0.24, p<0.001), lower local ESS (0.56Pa vs. 0.91Pa, p = 0.007), and higher ESSG (3.82 Pa/mm vs. 1.96 Pa/mm, p = 0.007), while high PSS HI (hazard ratio [HR] 3.9, p = 0.006), high ESSG (HR 3.4, p = 0.007) and plaque burden>70 % (HR 2.6, p = 0.02) were independent outcome predictors in multivariate analysis. Combining low ESS, high ESSG, and high PSS HI gave both high positive predictive value (80 %), which increased further combined with plaque burden>70 %, and negative predictive value (81.6 %). Low ESS, high ESSG, and high PSS HI co-localised spatially within 1 mm in lesions with events, and importantly, this cluster was distant from the minimum lumen area site. ConclusionsCombining complementary biomechanical and anatomical metrics significantly improves risk-stratification of individual coronary lesions. If confirmed from larger prospective studies, our results may inform targeted revascularisation vs. conservative management strategies.

Detection of monosodium urate depositions and atherosclerotic plaques in the cardiovascular system by dual-energy computed tomography

AimThe study aimed to explore the relationship between urate deposition and surrounding atherosclerotic plaques, and to confirm the contribution of urate deposition to the development of coronary atherosclerosis. Methods and resultsThe present study employed Dual-energy CT (DECT) material separation technology through calcium score scan to access the presence of MSU crystal deposition in coronary atherosclerotic plaques in patients with clinically suspected coronary heart diseases undergoing DECT. DECT showed that among 872 patients, 441 had plaques in coronary arteries; the incidence of plaque was 50.6 %. The patients were divided in the atherosclerotic plaque vs. non-plaque groups. There were significant differences in age, sex, blood pressure, blood glucose, serum creatinine, and history of gout and hyperuricemia between the plaque and non-plaque groups (all P < 0.05). Among the patients with coronary plaques, there were 348 patients (78.9 %) with simple atherosclerotic plaque (AP), 8 (1.8 %) with simple urate depositions (UD), and 85 (19.3 %) with urate depositions and atherosclerotic plaques (UDAP). The multivariable analysis showed that urate deposition was independently associated with plaques after adjustment for age, sex, blood pressure, blood glucose, serum creatinine, history of gout, and history of hyperuricemia (OR = 13.69, 95%CI: 7.53–22.95, P = 0.035). UPAP patients had significantly higher coronary calcium scores than AP patients [210.1 (625.2) AU vs 58.2 (182.5) AU, P < 0.001] Urate deposition (16.7 mm3) positively correlated with plaque calcification (73.8 mm³) in UPAP patients (r = 0.325, P < 0.001). ConclusionPatients with gout or a history of hyperuricemia were more likely to exhibit UDAP. Urate deposition was independently associated with plaques.

A Race Against Time: Coronary Computed Tomography Angiography Discovers a Highly Inflamed Plaque in 49-Year-Old Right Before STEMI

Abstract In the modern management of coronary artery disease (CAD), cardiac computed tomography angiography (CCTA) has emerged as a pivotal diagnostic tool, offering detailed visualization of coronary artery lumens and atherosclerotic plaques. We present the case of a 49-year-old woman, with no prior cardiovascular history but with several risk factors, in whom CCTA identified a highly inflamed atherosclerotic plaque, which led immediately to an acute myocardial infarction. Significantly, this case spotlights the vital role of perivascular inflammation mapping in CCTA, crucial for identifying high-risk plaques. The case emphasizes the necessity for a comprehensive, multifaceted diagnostic approach in the evaluation and management of CAD, incorporating advanced techniques like perivascular inflammation mapping for a more accurate and predictive assessment.

Associations Between Resolvin D1 and Culprit Plaque Morphologies: An Optical Coherence Tomography Study in Patients with ST-Segment Elevation Myocardial Infarction.

As a specialized pro-resolving lipid mediator, resolvin D1 (RvD1) inhibits atherosclerosis progression in vivo by reducing regional oxidative stress and chronic inflammation. However, it is unclear how RvD1 is involved in human coronary artery disease. This study aims to investigate the association between plasma levels of RvD1 and culprit-plaque characteristics in patients with ST-segment elevation myocardial infarction (STEMI). A total of 240 STEMI patients undergoing optical coherence tomography (OCT) examination were analyzed. RvD1 levels were measured in patient plasma samples using an enzyme-linked immunosorbent assay. Logistic regression was performed to assess the association between RvD1 levels and various culprit plaque morphologies, and the receiver operating curve was used to search for an optimal cutoff threshold to predict certain pathological features. The median RvD1 level was 129.7 (56.6-297.8) pg/mL. According to multivariable logistic regression, high RvD1 was associated with plaque rupture (≥111.5 pg/mL, odds ratio [OR]: 2.09, 95% confidence interval [CI]: 1.20-3.66, P = 0.010), healed plaques (≥246.4 pg/mL, OR: 2.17, 95% CI: 1.11-4.24, P = 0.023), and calcification (≥293.38 pg/mL, OR: 2.10, 95% CI: 1.21-3.66, P = 0.008) at culprit lesions. Increased levels of RvD1 were associated with higher instability of coronary atherosclerotic plaques in STEMI patients.

Ezetimibe and atherosclerotic cardiovascular disease: a systematic review and meta-analysis

IntroductionIndividuals diagnosed with atherosclerotic cardiovascular disease (ACD) are exposed to an increased risk of cardiovascular events. Reducing low-density lipoprotein cholesterol (LDL-C) levels has been established as an effective approach to mitigate these risks. However, a comprehensive and up-to-date meta-analysis investigating the LDL-C-lowering effectiveness and the impact on coronary atherosclerotic plaque compositions of Ezetimibe has been lacking.MethodsWe conducted a systematic review by meticulously analyzing databases such as MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials that evaluated the efficacy of ezetimibe in lowering LDL-C levels and its influence on coronary atherosclerotic plaques among individuals with ACD. This review encompassed studies available until August 1, 2023. In our analysis, we employed the weighted mean difference (WMD) as the aggregated statistical measure, accompanied by the corresponding 95% confidence interval (CI).ResultsWe encompassed a total of 20 eligible studies. Our findings unveiled that the combined therapy involving ezetimibe alongside statins led to a more substantial absolute decrease in LDL-C in comparison to using statins alone. This difference in means amounted to (−14.06 mg/dl; 95% CI −18.0 to −10.0; p = 0.0001). Furthermore, upon conducting subgroup analyses, it became evident that the intervention strategies proved effective in diminishing the volume of dense calcification (DC) in contrast to the control group.ConclusionsOur study findings indicate that the inclusion of ezetimibe in conjunction with statin therapy leads to a modest yet meaningful additional reduction in LDL-C levels when compared to using statins in isolation. Importantly, the introduction of ezetimibe resulted in a significant decrease in the volume of DC. However, it is worth noting that further investigation is warranted to delve deeper into this phenomenon.