Lipid-rich Necrotic Core Research Articles

Carotid Plaque Phenotyping by Correlating Plaque Morphology from Computed Tomography Angiography with Transcriptional Profiling

<h3>Objective</h3> Ischaemic strokes can be caused by unstable carotid atherosclerosis, but methods for identification of high risk lesions are lacking. Carotid plaque morphology imaging using software for visualisation of plaque components in computed tomography angiography (CTA) may improve assessment of plaque phenotype and stroke risk, but it is unknown if such analyses also reflect the biological processes related to lesion stability. Here, we investigated how carotid plaque morphology by image analysis of CTA is associated with biological processes assessed by transcriptomic analyses of corresponding carotid endarterectomies (CEAs). <h3>Methods</h3> Carotid plaque morphology was assessed in patients undergoing CEA for symptomatic or asymptomatic carotid stenosis consecutively enrolled between 2006 and 2015. Computer based analyses of pre-operative CTA was performed to define calcification, lipid rich necrotic core (LRNC), intraplaque haemorrhage (IPH), matrix (MATX), and plaque burden. Plaque morphology was correlated with molecular profiles obtained from microarrays of corresponding CEAs and models were built to assess the ability of plaque morphology to predict symptomatology. <h3>Results</h3> Carotid plaques (<i>n</i> = 93) from symptomatic patients (<i>n</i> = 61) had significantly higher plaque burden and LRNC compared with plaques from asymptomatic patients (<i>n</i> = 32). Lesions selected from the transcriptomic cohort (<i>n</i> = 40) with high LRNC, IPH, MATX, or plaque burden were characterised by molecular signatures coupled with inflammation and extracellular matrix degradation, typically linked with instability. In contrast, highly calcified plaques had a molecular signature signifying stability with enrichment of profibrotic pathways and repressed inflammation. In a cross validated prediction model for symptoms, plaque morphology by CTA alone was superior to the degree of stenosis. <h3>Conclusion</h3> The study demonstrates that CTA image analysis for evaluation of carotid plaque morphology, also reflects prevalent biological processes relevant for assessment of plaque phenotype. The results support the use of CTA image analysis of plaque morphology for risk stratification and management of patients with carotid stenosis.

Abstract MP47: Assessment Of Atherosclerosis In A Novel Transgenic Mouse Expressing Pathogenic Levels Of Human Lipoprotein(a)

Studying the role of elevated plasma levels of lipoprotein(a) (Lp(a)) in atherogenesis is challenging given that the LPA gene encoding apo(a) is absent in typical animal models. As such we created a novel transgenic mouse line expressing both human apolipoprotein(a) (apo(a)) and human apoB100 ((Tg(LPA +/0 ;APOB +/0 )) . The LPA transgene, assembled in the pLIV vector, produces a physiologically relevant 12-kringle apo(a) isoform. The APOB transgene contains the entire human APOB gene with a mutation preventing APOB editing. In our atherosclerosis model, male and female mice were injected weekly with an antisense oligonucleotide targeting the mouse LDL receptor (IONIS Pharmaceuticals), and fed a high-fat, high-cholesterol diet for 12 weeks. High plasma Lp(a) levels were observed in both male and female Tg(LPA +/0 ;APOB +/0 ) mice (219.0±11.9 and 133.7±12.1 mg/dL, respectively; n=12/group). Importantly, high levels of Lp(a) in plasma did not result in metabolic alterations, including differences in weight gain, energy expenditure, activity, RER, VO 2 /VCO 2 consumption/output, and glucose tolerance compared to Tg(APOB +/0 ) control mice. Both male and female Tg(LPA +/0 ;APOB +/0 ) and Tg(APOB +/0 ) mice exhibited enhanced proatherogenic lipoprotein profiles with the majority of the cholesterol and TG present in the VLDL and LDL fractions. Complex lesions developed in all transgenic mice, including large, lipid-rich necrotic cores, with overlying fibrous caps and intimal calcium deposition. Immunohistochemistry with a monoclonal apo(a) antibody revealed the presence of Lp(a) in the plaques of Tg(LPA +/0 ;APOB +/0 ) mice. Analysis of aortic sinus lesions revealed a 23% increase in total plaque area in female Tg(LPA +/0 ;APOB +/0 ) mice compared to female Tg(APOB +/0 ) mice (p=0.0836). Moreover, atherosclerotic plaques in female Tg(LPA +/0 ;APOB +/0 ) mice contained significantly more calcium deposition than female Tg( APOB +/0 ) mice (1.79±0.4% vs. 2.96 ±0.3% of total plaque area (p&lt;0.05)). No differences in plaque area or calcium were observed in male mice. In this ongoing study, detailed analyses of atherosclerotic plaque components in Tg(LPA +/0 ;APOB +/0 ) mice will be required to uncover the unique contribution of Lp(a) to atherogenesis.

A comparison of carotid atherosclerosis in symptomatic patients between 2002-2005 and 2012-2015 cohorts using multi-contrast magnetic resonance vessel wall imaging.

OBJECTIVETo compare the morphological and compositional characteristics of carotid plaques in two cohorts (2002−2005 and 2012−2015) of Chinese patients using magnetic resonance vessel wall imaging.METHODSSymptomatic patients with carotid atherosclerotic plaques who underwent carotid vessel wall magnetic resonance imaging between 2002−2005 and 2012−2015 were retrospectively recruited. Plaque morphology [including mean wall area, wall thickness, and maximum normalized wall index (NWI)] and composition [including calcification, intraplaque hemorrhage, and lipid-rich necrotic core (LRNC)] in symptomatic carotid arteries were evaluated and compared between patients in these two time periods.RESULTSA total of 258 patients, including 129 patients in the 2002−2005 cohort and 129 patients in the 2012−2015 cohort, were recruited. Statin use (49.6%vs. 32.6%, P = 0.004) and hypertension (76.0% vs. 62.8%, P = 0.015) were significantly more common in the 2012–2015 cohort than in the 2002−2005 cohort. Patients in the 2012−2015 cohort also exhibited significantly low plaque burden parameters (allP < 0.05), as well as a lower prevalence (68.2% vs. 89.9%, P < 0.001) and volume percentages of LRNC (11.2% ± 14.2% vs. 25.7% ± 17.7%, P < 0.001). These differences remained significant after adjustment for clinical factors. The differences in the volume percentages of LRNC also remained significant after an additional adjustment for maximum NWI ( P < 0.001). CONCLUSIONSPatients in the 2012−2015 cohort had a lower plaque burden and volume percentages of LRNC in symptomatic carotid arteries than those in the 2002−2005 cohort. These findings indicate that carotid plaques in the recent cohort had a lower severity and vulnerability.

Abdominal subcutaneous adipose tissue negatively associates with subclinical coronary artery disease in men with psoriasis

ObjectiveUnderstand the relationship between abdominal subcutaneous adipose tissue (ASAT) and coronary atherosclerosis defined as noncalcified and lipid-rich necrotic core burden in psoriasis. MethodsWe performed a cross-sectional study of 232 participants (92 women) with psoriasis and without known cardiovascular disease. Participants underwent coronary computed tomography angiography to characterize coronary atherosclerosis burden and low dose abdominal computed tomography to quantify subcutaneous and visceral adipose tissue. Fat depot volumes were first adjusted for each participant's BMI (ASATadjBMI). ResultsIn women, there was a positive correlation between ASATadjBMI and systemic inflammation as assessed by hs-C-reactive protein (r=0.30; p=.004) and GlycA (r=0.29; p=.007) as well as total cholesterol (r=0.24; p=.02) and low-density lipoprotein cholesterol (r=0.22; p=.04). In men, ASATadjBMI correlated with hs-C-reactive protein (r=0.18; p=.04) and insulin resistance (r=0.17; p=.04). In models fully adjusted for traditional cardiovascular risk factors, ASATadjBMI negatively associated with noncalcified and lipid-rich necrotic core burden in men (β= -0.17; p=.03, β= -0.20; p=.03, respectively), but not women (β= -0.06; p=.57, β= 0.09; p=.49, respectively) with psoriasis. ConclusionsFor a given BMI, ASAT negatively associated with coronary atherosclerosis burden in male participants with psoriasis. The observed sex-specific effects warrant further study of ASAT in states of chronic inflammation.

Correlation between computed tomography angiography and histology of carotid artery atherosclerosis: Can semi-automated imaging software predict a plaque's composition?

Using computed tomography angiography to differentiate between components of carotid atherosclerotic lesions remains largely elusive. This study sought to validate a semi-automated software for computed tomography angiography plaque analysis using histologic comparisons. A retrospective review was performed of consecutive patients that underwent a carotid endarterectomy, with pre-procedural computed tomography angiography imaging of the cervical arterial vasculature available for review. Images were evaluated using a commercially-available software package, which produced segmented analyses of intraplaque components (e.g. intraplaque hemorrhage, lipid-rich necrotic core, and calcifications). On imaging, each component was assessed in terms of its (1) presence or absence, and (2) both volume and proportion of the total plaque volume (if present). On histological evaluation of carotid endarterectomy specimens, each component was evaluated as an estimated proportion of total plaque volume. Of 80 included patients, 30 (37.5%) were female. The average age was 69.7 years (SD = 9.1). Based on imaging, intraplaque hemorrhage was the smallest contributor to plaque composition (1.2% of volumes on average). Statistically significant linear associations were noted between the proportion of intraplaque hemorrhage, lipid-rich necrotic core, and calcifications on histology and the volume of each component on imaging (p values ranged from 0.0008 to 0.01). Area under curve were poor for intraplaque hemorrhage and lipid-rich necrotic core (0.59 and 0.61, respectively) and acceptable for calcifications (0.73). Semi-automated analyses of computed tomography angiography have limited diagnostic accuracy in the detection of intraplaque hemorrhage and lipid-rich necrotic core in carotid artery plaques. However, volumetric imaging measurements of different components corresponded with histologic analysis.

Quantitative Magnetic Resonance Imaging Assessment of the Relationships Between Fat Fraction and R2* Inside Carotid Plaques, and Circulating Lipoproteins.

Lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH) are morphological features of high-risk atherosclerotic plaques. However, their relationship to circulating lipoproteins is unclear. To study associations between changes in lipoproteins vs. changes in LRNC (represented by fat fraction [FF]) and IPH (represented by R2*). Prospective. Fifty-two patients with carotid plaques, 33 males (63.5%), mean age 72 (±5). Four-point fast gradient Dixon magnetic resonance imaging (MRI) was used to quantify FF and R2* (to measure IPH) inside plaques and in vessel wall. Turbo-spin echo was used for T1 weighted sequences to guide manual segmentation. Carotid MRI and serum lipid levels were assessed at baseline and at 1-year follow-up. For patients, lipid-lowering therapy was customized to reduce low-density lipoprotein (LDL) levels below 1.8 mmol/L. Segmentation was performed with one set of regions of interest for the plaque and one for the vessel wall at the location of the plaque. Thereby MRI data for FF, R2*, and volumes in plaque- and vessel-wall segmentations could be obtained from baseline and follow-up, as well as changes over the study year. Pearson correlation coefficient for correlations. Paired samples t-test for changes over time. Significance at P < 0.05, 95% confidence interval. LDL decreased significantly (2.19-1.88 mmol/L, Z - 2.9), without correlation to changes in plaque composition, nor to the significant reduction in vessel-wall volume (-106.3 mm3 ). Plaque composition remained unchanged, FF +8.5% (P=0.366) and R2* +3.5% (P=0.304). Compared to plaque segmentations, R2* was significantly lower in the vessel-wall segmentations both at baseline (-9.3%) and at follow-up (-9.1%). The absence of correlations between changes in lipoproteins and changes in plaque composition indicates more complex relationships between these parameters than previously anticipated. The significant differences in both R2* and volume dynamics comparing plaque segmentations and vessel-wall segmentations suggest differences in their pathobiology of atherosclerosis. 1 TECHNICAL EFFICACY: Stage 4.

Emerging Role of Carotid MRI for Personalized Ischemic Stroke Risk Prediction in Patients With Carotid Artery Stenosis.

Rupture of a vulnerable carotid plaque is an important cause of ischemic stroke. Prediction models can support medical decision-making by estimating individual probabilities of future events, while magnetic resonance imaging (MRI) can provide detailed information on plaque vulnerability. In this review, prediction models for medium to long-term (>90 days) prediction of recurrent ischemic stroke among patients on best medical treatment for carotid stenosis are evaluated, and the emerging role of MRI of the carotid plaque for personalized ischemic stroke prediction is discussed. A systematic search identified two models; the European Carotid Surgery Trial (ECST) medical model, and the Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score. We critically appraised these models by means of criteria derived from the CHARMS (CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modeling Studies) and PROBAST (Prediction model Risk Of Bias ASsessment Tool). We found both models to be at high risk of bias. The ECST model, the most widely used model, was derived from data of large but relatively old trials (1980s and 1990s), not reflecting lower risks of ischemic stroke resulting from improvements in drug treatment (e.g., statins and anti-platelet therapy). The SCAIL model, based on the degree of stenosis and positron emission tomography/computed tomography (PET/CT)-based plaque inflammation, was derived and externally validated in limited samples. Clinical implementation of the SCAIL model can be challenging due to high costs and low accessibility of PET/CT. MRI is a more readily available, lower-cost modality that has been extensively validated to visualize all the hallmarks of plaque vulnerability. The MRI methods to identify the different plaque features are described. Intraplaque hemorrhage (IPH), a lipid-rich necrotic core (LRNC), and a thin or ruptured fibrous cap (TRFC) on MRI have shown to strongly predict stroke in meta-analyses. To improve personalized risk prediction, carotid plaque features should be included in prediction models. Prediction of stroke in patients with carotid stenosis needs modernization, and carotid MRI has potential in providing strong predictors for that goal.

A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease.

ObjectiveIn this narrative review, we aim to review imaging biomarkers that carry the potential to non-invasively guide stroke risk stratification for treatment optimization.BackgroundCarotid atherosclerosis plays a fundamental part in the occurrence of ischemic stroke. International guidelines select the optimal treatment strategy still mainly based on the presence of clinical symptoms and the degree of stenosis for stroke prevention in patients with atherosclerotic carotid plaques. These guidelines, based on randomized controlled trials that were conducted three decades ago, recommend carotid revascularization in symptomatic patients with high degree of stenosis versus a conservative approach for most asymptomatic patients. Due to optimization of best medical therapy and risk factor control, it is suggested that a subgroup of symptomatic patients is at lower risk of stroke and may not benefit from revascularization, whereas a selective subgroup of high-risk asymptomatic patients would benefit from this procedure.MethodsA literature search was performed for articles published up to December 2020 using PubMed, EMBASE and Scopus. Based on the literature found, change in stenosis degree and volume, plaque echolucency, plaque surface, intraplaque haemorrhage, lipid-rich necrotic core, thin fibrous cap, inflammation, neovascularization, microembolic signals, cerebrovascular reserve, intracranial collaterals, silent brain infarcts, diffusion weighted imaging lesions and white matters lesions have the potential to predict stroke risk.ConclusionsThe applicability of imaging biomarkers needs to be further improved before the potential synergistic prognostic ability of imaging biomarkers can be verified on top of the clinical biomarkers. In the future, the routine and combined assessment of both plaque and brain imaging biomarkers might help to improve optimization of treatment strategies in individual patients with atherosclerotic carotid artery disease.

Diagnostic Accuracy of Optical Frequency Domain Imaging for Identifying Necrotic Cores with Intraplaque Hemorrhage in Advanced Human Carotid Plaques

This study investigated whether optical frequency domain imaging (OFDI) can identify carotid artery vulnerable plaque characteristics, focusing on lipid-rich necrotic core (NC) and intraplaque hemorrhage (IPH). Fourteen patients scheduled for carotid endarterectomy underwent OFDI scan during preoperative angiography. Atherosclerotic plaque specimens obtained from carotid endarterectomy were cut every 3-4 mm into 4-μm transverse cross-sections and stained with standard methods. Each cross-section was matched with OFDI, and histologically classified into either fibrous, calcific, pathological intimal thickening (PIT), and NC. Of 75 histologic cross-sections, 6 were categorized as fibrous (8%), 18 as calcific (24%), 9 as PIT (12%), and 42 as NC (56%). Tissues categorized as NC had significantly higher OFDI signal attenuation rates than the other tissues (p <0.001), followed by PIT, calcific, and fibrous tissues. The receiver operating characteristic analysis indicated that attenuation rates of >0.023 and >0.031 predicted the presence of NC and IPH with high areas under the curve of 0.91 and 0.88, respectively. OFDI provides potential capability for the detection of NCs with IPH of carotid artery plaques by quantitatively analyzing the attenuation rate.

Subclinical Liver Disease Is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n= 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P= 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P= 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR= 3.5; P= 0.01). In the United States cohort (n= 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (β= 0.28; P < 0.001), fibrofatty (β= 0.49; P < 0.001), and lipid-rich necrotic core (β= 0.28; P= 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis.

18Fluorodeoxyglucose uptake in relation to fat fraction and R2* in atherosclerotic plaques, using PET/MRI: a pilot study

Inflammation inside Atherosclerotic plaques represents a major pathophysiological process driving plaques towards rupture. Pre-clinical studies suggest a relationship between lipid rich necrotic core, intraplaque hemorrhage and inflammation, not previously explored in patients. Therefore, we designed a pilot study to investigate the feasibility of assessing the relationship between these plaque features in a quantitative manner using PET/MRI. In 12 patients with high-grade carotid stenosis the extent of lipid rich necrotic core and intraplaque hemorrhage was quantified from fat and R2* maps acquired with a previously validated 4-point Dixon MRI sequence in a stand-alone MRI. PET/MRI was used to measure 18F-FDG uptake. T1-weighted images from both scanners were used for registration of the quantitative Dixon data with the PET images. The plaques were heterogenous with respect to their volumes and composition. The mean values for the group were as follows: fat fraction (FF) 0.17% (± 0.07), R2* 47.6 s−1 (± 10.9) and target-to-blood pool ratio (TBR) 1.49 (± 0.48). At group level the correlation between TBR and FFmean was − 0.406, p 0.19 and for TBR and R2*mean 0.259, p 0.42. The lack of correlation persisted when analysed on a patient-by-patient basis but the study was not powered to draw definitive conclusions. We show the feasibility of analysing the quantitative relationship between lipid rich necrotic cores, intraplaque haemorrhage and plaque inflammation. The 18F-FDG uptake for most patients was low. This may reflect the biological complexity of the plaques and technical aspects inherent to 18F-FDG measurements.Trial registration: ISRCTN, ISRCTN30673005. Registered 05 January 2021, retrospectively registered.

Correlation Between Calcification Characteristics of Carotid Atherosclerotic Plaque and Plaque Vulnerability

PurposeTo investigate the relationship between calcification characteristics of carotid atherosclerotic plaque and lipid rich necrotic core (LRNC) and intraplaque hemorrhage (IPH).MethodsPatients with severe carotid stenosis undergoing carotid endarterectomy (CEA) were selected. Ultrasound and CT angiography (CTA) were performed to evaluate the calcification characteristics of the plaque before the surgery.ResultsA total of 142 patients were included and 142 pathological specimens of postoperative plaque were obtained accordingly. There were 78 plaques (54.9%) with LRNC and 41 (28.9%) with IPH. The plaque with LRNC had higher calcification rate (93.6%) compared with the plaque with IPH (87.8%). LRNC was often found in multiple calcification (P = 0.003) and mixed type calcification (P = 0.001). Multiple calcification was more likely to combine with IPH (P = 0.008), while simple basal calcification was not likely to combine IPH (P = 0.002). Smaller granular calcification was more likely to be associated with IPH (P < 0.05). In multivariate regression analysis of IPH and calcification characteristics, simple basal calcification was still a protective factor for IPH (OR, 0.25; 95% CI, 0.09–0.66; P = 0.005), while multiple calcification was closely related to the occurrence of IPH (OR, 3.58; 95% CI, 1.49–8.61; P = 0.004).ConclusionCalcification characteristics of carotid atherosclerotic plaques are closely related to the vulnerability of plaques, especially multiple calcification and mixed type calcification.

Intra-plaque Hemorrhage And Lipid-rich Necrotic Core May Be Objectively Quantified Using Histopathologic Correlates Automatically From CTA

Introduction: Whereas CTA is increasingly appreciated for atherosclerosis phenotyping, the analyses are often subjective or qualitative. Methods for specific tissue characterization using histopathologic correlates have recently been reported. We extend this here to demonstrate accurate quantitation of both lipid-rich necrotic core (LRNC) and intraplaque hemorrhage (IPH), with the aim to reliably discriminate between them.

Reduction of Lipid-Core Burden Index in Nonculprit Lesions at Follow-Up after ST-Elevation Myocardial Infarction: A Randomized Study of Bioresorbable Vascular Scaffold versus Optimal Medical Therapy.

Background Non-flow-limiting nonculprit lesions (NCL) that contain a large lipid-rich necrotic core (nonculprit lipid-rich plaques (NC-LRP)) are most likely to cause recurrent acute coronary syndrome after ST-elevation myocardial infarction (STEMI). Near-infrared spectroscopy (NIRS) detects LRPs using the maximum 4 mm lipid-core burden index (maxLCBI4 mm). Few data are available regarding NIRS-guided therapy of these NC-LRPs, which are a potential target for preventive stenting. Bioresorbable vascular scaffold (BVS) provides local drug delivery and could facilitate plaque passivation after resorption. This study sought to assess the safety of BVS implantation in NC-LRPs and its efficacy in reducing maxLCBI4 mm at 2-year follow-up after STEMI. Methods and Results In total, 33 non-flow-limiting NCLs from 29 STEMI patients were included in this study. Of these, 15 were LRPs and were randomly assigned to either the BVS + optimal medical therapy (OMT) arm (group 1; N = 7) or the OMT arm (group 2; N = 8). At baseline, there were no differences in plaque characteristics between groups (fractional flow reserve: 0.85 ± 0.04 vs. 0.89 ± 0.06; diameter stenosis (DS): 43.4 ± 8 vs. 40.1 ± 10.7%; plaque burden 54.98 ± 5.8 vs. 49.76 ± 8.31%; and maxLCBI4 mm 402 [348; 564] vs. 373 [298; 516]; p=NS for all comparisons between groups 1 and 2, respectively). Seven BVSs were implanted 3 ± 1 days after STEMI in six patients, without complications. At angiographic follow-up (712 [657; 740] days), a significant and similar reduction of maxLCBI4 mm was observed in both groups, with a median change of 306 [257; 377] in group 1 vs. 300 [278; 346] in group 2 (p=0.44). DS was significantly lower in group 1 vs. group 2 (19.8 ± 7 vs. 41.7 ± 13%, p=0.003), while plaque burden remained unchanged in both groups. Overall survival was 100%, target lesion failure was 13%, and stent thrombosis was 0%. Conclusions BVS + OMT and OMT appear as similarly safe and effective in reducing maxLCBI4mm in NC-LRPs at 2-year follow-up after STEMI.

Lipoprotein(a) levels and atherosclerotic plaque characteristics in the carotid artery: The Plaque at RISK (PARISK) study

Background and aimsLipoprotein(a) is an independent risk factor for cardiovascular disease and recurrent ischemic stroke. Lipoprotein(a) levels are known to be associated with carotid artery stenosis, but the relation of lipoprotein(a) levels to carotid atherosclerotic plaque composition and morphology is less known. We hypothesize that higher lipoprotein(a) levels and lipoprotein(a)-related SNPs are associated with a more vulnerable carotid plaque and that this effect is sex-specific. MethodsIn 182 patients of the Plaque At RISK study we determined lipoprotein(a) concentrations, apo(a) KIV-2 repeats and LPA SNPs. Imaging characteristics of carotid atherosclerosis were determined by MDCTA (n = 161) and/or MRI (n = 171). Regressions analyses were used to investigate sex-stratified associations between lipoprotein(a) levels, apo(a) KIV-2 repeats, and LPA SNPs and imaging characteristics. ResultsLipoprotein(a) was associated with presence of lipid-rich necrotic core (LRNC) (aOR = 1.07, 95% CI: 1.00; 1.15), thin-or-ruptured fibrous cap (TRFC) (aOR = 1.07, 95% CI: 1.01; 1.14), and degree of stenosis (β = 0.44, 95% CI: 0.00; 0.88). In women, lipoprotein(a) was associated with presence of intraplaque hemorrhage (IPH) (aOR = 1.25, 95% CI: 1.06; 1.61). In men, lipoprotein(a) was associated with degree of stenosis (β = 0.58, 95% CI: 0.04; 1.12). Rs10455872 was significantly associated with increased calcification volume (β = 1.07, 95% CI: 0.25; 1.89) and absence of plaque ulceration (aOR = 0.25, 95% CI: 0.04; 0.93). T3888P was associated with absence of LRNC (aOR = 0.36, 95% CI: 0.16; 0.78) and smaller maximum vessel wall area (β = -10.24, 95%CI: -19.03; -1.44). ConclusionsIn patients with symptomatic carotid artery stenosis, increased lipoprotein(a) levels were associated with degree of stenosis, and IPH, LRNC, and TRFC, known as vulnerable plaque characteristics, in the carotid artery. T3888P was associated with lower LRNC prevalence and smaller maximum vessel wall area. Further research in larger study populations is needed to confirm these results.

Comparing Symptomatic and Asymptomatic Carotid Artery Atherosclerosis in Patients With Bilateral Carotid Vulnerable Plaques Using Magnetic Resonance Imaging.

We compared plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid vulnerable plaques using magnetic resonance imaging (MRI). Participants (n = 67; mean age: 65.8 ± 7.7 years, 61 males) with bilateral carotid vulnerable plaques were included. Vulnerable plaques were characterized by intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), or fibrous cap rupture (FCR) on MRI. Symptomatic vulnerable plaques showed greater plaque burden, LRNC volume (median: 221.4 vs 134.8 mm3, P = .003), IPH volume (median: 32.2 vs 22.5 mm3, P = .030), maximum percentage (Max%) LRNC (median: 51.3% vs 41.8%, P = .002), Max%IPH (median: 13.4% vs 9.5%, P = .022), cumulative slices of LRNC (median: 10 vs 8, P = .005), and more juxtaluminal IPH and/or thrombus (29.9% vs 6.0%, P = .001) and FCR (37.3% vs 16.4%, P = .007) than asymptomatic ones. After adjusting for plaque burden, differences in juxtaluminal IPH and/or thrombus (odds ratio [OR]: 5.49, 95% CI: 1.61-18.75, P = .007) and FCR (OR: 2.90, 95% CI: 1.16-7.24, P = .022) between bilateral sides remained statistically significant. For patients with bilateral carotid vulnerable plaques, symptomatic plaques had greater burden, more juxtaluminal IPH and/or thrombus, and FCR compared with asymptomatic ones. The differences in juxtaluminal IPH and/or thrombus and FCR between bilateral sides were independent of plaque burden.

Extracranial Vascular Disease: Carotid Stenosis and Plaque Imaging.

Carotid atherosclerosis is an important contributor to ischemic stroke. When imaging carotid atherosclerosis, it is essential to describe both the degree of luminal stenosis and specific plaque characteristics because both are risk factors for cerebrovascular ischemia. Carotid atherosclerosis can be accurately assessed using multiple imaging techniques, including ultrasonography, computed tomography angiography, and magnetic resonance angiography. By understanding the underlying histopathology, the specific plaque characteristics on each of these imaging modalities can be appreciated. This article briefly describes some of the most commonly encountered plaque features, including plaque calcification, intraplaque hemorrhage, lipid-rich necrotic core, and plaque ulceration.

Sex Differences in Carotid Plaque Composition in Patients With Embolic Stroke of Undetermined Source.

BackgroundWe examined sex differences in nonstenotic carotid plaque composition in patients with embolic stroke of undetermined source (ESUS).Methods and ResultsPatients with anterior circulation ischemic stroke imaged with neck computed tomographic angiography who met criteria for ESUS or had atrial fibrillation were identified. Patients with atrial fibrillation were included as a negative control. Semiautomated plaque quantification software analyzed carotid artery bifurcations. Plaque subcomponent (calcium, intraplaque hemorrhage [IPH], and lipid rich necrotic core) volumes were compared by sex and in paired analyses of plaque ipsilateral versus contralateral to stroke. Multivariate linear regressions tested for associations. Ninety‐four patients with ESUS (55% women) and 95 patients with atrial fibrillation (47% women) were identified. Men with ESUS showed significantly higher volumes of calcified plaque (63.9 versus 19.6 mm3, P<0.001), IPH (9.4 versus 3.3 mm3, P=0.008) and a IPH/lipid rich necrotic core ratio (0.17 versus 0.07, P=0.03) in carotid plaque ipsilateral to stroke side than women. The atrial fibrillation cohort showed no significant sex differences in plaque volumes ipsilateral to stroke. Multivariate analyses of the ESUS cohort showed male sex was associated with IPHipsi (β=0.49; 95% CI, 0.11–0.87) and calciumipsi (β=0.78; 95% CI, 0.33–1.23). Paired plaque analyses in men with ESUS showed significantly higher calcified plaque (63.9 versus 34.1 mm3, P=0.03) and a trend of higher IPHipsi (9.4 versus 7.5 mm3, P=0.73) and lipid rich necrotic coreipsi (59.0 versus 48.4 mm3, P=0.94) volumes.ConclusionsSex differences in carotid plaque composition in ESUS suggest the possibility of a differential contribution of nonstenosing carotid plaque as a stroke mechanism in men versus women.

Association between coexisting intracranial artery and extracranial carotid artery atherosclerotic diseases and ipsilateral cerebral infarction: a Chinese Atherosclerosis Risk Evaluation (CARE-II) study

BackgroundTo evaluate the association between coexisting intracranial and extracranial carotid artery atherosclerotic diseases and ipsilateral acute cerebral infarct (ACI) in symptomatic patients by using magnetic resonance (MR) vessel wall imaging.MethodsSymptomatic...

Focal pericoronary adipose tissue attenuation is related to plaque presence, plaque type, and stenosis severity in coronary CTA

ObjectivesTo investigate the association of pericoronary adipose tissue mean attenuation (PCATMA) with coronary artery disease (CAD) characteristics on coronary computed tomography angiography (CCTA).MethodsWe retrospectively investigated 165 symptomatic patients who underwent third-generation dual-source CCTA at 70kVp: 93 with and 72 without CAD (204 arteries with plaque, 291 without plaque). CCTA was evaluated for presence and characteristics of CAD per artery. PCATMA was measured proximally and across the most severe stenosis. Patient-level, proximal PCATMA was defined as the mean of the proximal PCATMA of the three main coronary arteries. Analyses were performed on patient and vessel level.ResultsMean proximal PCATMA was −96.2 ± 7.1 HU and −95.6 ± 7.8HU for patients with and without CAD (p = 0.644). In arteries with plaque, proximal and lesion-specific PCATMA was similar (−96.1 ± 9.6 HU, −95.9 ± 11.2 HU, p = 0.608). Lesion-specific PCATMA of arteries with plaque (−94.7 HU) differed from proximal PCATMA of arteries without plaque (−97.2 HU, p = 0.015). Minimal stenosis showed higher lesion-specific PCATMA (−94.0 HU) than severe stenosis (−98.5 HU, p = 0.030). Lesion-specific PCATMA of non-calcified, mixed, and calcified plaque was −96.5 HU, −94.6 HU, and −89.9 HU (p = 0.004). Vessel-based total plaque, lipid-rich necrotic core, and calcified plaque burden showed a very weak to moderate correlation with proximal PCATMA.ConclusionsLesion-specific PCATMA was higher in arteries with plaque than proximal PCATMA in arteries without plaque. Lesion-specific PCATMA was higher in non-calcified and mixed plaques compared to calcified plaques, and in minimal stenosis compared to severe; proximal PCATMA did not show these relationships. This suggests that lesion-specific PCATMA is related to plaque development and vulnerability.Key Points• In symptomatic patients undergoing CCTA at 70 kVp, PCATMAwas higher in coronary arteries with plaque than those without plaque.• PCATMAwas higher for non-calcified and mixed plaques compared to calcified plaques, and for minimal stenosis compared to severe stenosis.• In contrast to PCATMAmeasurement of the proximal vessels, lesion-specific PCATMAshowed clear relationships with plaque presence and stenosis degree.