Symptomatic Carotid Atherosclerosis Research Articles

Characteristics of the gut microbiota of patients with symptomatic carotid atherosclerotic plaques positive for bacterial genetic material.

The gut microbiota (GM) is believed to be closely associated with symptomatic carotid atherosclerosis (SCAS), yet more evidence is needed to substantiate the significant role of GM in SCAS. This study, based on the detection of bacterial DNA in carotid plaques, explores the characteristics of GM in SCAS patients with plaque bacterial genetic material positivity, aiming to provide a reference for subsequent research. We enrolled 27 healthy individuals (NHF group) and 23 SCAS patients (PFBS group). We utilized 16S rDNA V3-V4 region gene sequencing to analyze the microbiota in fecal samples from both groups, as well as in plaque samples from the carotid bifurcation extending to the origin of the internal carotid artery in all patients. Our results indicate significant differences in the gut microbiota (GM) between SCAS patients and healthy individuals. The detection rate of bacterial DNA in plaque samples was approximately 26%. Compared to patients with negative plaques (PRSOPWNP group), those with positive plaques (PRSOPWPP group) exhibited significant alterations in their GM, particularly an upregulation of 11 bacterial genera (such as Klebsiella and Streptococcus) in the gut, which were also present in the plaques. In terms of microbial gene function prediction, pathways such as Fluorobenzoate degradation were significantly upregulated in the GM of patients with positive plaques. In summary, our study is the first to identify significant alterations in the gut microbiota of patients with positive plaques, providing crucial microbial evidence for further exploration of the pathogenesis of SCAS.

Frailty in relation to the risk of carotid atherosclerosis and cardiovascular events in Chinese community-dwelling older adults: A five-year prospective cohort study

ObjectiveTo investigate the frailty, as estimated by accumulated health deficits, in association with the symptomatic carotid atherosclerosis and in relation to five-year cardiovascular (CVD) outcomes. MethodsThis is a five-year prospective cohort study. Secondary analysis of data from the Beijing Longitudinal Study on Aging. Community-dwelling people aged 55+ years (n = 1257) have been followed between 2009 and 2014, and having carotid ultrasonography examinations with no CVD events at baseline. Frailty was quantified using the deficit accumulation-based frailty index (FI), constructed from 37 health deficits assessed at baseline. The association between the degree of frailty and carotid atherosclerosis was examined using odds ratios (OR) with multivariate logistic regression analyses. Effects of frailty on the probability of five-year cardiovascular events and mortality were evaluated using Cox proportional hazard ratios (HR). The analyses were adjusted for demographics, baseline carotid atherosclerosis status, and CVD risk factors. ResultsThe FI showed characteristic properties and was independently associated with the major carotid atherosclerosis symptoms, including carotid artery intima-media thickening (the most frail vs. the least frail: OR = 4.39: 1.98–7.82), carotid plaque (OR = 3.41: 1.28–6.54), and carotid plaque stability (OR = 1.19, 95 % CI: 1.01–3.59). Compared with the least frail, the most frail individuals were more likely to develop a cardiovascular event in five years, including myocardial infarction (HR = 3.38, 95 % CI = 1.84–6.19), stroke (HR = 1.26, 95 % CI = 1.00–5.87), CVD death (HR = 6.33, 95 % CI = 1.69–11.02), and all-cause death (HR = 5.95, 95 % CI = 2.74–8.95). ConclusionDeficit accumulation was closely associated with carotid atherosclerosis risks and strongly predicted five-year CVD events. The frailty index can be used to help identify older adults at high risks of CVD for improved preventive healthcare.

Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis

Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092–2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability.

Increased plasma levels of non-sugar sweeteners in patients with symptomatic carotid atherosclerosis

Purpose. The non-sugar sweeteners acesulfame K and saccharin are considered safe, but there is conflicting evidence on their effects on cardiovascular health. Materials and methods. In this explorative pilot study, we measured plasma levels of acesulfame K and saccharin in 15 patients with symptomatic carotid atherosclerosis, 18 asymptomatic patients and 15 control subjects. Fecal microbiota and short-chain fatty acids were analyzed. Dietary and medical history was assessed. Results. Symptomatic patients had higher levels of acesulfame K and saccharin compared to controls. Acesulfame K was associated with increased leukocyte count. Saccharin was associated with more severe carotid stenosis, as well as lower fecal butyric acid.

Localized Elevation of Wall Shear Stress Is Linked to Recent Symptoms in Patients with Carotid Stenosis

Background: Estimation of symptomatic and asymptomatic carotid atherosclerosis differences can be the basis for prevention and management of carotid artery stenosis disease. In clinical practice, carotid plaque vulnerability is assessed only on the basis of luminal stenosis. However, the evolution of carotid plaque from an asymptomatic state to a symptomatic one is a complex process and the underlying hemodynamic mechanisms are unknown. We aimed to investigate the differences in hemodynamic parameters between patients with recently symptomatic carotid stenosis and asymptomatic ones. Methods: Hemodynamic simulations were performed on 26 carotid plaques from 25 patients with carotid artery stenosis ≥50%, 16 of whom had recent cerebrovascular ischemic events. Using human-specific flow parameters and 3D reconstruction of carotid computed tomography angiography images, we assessed hemodynamic characteristics such as wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index, and relative residence time (RRT) during the cardiac cycle in patients with and without symptoms. Results: We found that symptomatic carotid stenosis patients had greater local TAWSS (99.59 ± 26.29 vs. 60.40 ± 20.46 dyn/cm², p = 0.0007) and maximal WSS (116.65 ± 39.11 vs. 68.28 ± 23.67 dyn/cm², p = 0.003), but lower RRT (0.019 ± 0.006 vs. 0.013 ± 0.069 s, p = 0.049), than asymptomatic patients, but this hemodynamic difference was not associated with carotid stenosis severity (p = 0.70). Patients with transient ischemic attack (TIA) or stroke had higher local TAWSS and WSSmax than patients with asymptomatic stenosis (p < 0.05). Subgroup analysis showed that there was no statistical difference in local hemodynamic variables between TIA and stroke patients with carotid artery stenosis. Conclusions: Patients with carotid artery stenosis are more likely to experience acute ischemic cerebrovascular accidents if they have higher WSS. Simultaneous assessment with hemodynamic parameters like WSS along with stenosis severity may aid risk stratification in patients with asymptomatic carotid artery stenosis.

Reliability and Value of 3D Sequential QUantitative T1 -T2 -T2 * MAppings (SQUMA) MR Multi-Parametric Imaging in Characterizing Carotid Artery Atherosclerosis.

T1 , T2 , and T2 * mappings are seldom performed in a single examination, and their values in evaluating symptomatic atherosclerosis are lacking. To perform three-dimensional (3D) quantitative T1 , T2 , and T2 * mappings (SQUMA) multi-parametric imaging for carotid vessel wall and evaluate its reliability and value in assessing carotid atherosclerosis. Prospective. Eight healthy subjects and 20 patients with symptomatic carotid atherosclerosis. 3 T, SQUMA imaging T1 -, T2 -, and T2 *-mapping, multi-contrast vessel wall imaging including T1 - and T2 -weighted, time-of-flight, and SNAP sequences. SQUMA was acquired in all subjects and multi-contrast images were acquired in healthy subjects. T1 , T2 , and T2 * values and lumen area (LA), wall area (WA), mean wall thickness (MeanWT), and normalized wall index (NWI) of carotid arteries were measured. SQUMA and multi-contrast measurements were compared in healthy subjects and differences in SQUMA measurements between healthy subjects and patients were assessed. The discriminative value of SQUMA measurements for symptomatic vessel was determined. Paired t or Wilcoxon signed-rank test, independent t or Mann-Whitney U test, area under the receiver operating characteristic curve (AUC), intraclass correlation coefficients, and Bland-Altman plots. Statistically significant level, P < 0.05. There were no significant differences in LA (P=0.340), WA (P=0.317), MeanWT (P=0.088), and NWI (P=0.091) of carotid arteries between SQUMA and multi-contrast vessel wall images. The values of T2 (50.9 ± 2.9msec vs. 44.5 ± 4.2msec), T2 * (28.2 ± 4.3msec vs. 24.7 ± 2.6msec), WA (23.7 ± 4.6 mm2 vs. 36.2 ± 7.7 mm2 ), MeanWT (0.99 ± 0.05 mm vs. 1.50 ± 0.28 mm), and NWI (40.7 ± 3.0% vs. 53.8 ± 5.4%) of carotid arteries in healthy subjects were significantly different from those in atherosclerotic patients. The combination of quantitative T1 , T2 , and T2 * values and MeanWT showed greatest AUC (0.81; 95% CI: 0.65-0.92) in discriminating symptomatic vessels. Carotid MR 3D quantitative multi-parametric imaging of SQUMA enables acquisition of T1 , T2 , and T2 * maps, reliably measuring carotid morphology and discriminating carotid symptomatic atherosclerosis. 2 TECHNICAL EFFICACY: Stage 2.

Dose-Dependent Association of Inflammatory Cytokines with Carotid Atherosclerosis in Transient Ischaemic Attack: Implications for Clinical Trials

Introduction: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25–30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. Methods: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1β, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. Results: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1β, p_trend = 0.03; IL-6, p_trend < 0.0001; IL-8, p_trend = 0.01; interferon (IFN)-γ, p_trend = 0.005; TNF-α, p_trend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01–1.05], p = 0.003). Conclusion: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.

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.

Mass Spectrometry Imaging as a Tool to Investigate Region Specific Lipid Alterations in Symptomatic Human Carotid Atherosclerotic Plaques.

Atherosclerosis is characterized by fatty plaques in large and medium sized arteries. Their rupture can causes thrombi, occlusions of downstream vessels and adverse clinical events. The investigation of atherosclerotic plaques is made difficult by their highly heterogeneous nature. Here we propose a spatially resolved approach based on matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging to investigate lipids in specific regions of atherosclerotic plaques. The method was applied to a small dataset including symptomatic and asymptomatic human carotid atherosclerosis plaques. Tissue sections of symptomatic and asymptomatic human carotid atherosclerotic plaques were analyzed by MALDI mass spectrometry imaging (MALDI MSI) of lipids, and adjacent sections analyzed by histology and immunofluorescence. These multimodal datasets were used to compare the lipid profiles of specific histopathological regions within the plaque. The lipid profiles of macrophage-rich regions and intimal vascular smooth muscle cells exhibited the largest changes associated with plaque outcome. Macrophage-rich regions from symptomatic lesions were found to be enriched in sphingomyelins, and intimal vascular smooth muscle cells of symptomatic plaques were enriched in cholesterol and cholesteryl esters. The proposed method enabled the MALDI MSI analysis of specific regions of the atherosclerotic lesion, confirming MALDI MSI as a promising tool for the investigation of histologically heterogeneous atherosclerotic plaques.

Bilaterally Asymmetric Associations Between Extracranial Carotid Artery Atherosclerosis and Ipsilateral Middle Cerebral Artery Stenosis in Symptomatic Patients: A CARE-II Study.

To determine the bilaterally asymmetrical associations between extracranial carotid artery atherosclerosis and ipsilateral middle cerebral artery (MCA) stenosis in symptomatic patients using magnetic resonance vessel wall imaging. Approach and Results: Patients with symptomatic carotid artery atherosclerosis were recruited from the Chinese Atherosclerosis Risk Evaluation, a multicenter study. All subjects underwent intracranial magnetic resonance angiography and extracranial carotid artery magnetic resonance imaging. Severe stenosis (stenosis ≥50%) of MCA, carotid moderate-to-severe stenosis (stenosis ≥50%), plaque compositions, and high-risk plaque on symptomatic side were evaluated in all subjects. Associations between ipsilateral MCA stenosis and extracranial carotid plaque features were evaluated. A total of 363 patients (mean age: 61.2±10.4 years old; 254 males) were included. In the left symptomatic cerebrovascular group (n=186), carotid moderate-to-severe stenosis (odds ratio [OR], 3.00 [95% CI, 1.03-8.79]; P=0.045), intraplaque hemorrhage (OR, 3.68 [95% CI, 1.21-11.19]; P=0.021), fibrous cap rupture (OR, 5.70 [95% CI, 1.60-20.31]; P=0.007), and high-risk plaque (OR, 2.95 [95% CI, 1.19-7.35]; P=0.020) were significantly associated with ipsilateral severe MCA stenosis, after adjusting for confounding factors. In the right symptomatic cerebrovascular group (n=177), severe MCA stenosis was significantly associated with ipsilateral carotid moderate-to-severe stenosis (OR, 3.98 [95% CI, 1.54-10.32]; P=0.004) but not with other extracranial carotid plaque features (all P>0.05), after adjusting for confounding factors. In the symptomatic arteries, vulnerable plaque features are independently associated with ipsilateral severe MCA stenosis on the left side, but this association is not found on the right side, indicating the associations of atherosclerotic disease between intracranial and extracranial carotid arteries are asymmetrical.

Micro-structural white matter abnormalities and cognitive impairment in asymptomatic carotid plaque patients: A DTI study using TBSS analysis

BackgroundIt has been shown that symptomatic or severe carotid atherosclerosis is closely related to cognitive impairment and brain white matter damage. However, there is still a lack of effective and non-invasive imaging biomarkers to identify early high-risk cerebrovascular diseases. Therefore, the purpose of this study is to explore the integrity of brain white matter and cognitive impairment in patients with asymptomatic carotid plaques by using imaging technology. MethodsAll subjects were from a project of Stroke Risk Screening and Prevention and were defined as stroke high-risk patients (with three or more stroke risk factors). Tract-based spatial statistics (TBSS) based on diffusion tensor imaging (DTI) was used to analyze the whole brain white matter abnormalities in 61 patients with carotid artery plaque and in 40 healthy controls. At the same time, the general clinical data between the two groups were compared, such as age, gender, smoking, hypertension and cognitive function scores etc. Furthermore, the plaque group was divided into the have-hyperintensities group and the no-hyperintensities group to compare their microstructure of white matter injuries. ResultsThe cognitive scores of plaque group were significantly lower than that of control group. We found that when plaque group and control group were compared, no white matter fiber tracts with difference was found in FA, MD, AD and RD. However, the decrease of FA and the increase of RD were found in some white matter regions (P < 0.05) when comparing the have-hyperintensities group and the no-hyperintensities group. These white matter regions included anterior thalamic radiation, corticospinal tract, cingulum (cingulate gyrus), forceps minor, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus. What’s more, there were significant differences in blood pressure between the two groups. ConclusionThe cognitive function of patients with early high-risk cerebrovascular diseases (asymptomatic carotid plaques) has a downward trend. TBSS based on DTI can help to find out the actual damage of brain white matter in patients with early carotid plaque, and reflect the early pathological changes from the micro level.

Metabolic Profiling of Carotid Atherosclerosis

Introduction: Stroke is a leading cause of death and disability worldwide. Approximately one quarter of all strokes are secondary to carotid atherosclerosis. There is a clinical need to improve risk stratification of carotid atherosclerosis, to better target surgical or interventional therapy and prevent stroke. This study aimed to determine diagnostic biomarkers of high-risk carotid atherosclerosis, and ensure the validity of such markers in the presence of alternative phenotypes of atherosclerotic disease. Methods: 150 patients were recruited according to the following criteria:1.Symptomatic >50% carotid stenosis2.Non-carotid stroke/TIA3.Asymptomatic >50% carotid stenosis4.Asymptomatic controls with <50% carotid stenosis5.Abdominal aortic aneurysm6.Intermittent claudication Disease groups were matched for age, gender, cardiovascular risk factors, haematological parameters, renal function and lipid status. Blood and urine was collected from all patients and analysed through global metabolic profiling (1H-NMR Spectroscopy, HILIC-Mass Spectrometry and Lipid Profiling-Mass Spectrometry). Acquired spectra were compared across groups using computational multivariate data analysis to determine markers of high-risk carotid atherosclerosis. Results: Statistical models derived from urinary spectra proved stronger than serum datasets, in particular with HILIC-Mass Spectrometry (positive ionisation mode). Application of computational OPLS-DA resulted in discrimination of symptomatic carotid atherosclerosis from asymptomatic disease, aneurysmal disease, and intermittent claudication. Differentiating metabolites span a vast array of compounds including lipid derivatives, amino acid derivatives and nucleotide derivatives. Conclusion: This is the first study to identify urinary metabolic biomarkers of high-risk carotid atherosclerosis, differentiating symptomatic carotid atherosclerosis from asymptomatic disease, and aneurysmal and peripheral arterial disease. Targeted temporal studies are now required for clinical validation and to determine the variation of acute biomarkers with time.

Molecular imaging of carotid artery atherosclerosis with PET: a systematic review.

To conduct a systematic review of articles on PET imaging of carotid atherosclerosis with emphasis on clinical usefulness and comparison with other imaging modalities. Research articles reporting carotid artery PET imaging with different radiotracers until 30 November 2018 were systematically searched for in Medline/PubMed, Scopus, Embase, Google Scholar, and Cochrane Library. Duplicates were removed, and editorials, case studies, and investigations on feasibility or reproducibility of PET imaging and of patients with end-stage diseases or immunosuppressive medications were omitted. After quality assessment of included articles using Joanna Briggs Institute checklists, all eligible articles were reviewed. Of 1718 primary hits, 53 studies comprising 4472 patients, aged 47-91years (78.8% males), were included and grouped under the following headlines: diagnostic performance, risk factors, laboratory findings, imaging modalities, and treatment. 18F-fluorodeoxyglucose (FDG) (49/53) and 18F-sodium fluoride (NaF) (5/53) were the most utilized tracers to visualize carotid wall inflammation and microcalcification, respectively. Higher carotid FDG uptake was demonstrated in patients with than without symptomatic carotid atherosclerosis. Normal carotid arteries presented with the lowest FDG uptake. In symptomatic atherosclerosis, carotid arteries ipsilateral to a cerebrovascular event had higher FDG uptake than the contralateral carotid artery. FDG uptake was significantly associated with age, male gender, and body mass index in healthy individuals, and in addition with arterial hypertension, hypercholesterolemia, and diabetes mellitus in patients. Histological assessment indicated a strong correlation between microcalcification and NaF uptake in symptomatic patients. Histological evidence of calcification correlated inversely with FDG uptake, which was associated with increased macrophage and CD68 count, both accounting for increased local inflammatory response. FDG-PET visualizes the inflammatory part of carotid atherosclerosis enabling risk stratification to a certain degree, whereas NaF-PET seems to indicate long-term consequences of ongoing inflammation by demonstrating microcalcification allowing discrimination of atherosclerotic from normal arteries and suggesting clinically significant carotid atherosclerosis.

Cartilage Oligomeric Matrix Protein Associates With a Vulnerable Plaque Phenotype in Human Atherosclerotic Plaques.

Background and Purpose- Extracellular matrix proteins are important in atherosclerotic disease by influencing plaque stability and cellular behavior but also by regulating inflammation. COMP (cartilage oligomeric matrix protein) is present in healthy human arteries and expressed by smooth muscle cells. A recent study showed that transplantation of COMP-deficient bone marrow to apoE-/- mice increased atherosclerotic plaque formation, indicating a role for COMP also in bone marrow-derived cells. Despite the evidence of a role for COMP in murine atherosclerosis, knowledge is lacking about the role of COMP in human atherosclerotic disease. Methods- In the present study, we investigated if COMP was associated with a stable or a vulnerable human atherosclerotic plaque phenotype by analyzing 211 carotid plaques for COMP expression using immunohistochemistry. Results- Plaque area that stained positive for COMP was significantly larger in atherosclerotic plaques associated with symptoms (n=110) compared with asymptomatic plaques (n=101; 9.7% [4.7-14.3] versus 5.6% [2.8-9.8]; P=0.0002). COMP was positively associated with plaque lipids (r=0.32; P=0.000002) and CD68 cells (r=0.15; P=0.036) but was negatively associated with collagen (r=-0.16; P=0.024), elastin (r=-0.14; P=0.041), and smooth muscle cells (r=-0.25; P=0.0002). COMP was positively associated with CD163 (r=0.37; P=0.00000006), a scavenger receptor for hemoglobin/haptoglobin and a marker of Mhem macrophages, and with intraplaque hemorrhage, measured as glycophorin A staining (r=0.28; P=0.00006). Conclusions- The present study shows that COMP is associated to symptomatic carotid atherosclerosis, CD163-expressing cells, and a vulnerable atherosclerotic plaque phenotype in humans.

Abstract 42: CAS versus CEA Treatment Differences in Long-Term Outcomes and Post-Procedural Durability: the Carotid Stenosis Trialist Collaboration (CSTC)

Introduction: A 3.4% (95% CI: 2.1% to 4.7%) higher peri-procedural stroke and death risk has been previously documented for those treated with carotid artery stenting (CAS) relative to those treated with carotid endarterectomy (CEA). However, the CAS versus CEA treatment differences in long-term outcomes and the post-procedure durability have not been described. Methods: Data from the 4 largest CAS-versus-CEA randomized trials for treatment of symptomatic carotid atherosclerosis (EVA-3S, SPACE, ICSS, and CREST) were pooled, and treatment differences assessed for the outcome of any stroke or death during a 120-day peri-procedural period, plus ipsilateral stroke afterward. Results: Long-term follow-up was analysed for 4754 patients. Median length of follow-up across the studies ranged from 2.0 to 6.9 years, with 88 peri-procedural and 55 post-procedural events among those CEA-treated, and 169 and 64 for those CAS-treated. After the peri-procedural period, the annual rates of stroke following CAS was 0.6% (95% CI: 0.5 to 0.8) and following CEA 0.6% (95% CI: 0.5 to 0.8), resulting in non-significant durability differences of less than 1% over the period extending up to 9 years (see Table). The previously-documented 3.4% higher peri-procedural event rate in the CAS group contributed to a significant 3.1% (95% CI: 1.6% to 4.7%) treatment difference at 1-year, and the aforementioned similar durability implied that this significant difference remained relatively constant over the period extending up to 9 years (see table). Conclusions: The post-procedure durability of CAS and CEA were similar, both with event rates below 1%. The similarity of post-procedure events rates implies that the previously-documented higher peri-procedural in the CAS group is “carried forward” with a higher risk of outcomes extending to 9-years.

Analysis of 18F-Fluorodeoxyglucose and 18F-Fluoride Positron Emission Tomography in Korean Stroke Patients with Carotid Atherosclerosis.

ObjectiveThe objective of this study was to analyze uptake patterns and intensity of 18F-fluorodeoxyglucose (FDG) and 18F-sodium fluoride (NaF) radioligands in carotid atheroma among stroke patients according to carotid atheroma characteristics.MethodsBetween September 2015 and January 2017, consecutive acute stroke or transient ischemic attack patients with 50% or more proximal internal carotid artery stenosis on brain computed tomography angiography were prospectively enrolled. All patients received FDG and NaF positron emission tomography (PET) evaluation when their neurological status was stabilized. Uptake values of FDG and NaF were compared by target to blood ratio (TBR) according to the calcification burden, atheroma volume and the presence of a necrotic core of carotid atheroma.ResultsA total of 18 patients with 36 carotid arteries were finally enrolled, with 10 patients diagnosed as acute cerebral infarction due to symptomatic carotid stenosis. FDG uptake at symptomatic carotid arteries was significantly more increased than that at asymptomatic arteries (TBR: 1.17±0.23 vs. 1.01±0.15, Mann-Whitney U-test, p=0.02), but NaF uptake was not different (TBR: 1.38±0.49 vs. 1.51±0.40, p=0.40). In terms of calcification degree, NaF uptake increased as calcification burden increased (none, 1.28±0.36; spotty, 1.29±0.29; linear, 1.74±0.44; analysis of variance, p=0.02).ConclusionCarotid evaluation by FDG is superior to NaF PET in the detection of symptomatic carotid atherosclerosis among stroke patients. NaF PET uptake reflects the overall calcification burden.

IP127. Risk Factors for Major Adverse Clinical Events After Carotid Endarterectomy Based on Patient Age and Symptoms

Carotid endarterectomy (CEA) is a well-established surgical procedure in the treatment of symptomatic and asymptomatic carotid atherosclerosis. We reviewed the American College of Surgeons National Surgical Quality Improvement Program database to assess which factors contribute to major adverse clinical events (MACEs) in the 30-day postoperative period. The American College of Surgeons National Surgical Quality Improvement Program database was queried among all participating institutions for CEAs performed in 2011 to 2015. Patients’ demographic data, comorbid conditions, preprocedure medication use, and operative variables were analyzed using multivariate logistic regression analysis to determine predictors of postoperative MACEs. There were 17,888 patients who underwent CEA analyzed; the patients were grouped by age (<75 and ≥75 years old) and whether they presented symptomatically (SYM) or asymptomatically (AS) before the procedure. For AS patients <75 years, the rate of stroke, myocardial infarction (MI), death, and MACEs was 1.8%, 1.6%, 0.4%, and 3.6%, respectively; for patients ≥75 years, rates were 1.7%, 2.3%, 0.7%, and 4.3%. The rate of MI was significantly higher in older patients (P = .0133). The odds of postoperative stroke was 73% higher (P < .0011) in diabetics, 57% higher (P = .0109) with American Society of Anesthesiologists (ASA) score 4 or 5, and 34% higher with operative time >2.5 hours (P = .0189). SYM patients ≥75 years had 1.1 times higher risk of postoperative stroke if they had insulin-dependent diabetes (P = .0148). Reintubation and reoperation were associated with increased risk of postoperative stroke in both age groups, whether SYM or AS (P < .0001), as well as postoperative MI (P < .0001). AS patients <75 years had higher likelihood of postoperative MI if they had history of congestive heart failure (P = .0257) and operative time >2.5 hours (P = .0033). SYM patients ≥75 years had 46% higher likelihood of postoperative MI if operative time >2.5 hours (P = .0023). Mortality was higher in AS patients <75 years with ASA score 4 or 5 (P = .0006) and those ≥75 years (P = .0072) and in patients who were reintubated (P < .0001). In SYM patients <75 years, the rate of stroke, MI, death, and MACEs was 4.8%, 1.4%, 0.9%, and 6.3%, respectively. In those ≥75 years, rates were 4.9%, 2.6%, 1.6%, and 7.8%. Older patients had higher rates of MI and MACEs (P = .001 and P= .0103). SYM patients <75 years had higher mortality if they had chronic obstructive pulmonary disease (P = .0002) and diabetes (P = .0062). SYM patients of all ages had higher mortality with postoperative stroke or MI (P < 0.0001). Patients 75 years or older are at increased risk of postoperative MI after CEA regardless of symptomatic status. Diabetes, increased operative time, and ASA score 4 or 5 were associated with higher MACE rates among all age groups.

Detection of symptomatic carotid atherosclerosis from 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography after stroke: A prospective study

Detection of symptomatic carotid atherosclerosis from 18F-fluorodeoxyglucose and 18F-sodium fluoride positron emission tomography after stroke: A prospective study

Symptomatic carotid atherosclerosis detection by positron emission tomography imaging

Symptomatic carotid atherosclerosis detection by positron emission tomography imaging

NGAL and MMP-9/NGAL as biomarkers of plaque vulnerability and targets of statins in patients with carotid atherosclerosis.

Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis. We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays. Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels. Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.