Unstable Carotid Plaques Research Articles

Association between the triglyceride-glucose index and carotid plaque stability in nondiabetic adults

Background and aimsThe rupture of an unstable atherosclerotic plaque is one of the major causes of thrombosis. However, there was limited evidence on the relationship of triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, with the carotid plaque stability. This study aimed to investigate the association between the TyG index and carotid plaque stability in nondiabetic adults. Methods and resultsThe study included 4748 nondiabetic participants from the Asymptomatic Polyvascular Abnormalities Community study. Carotid plaque stability was assessed using ultrasonography. The TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Logistic regression was used to evaluate the association of the TyG index with carotid plaque stability by calculating odds ratio (OR) and 95% confidence interval (CI). Of the 4748 participants, 1192 (25.11%) participants had stable carotid plaque, and 1247 (26.26%) had unstable carotid plaque. The prevalence of unstable carotid plaque substantially increased with increasing TyG index tertile (P for trend <0.0001). In the fully adjusted model, the OR comparing participants in the highest versus the lowest tertile of the TyG index was 1.31 (95% CI, 1.09–1.57). The optimal cutoff point for the TyG index in case of unstable carotid plaque was 8.56. However, we did not observe a statistically significant association between the TyG index and stable carotid plaque. ConclusionsElevated the TyG index was significantly associated with the prevalence of unstable carotid plaque in nondiabetic adults.

Lipid Core Burden Index Assessed by Near-Infrared Spectroscopy of Symptomatic Carotid Plaques: Association with Magnetic Resonance T1-Weighted Imaging

Introduction: Vulnerable plaques are a strong predictor of cerebrovascular ischemic events, and high lipid core plaques (LCPs) are associated with an increased risk of embolic infarcts during carotid artery stenting (CAS). Recent developments in magnetic resonance (MR) plaque imaging have enabled noninvasive assessment of carotid plaque vulnerability, and the lipid component and intraplaque hemorrhage (IPH) are visible as high signal intensity areas on T1-weighted MR images. Recently, catheter-based near-infrared spectroscopy (NIRS) has been shown to accurately distinguish LCPs without IPH. This study aimed to determine whether the results of assessment of high LCPs by catheter-based NIRS correlate with the results of MR plaque imaging. Methods: We recruited 82 consecutive symptomatic carotid artery stenosis patients who were treated with CAS under NIRS and MR plaque assessment. Maximum lipid core burden index (max-LCBI) at minimal luminal areas (MLA), defined as max-LCBI_MLA, and max-LCBI for any 4-mm segment in a target lesion, defined as max-LCBI_AREA, were assessed by NIRS. Correlations were investigated between max-LCBI and MR T1-weighted plaque signal intensity ratio (T1W-SIR) and MR time-of-flight signal intensity ratio (TOF-SIR) in the same regions as assessed by NIRS. Results: Both T1W-SIR_MLA and T1W-SIR_AREA were significantly lower in the high LCP group (max-LCBI >504, p < 0.001 for both), while TOF-SIR_MLA and TOF-SIR_AREA were significantly higher in the high LCP group (p < 0.001 and p = 0.004, respectively). A significant linear correlation was present between max-LCBI_MLA and both TIW-SIR_MLA and TOF-SIR_MLA (r = −0.610 and 0.452, respectively, p < 0.0001 for both). Furthermore, logistic regression analysis revealed that T1W-SIR_MLA and TOF-SIR_MLA were significantly associated with a high LCP assessed by NIRS (OR, 44.19 and 0.43; 95% CI: 6.55–298.19 and 0.19–0.96; p < 0.001 and = 0.039, respectively). Conclusions: A high LCP assessed by NIRS correlates with the signal intensity ratio of MR imaging in symptomatic patients with unstable carotid plaques.

Association between carotid plaque vulnerability and high mobility group box-1 serum levels in a diabetic population

BackgroundCarotid atherosclerosis represents one of the complications of diabetes mellitus. In particular, plaque instability contributes to disease progression and stroke incidence. High mobility group box-1 (HMGB1) is a nuclear protein involved in promotion and progression of atherosclerosis and cardiovascular diseases. The aim of this study was to analyze the relationship between HMGB1 serum levels, main inflammatory cytokines, the presence of internal carotid stenosis and unstable plaque in a diabetic population.Research design and methodsWe studied 873 diabetic patients, including 347 patients with internal carotid artery stenosis (ICAS) who underwent carotid endarterectomy and 526 diabetic patients without internal carotid artery stenosis (WICAS). At baseline, HMGB1 and the main inflammatory cytokines serum levels were evaluated. For ICAS patients, the histological features of carotid plaque were also collected to differentiate them in patients with stable or unstable atherosclerotic lesions.ResultsWe found that HMGB1 serum levels, osteoprotegerin, high-sensitivity C-reactive protein, tumor necrosis factor-alpha and interleukin-6, were significantly higher in diabetic ICAS patients compared to diabetic WICAS patients. Among ICAS patients, individuals with unstable plaque had higher levels of these cytokines, compared to patients with stable plaque. A multivariable stepwise logistic regression analysis showed that HMGB1 and osteoprotegerin remained independently associated with unstable plaque in ICAS patients.ConclusionsThe present study demonstrated that HMGB1 is an independent risk factor for carotid plaque vulnerability in an Italian population with diabetes mellitus, representing a promising biomarker of carotid plaque instability and a possible molecular target to treat unstable carotid plaques and to prevent stroke.

Expression of Resistin, Chemerin, and Chemerin's Receptor in the Unstable Carotid Atherosclerotic Plaque.

Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques (P<0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques (P<0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability (P<0.05). No strong sex-specific relationship was observed between adipokines and plaque instability. This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.

Using Serum Biomarkers for Identifying Unstable Carotid Plaque: Update of Current Evidence.

Carotid atherosclerosis is responsible for a great proportion of ischemic strokes. Early identification of unstable or vulnerable carotid plaques, and therefore, of patients at high risk for stroke, is of significant medical and socioeconomical value. We reviewed the current literature and discussed the potential role of the most important serum biomarkers in identifying patients with carotid atherosclerosis who are at high risk for atheroembolic stroke.

Relationship between small dense low-density lipoprotein cholesterol with carotid plaque in Chinese individuals with abnormal carotid artery intima-media thickness

AimTo investigate the relationship of small dense low-density lipoprotein cholesterol (sdLDL-C) to carotid artery intima-media thickness (CA-IMT) and carotid plaque (CAP) in Chinese general population, and to evaluate whether sdLDL-C could be an independent risk factor for individuals with subclinical atherosclerosis.MethodsA total of 729 subjects were randomly collected from consecutive individuals from April 2019 to April 2020 for an annual health checkup. CA-IMT > 1.0 mm was defined as abnormal IMT. Plaque stability was measured by ultrasound examination based on the property of the echo. And sdLDL-C levels were detected by LipoPrint system. Multivariate logistic regression analysis was performed to identify factors associated with CA-IMT and carotid plaque.ResultsThe abnormal IMT group had significantly higher sdLDL-C levels than control group (p < 0.0001). And sdLDL-C levels were significantly positively correlated with IMT value (r = 0.1396, p = 0.0021) and presence of carotid plaque (r = 0.14, p = 0.002) in the subjects with abnormal IMT. In addition, subjects with higher levels of sdLDL-C (r = 0.11, p = 0.035) tended to have unstable CAP. After adjustment for age, gender and blood glucose, sdLDL-C level was an independent risk factor of the presence of CAP (OR = 1.59, 95% CI: 1.02–1.83, p = 0.034) in subjects with abnormal IMT.ConclusionSdLDL-C is an independent risk factor of the occurrence of CAP in the Chinese subjects with abnormal IMT. Our findings provide supporting evidence that sdLDL-C might be an alternative way to predict CVD in early stage.

Shear-Wave Elastography Enables Identification of Unstable Carotid Plaque

Shear-wave elastography (SWE) is a novel ultrasound technique for quantifying tissue elasticity. The aim of this study was to identify differences in atherosclerotic plaque elasticity measured using SWE among individuals with symptomatic, asymptomatic progressive and asymptomatic stable carotid plaques. Consecutive patients from the Atherosclerotic Plaque Characteristics Associated with a Progression Rate of the Plaque and a Risk of Stroke in Patients with the Carotid Bifurcation Plaque Study were screened for this research. Neurosonography examination of carotid arteries was performed to identify plaque stenosis of ≥50% using B-mode ultrasound and SWE imaging to measure the mean, maximal and minimal elasticity. The set consisted of 97 participants—74 with asymptomatic stable stenosis, 12 with asymptomatic progressive stenosis and 11 with symptomatic stenosis. The mean elasticity in the asymptomatic stable plaque group was significantly higher than in the asymptomatic progressive (52.2 vs. 30.4 kPa; p < 0.001) and symptomatic (52.2 vs. 36.4 kPa; p = 0.033) plaque groups. No significant differences were found between asymptomatic progressive and symptomatic (p > 0.1) plaque groups. Asymptomatic stable, asymptomatic progressive and symptomatic plaques did not differ in echogenicity, calcifications, homogeneity, occurrence of ulcerated surface, or intra-plaque hemorrhage (p > 0.05 in all cases). SWE was a helpful modality for differentiating between stable and unstable atherosclerotic plaques in carotid arteries.

The composition of vulnerable plaque and its effect on arterial waveforms

Carotid plaque composition is a key factor of plaque stability and it carries significant prognostic information. The carotid unstable plaques are characterized by a thin fibrous cap (FC) ≤65μm with large lipid core (LC), while stable plaques have a thicker FC and less LC. Identifying the percentage of plaque compositions could help surgeons to make a precise decision for their patients’ treatment protocol. This study aims to distinguish between stable and unstable plaque by defining the relationship between plaque composition and arterial waveform non-invasively. An in-vitro arterial system, composed of a Harvard pulsatile flow pump and artificial circulation system, was used to investigate the effect of the plaque compositions on the pulsatile arterial waveforms. Five types of arterial plaques, composed of the LC, FC, Collagen (Col) and Calcium (Ca), were implemented into the artificial carotid artery to represent the diseased arterial system with 30% of blockage. The pulsatile pressure, velocity and arterial wall movement were measured simultaneously at the site proximal to the plaque. Non-invasive wave intensity analysis (Non-WIA) was used to separate the waves into forward and backward components. The correlation between the plaque compositions and the reflected waveforms was quantitatively analysed. The experimental results indicate that the reflected waveforms are strongly correlated with the plaque compositions, where the percentages of the Col are linearly correlated with the amplitude of the backward diameter (correlation coefficient, r = 0.74) and the lipid content has a strong negative correlation with the backward diameter (r = 0.82). A slight weak correlation exists between the reflected waveform and the percentage of Ca. The strong correlation between the compositions of the plaques with the backward waveforms observed in this study demonstrates that the components of the arterial plaques could be distinguished by the arterial waveforms. This finding might lead to a potential novel non-invasive clinical tool to determine the composition of the plaques and distinguish between stable and vulnerable arterial plaques at the early stage.

RELATIONSHIP BETWEEN PCSK9 PLASMA LEVELS AND CAROTID ATEROSCLEROSIS IN HYPERTENSIVE PATIENTS

Objective: The objective of our study is to assess whether serum PSCK9 levels are associated with AT by measuring the CIMT, which allows the identification of an analytically independent risk factor in hypertensive patients, with the aim of improving early cardiovascular risk detection in these patients. Design and method: In a population of 166 patients with high blood pressure (HBP), the CIMT was evaluated and correlated with the analytical values of PCSK9. The age of the participants ranges between 30 and 86 years, with an average age of 59.5 years and a standard deviation of 11.4 years (CV-19.2%). 55.4% were men. Ultrasound variables related to the carotid arteries, specifically the CIMT and the presence of unstable plaques, were analysed. Results: We analyse the possible relationship between the plasma value of PCSK9 and the CIMT considering two situations: that the CIMT is normal or altered. The average PCSK9 levels for both situations are high, observing that the average value for people with altered CIMT is significantly higher (p = 0.001). If we calculate the mean values of CIMT for individuals with normal and altered PCSK9, it is observed that it is significantly higher in individuals with altered PCSK9 (p = 0.000). We also relate the percentage of individuals with altered CIMT with the presence of normal / altered PCSK9 values. The relationship between the variables is statistically significant (p = 0.000), indicating that the proportion of subjects with alteration of the PCSK9 is clearly higher in the group with altered CIMT (75.5% versus 39.3%). With respect to the relationship between PCSK9 values and the presence or absence of unstable carotid plaques, in individuals with this type of plaque, the average level of PCSK9 is clearly higher. However, since the group with this situation is very small, the difference cannot be considered significant (p = 0.170). Conclusions: The serum levels of PSCK9 are positively correlated with an early CV risk factor (CIMT). Therefore, we can conclude that PSCK9 can become an independent risk factor for AT in hypertensive patients. More studies are needed to confirm our preliminary results

YKL-40 Is Associated With Ultrasound-Determined Carotid Atherosclerotic Plaque Instability.

Background and Aims: YKL-40, an inflammatory biomarker, has been reported to be involved in the process and progression of atherosclerosis. Several studies have investigated the association between YKL-40 and plaque and suggested YKL-40 might be a potential biomarker for plaque instability. This study aimed to investigate the association between YKL-40 and carotid plaque instability.Methods: Based on a community-based study in Beijing from February 2014 to May 2016, 1,132 participants with carotid plaques were enrolled in this study. Data on demographics and medical history were collected through face-to-face interviews, and fasting blood samples were collected and stored. We used ultrasound to evaluate the presence of carotid plaque and its instability. The level of YKL-40 was measured by enzyme-linked immunosorbent assay (ELISA). Multivariate logistic regression analysis was performed to investigate the association between YKL-40 level and carotid atherosclerotic plaque instability.Results: The mean age of the 1,132 participants was 58.0 (52.0–64.0) years, and 560 (49.5%) were male. Unstable plaques were detected in 855 (75.53%) participants. YKL-40 level was classified into four groups according to its quartile: quartile 1: <25.47 ng/mL, quartile 2: 25.47–39.53 ng/mL, quartile 3: 39.53–70.55 ng/mL, quartile 4: ≥70.55 ng/mL. After adjusting for age, sex, smoking, alcohol drinking, medical history, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, homocysteine, high-sensitivity C-reactive protein, and plaque thickness, the top quartiles of YKL-40 level were significantly associated with unstable plaque (quartile 3: OR 2.10, 95% CI 1.29–3.40; quartile 4: OR 1.70, 95% CI 1.04–2.80).Conclusion: This study found that YKL-40 was associated with carotid plaque instability determined by ultrasound. Individuals with high YKL-40 may have a higher risk of unstable carotid plaque.

SIRT6 promotes angiogenesis and hemorrhage of carotid plaque via regulating HIF-1\u03b1 and reactive oxygen species

As a member of Sirtuins family, SIRT6 participates in the physiological and pathological progress of DNA repair, anti-aging, metabolism, and so on. Several studies have demonstrated that knockdown of SIRT6 inhibited the development of atherosclerosis (AS), indicated SIRT6 as a protective factor for AS. However, we confirmed SIRT6 was significantly overexpressed in human unstable carotid plaques compared with stable carotid plaques. This result indicated a more complex role of SIRT6 in AS. Furthermore, we constructed mice model with unstable carotid plaque and injected them with SIRT6 overexpressed adeno-associated virus (AAV-SIRT6). AAV-SIRT6 significantly promoted angiogenesis as well as hemorrhage in plaques. In vitro, we demonstrated overexpression of SIRT6 prevented HIF-1α from degradation by deubiquitination at K37 and K532 of HIF-1α, thus promoted the expression of HIF-1α under both normoxia and hypoxia in human umbilical vein endothelial cells (HUVECs). Through regulating HIF-1α, overexpression of SIRT6 promoted invasion, migration, proliferation, as well as tube formation ability of HUVECs. Interestingly, under different conditions, SIRT6 played different roles in the function of HUVECs. Under oxidative stress, another important pathological environment for AS, SIRT6 bound to the promoter of Catalase, a main reactive oxygen species scavenger, and depleted H3K56 acetylation, thus inhibited expression and activity of Catalase at the transcriptional level. Subsequently, inhibited Catalase promoted reactive oxygen species (ROS) under oxidative stress. Accumulated ROS further aggravated oxidative stress injury of HUVECs. On one hand, SIRT6 promoted angiogenesis in plaque via HIF-1α under hypoxia. On the other hand, SIRT6 promoted injury of neovascular via ROS under oxidative stress. It is this process of continuous growth and damage that leads to hemorrhage in carotid plaque. In conclusion, we innovatively confirmed SIRT6 promoted the angiogenesis and IPH via promoting HIF-1α and ROS in different environments, thus disclosed the unknowing danger of SIRT6.

The role of magnetic resonance imaging and the expression of MMP-9 protein in the analysis of carotid atherosclerotic plaques in patients undergoing carotid endarterectomy: a prospective pilot study.

Components of carotid atherosclerotic plaque can be analysed preoperatively by non-invasive advanced imaging modalities such as magnetic resonance imaging (MRI). The expression of matrix metalloproteinase-9 protein (MMP-9), which has a potential role in remodelling of atherosclerotic plaques, can be analysed immunohistochemically. The aim of the present prospective pilot study is to analyse histological characteristics and expression of MMP-9 in carotid plaques of patients undergoing carotid endarterectomy (CEA) and to investigate the correlation with preoperative clinical symptoms and MRI features. Preoperative clinical assessment, MRI imaging, postoperative histological and immunohistochemical analyses were performed. Fifteen patients with symptomatic (7/15; 47%) and asymptomatic carotid artery stenosis undergoing CEA were included. Among symptomatic patients, 5 (71%) had recent stroke and 2 (29%) had recent transient ischaemic attack with a median timing of 6 weeks (IQR: 1, 18) before the surgery. Both groups did not significantly differ in respect to preoperative characteristics. Prevalence of unstable plaque was higher in symptomatic than asymptomatic patients, although it was not significant (63% vs. 37%, p = 0.077). The expression of MMP-9 in CD68 cells within the plaque by semiquantitative analysis was found to be significantly higher in symptomatic as compared to asymptomatic patients (86% vs. 25% with the highest expression, p = 0.014). The average microvascular density was found to be higher and lipid core area larger among both symptomatic patients and unstable carotid plaque specimens, although this did not reach statistical significance (p = 0.064 and p = 0.132, p = 0.360 and p = 0.569, respectively). Our results demonstrate that MRI is reliable in classifying carotid lesions and differentiating unstable from stable plaques. We have also shown that the expression of MMP-9 is significantly higher among symptomatic patients undergoing CEA.

Unstable Carotid Plaque as a Phenotype of Chronic Systemic Inflammation Enhances Renal Insufficiency

Maruyama, Kunitaka; Kashiwazaki, Daina; Yamamoto, Shusuke; Hori, Emiko MD; Akioka, Naoki; Shibata, Takashi; Akai, Takuya; Kuwayama, Naoya; Kuroda, Satoshi Author Information

Dilated microvessel with endothelial cell proliferation involves intraplaque hemorrhage in unstable carotid plaque.

The purpose of the present study was to clarify the characteristics of endothelial cell (EC) proliferation in intraplaque microvessels in vulnerable plaques and impact on clinical results. The present study included 76 patients who underwent carotid endarterectomy. Patients were classified into three groups based on their symptoms: asymptomatic, symptomatic without recurrent ischemic event, and symptomatic with recurrent ischemic event. MR plaque imaging was performed and surgical specimens underwent immunohistochemical analysis. The number of CD31+ microvessels, and Ki67+ and CD105+ ECs in the carotid plaques was quantified, as measurements of maximum CD31+ microvessel diameter. MR plaque imaging yielded 41 subjects (54.0%) diagnosed with plaque with intraplaque hemorrhage (IPH), 14 subjects (18.4%) diagnosed with fibrous plaques, and 21 (27.6%) subjects diagnosed with lipid-rich plaques. The average largest diameter of microvessel in fibrous plaques, lipid-rich plaques, and plaque with IPH was 12.7 ± 4.1 μm, 31.3 ± 9.3 μm, and 56.4 ± 10.0 μm, respectively (p < 0.01). Dilated microvessels (>40 μm) were observed in 9.6% of plaques with IPH but only in 2.8% of lipid-rich plaques and 0% of fibrous plaques (p < 0.01). Ki67+/CD31+ ECs were identified in 2.8 ± 1.2% of fibrous plaques, 9.6 ± 6.9% of lipid-rich plaques, and in 19.5 ± 5.9% of plaques with IPH (p < 0.01). The average largest diameter of microvessels in the asymptomatic group was 17.1 ± 8.7 μm, 32.3 ± 10.8 μm in the symptomatic without recurrence group, and 55.2 ± 13.2 μm in the symptomatic with recurrence group (p < 0.01). Dilated microvessels with proliferative ECs may play a key role in IPH pathogenesis. Furthermore, dilated microvessels are likely related to clinical onset and the recurrence of ischemic events. The purpose of the present study was to clarify the characteristics of EC proliferation in intraplaque microvessels in vulnerable plaques and their impact on clinical results, focusing on dilated intraplaque microvessels.

Hemorrhagic Plaques in Mild Carotid Stenosis: The Risk of Stroke.

Embolic ischemic strokes cause significant mortality and morbidity worldwide. It has been proposed that some of these strokes are due to unstable carotid plaques with intraplaque hemorrhage (IPH) but a low overall degree of stenosis. Our aim was to test a fat-saturated T1-weighted (T1WI) black-blood sequence on MRI for the detection of IPH in symptomatic individuals and to quantify the relation between IPH, severity of stenoses, and ischemic brain lesions. Sixty-two patients were examined by 3T MRI. Sequences included brain diffusion-weighted imaging (DWI) as well as 3D turbo spin echo (TSE) fat-saturated black-blood T1 of the carotid bifurcations, to detect IPH as a focal intraplaque hyperintensity. Both carotid arteries were analyzed in each patient. The North American Symptomatic Carotid Endarterectomy Trial scale was used for quantification of stenosis degree. Thirty-six out of 62 patients (mean age, 74) showed brain ischemia on DWI. Fifteen of these 36 patients (42%) had associated ipsilateral IPH at the carotid bifurcation or the proximal internal carotid artery. Mean degree of stenosis in this group was 50%. In 21 patients with ischemia without IPH, the mean degree of stenosis was 44%. MRI with 3D TSE fat-saturated black-blood T1 technique is a safe, reliable, and noninvasive tool for the detection of IPH. A high percentage (42%) of ischemic events in patients with low- to moderate-degree stenosis were associated with IPH, an easily detectable imaging biomarker of plaque vulnerability. The ability to confirm IPH by MRI may help stratify patients into different risk and treatment groups in the future.

Carotid Intraplaque Hemorrhage Is Associated with Cardiovascular Risk Factors

Introduction: Intraplaque hemorrhage (IPH) is a known predictor of symptomatic cervical carotid artery disease. However, the association between IPH and modifiable cardiovascular risk factors, patient demographics, and pertinent laboratory values has not been extensively studied. Methods: A retrospective review was performed of consecutive patients who have undergone dedicated carotid plaque imaging over a 3-year period. Patients were excluded if the MR examination did not include high-resolution carotid plaque imaging. Intraplaque hyperintense signal on carotid plaque images was presumed to represent IPH. The presence or absence of IPH was compared to various demographic and clinical variables. Multivariable regression analysis was performed in order to determine an independent association between variables and IPH. Results: Of 643 included patients, 114 patients (17.7%) had IPH in one or both carotids, 529 patients (82.3%) did not; 39.5% of patients with IPH had coronary artery disease compared to 23.1% of patients without (p = 0.0003). Patients with IPH also had higher proportions of hypertension (77.2 vs. 60.7%, p = 0.009), hyperlipidemia (HLD; 89.5 vs. 62.4%, p < 0.0001), diabetes mellitus (29.0 vs. 18.7%, p = 0.01), and a history of tobacco smoking (63.2 vs. 52.6%, p = 0.003). Patients without IPH had, on average, higher high-density lipoprotein levels (46.1 vs. 56.7%, p = 0.003). Factors independently associated with IPH were advanced age (odds ratio [OR]: 1.1, 95% CI: [1.0–1.05], p <0.0001), male sex (OR: 2.5, 95% CI: [1.4–4.4], p = 0.0001), presence of carotid stenosis (OR: 8.4, 95% CI: [4.6–15.3], p < 0.0001), and HLD (OR: 2.6, 95% CI: [1.3–5.2], p = 0.009). Conclusions: IPH is associated with multiple cardiovascular risk factors, in particular advanced age, male sex, presence of carotid stenosis, and HLD. Such risk factors likely play a role in the development of IPH and may provide insight into the pathophysiology of unstable carotid plaques.

Abolition of micro embolic signals in symptomatic carotid stenosis using dual antiplatelet therapy

Introduction : Micro-Embolic Signals (MES) detected by Trans-Cranial Doppler (TCD) in symptomatic carotid stenosis (CS) are considered a marker of subsequent stroke. We aimed to investigate the role of antiplatelet and antithrombotic agents in abolishing the MES in recently symptomatic CS. Materials and Methods: Transient ischemic attack/stroke patients with 50%CS or unstable carotid plaque, who were prospectively enrolled within 48hours of symptom onset, underwent bilateral middlecerebral artery one-hour TCD emboli monitoring within 48hours. Those with MES underwent second monitoring at 48hours of the initial study. Treatment given during the interval period was recorded. Results: Out of 73 patients enrolled from April 2016 to March 2019, 22 (17 males, mean age 67.4years) had ipsilateral MES on initial TCD (30.1%). Ten were on a single-antiplatelet agent (aspirin/clopidogrel) and one was on dual (aspirin&clopidogrel) therapy prior to this. Single-antiplatelet agent was started after TCD in seven, dual-agents in six and unfractionated-heparin in seven patients. Second TCD showed no MES in 14 patients. Only one out of three on a single antiplatelet agent alone had abolition of MES while all ten patients on dual-antiplatelet agents had a complete suppression (p=0.027,Chi-square test). Although heparin suppressed MES in 5/7 patients, all five had additional dual-agent therapy. MES was not abolished in one patient treated with heparin alone and another one on a combination of heparin and single-antiplatelet agent. Conclusion: Aspirin/Clopidogrel combination is very effective in suppressing arterial emboli in recently symptomatic carotid stenosis whereas unfractionated-heparin, single-antiplatelet agent or their combination is not useful for the same. Keywords: Micro-Embolic Signals, Trans-Cranial Doppler, Carotid stenosis.

A model to predict unstable carotid plaques in population with high risk of stroke

BackgroundSeveral models have been developed to predict asymptomatic carotid stenosis (ACS), however these models did not pay much attention to people with lower level of stenosis (<50% or carotid plaques, especially instable carotid plaques) who might benefit from early interventions. Here, we developed a new model to predict unstable carotid plaques through systematic screening in population with high risk of stroke.MethodsCommunity residents who participated the China National Stroke Screening and Prevention Project (CNSSPP) were screened for their stroke risks. A total of 2841 individuals with high risk of stroke were enrolled in this study, 266 (9.4%) of them were found unstable carotid plaques. A total of 19 risk factors were included in this study. Subjects were randomly distributed into Derivation Set group or Validation Set group. According to their carotid ultrasonography records, subjects in derivation set group were further categorized into unstable plaque group or stable plaque group.Results174 cases and 1720 cases from Derivation Set group were categorized into unstable plaque group and stable plaque group respectively. The independent risk factors for carotid unstable plaque were: male (OR 1.966, 95%CI 1.406–2.749), older age (50–59, OR 6.012, 95%CI 1.410–25.629; 60–69, OR 13.915, 95%CI 3.381–57.267;≥70, OR 31.267, 95%CI 7.472–130.83), married(OR 1.780, 95%CI 1.186–2.672), LDL-C(OR 2.015, 95%CI 1.443–2.814), and HDL-C(OR 2.130, 95%CI 1.360–3.338). A predictive scoring system was generated, ranging from 0 to 10. The cut-off value of this predictive scoring system is 6.5. The AUC value for derivation and validation set group were 0.738 and 0.737 respectively.ConclusionsFor those individuals with high risk of stroke, we developed a new model which could identify those who have a higher chance to have unstable carotid plaques. When an individual’s predictive model score exceeds 6.5, the probability of having carotid unstable plaques is high, and carotid ultrasonography should be conducted accordingly. This model could be helpful in the primary prevention of stroke.

The association between carotid atherosclerosis and ischemic stroke in patients with nonvalvular atrial fibrillation

Objective: To investigate the relationship between indicators of carotid atherosclerosis and onset of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF). Methods: This is a case-control study, a total of 397 NVAF patients with newly diagnosed ischemic stroke (case group) and 3 038 NVAF patients without ischemic stroke (control group) from January 2015 to December 2017 were included in the study. Differences in general clinical features and carotid atherosclerosis indexes between the two groups were compared. Univariate and multivariate logistic regressions were used to analyze the correlation between carotid atherosclerosis indexes and ischemic stroke. Results: Proportions of patients with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, and moderate to severe stenosis were higher in the ischemic stroke group than those in the control group (82.1% vs. 64.4%, 69.3% vs. 50.3%, 43.6% vs. 30.6%, 25.7% vs. 19.7%, and 7.3% vs. 4.0%, respectively, all P <0.05). After adjustment of age, gender, heart failure, hypertension, low density lipoprotein -cholesterol and drug use, multivariate analyses showed that subjects with carotid intima thickening, carotid plaque, stable plaque, unstable plaque, moderate to severe stenosis had 1.766, 2.111, 1.892, 2.256 and 1.824 times the risk for the development of ischemic stroke compared with the subjects without any carotid atherosclerosis indicators. Conclusion: Carotid atherosclerosis, especially with unstable carotid plaque, is associated with ischemic stroke in patients with NVAF.

Association between Pericytes in Intraplaque Neovessels and Magnetic Resonance Angiography Findings.

(1) Background: Pericytes are involved in intraplaque neovascularization of advanced and complicated atherosclerotic lesions. However, the role of pericytes in human carotid plaques is unclear. An unstable carotid plaque that shows high-intensity signals on time-of-flight (TOF) magnetic resonance angiography (MRA) is often a cause of ischemic stroke. The aim of the present study is to examine the relationship between the pericytes in intraplaque neovessels and MRA findings. (2) Methods: A total of 46 patients with 49 carotid artery stenoses who underwent carotid endarterectomy at our hospitals were enrolled. The patients with carotid plaques that were histopathologically evaluated were retrospectively analyzed. Intraplaque hemorrhage was evaluated using glycophorin A staining, and intraplaque neovessels were evaluated using CD34 (Cluster of differentiation) stain as an endothelial cell marker or NG2 (Neuron-glial antigen 2) and CD146 stains as pericyte markers. Additionally, the relationships between the TOF-MRA findings and the carotid plaque pathologies were evaluated. (3) Results: Of the 49 stenoses, 28 had high-intensity signals (TOF-HIS group) and 21 had iso-intensity signals (TOF-IIS group) on TOF-MRA. The density of the CD34-positive neovessels was equivalent in both groups. However, the NG2- and CD146-positive neovessels had significantly higher densities in the TOF-HIS group than in the TOF-IIS group. (4) Conclusion: The presence of a high-intensity signal on TOF-MRA in carotid plaques was associated with intraplaque hemorrhage and few pericytes in intraplaque neovessels. These findings may contribute to the development of new therapeutic strategies focusing on pericytes.