Asymptomatic Carotid Atherosclerosis Research Articles

Prediction model for asymptomatic carotid atherosclerosis using retinal microvascular intelligent analysis: A retrospective study

ImportanceEarly detection and timely diagnosis of asymptomatic carotid atherosclerosis significantly assist in the prevention of ischemic stroke for them. ObjectiveThis observational study aimed to develop and validate a novel prediction model to assist in the early diagnosis of carotid atherosclerosis based on new characteristic variables screened by retinal microvascular intelligence analysis. Main Outcome(s) and Method (s)The least absolute shrinkage and selection operator (LASSO) combined with 10-fold cross-validation were screened for characteristic variables, and nomograms were plotted to demonstrate the prediction model. Receiver operating characteristic (ROC) curves and area under the curve (AUC), calibration plots and brier score (BS), and decision curve analysis (DCA) were used to evaluate the risk model's discrimination, calibration, and clinical applicability. ResultsAge, gender, diabetes mellitus (DM), drinking history, vascular branching angle, mean vascular diameter within 0.5–1.0 papillary diameter (PD), curvature tortuosity arteriole in the inferior region of the optic disc, and vascular density in the nasal region of the optic disc were identified as characteristic variables for carotid atherosclerosis with retinal microvascular intelligence analysis. The predictive nomogram model presented good discrimination with AUCs of 0.790 (0.774–0.806), and the calibration curve displayed high consistency between predicted and actual probability. The DCA demonstrated that this nomogram model led to net benefits in a threshold probability range of 20 %–94 % and could be adapted for clinical decision-making. The results of the 100-bootstrap resampling strategy for internal validation also show that the risk model is well discriminated with an AUC of 0.789 and excellent calibration. External validation showed good discrimination with AUCs of 0.703 (0.627 - 0.779) and good calibration, the risk threshold is 10 %–92 % in terms of DCA. Conclusions and RelevanceThe novel prediction model based on retinal microvascular intelligence analysis constructed in this study could be effective prognoses for predicting the risk of asymptomatic carotid atherosclerosis in a Chinese screening population.

Neutrophil/HDL-C, Lymphocyte/HDL-C and Monocyte/HDL-C in subjects with asymptomatic carotid atherosclerosis.

Leukocyte count is a prognostic marker for cardiovascular diseases, with key role in atherosclerosis development. Specific number of neutrophils, lymphocytes and monocytes can predict cardiovascular risk, also in asymptomatic subjects. Among the lipoprotein fractions, HDL-C is a protective factor in the cardiovascular disorders. For the above reason, we have examined the peripheral count of leukocytes, neutrophils, lymphocytes and monocytes, and the ratios between neutrophils/HDL-cholesterol, lymphocytes/HDL-cholesterol, and monocytes/HDL-cholesterol, to evaluate the possible utility of the obtained values in progression of asymptomatic carotid atherosclerosis. We performed our analysis in a cohort of 100 subjects with asymptomatic carotid atherosclerosis, of which 43 men and 57 women. The data were expressed as medians and IQR. To analyse the differences in leukocyte, neutrophil, lymphocyte, monocytes count and their ratio with HDL-cholesterol the Mann-Whitney test was employed. The peripheral count of leukocyte subtypes and the ratios, they change in relation to the number of cardiovascular risk factors and the degree of insulin resistance. In this cohort of subjects, the percentage of observed cardiovascular risk factors significantly affect some leukocyte parameters. These results, allow us to underline the importance of the leukocyte indices in the evaluation of subjects with asymptomatic vascular atherosclerosis.

Combined Effects of Clonal Hematopoiesis and Carotid Stenosis on Cardiovascular Mortality

BackgroundThe expansion of hematopoietic stem cells caused by acquired somatic mutations (clonal hematopoiesis [CH]) is a novel cardiovascular risk factor. The prognostic value of CH in patients with carotid atherosclerosis remains to be evaluated. ObjectivesThis study assessed the prognostic significance of CH in patients with atherosclerosis as detected by ultrasound of the carotid artery. MethodsWe applied deep sequencing of selected genomic regions within the genes DNMT3A, TET2, ASXL1, and JAK2 to screen for CH in 968 prospectively collected patients with asymptomatic carotid atherosclerosis evaluated by duplex sonography. ResultsWe detected clonal markers at variant allele frequency ≥2% in 133 (13.7%) of 968 patients (median age 69.2 years), with increasing prevalence at advanced age. Multivariate analyses including age and established cardiovascular risk factors revealed overall presence of CH to be significantly associated with increased risk of cardiovascular death (HR: 1.50; 95% CI: 1.12-2.00; P = 0.007), reflected also at the single gene level. The effect of CH was more pronounced in older patients and independent of the patients’ inflammatory status as measured by high-sensitivity C-reactive protein. Simultaneous assessment of CH and degree of carotid stenosis revealed combined effects on cardiovascular mortality, depicted by a superior risk for patients with >50% stenosis and concomitant CH (adjusted HR: 1.60; 95% CI: 1.08-2.38; P = 0.020). ConclusionsCH status in combination with the extent of carotid atherosclerosis jointly predict long-term mortality. Determination of CH can provide additional prognostic information in patients with asymptomatic carotid atherosclerosis.

Qualitative and quantitative ultrasound parameters of carotid atherosclerotic plaques in patients with moderate cardiovascular risk according to the SCORE scale: 7-year prospective follow-up study

Aim. To assess asymptomatic carotid atherosclerosis in patients with moderate cardiovascular risk over a 7-year prospective follow-up using non-invasive ultrasound markers.Material and methods. Eighty patients (47 men and 33 women) aged 53,1±5,9 years with moderate Systematic Coronary Risk Evaluation (SCORE) level, low-density lipoprotein cholesterol (LDL-C) of 2,7-4,8 mmol/l and asymptomatic hemodynamically insignificant (stenosis <50%) carotid atherosclerosis (CA). Patients underwent CA ultrasound (PHILIPS IU22) at baseline and after 7 years. Plaque number, maximum plaque height, total plaque height, total CA stenosis, visual plaque morphology, gray-scale median (GSM), and intima- media thickness of the right and left common CAs were assessed. All patients were prescribed atorvastatin therapy at a dose of 10-40 mg until a target LDL-С level <2,6 mmol/l was achieved.Results. During the follow-up period, a significant increase was noted in the number of plaques, the maximum and total plaque height, total CA stenosis, and intima- media thickness of the right and left common CAs. An increase in GSM was detected in 79% of plaques on statin therapy. Plaque echoicity increased by 4,90 [0,51; 17,41] (p <0,001) or 7,2% [0,7%; 29%] (p<0,001) over seven years. Regression analysis adjusted for sex and age showed the dependence of GSM changes (ΔGSM) on changes in the LDL-C level (ΔLDL-C) (p=0,049). With a decrease in LDL-C by 1 mmol/l, an increase in average GSM was noted by 5,9 (0,03-11,78). The maximum plaque height increased significantly after 7-year follow-up from 1,80 [1,50; 2,20] to 2,00 [1,63; 2,68] mm (p=0,044). In patients who reached a LDL-C level of 1,8 mmol/l, the maximum plaque height decreased more than in patients who did not reach this level (-0,07 [-0,45; 0,14] mm and 0,20 [-0,05; 0,40] mm, respectively (p=0,028)). Regression analysis adjusted for sex and age did not reveal a relationship between the change of maximum plaque height with ΔLDL-C and Δhigh-density lipoprotein cholesterol, but with LDL-C level after 7 years.Conclusion. Statin therapy in patients with CA stenosis <50% stabilizes the plaques due to echogenicity increase. LDL-C <1,8 mmol/l can lead to a decrease in maximum plaque height.

Stroke risk in patients with asymptomatic carotid atherosclerosis: should it be treated medically or surgically?

Stroke risk in patients with asymptomatic carotid atherosclerosis: should it be treated medically or surgically?

Commentary: Effect of aspirin in patients with established asymptomatic carotid atherosclerosis: a systematic review and meta-analysis.

Commentary: Effect of aspirin in patients with established asymptomatic carotid atherosclerosis: a systematic review and meta-analysis.

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.

Leukocyte subtypes, gelatinases, and their tissue inhibitors in a group of subjects with asymptomatic carotid atherosclerosis.

In a cohort of subjects with asymptomatic carotid atherosclerosis (ACA), we have evaluated the neutrophil and lymphocyte count and their ratio (NLR), the gelatinases (MMP-2 and MMP-9) and their tissue inhibitors (TIMP-1 and TIMP-2). At baseline, no difference was observed between ACA subjects and subject control group regarding neutrophil and lymphocyte count while was evident in ACA subjects a significant increase in MMP-2, MMP-9 and TIMP-2 associated to a significant decrease in TIMP-1. Dividing the ACA according to the number of cardiovascular risk factors (CRFs) we have observed an increase in lymphocyte count in the subgroup with 3-5 CRFs. Evaluating the leukocyte subtypes according to all the surrogate markers of insulin resistance has been noted, in the subgroups that exceed the medians of these markers, a significant increase in neutrophil and lymphocyte count without any variation of the NLR. Effecting the same evaluation for the MMP/TIMP pattern we observed, instead, that the same subgroups tend to show a decrease in MMP-2 and an increase in MMP-9. No difference instead for TIMP-1 and TIMP-2. The abnormality of the MMP/TIMP pattern, bearing in mind the cardiometabolic clustering present in this cohort of ACA subjects, would induce to use drugs able not only to cure the cardiometabolic risk factors but also to influence the MMP/TIMP profile.

Inhibition of macrophage-derived foam cells by Adipsin attenuates progression of atherosclerosis

Phagocytosis of oxidized low-density lipoprotein (OxLDL) by macrophages yields “foam cells” and serves as a hallmark of atherosclerotic lesion. Adipsin is a critical component of the complement activation pathway. Recent evidence has indicated an obligatory role for Adipsin in pathological models including ischemia-reperfusion and sepsis. Adipsin levels are significantly decreased in patients with asymptomatic carotid atherosclerosis, implying the role for Adipsin as a potential marker of asymptomatic carotid atherosclerosis. This study was designed to evaluate the role for Adipsin in atherosclerosis and the mechanisms involved using both in vivo and in vitro experiments. ApoE−/−/AdipsinTg mice were constructed and were fed a high-fat diet for 12 weeks. Compared with ApoE−/− mice, area of the sclerotic plaques was reduced, along with lower macrophage deposition within the plaque in ApoE−/−/AdipsinTg mice. RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were stimulated with oxLDL (50 μg/ml). Adenovirus vectors containing the Adipsin gene were transfected into macrophages. Lipid accumulation was observed by Oil red O staining. Western blot and reverse transcription-polymerase chain reaction data revealed that Adipsin overexpression inhibited oxLDL-induced lipid uptake and foam cell formation and upregulation of CD36 and PPARγ in Ad-Adipsin-transfected macrophages. In addition, the PPARγ-specific agonist GW1929 reversed Adipsin overexpression-evoked inhibitory effect on lipid uptake. These results demonstrate unequivocally that Adipsin inhibits lipid uptake in a PPARγ/CD36-dependent manner and prevents the formation of foam cells, implying that Adipsin may be a potential therapeutic target against atherosclerosis.

How Unawareness of Weight Excess Can Increase Cardiovascular Risk?

Background: Obesity is a chronic disease with high prevalence in all age groups. Many overweight and obese people seem to be unaware of excess body weight. Aim: Analysis of people affected by the misperception of excess body weight and their eating behaviors simultaneously with selected health parameters. Methods: The study was conducted in 2017–2019 among 658 participants aged 20–79 from the population study—Bialystok PLUS (Poland). Results were based on clinical examinations and questionnaires. Results: Unawareness of overweight and obesity is common among adults (21.7%). Participants unaware of their overweight and obesity presented much higher risk factors. A high cardiovascular risk profile was observed more often among people not aware of overweight and obesity than among normal weight people (23.0% vs. 10.0%) as well as more common asymptomatic carotid artery atherosclerosis (49.7% vs. 31.3%). The subjective perception of overweight and obesity based on BMI (body mass index) was equal to 26.4 kg/m2 in women and 27.9 kg/m2 in men. The assessment of their diet was less favorable than that of people with normal weight. Conclusions: Unawareness of one’s excessive weight and its health consequences may lead to hesitancy to apply a healthy lifestyle and hence increase the cardiovascular risk in a substantial part of society. Therefore, it should be considered a part of the cardiovascular disease risk spectrum. Measurement of BMI and discussion about its health implications should be a routine procedure during healthcare contacts.

Monomeric form of C-reactive protein in the assessment of the residual inflammatory cardiovascular risk in patients with subclinical carotid atherosclerosis.

Aim To study the relationship between monomeric C-reactive protein (mCRP) and the progression of asymptomatic carotid atherosclerosis in patients with a moderate risk for cardiovascular diseases (CVD) as assessed with the SCORE model.Material and methods The study included 80 men and women aged 53.1±5.8 years assigned to the category of a moderate risk for CVDs by the SCORE model with a low-density lipoprotein cholesterol (LDL-C) level of 2.7-4.8 mmol/l and asymptomatic, hemodynamically insignificant (&lt;50% luminal narrowing) carotid atherosclerosis according to ultrasonic data. All patients were prescribed atorvastatin to achieve a LDL-C level &lt;2.6 mmol/l. After 7 years of follow-up, ultrasonic examination of carotid arteries was performed, and concentrations of high-sensitivity C-reactive protein (hsCRP) and mCRP were measured.Results A concentration of LDL-C &lt;2.6 mmol/l was achieved in all patients. The progression of atherosclerosis as determined by an increased number of atherosclerotic plaques (ASPs), was observed in 45 (56 %) patients. At 7 months of follow-up, concentrations of cCRP were higher in the group of patients with progressive carotid atherosclerosis, while the levels of hsCRP did not differ between the groups. Increased mCRP concentrations were associated with changes in variables of the "atherosclerotic load", including the number of ASPs, total ASP height, and the intima-media thickness (IMT). In patients with a median mCRP concentration of 5.2 [3.3; 7.1] µg/l and more, the increases in mean ACP number and total ASP height were considerably higher than in patients with mCRP concentrations lower than the median (3.9 and 2.7 times, respectively), whereas the odds ratio for the progression of asymptomatic carotid atherosclerosis was 5.5 (95 % confidence interval, CI: 2.1-14.6; p=0.001). ROC analysis showed that the concentration of hsCRP had no predictive value for prognosis of asymptomatic carotid atherosclerosis (p=0.16), while the area under the ROC curve (AUC) for mCRP was 0.75±0.056 (95 % CI: 0.64-0.86; p=0.001).Conclusion According to the results of 7-year follow-up, the plasma concentration of mCRP was significantly higher in patients with an increased number of ASPs than in patients without this increase. An increased level of mCRP may indicate a higher inflammatory risk of CVD.

Asymptomatic carotid atherosclerosis stenosis, inflammation, and cognitive impairment

It is well-established that atherosclerosis is a systemic inflammatory process involving the vessel wall intima media complex.1 Systemic inflammation is also thought to be involved in aging related cognitive decline.2 In addition, numerous studies have demonstrated a strong association between subclinical arteriosclerosis as measured by carotid artery intimal media thickness and cognitive impairment.3

Is carotid artery atherosclerosis associated with poor cognitive function assessed using the Mini-Mental State Examination? A systematic review and meta-analysis

ObjectivesTo determine associations between carotid atherosclerosis assessed by ultrasound and the Mini-Mental State Examination (MMSE), a measure of global cognitive function.DesignSystematic review and meta-analysis.MethodsMEDLINE and EMBASE databases were searched up...

Asymptomatic Carotid Disease and Cognitive Impairment: What Is the Evidence?

The development of cognitive dysfunction and dementia is a complex, multifactorial process. One of the contributors to various types of cognitive dysfunction is carotid atherosclerosis which can frequently be seen in asymptomatic individuals. There are a number of different manifestations of asymptomatic carotid atherosclerosis including arterial stiffness, carotid intima-media thickening, flow-limiting stenosis, and complex, atherosclerotic plaque. Each of these forms of atherosclerosis may contribute to cerebral parenchymal damage, contributing to cognitive dysfunction. In this review article, we will discuss each of these forms of carotid atherosclerosis, present the potential mechanistic underpinnings behind an association, and then review the scientific evidence supporting potential associations to cognitive dysfunction and dementia.

Machine learning models for screening carotid atherosclerosis in asymptomatic adults

Carotid atherosclerosis (CAS) is a risk factor for cardiovascular and cerebrovascular events, but duplex ultrasonography isn’t recommended in routine screening for asymptomatic populations according to medical guidelines. We aim to develop machine learning models to screen CAS in asymptomatic adults. A total of 2732 asymptomatic subjects for routine physical examination in our hospital were included in the study. We developed machine learning models to classify subjects with or without CAS using decision tree, random forest (RF), extreme gradient boosting (XGBoost), support vector machine (SVM) and multilayer perceptron (MLP) with 17 candidate features. The performance of models was assessed on the testing dataset. The model using MLP achieved the highest accuracy (0.748), positive predictive value (0.743), F1 score (0.742), area under receiver operating characteristic curve (AUC) (0.766) and Kappa score (0.445) among all classifiers. It’s followed by models using XGBoost and SVM. In conclusion, the model using MLP is the best one to screen CAS in asymptomatic adults based on the results from routine physical examination, followed by using XGBoost and SVM. Those models may provide an effective and applicable method for physician and primary care doctors to screen asymptomatic CAS without risk factors in general population, and improve risk predictions and preventions of cardiovascular and cerebrovascular events in asymptomatic adults.

Circulating adipsin is associated with asymptomatic carotid atherosclerosis in obese adults

BackgroundAdipsin has been identified as a secreted adipokine that plays a critical pathogenic role in metabolic disorders. However, it is not clear regarding the association of circulating adipsin with cardiovascular disease (CVD). This study will explore the association between circulating adipsin and asymptomatic carotid atherosclerosis in Chinese obese adults.MethodsA total of 483 obese adult subjects (aged 40 years or older) were enrolled in this study. Serum adipsin concentrations and carotid intima-media thickness (CIMT) were measured to determine these associations.ResultsIndividuals with increased CIMT and asymptomatic carotid atherosclerosis had lower levels of circulating adipsin than controls (both p < 0.05). The prevalence of asymptomatic carotid atherosclerosis was significantly higher in subjects with lower levels of serum adipsin than those with higher values (42.5% vs. 36.7%, p < 0.05). Notably, subjects in the lowest quartile of serum adipsin were 1.94 times (p = 0.059) more likely to have increased CIMT and 2.91 times (p = 0.03) more likely to have asymptomatic carotid atherosclerosis than those in the highest quartile in multivariable logistic regression analyses, adjusting for age, gender, current smoking, alcohol consumption, physical activity, BMI, systolic BP, fasting glucose, total cholesterol, HDL-c, and HOMA-IR. However, such associations with circulating adipsin were not noted for atherosclerotic plaque.ConclusionsThese findings suggest that circulating adipsin concentrations are a potential marker of risks of increased CIMT and asymptomatic carotid atherosclerosis in obese Chinese adults.

Monomeric C-reactive protein as a marker of residual inflammatory risk in patients with asymptomatic carotid atherosclerosis

Background and Aims: C-reactive protein (CRP) can dissociate into monomeric subunits (mCRP) in proinflammatory milieu. The ability of mCRP to accumulate in atherosclerotic plaques and stimulate inflammatory response may enhance the progression of atherosclerosis. The aim of this study was to find whether novel mCRP or high-sensitivity CRP (hsCRP) assays correlate with plaque burden in non-obstructive asymptomatic carotid atherosclerosis (ACA).

Different fractions of cytokines in blood of patients with asymptomatic carotid atherosclerosis

Background and Aims: Inflammation with activation of the cytokine signaling system is considered one of the main mechanisms that drive atherosclerotic plaque progression. The association of the released cytokines with extracellular vesicles (EVs) may shed a light on the intercellular communications promoting atherosclerosis. Thus, this study investigated the involvement of EVs in the transportation of cytokines in patients with carotid atherosclerosis.

Beta-2-Microglobulin is an Independent Risk Factor for Asymptomatic Carotid Atherosclerosis in Patients with Primary Aldosteronism.

Aim: To identify the association between serum beta-2-microglobulin (B2M) or cystatin C (CysC) and asymptomatic carotid atherosclerosis in patients with primary aldosteronism (PA). Methods: In this cross-sectional study, 265 subjects were enrolled, including 83 patients with PA, 91 with essential hypertension (EH), and 91 normotensive (NT) controls. B2M, CysC, plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were measured, and the aldosterone-to-renin ratio (ARR) was calculated. Carotid intima-media thickness (cIMT), increased cIMT, and presence of carotid plaque or carotid stenosis ＜50% in the carotid artery were measuredvia ultrasonography to evaluate the degree of asymptomatic carotid atherosclerosis. Results: CIMT increased in the NT, EH, and PA groups (0.60 (0.50, 0.80) mm vs. 0.80 (0.60, 1.00) mm vs. 0.90 (0.70, 1.10) mm,P＜0.01), so as the prevalence of increased cIMT and presence of carotid plaque (bothP＜0.05). The B2M and CysC levels exhibited the same trend (B2M: 1.60±0.34 mg/L, 1.80±0.41 mg/L, 1.98±0.64 mg/L,P＜0.05; CysC: 0.76±0.12 mg/L, 0.88±0.17 mg/L, 0.94±0.23 mg/L,P＜0.05). B2M, CysC, PAC, and ARR were all positively associated with cIMT (allP＜0.01) in the PA group. After adjusting for potential confounders, B2M, PAC, but not CysC or ARR were independently associated with increased cIMT and presence of carotid plaque and carotid stenosis ＜50%, respectively. The receiver operating characteristic (ROC) curve analysis revealed that B2M and PAC demonstrated significant predictive ability for increased cIMT and presence of carotid plaque and carotid stenosis ＜50%. Conclusion: B2M is an independent risk factor for asymptomatic carotid atherosclerosis in patients with PA.

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.