Carotid Intraplaque Neovascularization Research Articles

Incremental clinical value of intraplaque neovascularization in predicting recurrent ischemic stroke.

Carotid intraplaque neovascularization (IPN) detected by contrast-enhanced ultrasound (CEUS) is a risk factor for recurrent ischemic stroke. However, it is still unclear whether IPN can be used to accurately identify patients with recurrent ischemic stroke in clinical practice. Herein, we investigated the clinical predictive value of IPN for recurrent ischemic stroke in a real-world setting. We enrolled 200 patients with ischemic stroke and atherosclerotic carotid stenosis who were followed up for 2 years. The endpoint was recurrent ischemic stroke. Cox regression and subgroup analyses were employed to assess whether treatment affected the relationship between IPN and recurrent ischemic stroke. The net classification index (NRI) and integrated discriminant improvement index (IDI) were used to validate the additional clinical value of IPN in identifying recurrent ischemic stroke. During the 2-year follow-up, 36 patients experienced recurrent ischemic stroke. Cox regression analyses showed that IPN (grade 2), hypoechoic plaque, high homocysteine levels, and smoking were independent risk factors for recurrent ischemic stroke. Additional IPN evaluation may increase the NRI (0.512; 95% confidence interval [CI]: 0.083-0.624) and IDI (0.151; 95% CI: 0.010-0.213) for identifying high-risk patients with recurrent ischemic stroke. In addition, in the subgroup undergoing revascularization, the proportion of IPN (grade 2) was significantly higher in patients with recurrent ischemic stroke than in patients with nonrecurrent ischemic stroke (p = 0.001). In clinical settings, IPN, assessed by CEUS, may provide additional clinical value for predicting recurrent ischemic stroke, helping to identify patients with ischemic stroke who require close follow-up.

Neovascularization as a Leading Mechanism of Intraplaque Hemorrhage and Carotid Plaque Destabilization: A Narrative Review.

Intraplaque neovascularization (IPN) is considered a leading mechanism causing carotid plaque destabilization. We provide an objective and comprehensive summary of the biology, imaging techniques, and treatment options related to carotid IPN. Plaque neovascularization has been reported to originate mainly from the adventitial vasa vasorum as a response to hypoxia. The leakage and rupture of neovessels lead to the formation of extravasations and foci of inflammation that destabilize the plaque. Vascular endothelial growth factor and its receptors are key regulators of neoangiogenesis. Neovascularization can be analyzed by advanced computed tomography and magnetic resonance imaging. The basic tools for the ultrasound assessment of IPN are contrast-enhanced ultrasound, superb microvascular imaging, and ultrasound molecular imaging. A promising direction of research seems to be the identification of patients with advanced plaque neovascularization. A simple test assessing low-velocity flow in the IPN can detect patients at risk of stroke before they experience rupture of defective neovessels and intracerebral embolism. In addition to surgical treatment, the stabilization of carotid atherosclerotic plaque can be supported pharmacologically. Statins have the best-documented role in this respect. The ideal moment of intensified therapeutic intervention in patients with previously stable carotid plaque is its increased neovascularization. However, the time frame in which intracerebral embolization may occur is unknown, and therapeutic intervention may be too late. The formation of deficient neovessels can currently be non-invasively evaluated with ultrasound. Superb microvascular imaging may change the clinical approach for asymptomatic patients at risk of cerebral ischemia.

The Monocyte-to-Lymphocyte Ratio Was Associated With Intraplaque Neovascularization of the Carotid Artery on AngioPLUS.

The monocyte-lymphocyte ratio (MLR) is a hematological test parameter that reflects the status of both monocytes and lymphocytes as inflammatory cells. This study aims to investigate the relationship between MLR and carotid intraplaque neovascularization (IPN) in patients with asymptomatic carotid stenosis. We performed the Angio Planewave Ultrasensitive (AngioPLUS) screening for patients with carotid plaques. The carotid plaque stability was evaluated by semiquantitative visual grading of carotid IPN. Binary logistic regression models were performed to determine the associations between different clinical and laboratory indicators and the presence of high IPN. A total of 160 patients were eventually enrolled with 99 in the low IPN group (Scores 0-1) and 61 in the high IPN group (Score 2). Univariate logistic regression showed that age, monocytes, lymphocytes, glycated hemoglobin (HbA1c), fibrinogen, d-dimmer, and MLR were significantly associated with the presence of high IPN (all p<0.05). Multivariate logistic regression models showed that MLR was significantly associated with the presence of high IPN after adjusting for other covariates. An MLR value of 32.9 was the optimal cutoff value to differentiate high and low IPN. High MLR was also significantly correlated with the presence of high IPN (odds ratio [OR]=4.08, 95% confidence interval [CI]: 1.69-9.88, p=0.002) when included in the above multivariate logistic regression model. Elevated MLR is closely associated with the presence of high IPN and may serve as a surrogate biomarker for carotid IPN.

Association of cardiovascular risk factors and intraplaque neovascularization in symptomatic carotid plaque.

Cardiovascular risk factors are known to contribute to the formation of atherosclerotic plaques, which can result in carotid stenosis. However, the extent to which these factors are associated with intraplaque neovascularization, a key indicator of plaque vulnerability, remains unclear. To investigate this relationship, a study was conducted utilizing contrast-enhanced ultrasound (CEUS) to assess intraplaque neovascularization in symptomatic patients. A cohort of 157 symptomatic patients underwent evaluation using Contrast-Enhanced Ultrasound (CEUS) imaging to assess carotid intraplaque neovascularization, which was quantified based on the degree of plaque enhancement. The collected data encompassed baseline patient characteristics, results from biochemical examinations, cardiovascular risk factors, and medication usage history. Regression analyses were conducted to elucidate the relationship between carotid plaque neovascularization and various cardiovascular risk factors. Patients with intraplaque neovascularization were more prone to have diabetes mellitus (OR 3.81, 95% CI 1.94-7.46, p < 0.001), dyslipidemia (OR 2.36, 95% CI 1.22-4.55, p = 0.011) and hypertension (OR 2.92, 95% CI 1.50-5.71, p = 0.002). Smoking increased the risk of having intraplaque neovascularization (OR 2.25, 95% CI 1.12-4.54, p = 0.023). Treatment with statins was significantly lower in patients with intraplaque neovascularization (OR 0.37, 95% CI 0.19-0.72, p = 0.003). In the multivariate analysis, diabetes mellitus (OR 3.27, 95% CI 1.10-9.78, p = 0.034) was independently related to the presence of intraplaque neovascularization. Meanwhile, compared to the patients in the first tertile of serum glucose (< 6.20 mmol/L), the patients in the third tertile (> 13.35 mmol/L) had the most significance of intraplaque neovascularization (OR 5.55, 95% CI 1.85-16.66, p = 0.002). The findings indicated that diabetes mellitus is a significant cardiovascular risk factor that is strongly associated with carotid intraplaque neovascularization.

Remnant Cholesterol and Carotid Intraplaque Neovascularization Assessed by Contrast-Enhanced Ultrasonography in Patients With Ischemic Stroke.

We investigated the relationship between remnant cholesterol and carotid intraplaque neovascularization (IPN) assessed by contrast-enhanced ultrasonography (CEUS) in patients with ischemic stroke. This was a single-center study. Remnant cholesterol is calculated as total cholesterol minus low-density lipoprotein cholesterol (LDL-C) minus high-density lipoprotein cholesterol (HDL-C). All patients underwent CEUS. IPN is graded according to the presence and location of microbubbles within each plaque. The cohort included 110 patients with ischemic stroke. Patients with an IPN grading of 2 had higher triglyceride (TG), non-HDL-C, and remnant cholesterol concentrations than those with an IPN grading of < 2 (TG: 1.45 ± 0.69 vs. 0.96 ± 0.24 mmol/L, P < 0.001; non-HDL-C: 2.63 ± 0.85 vs. 2.31 ± 0.64 mmol/L, P = 0.037; remnant cholesterol: 0.57 ± 0.23 vs. 0.44 ± 0.07 mmol/L, P < 0.001). The multivariate-adjusted odds ratio (95% confidence interval) for remnant cholesterol was 27.728 (2.714 - 283.253) for an IPN grading of 2 in the subset of patients with an optimal LDL-C concentration. The remnant cholesterol concentration is significantly associated with carotid IPN on CEUS in patients with ischemic stroke with an optimal LDL-C concentration. Remnant cholesterol may be an important indicator of risk stratification in patients with ischemic stroke.

Effect of combining evolocumab with statin on carotid intraplaque neovascularization in patients with premature coronary artery disease (EPOCH)

Background and aimsWe aimed to explore the effect of PCSK9 inhibitor based on the background of statin on carotid intraplaque neovascularization (IPN) assessed by serial contrast-enhanced ultrasound (CEUS) analysis in Chinese patients with premature coronary artery disease (PCAD). Methods41 patients were included to receive treatments with biweekly evolocumab (n = 22) or placebo (n = 19) in addition to statin therapy for 52 weeks. All patients were newly diagnosed with PCAD and treatments were initiated at baseline of the observations. Baseline and 52-week CEUS were acquired to measure the max plaque height (MPH) and IPN. The primary outcome was the 52-week IPN changes, the secondary endpoints included the 52-week MPH changes and major adverse cardiovascular events. ResultsThe mean ± SD age of the participants was 46.76 ± 8.56 years, and 61% (25/41) of patients were on statins before the start of the study. There was no statistically significant difference in the history of statins treatment and the initiated lipid-lowering therapy of atorvastatin and rosuvastatin between groups (p > 0.05). At 52 weeks, the evolocumab group showed a lower LDL level (0.84 ± 0.45 mmol/L vs. 1.58 ± 0.51 mmol/L, p < 0.001) and a greater decrease in percent reduction of LDL-C level (−65% vs. −32%) and a higher percent of achieving lipid-lowering target (95% vs. 53%, p < 0.05) compared with the placebo group. At 52 weeks, IPN (evolocumab group: 0.50 ± 0.60 vs. 1.50 ± 0.80, p < 0.001; placebo group: 0.79 ± 0.54 vs. 1.26 ± 0.65, p < 0.05) and MPH (evolocumab group: 2.01 ± 0.44 mm vs. 2.57 ± 0.90 mm, p < 0.05, placebo group: 2.21 ± 0.58 mm vs. 2.92 ± 0.86 mm, p < 0.05) reduced significantly in both groups from baseline to 52-week follow-up. IPN and MPH were decreased by both treatments. Still, there was no significant difference in delta (52 weeks - baseline) MPH by an ANOVA analysis between the two groups [evolocumab group: −0.56 mm (2.01 mm–2.57 mm); placebo group: −0.71 mm (2.21 mm–2.92 mm), p > 0.05]. In the evolocumab group, the change in the mean reduction of IPN from baseline [-1.00 (0.50–1.50) vs. −0.47 (0.79–1.26), p < 0.05] and the incidence of patients with carotid IPN decrease were significantly greater reduction (90% vs. 58%, p < 0.05). ConclusionsIf compared to placebo, the PCSK9 inhibitor evolocumab combined with statins resulted in a greater decrease in LDL-C and plaque neovascularization in Chinese patients with PCAD.

Effect of moderate-intensity statin on carotid intraplaque neovascularization of coronary artery disease: a retrospective cohort study.

Statin treatment can reduce atherosclerotic plaque as detected via invasive intracoronary methods. However, few studies have evaluated the effect of moderate-intensity statin therapy on carotid intraplaque neovascularization (IPN) using semiquantitative indices. This study thus aimed to assess the effect of statin on the carotid IPN of coronary artery disease with contrast-enhanced ultrasound (CEUS). In this noncontrol, retrospective, cohort study, 35 inpatients who underwent coronary angiography, serial CEUS, and laboratory evaluations were consecutively enrolled from June 2020 to December 2022 at the Department of Cardiology, Chinese PLA General Hospital. All patients were administered moderate-intensity statin during serial CEUS, and continuous and categorical assessment of IPN and maximum plaque height (MPH) of carotid plaque was performed. Patients with a target low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L at 12-month follow-up were compared with those who did not reach the LDL-C 1.8 mmol/L target. From baseline to 12-month follow-up, there were significant differences in the LDL-C levels between patients (2.71±1.29 vs. 1.35±0.83 mmol/L), those with 12-month follow-up LDL-C <1.8 mmol/L (2.58±1.24 vs. 1.08±0.52 mmol/L), and those with 12-month follow-up LDL-C ≥1.8 mmol/L (3.24±1.44 vs. 2.56±0.85 mmol/L) all P values <0.05, with decreases of 41%, 49%, and 11% from baseline, respectively. The mean MPH (12 months to baseline) decreased from 2.47±0.63 to 2.22±0.60 mm (P<0.05), and the IPN also decreased from 1.15±0.62 to 0.58±0.56, representing a reduction of 0.57±0.59 from baseline (P<0.001). In the LDL-C <1.8 mmol/L patients, there were significant differences between baseline and 12 months in MPH (2.37±0.56 vs. 2.03±0.52 mm; P<0.05) and IPN (1.32±0.77 vs. 0.54±0.63; P<0.05) compared with those with a follow-up LDL-C ≥1.8 mmol/L. Patients with a follow-up LDL-C <1.8 mmol/L, compared with those with a follow-up LDL-C ≥1.8 mmol/L, showed a significantly greater reduction in MPH (-0.34±0.46 vs. -0.13±0.39; P<0.05) and IPN (-0.79±0.63 vs. -0.57±0.79; P<0.05). Additionally, patients with carotid IPN regression showed a higher percent change in LDL-C compared with those without carotid IPN regression (-53.31±23.20 vs. -29.55±19.47; P<0.05). Controlling the LDL-C to <1.8 mmol/L under moderate-intensity statin can stabilize and reduce carotid IPN as detected by the semiquantitative noninvasive CEUS.

Diagnostic accuracy of superb microvascular imaging for detecting intraplaque neovascularization: a systematic review and meta-analysis.

Atherosclerotic plaques can cause carotid artery stenosis, and "vulnerable plaques" can even lead to ischemic stroke. The objective of this study was to assess the accuracy of superb microvascular imaging (SMI) for the detection of carotid intraplaque neovascularization (IPN) in patients with atherosclerotic plaques. We searched the Cochrane Library, Embase, Medline, and Wanfang databases until January 17, 2023. We included original studies with information on diagnostic accuracy of SMI for the evaluation of carotid IPN. The primary outcome was the accuracy of SMI for detecting carotid IPN. A meta-analysis was performed to estimate the accuracy of each parameter. We used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) to assess the risk of bias for each included article. Meta-regression was performed to determine items that may have contributed to heterogeneity in the sensitivity or specificity of the test. This meta-analysis included 20 studies with 1,589 carotid plaques in 1,225 patients. The analysis showed a sensitivity and specificity of SMI for detecting IPN of 93% [95% confidence interval (CI): 87-96%] and 80% (95% CI: 71-87%), respectively. The risk of bias across the QUADAS-2 domains was low. Only the proportion of dyslipidemia influenced the estimates of sensitivity and specificity. This review suggests that SMI has a good diagnostic performance for detecting carotid IPN. The very high sensitivity with excellent post-test probability indicated that SMI can be recommended to screen for carotid IPN among patients with carotid plaques.

Effect of evolocumab on the progression of intraplaque neovascularization of the carotid based on contrast-enhanced ultrasonography (EPIC study): A prospective single-arm, open-label study.

Background and Purpose: The aim of this study was to explore the effect of half a year of evolocumab plus moderate-intensity statin treatment on carotid intraplaque neovascularization (IPN) and blood lipid levels. Methods: A total of 31 patients with 33 carotid plaques who received evolocumab plus statin treatment were included. Blood lipid levels, B-mode ultrasound and contrast-enhanced ultrasonography (CEUS) at baseline and after half a year of evolocumab plus statin therapy were collected. The area under the curve (AUC) reflected the total amount of acoustic developer entering the plaque or lumen within the 180s measurement period. The enhanced intensity reflected the peak blood flow intensity during the monitoring period, and the contrast agent area reflected the area of vessels in the plaques. Results: Except for high-density lipoprotein cholesterol (HDL-c), all other lipid indices decreased. Compared with baseline, low-density lipoprotein cholesterol (LDL-c) decreased by approximately 57% (p < 0.001); total cholesterol (TC) decreased by approximately 34% (p < 0.001); small dense low-density lipoprotein (sd-LDL) decreased by approximately 52% (p < 0.001); and HDL-c increased by approximately 20% (p < 0.001). B-mode ultrasonography showed that the length and thickness of the plaque and the hypoechoic area ratio were reduced (p < 0.05). The plaque area, calcified area ratio, and lumen cross-sectional area changed little (p > 0.05). CEUS revealed that the area under the curve of plaque/lumen [AUC (P/L)] decreased from 0.27 ± 0.13 to 0.19 ± 0.11 (p < 0.001). The enhanced intensity ratio of plaque/lumen [intensity ratio (P/L)] decreased from 0.37 ± 0.16 to 0.31 ± 0.14 (p = 0.009). The contrast agent area in plaque/area of plaque decreased from 19.20 ± 13.23 to 12.66 ± 9.59 (p = 0.003). The neovascularization score decreased from 2.64 ± 0.54 to 2.06 ± 0.86 (p < 0.001). Subgroup analysis based on statin duration (<6months and ≥6months) showed that there was no significant difference in the AUC (P/L) or intensity ratio (P/L) at baseline or after half a year of evolocumab treatment. Conclusion: This study found that evolocumab combined with moderate-intensity statins significantly improved the blood lipid profile and reduced carotid IPN. Clinical Trial Registration: https://www.clinicaltrials.gov; identifier: NCT04423406.

Association between Carotid Intraplaque Neovascularization Detected by Contrast-Enhanced Ultrasound and the Progression of Coronary Lesions in Patients Undergoing Percutaneous Coronary Intervention

It is thought that the progression of vulnerable plaque is due in part to neovascularization, and plaque vulnerability is a useful approach for classifying cardiovascular risk. The aim of this retrospective study was to evaluate the correlation between carotid intraplaque neovascularization (IPN) detected on contrast-enhanced ultrasound and the progression of coronary lesions in patients undergoing percutaneous coronary intervention (PCI). Contrast-enhanced ultrasound and angiography were performed in 131 patients undergoing PCI. All patients had angiograms obtained ≥12months after PCI, and progression was defined using those angiograms. On the basis of angiographic images, patients were divided into progression and nonprogression groups. IPN was graded from 0 to 3 according to each plaque's microbubble appearance and extent, detected using contrast-enhanced ultrasound. The plaque with the highest IPN was used for analysis. Logistic regression and receiver operating characteristic analyses were applied to evaluate risk factors for predicting the progression of coronary lesions in patients undergoing PCI. In the progression group, the numbers of patients with IPN values of 0, 1, 2, and 3 were one (3.3%), nine (30.0%), 16 (53.3%), and four (13.3%), respectively. Significant differences were found in maximum plaque height and IPN between groups. IPN and maximum plaque height were independent risk contributors to coronary lesion progression in patients undergoing PCI. The sensitivity, specificity, positive predictive value, and negative predictive value of IPN of 1.5 and to predict the progression of coronary lesions were 67%, 91%, 68%, and 89%, respectively. The area under the curve was 0.822. Carotid plaque neovascularization was correlated with the progression of coronary lesions in patients undergoing PCI. IPN is a clinically useful tool for detecting the progression of coronary lesions and for risk stratification, especially in patients >60years old.

Carotid intraplaque neovascularization is correlated with the risk of revascularization following percutaneous coronary intervention

To investigate the correlation of intraplaque neovascularization (IPN) detected by carotid contrast-enhanced ultrasound (CEUS) with revascularization in patients following percutaneous coronary intervention (PCI). This study was conducted among 105 patients who were followed up for more than 12 months after PCI. All the patients received CEUS examination for assessment of carotid plaque formation and IPN, which were compared between patients with revascularization (REV group, n=27) and those without revascularization (N-REV group, n=78). ROC curve was used to analyze the diagnostic efficacy of CEUS for predicting revascularization. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with revascularization. In the REV group, the IPN score was 0 in 1 (3.7%) patient, 1 in 8 (29.6%) patients, 2 in 15 (55.6%) patients and 3 in 3 (11.1%) patients. Significant differences were noted between REV and N-REV groups in plaque length (15.70±6.93 vs 12.10±6.64, P < 0.05), maximum plaque thickness (3.69±1.12 vs 3.14±1.18, P < 0.05) and IPN (1.74±0.71 vs 0.87±0.63, P < 0.001). IPN score was identified as an independent risk factor for revascularization in patients following PCI, and at the cutoff value of 1.5, its sensitivity, specificity, positive predictive value, and negative predictive value for predicting the occurrence of revascularization were 74%, 89%, 69%, and 91%, respectively, with an AUC of 0.848 (95% CI: 0.703-0.905, P < 0.001). CEUS allows noninvasive and semi-quantitative assessment of neovascularization in carotid artery plaques, and IPN detected by CEUS is correlated with the risk of revascularization in patients following PCI.

Carotid Intraplaque Neovascularization and Future Vascular Events in Patients With Asymptomatic Carotid Stenosis.

Objective: Intraplaque neovascularization is a marker of plaque vulnerability and is used to predict the risk of future vascular events in patients with symptomatic carotid stenosis; however, its association with asymptomatic carotid stenosis has not been prospectively evaluated. Therefore, this study aimed to explore the association between intraplaque neovascularization assessed using contrast-enhanced ultrasound and the occurrence of future ischemic events in asymptomatic patients diagnosed with carotid stenosis. Methods: We recruited patients with asymptomatic carotid stenosis from our center. Contrast-enhanced ultrasound was performed at baseline. The outcomes were ischemic stroke and cardiovascular events. We plotted Kaplan-Meier survival curves and performed a log-rank test to compare endpoint event probability in patients with and without grade 2 intraplaque neovascularization. Univariate and multivariate Cox proportional hazards models were used to assess predictors of future vascular events. Results: The data of 50 participants were included in the analysis (median follow-up, 43.7 months). Endpoint events occurred in 12 participants (24%). The Kaplan-Meier survival curves showed that patients with grade 2 intraplaque neovascularization had a higher probability of future vascular events than those with grades 0 and 1 (p < .05). Grade 2 intraplaque neovascularization (hazard ratio: 4.530, 95% confidence interval, 1.337–15.343, p < .05) was an independent predictor of future vascular events in patients with asymptomatic carotid stenosis. Conclusion: Grade 2 intraplaque neovascularization assessed using contrast-enhanced ultrasound independently predicted future ischemic events in patients with asymptomatic carotid stenosis, and contrast-enhanced ultrasound may be an effective screening method to identify high-risk subgroups of patients with asymptomatic carotid stenosis.

Neutrophil-to-lymphocyte ratio is associated with carotid intraplaque neovascularization in asymptomatic carotid stenosis patients.

Neutrophil-to-lymphocyte ratio (NLR) has been suggested as an available systemic inflammatory biomarker. This study aims to evaluate whether intraplaque neovascularization assessed by contrast-enhanced ultrasound (CEUS) is associated with NLR in asymptomatic carotid stenosis patients. One hundred and forty-four asymptomatic patients with carotid luminal stenosis >30% were assessed using contrast-enhanced ultrasound imaging. The contrast enhancement within the plaque was classified on a visual semiquantitative grading scale. The data collected included the patient's risk factors, laboratory results, cardiovascular disease history, and drug use history. Univariate and multivariate analyses were assessed to identify independent factors related to intraplaque neovascularization with adjustment for potential confounders. Patients with CEUS grade 2 plaques had a higher level of LDL-C (p < .001), neutrophil count (p < .001), and blood glucose (p=.005), but lower level of lymphocyte count (p=.021). The presence of grade 2 plaques was significantly associated with high NLR values (OR 1.21, 95% CI 1.03-1.43, p=.017). Patients were divided into four groups according to the quartile of NLR values. Compared to the patients in the first quartile of NLR (<1.73), the patients in the fourth NLR quartile (≥3.38) were characterized by the most prevalence of CEUS grade 2 plaques (OR 4.55, 95% CI 1.69-12.25, p=.003). Multivariate logistic regression analysis after adjusting various variables demonstrated NLR remained an independent risk factor for the presence of CEUS grade 2 plaques. Intraplaque neovascularization is significantly associated with NLR in asymptomatic carotid stenosis patients.

Relationship Between Serum Lipid Profiles and Carotid Intraplaque Neovascularization in a High-Stroke-Risk Population: A Cross-Sectional Study in China.

BackgroundEvidence of the association between serum lipid profiles and intraplaque neovascularization (IPN) is still limited. We aimed to study the value of a novel Doppler method, superb microvascular imaging, in correlating serum lipid profiles and evidence of IPN in a population with a high risk of stroke.Methods and ResultsA community‐based cross‐sectional study was conducted in Beijing, China. Residents (aged ≥40 years) underwent questionnaire interviews, physical examinations, and laboratory testing in 2018 and 2019. Subjects with a high risk of stroke were then selected. Standard carotid ultrasound and carotid plaque superb microvascular imaging examinations were then performed on the high–stroke‐risk participants. Logistic regression was used to evaluate the relationship between serum lipid profiles and carotid plaque IPN. Overall, a total of 250 individuals (mean age, 67.20±8.12 years; 66.4% men) met the study inclusion criteria. Superb microvascular imaging revealed carotid plaque IPN in 96 subjects (38.4%). Subjects with IPN were more likely to be current smokers (34.0% versus 46.9%, P=0.046), and their identified carotid plaques were much thicker (2.35±0.63 mm versus 2.75±0.80 mm, P=0.001). Serum lipids, including total cholesterol, non–high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol were positively associated with the presence of IPN (4.33±1.00 mmol/L versus 4.79±1.12 mmol/L, P=0.001; 2.96±0.92 mmol/L versus 3.40±1.01 mmol/L, P=0.001; 2.18±0.76 mmol/L versus 2.46±0.80 mmol/L, P=0.005, respectively), and after adjustment for other confounders, the positive relationship remained significant. Furthermore, non–high‐density lipoprotein cholesterol (odds ratio, 2.62 [95% CI, 1.35–5.06]) was significantly associated with the presence of carotid plaque IPN even after adjusting for low‐density lipoprotein cholesterol.ConclusionsTotal cholesterol, non–high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol were positively associated with the presence of carotid IPN in a Chinese high–stroke‐risk population. Further prospective studies should be conducted to better understand how much finding IPN adds to current stroke prediction tools.

Role of artificial intelligence in cardiovascular risk prediction and outcomes: comparison of machine-learning and conventional statistical approaches for the analysis of carotid ultrasound features and intra-plaque neovascularization.

The aim of this study was to compare machine learning (ML) methods with conventional statistical methods to investigate the predictive ability of carotid plaque characteristics for assessing the risk of coronary artery disease (CAD) and cardiovascular (CV) events. Focused carotid B-mode ultrasound, contrast-enhanced ultrasound, and coronary angiography were performed on 459 participants. These participants were followed for 30days. Plaque characteristics such as carotid intima-media thickness (cIMT), maximum plaque height (MPH), total plaque area (TPA), and intraplaque neovascularization (IPN) were measured at baseline. Two ML-based algorithms-random forest (RF) and random survival forest (RSF) were used for CAD and CV event prediction. The performance of these algorithms was compared against (i) univariate and multivariate analysis for CAD prediction using the area-under-the-curve (AUC) and (ii) Cox proportional hazard model for CV event prediction using the concordance index (c-index). There was a significant association between CAD and carotid plaque characteristics [cIMT (odds ratio (OR) = 1.49, p = 0.03), MPH (OR = 2.44, p < 0.0001), TPA (OR = 1.61, p < 0.0001), and IPN (OR = 2.78, p < 0.0001)]. IPN alone reported significant CV event prediction (hazard ratio = 1.24, p < 0.0001). CAD prediction using the RF algorithm reported an improvement in AUC by ~ 3% over the univariate analysis with IPN alone (0.97 vs. 0.94, p < 0.0001). Cardiovascular event prediction using RSF demonstrated an improvement in the c-index by ~ 17.8% over the Cox-based model (0.86 vs. 0.73). Carotid imaging phenotypes and IPN were associated with CAD and CV events. The ML-based system is superior to the conventional statistically-derived approaches for CAD prediction and survival analysis.

Detection of Carotid Atherosclerotic Intraplaque Neovascularization Using Superb Microvascular Imaging: A Meta‐Analysis

Although superb microvascular imaging (SMI) (Toshiba/Canon, Tokyo, Japan) has enabled routine characterization of intraplaque neovascularization (IPN) features in patients with carotid stenosis, no reports have been published on the multicenter and large sample size research in this aspect. The efficacy of SMI in detecting carotid IPN has not been concluded. This study aimed to assess the efficacy of SMI comparing with contrast-enhanced carotid ultrasonography (CEUS) in the detection of carotid IPN or pathologic evaluations of IPN correlated with a history of stroke or transient ischemic attack (TIA). Web of Science, Cochrane Library, PubMed, Embase, and Scopus were searched up to August 2020 to identify peer-reviewed human studies on the diagnostic accuracy of SMI in detecting IPN. For the selected study, the correlation coefficient R and Kappa index between SMI and CEUS in detecting IPN were calculated. The correlation coefficient R between SMI in identifying IPN and pathologic evaluations of IPN and the odds ratio of IPN detected by SMI and history of stroke or TIA were also extracted. The subgroup analysis was performed to indicate the source of heterogeneity. Our search identified 11 reports enrolling a total of 605 carotid stenosis patients. Carotid IPN detected by SMI was significantly correlated with which detected by CEUS (R, 0.89; 95% CI, 0.80-0.94; P = .00, and Kappa index, 0.73; 95% CI, 0.67-0.80; P = .00). Notably, a significant correlation was observed in SMI in detecting IPN and pathologic evaluations of IPN (R, 0.52; 95% CI, 0.40-0.62; P = .00). The odds ratio of IPN detected by SMI and history of stroke or TIA was pooled summary with statistical significance (OR, 3.33; 95% CI, 1.78-6.23; P = 0.00). In subgroup analysis, lower heterogeneity was associated with the degree of carotid stenosis, patients from which country, and types of equipment. SMI and CEUS display an excellent agreement in detecting carotid IPN. IPN detected by SMI shows high consistency with pathologic evaluations of IPN. Individuals with carotid IPN are more likely to develop stroke or TIA than those without carotid IPN.

Carotid Intraplaque Neovascularization Predicts Ischemic Stroke Recurrence in Patients with Carotid Atherosclerosis

Introduction: This study aimed to examine whether intraplaque neovascularization (IPN) of carotid plaques, as characterized by contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke recurrence in patients with carotid atherosclerosis. Methods: We conducted a prospective study of consecutive patients with a recent stroke and at least one atherosclerotic plaque in the carotid artery on the side consistent with symptoms. All patients underwent CEUS after their first admission. IPN was graded on the basis of the presence and location of microbubbles within each plaque. Results: We eventually included 155 patients, all of whom underwent IPN analysis. After a follow-up of 24 months, we recorded 25 (16.1%) stroke recurrences in the whole population. All the recurrences occurred in patients presenting IPN. There was significant difference in the IPN between the 2 groups (p = 0.002). In the final Cox proportional-hazards multivariable models, IPN of grade 2 was independently associated with the risk of stroke recurrence (HR = 4.535; 95% CI: 1.892–10.870; p = 0.001). This association remained after adjusting for the degree of carotid stenosis (HR = 3.491; 95% CI: 1.410–8.646; p = 0.007). Conclusions: IPN was an independent predictor of stroke recurrence in patients with a recent ischemic stroke and carotid atherosclerosis. In predicting stroke recurrence, IPN may be an earlier indicator than carotid stenosis and may help stratify the risk of stroke recurrence.

Relationship between carotid intraplaque neovascularization and haemoglobin A1c in diabetic patients

IntroductionWe aimed to evaluate the characteristics of carotid artery plaques and the relationship between intraplaque neovascularization (IPN) and hemoglobin A1c (HbA1c) in patients of <60 years old with diabetes mellitus (DM) by comparison with diabetes ≥60 years of age. MethodsOne-hundred-and-one patients with DM were studied into two groups: those <60 and those ≥60 years of age. All the patients underwent standard carotid ultrasonography and contrast-enhanced ultrasonography, which we used to evaluate IPN. ResultsDiabetic complications were present in 41 of 50 patients (82 %) in the <60-year-old group, of whom 17 (34 %) had diabetes-related vascular complications. Of the 47 plaques in the <60-year-old group, six (13 %) had IPN Grade 0, 16 (34 %) had IPN Grade 1, and 25 (53 %) had IPN Grade 2. The AUC and RAUC of the plaque in the <60-year-old group were significantly higher than those of the ≥60-year-old group (P = 0.012 and 0.031, respectively). There were also differences in the AUC, RAUC and semi-quantitative grades between patients with and without diabetic macrovasculopathy and diabetic peripheral artery disease (all P < 0.05). The AUC, RAUC and semi-quantitative grading of IPN positively correlated with blood glucose and HbA1c (P < 0.05). ConclusionIPN is more common in DM patients who are younger, and have higher blood glucose and HbA1c concentrations, and these plaques are more vulnerable.

Prognostic Value of Intraplaque Neovascularization Detected by Carotid Contrast-Enhanced Ultrasound in Patients Undergoing Stress Echocardiography

Stress echocardiography (SE) is used for diagnosis and risk stratification of patients with known or suspected coronary artery disease (CAD). Contrast-enhanced ultrasound (CEUS) detects carotid intraplaque neovascularization (IPN). The aim of this study was to test the hypothesis that combining SE with carotid CEUS in patients with known or suspected CAD might provide incremental prognostic value beyond clinical risk factors and either test alone for the occurrence of cardiovascular events. One hundred eighty-five patients (mean age, 69±8years; 79% men) with known or suspected CAD referred for SE and found to have carotid plaque on screening were recruited for carotid CEUS imaging. IPN was graded by presence and location within plaque. Patients were followed for cardiovascular events (CVEs) including cardiac death, myocardial infarction, unstable angina, and transient ischemic attack or stroke. A subset of patients (n=27) underwent carotid magnetic resonance imaging within 1month of CEUS; carotid plaque was assessed for lipid-rich necrotic core, loose matrix, and presence of intraplaque hemorrhage. Sixty-nine patients had abnormal findings on SE. IPN was identified in 112 patients; 52 patients had IPN localized to plaque shoulder (IPNS). Plaques with IPNS had larger lipid-rich necrotic cores and were more likely to have intraplaque hemorrhage. During follow-up (median, 31months), 26 CVEs occurred. Multivariate Cox proportional-hazard analysis showed IPN and IPNS to be predictors of CVEs (hazard ratios, 3.34 [95% CI, 1.25-8.93; P=.02] and 4.88 [95% CI, 1.77-13.49; P=.002], respectively). The presence of IPNS increased the likelihood of CVEs beyond SE and history of CAD (χ2=9.0, P=.02). Carotid IPN detected by CEUS and localized to plaque shoulder was an independent predictor of CVEs in patients referred for SE.

Correlation of Cerebral White Matter Lesions with Carotid Intraplaque Neovascularization assessed by Contrast-enhanced Ultrasound

PurposeCarotid atherosclerotic plaque is closely associated with cerebral white matter lesions (WMLs), while intraplaque neovascularization (IPN) contributes significantly to arterial remodeling and plaque vulnerability. In this study, we aim to evaluate the correlation of carotid IPN with cerebral WMLs. MethodsThe presence of IPN and WMLs were assessed by contrast-enhanced ultrasound (CEUS) and MRI respectively. IPN was evaluated utilizing semi-quantification visual grading scale and WMLs was divided according to Fazekas grading scale. We investigated the baseline data, Fazekas grades, and IPN grades among 269 participants. We explored the influences of each variable on Fazekas grades using ordinal logistic regression and evaluated the relationship between IPN grades and WMLs Fazekas grades. ResultsIncreased age (OR: 1.06, P<0.001), hypertension (OR: 2.17, P=0.002), cerebral infarction (OR: 1.74, P=0.046), and elevated carotid IPN grading were significantly associated with aggravated Fazekas grades (grade 2 or 3). To be specific, people having grade 3, 2, and 1 carotid IPN were 25.84 (P<0.001), 10.64 (P<0.001), and 5.96 (P=0.010) times as likely to have elevated Fazekas grades compared with those who having grade 0 carotid IPN. ConclusionIncreased carotid IPN is independently correlated with aggravated cerebral WMLs.