Plaque Ruptures Are Related to High Plaque Stress and Strain Conditions: Direct Verification by Using In Vivo OCT Rupture Data and FSI Models.

BACKGROUND: While it has been hypothesized that high plaque stress and strain may be related to plaque rupture, its direct verification using in vivo coronary plaque rupture data and full 3-dimensional fluid-structure interaction models is lacking in the current literature due to difficulty in obtaining in vivo plaque rupture imaging data from patients with acute coronary syndrome. This case-control study aims to use high-resolution optical coherence tomography-verified in vivo plaque rupture data and 3-dimensional fluid-structure interaction models to seek direct evidence for the high plaque stress/strain hypothesis. METHODS: In vivo coronary plaque optical coherence tomography data (5 ruptured plaques, 5 no-rupture plaques) were acquired from patients using a protocol approved by the local institutional review board with informed consent obtained. The ruptured caps were reconstructed to their prerupture morphology using neighboring plaque cap and vessel geometries. Optical coherence tomography-based 3-dimensional fluid-structure interaction models were constructed to obtain plaque stress, strain, and flow shear stress data for comparative analysis. The rank-sum test in the nonparametric test was used for statistical analysis. RESULTS: Our results showed that the average maximum cap stress and strain values of ruptured plaques were 142% (457.70 versus 189.22 kPa; P=0.0278) and 48% (0.2267 versus 0.1527 kPa; P=0.0476) higher than that for no-rupture plaques, respectively. The mean values of maximum flow shear stresses for ruptured and no-rupture plaques were 145.02 dyn/cm2 and 81.92 dyn/cm2 (P=0.1111), respectively. However, the flow shear stress difference was not statistically significant. CONCLUSIONS: This preliminary case-control study showed that the ruptured plaque group had higher mean maximum stress and strain values. Due to our small study size, larger scale studies are needed to further validate our findings.

Symptomatic Nonstenotic Carotids: A Topical Review.

Historically, the management of carotid artery disease has primarily focused on the degree of stenosis as the main indicator for assessing stroke etiology, risk, and need for intervention. However, accumulating evidence suggests that structural and biological features within the arterial wall, such as intraplaque hemorrhage, may have superior diagnostic, prognostic, and therapeutic values. Under current guidelines, unless an atheroma results in ≥50% stenosis, it is not considered the cause of a cerebrovascular event. This results in extensive and often unproductive diagnostic workup, prescription of ineffective medical therapy, and preclusion of patients from receiving revascularization procedures that have been shown to prevent recurrent cerebrovascular events in cases of ≥50% stenosis. A subset of embolic strokes of undetermined source, which account for up to 25% of all ischemic cerebrovascular events, are thought to be due to thromboembolic phenomena from undiagnosed plaque disruptions in nonstenotic arteries (<50% stenosis). Recently, it has been proposed to reclassify this subgroup of patients as symptomatic nonstenotic carotid if the carotid plaque ipsilateral to the cerebrovascular event presents with high-risk features including intraplaque hemorrhage, lipid-rich necrotic core, thinning/rupture of the fibrous cap, and ulceration. In this review, we first provide a historical overview of the chain of events and circumstances that resulted in the present management of carotid artery disease. Second, we embed the contemporary biomarkers of plaque vulnerability in a modern mechanistic paradigm of carotid plaque disruption and thromboembolization. Third, we review the clinically available imaging tools to detect these biomarkers, and how their use has started to shed light on the prevalence and natural history of this underdiagnosed condition. Fourth, we review recent clinical studies employing a contemporary definition of symptomatic nonstenotic carotid and discuss targeted treatments for this condition. Finally, we make a case to generate the much-needed high-level evidence to align the clinical management of patients with symptomatic nonstenotic carotid with a contemporary understanding of plaque disruption and thromboembolization.

Histological Validation of 3D Variable Flip Angle TSE Multi-Contrast Magnetic Resonance Vessel Wall Imaging in Characterizing Carotid Vulnerable Atherosclerotic Plaques.

BACKGROUND: Accurate assessment of the vulnerability of carotid atherosclerotic plaques is crucial for stroke prevention. The three-dimensional (3D) magnetic resonance (MR) vessel wall imaging (VWI) has been increasingly employed to evaluate carotid plaques due to its extensive coverage and isotropic high spatial resolution. However, the accuracy of such technique lacks validation by histology. OBJECTIVE: This study aims to validate the accuracy of 3D multi-contrast MR VWI used variable-flip-angle (VFA) and turbo spin echo (TSE) readout in identifying vulnerable carotid plaques, using histological analysis as a reference. METHODS: Twenty-one male patients (mean age: 64.4 ± 7.2 years) scheduled for carotid endarterectomy (CEA) were recruited for this study. All patients underwent carotid multi-contrast MR VWI, including 3D T1- and T2-weighted variable flip angle-based turbo spin echo (VFA-TSE) sequences, as well as 3D time of flight (TOF) MR angiography (MRA), using a 3.0T MR system. Histological processing was performed for carotid plaque specimens. The presence or absence, along with the area measurements, of lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and calcifications (CA) were independently evaluated on both MR images and histological sections. Cohen's kappa (κ) analysis was utilized to determine the agreement between 3D multi-contrast MR VWI and histology in identifying carotid plaque compositions before and after excluding compositions bellow certain size threshold. Spearman's correlation analysis was also conducted to assess the agreement in quantifying plaque compositions. RESULTS: A total of 81 slices of MR images were successfully matched with histological sections. Moderate to almost perfect agreements were observed between 3D MR VWI and histology in the identification of LRNC (κ: 0.85 and 0.89), IPH (κ: 0.65 and 0.69), and CA (κ: 0.46 and 0.62) before and after excluding compositions smaller than 0.79 mm2. Strong to very strong correlations were found in the quantification of plaque compositions including LRNC (r=0.88), IPH (r=0.80), and CA (r=0.74) between MR imaging and histology. CONCLUSION: The 3D VFA-TSE multi-contrast MR VWI is capable of accurately characterizing vulnerable carotid atherosclerotic plaques.

Body mass index and characteristics of coronary plaque in younger patients with type 2 diabetes.

BACKGROUND AND AIMS: The association between the body mass index (BMI) and the characteristics of coronary plaque in younger type 2 diabetes (T2D) patients with coronary artery disease (CAD) remains to be elucidated. METHODS AND RESULTS: A total of 138 consecutive younger (<65 years) T2D patients with CAD, who underwent optical coherence tomography imaging of the culprit lesion were included. The patients were classified into either the higher BMI group (n = 68) or the lower BMI group (n = 70) according to the median of BMI (25.9 kg/m2). The prevalence of thin-cap fibroatheroma (TCFA) (35.3 vs. 17.1 %, p = 0.015) was significantly higher in the higher BMI group than in the lower BMI group. The prevalence of TCFA was significantly higher in patients with higher BMI than in those with lower BMI among patients with hemoglobin A1c (HbA1c) ≥7.0 % (odds ratio [OR] 5.40, 95 % confidence interval [CI] 1.72-17.0, p = 0.003) although the significant difference was not observed among patients with HbA1c <7.0 % (OR 0.89, 95 % CI 0.25-3.13, p = 0.851). CONCLUSION: Higher BMI was associated with a higher prevalence of TCFA in younger T2D patients with CAD, particularly in patients with HbA1c ≥ 7.0 %.

Higher triglyceride levels are associated with the higher prevalence of layered plaques in non-culprit coronary plaques.

High triglyceride (TG) levels have been recognized as a risk factor for cardiovascular events in patients with coronary artery disease (CAD). This study aimed to clarify the association between TG levels and characteristics of non-culprit coronary plaques in patients with CAD. A total of 531 consecutive patients with stable CAD who underwent percutaneous coronary intervention for culprit lesions and optical coherence tomography (OCT) assessment of non-culprit plaques in the culprit vessel were included in this study. The morphology of the non-culprit plaques assessed by OCT imaging were compared between the higher TG (TG ≥ 150 mg/dL, n = 197) and lower TG (TG < 150 mg/dL, n = 334) groups. The prevalence of layered plaques (40.1 vs. 27.5%, p = 0.004) was significantly higher in the higher TG group than in the lower TG group, although the prevalence of other plaque components was comparable between the two groups. High TG levels were an independent factor for the presence of layered plaques (odds ratio 1.761, 95% confidence interval 1.213-2.558, p = 0.003) whereas high low-density lipoprotein cholesterol levels (≥ 140 mg/dL) and low eicosapentaenoic acid/arachidonic acid ratios (< 0.4) were independently associated with a higher prevalence of thin-cap fibroatheroma and macrophages. Higher TG levels were associated with a higher prevalence of layered plaques in non-culprit plaques among patients with stable CAD. These results may partly explain the effect of TG on the progression of coronary plaques and the increased incidence of recurrent events in patients with CAD.

Notoginsenoside R1 decreases intraplaque neovascularization by governing pericyte-endothelial cell communication via Ang1/Tie2 axis in atherosclerosis.

Atherosclerosis represents the major cause of mortality worldwide and triggers higher risk of acute cardiovascular events. Pericytes-endothelial cells (ECs) communication is orchestrated by ligand-receptor interaction generating a microenvironment which results in intraplaque neovascularization, that is closely associated with atherosclerotic plaque instability. Notoginsenoside R1 (R1) exhibits anti-atherosclerotic bioactivity, but its effect on angiogenesis in atherosclerotic plaque remains elusive. The aim of our study is to explore the therapeutic effect of R1 on vulnerable plaque and investigate its potential mechanism against intraplaque neovascularization. The impacts of R1 on plaque stability and intraplaque neovascularization were assessed in ApoE-/- mice induced by high-fat diet. Pericytes-ECs direct or non-direct contact co-cultured with VEGF-A stimulation were used as the in vitro angiogenesis models. Overexpressing Ang1 in pericytes was performed to investigate the underlying mechanism. In vivo experiments, R1 treatment reversed atherosclerotic plaque vulnerability and decreased the presence of neovessels in ApoE-/- mice. Additionally, R1 reduced the expression of Ang1 in pericytes. In vitro experiments demonstrated that R1 suppressed pro-angiogenic behavior of ECs induced by pericytes cultured with VEGF-A. Mechanistic studies revealed that the anti-angiogenic effect of R1 was dependent on the inhibition of Ang1 and Tie2 expression, as the effects were partially reversed after Ang1 overexpressing in pericytes. Our study demonstrated that R1 treatment inhibited intraplaque neovascularization by governing pericyte-EC association via suppressing Ang1-Tie2/PI3K-AKT paracrine signaling pathway. R1 represents a novel therapeutic strategy for atherosclerotic vulnerable plaques in clinical application.

Association between elevated lipoprotein(a) levels and vulnerability of carotid atherosclerotic plaque: A systematic review.

BACKGROUND: The role of lipoprotein(a) [Lp(a)] as a potential risk factor for atherosclerotic arterial disease has been extensively studied. However, the available data regarding its association with the vulnerability of carotid atherosclerotic plaque is limited. The main objective of the present systematic review was to assess the association between elevated Lp(a) levels and carotid vulnerable plaque features. METHODS: This systematic review adhered to PRISMA guidelines, conducting a comprehensive literature search to identify studies examining the association between Lp(a) levels and vulnerability of carotid atherosclerotic plaque. Experimental or observational studies were eligible, without language, country, or publication type restrictions. RESULTS: Nine studies including 2058 patients were eligible for this systematic review. Five cross-sectional studies, 3 prospective/retrospective cohorts, and 1 subanalysis of a randomized controlled trial were analyzed. Two cross-sectional studies that compared Lp(a) levels between patients with and without vulnerable carotid plaque showed discordant results. Nevertheless, all the studies that evaluated the prevalence or incidence of vulnerable carotid plaque according to Lp(a) levels showed a positive association. Similarly, one study found a significant correlation between vulnerability of carotid plaque and Lp(a) levels. CONCLUSION: Almost all studies analyzed in the present review showed a positive association between elevated Lp(a) levels and carotid vulnerable plaque features. However, further research is needed to clarify this issue.

MicroRNA Inhibiting Atheroprotective Proteins in Patients with Unstable Angina Comparing to Chronic Coronary Syndrome.

Patients with unstable angina present clinical characteristics of atherosclerotic plaque vulnerability, contrary to chronic coronary syndrome patients. The process of athersclerotic plaque destabilization is also regulated by microRNA particles. In this study, the investigation on expression levels of microRNAs inhibiting the expression of proteins that protect from atherosclerotic plaque progression (miR-92a inhibiting KLF2, miR-10b inhibiting KLF4, miR-126 inhibiting MerTK, miR-98 inhibiting IL-10, miR-29b inhibiting TGFß1) was undertaken. A number of 62 individuals were enrolled-unstable angina (UA, n = 14), chronic coronary syndrome (CCS, n = 38), and healthy volunteers (HV, n = 10). Plasma samples were taken, and microRNAs expression levels were assessed by qRT-PCR. As a result, the UA patients presented significantly increased miR-10b levels compared to CCS patients (0.097 vs. 0.058, p = 0.033). Moreover, in additional analysis when UA patients were grouped together with stable patients with significant plaque in left main or proximal left anterior descending ("UA and LM/proxLAD" group, n = 29 patients) and compared to CCS patients with atherosclerotic lesions in other regions of coronary circulation ("CCS other" group, n = 25 patients) the expression levels of both miR-10b (0.104 vs. 0.046; p = 0.0032) and miR-92a (92.64 vs. 54.74; p = 0.0129) were significantly elevated. In conclusion, the study revealed significantly increased expression levels of miR-10b and miR-92a, a regulator of endothelial protective KLF factors (KLF4 and KLF2, respectively) in patients with more vulnerable plaque phenotypes.

Intracoronary Imaging for Changing Therapeutic Decisions in Patients with Multivascular Coronary Artery Disease.

Background and Objectives: Atherosclerotic disease is a major contributor to heart failure, stroke, and myocardial infarction, significantly lowering the quality of life and life expectancy and placing a significant burden on healthcare. Not all lesions deemed non-significant are benign, and conversely, not all significant lesions are causative of ischemia. Fractional flow reserve (FFR) provides a functional assessment of coronary lesions, while optical coherence tomography (OCT) offers detailed imaging of plaque morphology, aiding in therapeutic decision-making. The objective of this study was to evaluate the utility of OCT and FFR as adjunctive tools in the catheterization laboratory for guiding therapeutic decisions in patients with multivessel disease for non-culprit vessels. Specifically, we aimed to assess how OCT and FFR influence therapeutic decision-making in patients with multivessel coronary artery disease. Materials and Methods: A total of 36 patients with acute coronary syndrome (ACS) and multivessel disease were randomized 1:1 into two groups: one guided by FFR alone and the other by a combination of FFR and OCT. For the FFR group, revascularization decisions for non-culprit lesions were based solely on FFR measurements. If the FFR was >0.8, the procedure was concluded, and the patient received maximal medical treatment. If the FFR was ≤0.8, a stent was placed. For the FFR + OCT group, if the FFR was >0.8, the revascularization decision was based on OCT findings. If there were no vulnerable plaques (VP), the procedure was concluded, and the patient received maximal medical treatment. If OCT imaging indicated VP, then the patient underwent revascularization. If the FFR was ≤0.8, the patient underwent revascularization regardless of OCT findings. Results: OCT imaging altered the therapeutic decision in 11 cases where FFR measurements were above 0.8, but the lesions were characterized as VP. Analyzing the total change in the decision to stent, 4 cases in the FFR group and 15 cases in the FFR and OCT groups (4 based on FFR and 11 on OCT) revealed a statistically significant difference (p = 0.0006; Relative Risk = 0.2556; 95% CI: 0.1013 to 0.5603). When analyzing the change in the total decision both to stent and not to stent, we observed a statistically significant difference, with Group 1 having 7 cases and Group 2 having 15 cases (p = 0.0153; Relative Risk = 0.4050; 95% CI: 0.2004 to 0.7698. Conclusions: Based on the findings of this study, OCT significantly increases the percentage of stenting procedures by identifying vulnerable lesions. The use of intracoronary imaging facilitates the timely identification and treatment of these vulnerable lesions. This underscores the crucial role of OCT in enhancing the precision of coronary interventions by ensuring timely intervention for vulnerable lesions, thereby potentially improving patient outcomes.

Exploring new insights in coronary lesion assessment and treatment in patients with diabetes mellitus: the impact of optical coherence tomography.

In this review, we summarise new insights into diagnostic approaches and treatment strategies for coronary artery disease (CAD) in patients with diabetes mellitus (DM). Despite the improvements in therapy, the clinical management of DM patients remains challenging as they develop more extensive CAD at a younger age and consistently have worse clinical outcomes than non-DM patients. Current diagnostic modalities as well as revascularisation treatments mainly focus on ischemic lesions. However, the impact of plaque morphology and composition are emerging as strong predictors of adverse cardiac events even in the absence of identified ischemia. In particular, the presence of vulnerable plaques such as thin-cap fibroatheroma (TCFA) lesions has been identified as a very strong predictor of future adverse events. This emphasises the need for an approach combining both functional and morphological methods in the assessment of lesions. In particular, optical coherence tomography (OCT) has proven to be a valuable asset by truly identifying TCFAs. New treatment strategies should consist of individualised and advanced medical regimens and may evolve towards plaque sealing through percutaneous treatment.

Elevated EMMPRIN Serum Levels Indicate Plaque Vulnerability in Patients With Asymptomatic High Grade Carotid Stenosis.

OBJECTIVE: Carotid atherosclerosis is an important cause of cerebral ischaemic stroke. Sonographic plaque characteristics are inappropriate for exact prediction of possible future ischaemic events. Additional markers are needed to predict the clinical outcome in high grade carotid stenosis. This study aimed to test extracellular matrix metalloproteinase inducer (EMMPRIN), due to its involvement in plaque formation and destabilisation, as a potential marker of high risk vulnerable plaques. METHODS: EMMPRIN was analysed in pre-operative serum samples from patients with symptomatic and asymptomatic carotid artery stenosis by a specific ELISA. Pre-operative duplex sonography classified the atherosclerotic plaque due to echogenicity. Histopathological analysis of vulnerable and non-vulnerable plaques was based on the American Heart Association (AHA) classification. RESULTS: The study included 265 patients undergoing carotid endarterectomy: 90 (m:f, 69:21) patients with symptomatic and 175 (m:f, 118:57) with asymptomatic disease. Analysis of circulating EMMPRIN revealed significantly higher levels in patients with echolucent plaques (4 480; IQR 3 745, 6 144 pg/mL) compared with echogenic plaques (4 159; IQR 3 418, 5 402 pg/mL; p = .025). Asymptomatic patients with vulnerable plaques had significantly higher levels of EMMPRIN (4 875; IQR 3 850, 7 016 pg/mL) compared with non-vulnerable plaques (4 109; IQR 3 433, 5 402 pg/mL; p < .001). In logistic regression analysis, duplex sonography combined with age, gender, and clinical risk factors predicted vulnerable plaques in asymptomatic patients with an AUC of 0.71 (95% CI 0.61 - 0.80). EMMPRIN significantly improved the AUC in asymptomatic patients (AUC 0.79; 95% CI 0.71 - 0.87; p = .014). CONCLUSION: Patients with high risk plaques according to ultrasound and histopathological characteristics demonstrated increased serum EMMPRIN levels. EMMPRIN on top of clinical risk factors, including age, gender, and duplex sonography may be used for pre-operative risk stratification in asymptomatic patients.

Relationship between coronary high-intensity plaques on T1-weighted imaging by cardiovascular magnetic resonance and vulnerable plaque features by near-infrared spectroscopy and intravascular ultrasound: a prospective cohort study.

BACKGROUND: This study aimed to compare the coronary plaque characterization by cardiovascular magnetic resonance (CMR) and near-infrared spectroscopy (NIRS)-intravascular ultrasound (IVUS) (NIRS-IVUS), and to determine whether pre-percutaneous coronary intervention (PCI) evaluation using CMR identifies high-intensity plaques (HIPs) at risk of peri-procedural myocardial infarction (pMI). Although there is little evidence in comparison with NIRS-IVUS findings, which have recently been shown to identify vulnerable plaques, we inferred that CMR-derived HIPs would be associated with vulnerable plaque features identified on NIRS-IVUS. METHODS: 52 patients with stable coronary artery disease who underwent CMR with non-contrast T1-weighted imaging and PCI using NIRS-IVUS were studied. HIP was defined as a signal intensity of the coronary plaque-to-myocardial signal intensity ratio (PMR) ≥ 1.4, which was measured from the data of CMR images. We evaluated whether HIPs were associated with the NIRS-derived maximum 4-mm lipid-core burden index (maxLCBI4mm) and plaque morphology on IVUS, and assessed the incidence and predictor of pMI defined by the current Universal Definition using high-sensitive cardiac troponin-T. RESULTS: Of 62 lesions, HIPs were observed in 30 lesions (48%). The HIP group had a significantly higher remodeling index, plaque burden, and proportion of echo-lucent plaque and maxLCBI4mm ≥ 400 (known as large lipid-rich plaque [LRP]) than the non-HIP group. The correlation between the maxLCBI4mm and PMR was significantly positive (r = 0.51). In multivariable logistic regression analysis for prediction of HIP, NIRS-derived large LRP (odds ratio [OR] = 5.41; 95% confidence intervals [CIs] 1.65-17.8, p = 0.005) and IVUS-derived echo-lucent plaque (OR = 5.12; 95% CIs 1.11-23.6, p = 0.036) were strong independent predictors. Furthermore, pMI occurred in 14 of 30 lesions (47%) with HIP, compared to only 5 of 32 lesions (16%) without HIP (p = 0.005). In multivariable logistic regression analysis for prediction of incidence of pMI, CMR-derived HIP (OR = 5.68; 95% CIs 1.53-21.1, p = 0.009) was a strong independent predictor, but not NIRS-derived large LRP and IVUS-derived echo-lucent plaque. CONCLUSIONS: There is an important relationship between CMR-derived HIP and NIRS-derived large LRP. We also confirmed that non-contrast T1-weighted CMR imaging is useful for characterization of vulnerable plaque features as well as for pre-PCI risk stratification. Trial registration The ethics committee of Juntendo Clinical Research and Trial Center approved this study on January 26, 2021 (Reference Number 20-313).

Prediction of Slow-Flow Phenomenon After Stent Implantation Using Near-Infrared Spectroscopy in Patients With Acute and Chronic Coronary Syndrome.

BACKGROUND: The slow-flow phenomenon is associated with worse clinical outcomes after percutaneous coronary intervention (PCI), so our goal for this study was to see how predictive how near-infrared spectroscopy (NIRS) could be.Methods and Results: We enrolled 179 lesions from 152 patients who had de novo coronary stent implantation guided by NIRS-intravascular ultrasound (IVUS) (male: 69.1%, mean age: 74.3±11.5 years, acute coronary syndrome: 65.1%, diabetes: 42.1%). NIRS automatically determined the maximum 4-mm lipid core burden index (maxLCBI4 mm) value at pre- and post-PCI procedures. The slow-flow phenomenon was defined as the deterioration of TIMI (Thrombolysis in Myocardial Infarction) flows on angiography during the PCI procedure in the absence of mechanical obstruction. The slow-flow phenomenon occurred in 13 (7.3%) lesions, and the slow-flow phenomenon group had a significantly higher maxLCBI4 mm(740±147 vs. 471±223, P<0.001). The best maxLCBI4 mmcutoff point in both acute and chronic coronary syndrome was 578 and 480, with sensitivity of 100%, for predicting the slow-flow phenomenon. In the receiver-operating characteristics analysis, the area under the curve for acute and chronic coronary syndrome was 0.849 and 0.851, respectively. CONCLUSIONS: The results of this study support the utility of NIRS-IVUS-guided PCI for the prediction of the slow-flow phenomenon.

Analysis of carotid vulnerable plaque MRI high-risk features and clinical risk factors associated with concomitant acute cerebral infarction.

BACKGROUND: This study aimed to investigate the correlation between the high-risk characteristics of high-resolution MRI carotid vulnerable plaques and the clinical risk factors and concomitant acute cerebral infarction (ACI). METHODS: Forty-five patients diagnosed with a single vulnerable carotid plaque by MRI were divided into two groups based on whether they had ipsilateral ACI. The clinical risk factors and the observation values or frequency of occurrence of high-risk MRI phenotypes of plaque volume, LRNC, IPH and ulcer were statistically compared between the two groups. RESULTS: A total of 45 vulnerable carotid artery plaques were found in 45 patients, 23 patients with ACI and 22 patients without ACI. There were no significant differences in age, sex, smoking, serum TC, TG and LDL between the two groups (all P > 0.05), but the ACI group had significantly more patients with hypertension (P < 0.05) and the without ACI group coronary heart disease (P < 0.05). The volume of vulnerable carotid plaque in the group with ACI (1004.19 ± 663.57 mm3) was significantly larger than that in the group without ACI (487.21 ± 238.64 mm3) (P < 0.05). The phenotype of vulnerable carotid artery plaque was 13 cases of LRNC, 8 cases of LRNC + IPH, 5 cases of LRNC + Ulcer, and 19 cases of LRNC + IPH + Ulcer. There was no significant difference in this distribution between the two groups (all P > 0.05) with the exception of LRNC + IPH + Ulcer. The 14 cases of LRNC + IPH + LRNC + IPH + Ulcer (60.87%) in the group with ACI and was significantly greater than the 5 (22.73%) in patients without ACI (P < 0.05). CONCLUSION: It is preliminarily thought that hypertension is the main clinical risk factor for vulnerable carotid plaques with ACI and the combination of plaque volume with vulnerable carotid plaque and LRNC + IPH + Ulcer is a high-risk factor for complicated ACI. It has high clinical therapeutic value due to the accurate diagnosis of responsible vessels and plaques with high-resolution MRI.

The Value of Multimodal Ultrasonic Scoring System in the Diagnosis of Carotid Vulnerable Plaque: A Comparative Study With Pathology.

BACKGROUND AND AIMS: Vulnerable plaques are closely related to ischemic stroke. To investigate the diagnostic value of multimodal plaque vulnerability ultrasound scoring system (PV-USS) using histopathology as the gold standard. METHODS: A total of 45 subjects who would be underwent carotid endarterectomy were recruited. The postoperative specimens were examined by histopathology. All responsible plaques were scanned dynamically in multiple sections by carotid ultrasound to measure maximum thickness and lumen stenotic degree, as well as, the echo, homogeneity, surface morphology, and echo type were observed. The above two-dimensional (2D) ultrasonic features were systematically scored, that is, PV-USS2D . Combined with contrast-enhanced ultrasonography (CEUS), neovascularization grade in plaque was scored, which is PV-USS2D+CEUS . RESULTS: According to the pathological results, 45 subjects were divided into vulnerable plaque group (27 cases, 60%) and non-vulnerable plaque group (18 cases, 40%). PV-USS2D and PV-USS2D+CEUS in vulnerable plaque group were higher than those in non-vulnerable plaque group (PV-USS2D : 9.44 ± 2.10 vs 7.22 ± 1.73; PV-USS2D+CEUS: 12.37 ± 2.10 vs 8.28 ± 1.81, P < .001). ROC curve analysis showed that the AUC of PV-USS2D and PV-USSCEUS was 0.783 and 0.929, respectively (P < .001). The best cutoff values of PV-USS2D and PV-USS2D+CEUS were, respectively, 9.5 (the maximum Youden index was 0.425, the sensitivity was 48.1%, the specificity was 94.4%) and 10.5 (the maximum Youden index was 0.667, the sensitivity was 77.8%, the specificity was 88.9%). CONCLUSIONS: Ultrasound scoring system may be used as an effective method to evaluate the vulnerability of plaque. The diagnostic efficiency of PV-USS2D+CEUS is more higher than PV-USS2D .

Investigation of the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis.

OBJECTIVE: To investigate the clinical effects of acipimox in patients with vulnerable carotid atherosclerosis. METHODS: 80 patients with vulnerable carotid atherosclerosis who were admitted to the Department of Cardiology in Wuxi Second People's Hospital between February 2020 and October 2021 were enrolled in this study. All of these patients were randomly divided into an observation group (n = 40), who were given acipimox and conventional treatment, and a control group (n = 40), who were given conventional treatment. The levels of blood lipids and adiponectin (APN), the carotid intima-media thickness (IMT), the area, thickness and number of CAS, peak systolic velocities (PSV) and end-diastolic blood velocity (EDV) of common carotid artery (CCA), and the level of inflammatory markers were measured and compared between the two groups pretherapy and posttreatment. Then, the adverse events were collected and compared between the two groups posttreatment. RESULTS: The demographics and basic clinical characteristics were not significantly different between the two groups. At posttreatment, the levels of TC, LDL-C, ANP, IL-6, TNF-α and hs-CRP in the observation group were significantly lower than those in the control group at posttreatment. Moreover, the IMT and the area and thickness of CAS in the observation group were significantly lower than those in the control group. After treatment, PSV was lower and EDV was higher in two groups than before treatment; after treatment, compared with control group, PSV in observation group was lower, while EDV was higher. Most importantly, the rate of adverse events was similar in the two groups. CONCLUSIONS: Acipimox reduced the blood lipid levels in patients with vulnerable carotid atherosclerosis. It also stabilized vulnerable plaques and reduced CAS.

Significance of Intra-plaque Hemorrhage for the Development of High-Risk Vulnerable Plaque: Current Understanding from Basic to Clinical Points of View.

Acute coronary syndromes due to atherosclerotic coronary artery disease are a leading cause of morbidity and mortality worldwide. Intra-plaque hemorrhage (IPH), caused by disruption of intra-plaque leaky microvessels, is one of the major contributors of plaque progression, causing a sudden increase in plaque volume and eventually plaque destabilization. IPH and its healing processes are highly complex biological events that involve interactions between multiple types of cells in the plaque, including erythrocyte, macrophages, vascular endothelial cells and vascular smooth muscle cells. Recent investigations have unveiled detailed molecular mechanisms by which IPH leads the development of high-risk "vulnerable" plaque. Current advances in clinical diagnostic imaging modalities, such as magnetic resonance image and intra-coronary optical coherence tomography, increasingly allow us to identify IPH in vivo. To date, retrospective and prospective clinical trials have revealed the significance of IPH as detected by various imaging modalities as a reliable prognostic indicator of high-risk plaque. In this review article, we discuss recent advances in our understanding for the significance of IPH on the development of high-risk plaque from basic to clinical points of view.

Urotensin II Enhances Advanced Aortic Atherosclerosis Formation and Delays Plaque Regression in Hyperlipidemic Rabbits.

Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% high cholesterol diet (HCD) feeding, and either UII (5.4 µg/kg/h) or saline was chronically infused via osmotic mini-pumps. UII promoted atherosclerotic fatty streak formation in ovariectomized female rabbits (34% increase in gross lesion and 93% increase in microscopic lesion), and in male rabbits (39% increase in gross lesion). UII infusion significantly increased the plaque size of the carotid and subclavian arteries (69% increase over the control). In addition, UII infusion significantly enhanced the development of coronary lesions by increasing plaque size and lumen stenosis. Histopathological analysis revealed that aortic lesions in the UII group were characterized by increasing lesional macrophages, lipid deposition, and intra-plaque neovessel formation. UII infusion also significantly delayed the regression of atherosclerosis in rabbits by increasing the intra-plaque macrophage ratio. Furthermore, UII treatment led to a significant increase in NOX2 and HIF-1α/VEGF-A expression accompanied by increased reactive oxygen species levels in cultured macrophages. Tubule formation assays showed that UII exerted a pro-angiogenic effect in cultured endothelial cell lines and this effect was partly inhibited by urantide, a UII receptor antagonist. These findings suggest that UII can accelerate aortic and coronary plaque formation and enhance aortic plaque vulnerability, but delay the regression of atherosclerosis. The role of UII on angiogenesis in the lesion may be involved in complex plaque development.

Novel treatment from a botanical formulation Si-Miao-Yong-an decoction inhibits vasa vasorum angiogenesis and stabilizes atherosclerosis plaques via the Wnt1/ß-catenin signalling pathway.

CONTEXT: Si-Miao-Yong-An (SMYA) has been widely used for the clinical treatment of atherosclerosis (AS). Yet, its complete mechanism of action is not fully understood. OBJECTIVE: To investigate the mechanism by which SMYA stabilizes AS plaques from the perspective of inhibiting vasa vasorum (VV) angiogenesis. MATERIALS AND METHODS: We used male ApoE-/- mice to establish an AS model. The mice were divided into model, SMYA (11.7 mg/kg/d), and simvastatin (SVTT) (2.6 mg/kg/d) groups. Mice were given SMYA or SVTT by daily gavage for 8 weeks. HE staining, immunofluorescence double-labelling staining, and immunohistochemical staining were used to observe the pathological changes in the plaques. Finally, the protein and mRNA expression levels of the Wnt1/ß-catenin signalling pathway were detected by Western blot and qRT-PCR, respectively. RESULTS: SMYA significantly attenuated cholesterol crystallization, and lipid accumulation in AS plaques, resulting in smaller plaque size (0.25 mm2 vs. 0.46 mm2), and lowering ratio of plaque to lumen area (20.04% vs. 38.33%) and VV density (50.64/mm2 vs. 98.02/mm2). Meanwhile, SMYA suppressed both the positive area percentage of Wnt1 (2.53 vs. 3.56), ß-catenin (3.33 vs. 5.65) and Cyclin D1 (2.10 vs. 3.27) proteins in the aortic root plaques, and mRNA expression of Wnt1 (1.38 vs. 2.09), ß-catenin (2.05 vs. 3.25) and Cyclin D1 (1.39 vs. 2.57). DISCUSSION AND CONCLUSIONS: SMYA has a protective effect against AS, which may be related to its anti-VV angiogenesis in plaques, suggesting that SMYA has the potential as a novel botanical formulation in the treatment of AS.

Identification and treatment of the vulnerable coronary plaque.

Acute coronary syndrome mostly arises from rupture or erosion of a vulnerable plaque. Vulnerable plaques typically appear as lipid-rich plaques with a thin cap, called thin-cap fibroatheromas. Various intracoronary imaging techniques can be used to detect vulnerable plaques, such as intravascular ultrasound (IVUS), optical coherence tomography (OCT) and near-infrared spectroscopy (NIRS), each visualizing different high-risk plaque characteristics. IVUS and its post-processing techniques, such as virtual histology IVUS, can primarily be used to identify calcified and soft plaques, while OCT is also able to quantitatively measure the cap thickness. The addition of NIRS allows the exact measurement of lipid content in the plaque. Non-invasive imaging techniques to identify vulnerable plaques, such as computed tomography, are less often used but are evolving and may be of additional diagnostic use, especially when prophylactic treatments for vulnerable plaques are further established. Pharmacological treatment with lipid-lowering or anti-inflammatory medication leads to plaque stabilization and reduction of cardiovascular events. Moreover, the implantation of a stent or scaffold for the local treatment of vulnerable plaques has been found to be safe and to stabilize high-risk plaque features. The use of drug-coated balloons to treat vulnerable plaques is the subject of ongoing research. Future studies should focus on non-invasive imaging techniques to adequately identify vulnerable plaques and further randomized clinical studies are necessary to find the most appropriate treatment strategy for vulnerable plaques.