Noninvasive diagnosis of vulnerable coronary plaque

Myocardial infarction and sudden cardiac death are frequently the first manifestation of coronary artery disease.For this reason,screening of asymptomatic coronary atherosclerosis has become an attractive field of research in cardiovascular medicine.Necropsy studies have described histopathological changes associated with the development of acute coronary events.In this regard,thin-cap fibroatheroma has been identified as the main vulnerable coronary plaque feature.Hence,many imaging techniques,such as coronary computed tomography,cardiac magnetic resonance or positron emission tomography,have tried to detect noninvasively these histomorphological characteristics with different approaches.In this article,we review the role of these diagnostic tools in the detection of vulnerable coronary plaque with particular interest in their advantages and limitations as well as the clinical implications of the derived findings.

Relation of coronary vulnerable plaque instability to serum levels of C-reactive protein and B-type natriuretic peptide in ACS.

Objective To explore the relationship between coronary vulnerable plaque instability and serum C-reactive protein(CRP) , B-type natriuretic peptide(BNP) levels in 85 patients with coronary heart disease. Methods Eighty-five patients( aged 63±16,M= 52 ) were divided into two groups.The control group was 28 patients with stable angina pectoris (SAP). The study group was 57 patients with acute coronary syndrome (ACS) .which were further divided into 21 patients with non ST elevated myocardial infarction (NSTEMI) and 36 patients with unstable angina pectoris (UAP). Plasma BNP and CRP were measured as well as coronary angiography made for all 85 patients. Plaques of coronary culprit arteries were classified as I -III three types according to Ambrose classification. Results (1). BNP and CRP levels of NSTEMI and UAP groups were significant higher than in SAP group. (2).The levels of BNP and CRP correlated with Ambrose classification, especially positively with Ambrose II type ,but no relation with coronary narosis. (3). The levels of BNP was much higher in patients of left anterior descending or multiple coronary artery diseases .(4). The Plaques of coronary culprit arteries in high risk of NSTEMI and UAP patients were mostly Ambrose II or III type. Conclusions The prevalence of higher levels of plasma BNP and CRP in patients with ACS ,when compared with those of SAP, was associated with the instability of coronary vulnerable plaques (ie, Ambrose II type). The level of BNP was much higher in patients of left anterior descending or multiple complicated coronary diseases. So, BNP and CRP are not only markers of vulnerable plaques, but also indicators of ACS prognosis.

The Usefulness of Ryusei^®Perfusion Balloon for Treating Acute Coronary Syndrome with Vulnerable Plaque

Background: Intracoronary thrombus followed by a rupture of unstable vulnerable plaque is a well-known cause of acute coronary syndrome (ACS). The no reflow/slow flow phenomenon is sometimes observed during a primary percutaneous coronary intervention (PCI) against ACS. It has already been shown that long inflation using a perfusion balloon (PB) is useful to remediate a coronary perforation. Thus, we investigated the usefulness of a PB for treating ACS. Methods: This study was a retrospective, single-center, observational study. One hundred-seven patients with ACS underwent PCI from January 2015 to December 2017 in our hospital. Fifty patients were treated by PB directly (PB group) and the remaining 57 patients were treated by another conventional balloon (C group). We used the Ryuseiò balloon (Kaneka, Japan) as a PB. The clinical outcome was the incidence of the no reflow or slow flow phenomenon, the incidence of using IABP. Results: One patient in the PB group demonstrated slow flow phenomenon temporarily, and the coronary flow was quickly restored by thromboaspiration. In contrast, nine patients in the C group had occurrences of no reflow/slow flow phenomenon. Although all patients in the C group required stenting, some patients (24%) of the PB group did not require stenting. Conclusion: We found that the use of PB had a favorable effect on the treatment of ACS. Some patients completed PCI without a need for stenting.

Study on the relationship between Lp-PLA2, D- dimer and Galectin-3 and atherosclerotic vulnerable plaque in patients with coronary heart disease

Objective: To explore the relationship and clinical value of serum phospholipase A2 (Lp-PLA2), d-dimers, and serum galectin-3 (galectin-3) with atherosclerotic vulnerable plaques in coronary artery patients with coronary heart disease. Methods: A total of 248 patients who underwent coronary angiography (CAG) and intravascular ultrasound (IVUS) in our hospital from June 2017 to September 2018 were selected and divided into vulnerable plaque group (89), stable plaque group (89) and control group (70) according to the examination results. The serum levels of Lp-PLA2, d-dimer and galectin-3 in three groups were compared, as well as their correlation with the detection parameters. To evaluate the clinical value of Lp-PLA2, d-dimer and galectin-3 in patients with coronary heart disease (CHD) with atherosclerotic vulnerable plaque. Results: Serum Lp-PLA2, d-dimer and galectin-3 levels were significantly different from the three groups (P<0.05), and the control group < stable plaque group <vulnerable plaque group (P<0.05). Correlation analysis showed that Lp-PLA2, d-dimer and galectin-3 were significantly positively correlated with plaque area, plaque load, necrotic core and calcified tissue (P<0.01), and negatively correlated with fibrous lipid and fibrous tissue (P<0.01). ROC curve showed that Lp-PLA2, d-dimer and galectin-3 had certain predictive value for vulnerable coronary atherosclerotic plaques (AUC=0.939, 0.977, 0.920, P<0.01), and the three combinations (AUC=0.986, P<0.01) had higher predictive value. Conclusion: Serum Lp-PLA2, d-dimer and galectin-3 are significantly correlated with coronary atherosclerotic vulnerable plaques in patients with coronary heart disease, with high sensitivity and specificity, which can be used for the diagnosis and treatment of early atherosclerotic vulnerable plaques.

18F-FDG PET/CT for Detecting Vulnerable Carotid Plaque:A Systematic Review of Literatures

Objectives:To evaluate the efficacy of 18F-FDG-PET/CT in detection toward the vulnerabilities of carotid plaque and review systematically best evidence to prevent acute stroke from unstable carotid plaque.Methods:A search was conducted on Medline(PubMed),Web of science,Cochrane and WHIC using the search terms‘PET/CT’AND‘18F-FDG’AND‘fluorodeoxyglucose’AND‘carotid plaque’,from 2013/01/01 to now.Two authors will independently extract data following the study characteristics,eligibility criteria,interventions,outcome measurements,duration,adverse events,results and the type of needle used.All searched articles were inserted into in EndNote software that can automatically save,manage,and delete duplicate documents.Results:There were 3 articles included in the systematic review finally and form the study population analysis.The total 89 patients(64 males and 25 females)identified from the included studies.The mean 18F-FDG injected dose was 4.58 MBq/kg.The last three articles have demonstrated that 18F-FDG can accurately identify the stability of carotid plaques and can accurately locate and identify high-inflammation areas by histological analysis.Conclusions:18F-FDG-PET/CT is very efficient and practical for the identification of carotid vulnerable plaques.TBR(max and mean values)as a parameter for identifying inflammatory plaques is more reliable than SUV.

Effect of adjuvant ginkgo-damole therapy on the plaque stability, apoptosis and coagulation indicators in patients with unstable angina

Objective:To study the effect of adjuvant ginkgo-damole therapy on the plaque stability, apoptosis and coagulation indicators in patients with unstable angina.Methods: A total of 80 patients with unstable angina who received inpatient treatment in our hospital between July 2014 and July 2016 were collected and divided into control group (conventional therapy) and observation group (conventional therapy+ginkgo-damole) according to the random number table, 40 cases in each group. The plaque stability, apoptosis and coagulation indicator contents were compared between two groups of patients before and after treatment.Results: Before treatment, differences in serum levels of plaque stability, apoptosis and coagulation indicators were not statistically significant between two groups of patients;after treatment, serum plaque stability indicators PTX3, Lp-PLA2, sCD40 and sCD40L contents in observation group were lower than those in control group;pro-apoptosis indexes sFas and Bax contents were lower than those in control group, and anti-apoptosis index Bcl-2 content was higher than that in control group;coagulation indicators Fg and D-D contents were lower than those in control group while t-PA content was higher than that in control group.Conclusion: Adjuvant ginkgo-damole therapy helps to improve the plaque stability, inhibit myocardial apoptosis and also reduce the hypercoagulable state in patients with unstable angina.

Changes in plaque stability, cell apoptosis and coagulation indexes after patients with unstable angina pectoris accept adjuvant salvianolate therapy

Objective:To investigate the effect of adjuvant salvianolate therapy on plaque stability, cell apoptosis and coagulation indexes in patients with unstable angina pectoris.Methods: 92 patients with unstable angina pectoris treated in our hospital between May 2011 and August 2015 were collected, and after the treatment process and auxiliary examination results were retrospectively analyzed, they were divided into the control group (n=45) who accepted conventional treatment and the observation group (n=47) who accepted adjuvant salvianolate treatment. Before and after treatment, diasonograph was used to evaluate the plaque stability parameters of two groups of patients;ELISA was used to detect apoptosis-related molecule levels;immunoturbidimetry was used to detect blood coagulation indexes.Results: Before treatment, differences in plaque stability parameters, cell apoptosis molecules and coagulation indexes were not statistically significant between two groups of patients (P>0.05). After treatment, the plaque stability parameters plaque thickness, enhanced intensity, rise time and time to peak of observation group were significantly lower than those of control group (P<0.05);serum sFas, sFasL, fibrinogen (Fib), platelet (PLT), and D-Dimer (D-D) levels of observation group were significantly lower than those of control group while Bcl-2, prothrombin time (PT) and activated partial thromboplastin time (APTT) levels were significantly higher than those of control group (P<0.05).Conclusions: Adjuvant salvianolate treatment can increase the plaque stability, also inhibit myocardial cell apoptosis and improve the coagulation function in patients with unstable angina pectoris.

Image-Based Modeling for Atherosclerotic Coronary Plaque Progression and Vulnerability Research

China Cardiovascular Disease Report 2017(Summary)pointed out that at present,cardiovascular diseases(CVD)account for the highest number of deaths among urban and rural residents.In the middle or later stages of atherosclerosis,the plaques become increasingly unstable with high chance to rupture,which may lead acute death from coronary heart diseases.Medical imaging and image-based computational modeling have been used in recent years to quantify ather-osclerotic plaque morphological and biomechanical characteristics and predict the coronary plaque growth and rupture processes.Analyzing the vulnerability of plaques effectively could lead to better patient screening strategies and enable physicians to adopt timely and necessary intervention or conservative treatment.Earlier investigations of vulnerable plaques were mostly based on histopathological data.With the accumulation of experience in pathology and the gradual enrichment of autopsy materials,the criteria for the diagnosis of vulnerable plaques appeared in 2001,mainly manifested as the necrotic lipid nuclei,fibrous caps that are infiltrated by a large number of macrophages,and fibrous cap thickness less than 65μm.Because of the obvious importance of the thin fibrous cap in the study of plaque vulnerability,it has been a focus of attention by many investigations.Watson,M.G.et al.are concerned about the formation of early fibrous caps in recent years.The presentation of local maximum stress on plaque further confirmed the importance of thin fibrous cap.The development of medical images has greatly promoted the study of coronary atherosclerosis.Compared with autopsy ex vivo,medical image could provide plaque data under in vivo conditions and greatly promote the study of coronary atherosclerosis.Huang XY et al.used ex vivo magnetic resonance imaging(MRI)to study the relationship between plaque wall stress(PWS)and death caused by coronary artery disease.Due to technical limitations and the accessibility of the coronary artery in the body,MRI is not widely used for in vivo coronary studies.Interventional intravascular ultrasound(IVUS),with an image resolution of 150-200μm,has been used in research and clinical practice to identify plaques,quantify plaque morphology,and characterize plaque components.More recently,optical coherence tomography(OCT),with its resolution of 5-10μm,has emerged as an imaging modality which can be used to detect thin fibrous caps and improve diagnostic accuracy.It is commonly believed that mechanical forces play an important role in plaque progression and rupture.Image-based biomechanical plaque models have been developed and used to quantify plaque mechanical conditions and seek their linkage to plaque progression and vulnerability development activities.Based on recent advances in imaging and modeling,this paper attempts to provide a brief review on plaque research,including histological classification,image preparation,biomechanical modeling and analysis methods including medical imaging techniques represented by intravascular ultrasound(IVUS)and optical coherence tomography(OCT),computational modeling and their applications in plaque progression and vulnerability analyses and predictions.The clinical application and future development direction are also briefly described.We focus more on human coronary plaque modeling and mainly included results from our group for illustration purpose.We apologize in advance for our limitations.

Angiographical and histopathologic study of atherosclerotic plaques in acute myocardial infarction

Objective Compare the morphology of atherosclerotic plaquesmgiographically and histopathologically in acute myocardialmfarction m order to accumulate experience in recognizing plaquerupture and thrombus by angiogrames.Material and methods 16postmortem cases of acute myocardial infarction were studied.The coronary arteries were romoved en block,filled with barium the lumen and ridiographed.Then the arteries wereontinuously insetted and routin HE sections were made.Results 16 cases had plaque ruptures and thrombi.Among the total98 blocks,21 had plaque ruptures on which 20 thrombiccur(95.23%).while the other 777 unrupured blocks had only 2hrombi(0.25%).The difference was significant(p【0.001).Therupture mostly occur on unstable plaques.The ruptured plaqueswith thrombi had different angiographical morphology withunruptured plaques.The former had irregular borders andunraluminal lucencies;while the Iatter had smooth borders and nointraluminal lucencies.Conclusions Plaque ruprure withthrumbus was the major cause of acute myocardial infarction andthe ruptured plaques with thrombus had different angiographicalapperances with unruptured plaques.

Contrast-enhanced ultrasound imaging of the vasa vasorum of carotid artery plaque

The vasa vasorum of carotid artery plaque is a novel marker of accurately evaluating the vulnerability of carotid artery plaque, which was associated with symptomatic cerebrovascular and cardiovascular disease. The presence of ultrasound contrast agents in carotid artery plaque represents the presence of the vasa vasorum in carotid artery plaque because the ultrasoundcontrast agents are strict intravascular tracers. Therefore, contrast-enhanced ultrasound(CEUS) is a novel and safe imaging modality for evaluating the vasa vasorum in carotid artery plaque. However, there are some issues that needs to be assessed to embody fully the clinical utility of the vasa vasorum in carotid artery plaque with CEUS.

Evaluation of Carotid Plaque Neovascularization in Patients with Diabetes Mellitus by Contrast-enhanced Ultrasonography

This study investigated the relationship between carotid plaque neovascularization and diabetes mellitus（DM） by using contrast-enhanced ultrasonography. Contrast-enhanced ultrasonography was performed in 104 patients with carotid plaque thicker than 2.0 mm. There were 36 patients with DM and 68 patients without DM. The enhanced intensity in the plaque and the ratio of enhanced intensity in the plaque to that in the lumen of the carotid artery in patients with DM were significantly greater than those in patients without DM. Our study demonstrated that the enhanced intensity in patients with DM is greater than that their counterparts without DM, suggesting that carotid plaque in DM patients may have more neovessels and may be more vulnerable.

Coronary plaque imaging by coronary computed tomography angiography

Coronary computed tomography angiography(CTA) has become the useful noninvasive imaging modality alternative to the invasive coronary angiography for detecting coronary artery stenoses in patients with suspected coronary artery disease(CAD). With the development of technical aspects of coronary CTA, clinical practice and research are increasingly shifting toward defining the clinical implication of plaque morphology and patients outcomes by coronary CTA. In this review we discuss the coronary plaque morphology estimated by CTA beyond coronary angiography including the comparison to the currently available other imaging modalities used to examine morphological characteristics of the atherosclerotic plaque. Furthermore, this review underlies the value of a combined assessment of coronary anatomy and myocardial perfusion in patients with CAD, and adds to an increasing body of evidence suggesting an added diagnostic value when combining both modalities. We hope that an integrated, multi-modality imaging approach will become the gold standard for noninvasive evaluation of coronary plaque morphology and outcome data in clinical practice.

Predicting Coronary Plaque Morphology Changes Based on Multimodality FSI Models Using Follow-Up IVUS and OCT Data

Background Current bottleneck of patient-specific coronary plaque model construction is the resolution of in vivo medical imaging.The threshold of cap thickness of vulnerable coronary plaques is 65 microns,while the resolution of in vivo coronary intravascular ultrasound(IVUS)images is 150-200 microns,which is not enough to identify vulnerable plaques with thin caps and construct accurate biomechanical plaque models.Optical coherence tomography(OCT)with a 15-20μm resolution has the capacity to identify thin fibrous cap.IVUS and OCT images could complement each other and provide for more accurate plaque morphology,especially,fibrous cap thickness measurements.A modeling approach combining IVUS and OCT was introduced in our previous publication for cap thickness quantification and more accurate cap stress/strain calculations.In this paper,patient baseline and follow-up IVUS and OCT data were acquired and multimodality image-based Fluidstructure interaction(FSI)models combining 3D IVUS,OCT,angiography were constructed to better quantify human coronary atherosclerotic plaque morphology and plaque stress/strain conditions and investigate the relationship of plaque vulnerability and morphological and mechanical factors.Methods Baseline and 10-Month follow-up in vivo IVUS and OCT coronary plaque data were acquired from one patient with informed consent obtained.Co-registration and segmentation of baseline and follow-up IVUS and OCT images were performed for modeling use.Baseline and follow-up 3D FSI models based on IVUS and OCT were constructed to simulate the mechanical factors which integrating plaque morphology were employed to predict plaque vulnerability.These 3D models were solved by ADINA(ADINA R&D,Watertown,MA,USA).The quantitative indices of cap thickness,lipid percentage were classified according to histological literatures and denoted as Cap Index and Lipid Index.Cap Index,Lipid Index and Morphological Plaque Vulnerability Index(MPVI)were chosen to quantify plaque vulnerability,respectively.Random forest(RF)which was based 13 extracted features including morphological and mechanical factors was used for plaque vulnerability classification and prediction.Over sampling scheme and a 5-fold crossvalidation procedure was employed in all 45 slices for training and testing sets.Single and all different combinations of morphological and mechanical risk factors were used for plaque progression prediction.Results When Cap Index was used as the measurement,minimum cap thickness(MCT)was the best single predictor which area under curve(AUC)is 0.782 0;the combination of MCT,critical plaque wall strain(CPWSn),critical wall shear stress(CWSS)and cap wall shear stress(CapWSS)was the best predictor with ACU=0.868 6.When Lipid Index was used as the measurement,the lipid percentage(LP)was the best single predictor which AUC value is 0.857 8;the combination of Mean cap thickness(MeanCT),LP,CWSS and cap plaque wall stress(CapPWS)and was the best predictor with ACU=0.9821.When MPVI was used as the measurement,MCT was the best single predictor which AUC value is 0.782 9;the combination of MCT,LP,plaque area(PA),CPWSn and CapWSS was the best predictor with ACU=0.872 9.Conclusions Combinations of morphological and mechanical risk factors had higher prediction accuracy,compared to the prediction of single factors and other combination of morphological factors.

Atheromatous plaque rupture may due to fatigue crack growth under cyclic blood pressure:A comparison between symptomatic and asymptomatic individuals

Introduction Stroke or heart attack,the leading cause of death and disability worldwide,is usually caused by rupture of atheromatous plaque.Therefore,the identification of vulnerable atheroma pre rupture has become extremely important for patient risk stratification.Previous studies have shown that the vulnerable plaque,i.e.one that is prone to rupture with thromboembolic complications,is often associated with a thin fibrous cap,a large lipid core and a high inflammatory burden.The mechanism of plaque rupture is not entirely clear but is thought to be a multi-factorial process involving thinning and weakening of the fibrous cap by enzymes secreted by activa-

The possible value of ~18F-FDG positron emission tomography/computerized tomography imaging in detection of atherosclerotic plaque

Objective：To evaluate the clinical value with positron emission tomography/computerized tomography（PET/CT） imaging for the detection of vulnerable plaque in atherosclerotic lesions. Methods：Sixty people with a age of over 60[mean age （69.2 ± 7.1）years] underwent three dimension（3D） whole-body fluorine-18-2-fluoro-2-deoxy-D-glucose（^18F-FDG） PET/CT imaging and were evaluated retrospectively, including 6 cases assessed as normal and 54 cases with active atherosclerotic plaque. Fifty-four cases with SUVs and CT values in the aortic wall of high-FDG-uptake were measured retrospectively. These high-FDG-uptake cases in the aortic wall were divided into three groups according their CT value. Cases in group 1 had high uptake in atherosclerotic lesions of the aortic wall with CT value of less than 60 Hu（soft plaque）. Cases in group 2 had high uptake with CT value between 60-100 Hu （intermediate plaque）, Cases in group 3 had high uptake with CT value more than 100 Hu（calcified plaque）, Group 4 was normal. Results： In group 1, there were 42 high-FDG-uptake sites （average SUV 1.553 ± 0.486）. In group 2, there were 30 high-FDG-uptake sites（average SUV 1.393 ± 0.296）. In group 3, there were 36 high-FDG-uptake sites（average SUV 1.354 ± 0.189）. In group 4, there were 33 normal-FDG-uptake sites （average SUV was 1.102 ± 0.141）, The SUVs showed significant difference among the four groups（F = 678.909, P = 0.000）. There were also significant difference found between the normal-FDG-uptake group and the high-FDG-uptake groups（P = 0.000, 0.000, 0.001, respectively）. Conclusion：Different degrees of ^18F-FDG uptake in active large atherosclerotic plaque were shown in different stages of atherosclerotic plaque formation. The soft plaque had the highest FDG uptake in this study. This suggested that ^18F- FDG PET/CT imaging may be of great potential value in early diagnosis and monitoring of vulnerable soft plaque in atherosclerotic lesions.

Clinical study on the correlation between plasma lipopolysaccharide and the structural characteristics of coronary intravascular ultrasound plaques

Objective:To study the correlation between plasma lipopolysaccharide and coronary atherosclerotic heart disease risk factors and plaque stability.Methods:136 patients with unstable angina pectoris who underwent coronary angiography and intravascular ultrasound were selected from the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine.According to the results of IVUS,they were divided into stable plaques(stable plaques,SP)group of 72 patients With 64 cases in the Unstable plaques(UP)group,venous blood was drawn from the two groups of patients for blood lipid and lipopolysaccharide index detection,and the general baseline data of the two groups were recorded;the structural characteristics of the intravascular ultrasound plaques in the two groups were analyzed.To study the influencing factors of unstable plaques,the correlation between lipopolysaccharide and plaque structural characteristics,and the diagnostic efficacy of unstable plaques.Results:The expression levels of cholesterol,low-density lipoprotein,and LPS in the UP group were higher than those in the SP group(P<0.05),and the high-density lipoprotein expression levels were lower than those in the SP group(P=0.035);and the intravascular ultrasound structure of the plaque was UP The lipid pool area,the ratio of lipid pool to plaque area,the plaque eccentricity index,and the maximum plaque thickness of the group were higher than those of the SP group(P<0.05),and the minimum plaque thickness was smaller than that of the SP group and the difference was statistically significant(P<0.05);LPS was positively correlated with cholesterol,low-density lipoprotein,lipid pool area,ratio of lipid pool to plaque area,plaque eccentricity index,and maximum plaque thickness by Pearson correlation test(P<0.05),Is negatively correlated with high-density lipoprotein(P=0.021);LPS is a risk factor for coronary plaque stability,and HDL is a protective factor for coronary plaque stability by binary logistic regression test.The difference is statistically significant Scientific significance(P=0.049,P=0.002);LPS diagnosis of coronary atherosclerotic plaque stability ROC area under the curve(AUC)is 0.889,95%CI is(0.805,0.974),the best diagnosis point is 57.485 mg/L,the sensitivity is 80.60%,and the specificity is 73.70%.Conclusion:Plasma lipopolysaccharide is a risk factor of unstable plaque,which has certain diagnostic value for coronary artery plaque,and can be used as a quantitative diagnostic index of plaque vulnerability.

Molecular imaging of plaques in coronary arteries with PET and SPECT

Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography （PET） and single photon emission computed tomography （SPECT） has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.

Relationship between tissue type plasminogen activator and coronary vulnerable plaque in patients with acute coronary syndrome： virtual histological study

Background The association between vulnerability of plaque assessed with intravascular ultrasound （IVUS） and plasma levels of fibrinolytic biomarkers was determined in patients with acute coronary syndrome （ACS）. However, few data are available on the relationship between the levels of tissue type plasminogen activator （t-PA） and virtual histological intravascular ultrasound （VH-IVUS） signs of plaque instability. Methods Eighty-nine patients with ACS were enrolled in the study. Blood was collected to measure t-PA levels by liquid phase bead flow cytometry. Eighty-nine nonbifurcate lesions （identified by coronary angiography and ECG） were investigated using IVUS before catheterization. IVUS radiofrequency data obtained with a 20 MHz catheter were analyzed with IVUS virtual histological software. The areas of plaque and media were calculated and lesions were classified into two groups： VH-IVUS derived thin cap fibroatheroma （VH-TCFA） and non-VH-TCFA plaque. Results Plasma t-PA level in the patients with TCFA was significantly lower than that with non-TCFA （（1489 ± 715） pg/ml vs （2163 ± 1004） pg/ml）. Decreased plasma levels of t-PA were associated with plaque vulnerability. Plasma levels of t-PA correlated negatively with plaque plus media and necrotic core in plaque in patients with ACS. Conclusions t-PA is an independent risk factor and a powerful predictor of vulnerable plaques. Decreased levels of t-PA may reflect instability of atherosclerotic plaques and might therefore serve as noninvasive determinants of those at high risk for consequent adverse events.

High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis

Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes.Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts.Shear stress(SS)influences the formation and development of atherosclerosis.The current review focuses on the vulnerable plaques observed in the high shear stress(HSS)regions,which localizes at the proximal region of the plaque intruding into the lumen.The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation.These results greatly challenge the established belief that low shear stress is important for expansive remodelling,which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions.

Coronary spasm, a pathogenic trigger of vulnerable plaque rupture

Objective This coronary artery spasm review aimed to explore the most possible pathogenic trigger mechanism of vulnerable plaque rupture. Data sources Data used in this coronary artery spasm review were mainly from Medline and Pubmed in English. Study selection These reports from major review on coronary artery spasm .and these research included coronary artery conception, pathogenesis of spasm, mechanisms of plaque rupture, epidemiological evidence, clinical manifestation and the relationship between coronary artery spasm and vulnerable plaque rupture. Results Coronary artery spasm is somehow related to the presence of atherosclerotic intima disease in the coronary artery. However, chronic low-grade inflammation causes coronary vessel smooth muscle cell hypersensitivity, which can directely cause coronary artery spasm. Myocardial infarction and sudden cardiac death may be initiated by a sudden intense localized contraction of coronary artery smooth muscle. Conclusion Coronary artery spasm may be one trigger that can initiate and exacerbate vulnerable plaque rupture.