新的易损斑块血清标志物妊娠相关蛋白A研究进展

冠状动脉易损斑块破裂或腐蚀继发血栓形成是急性冠脉事件发生的病理基础,寻找易损斑块新血清标记物对于早期识别和干预高危患者至关重要。新近发现妊娠相关蛋白A(PAPP-A)参与动脉粥样硬化的发生发展,并且与斑块的不稳定性关系密切,是冠心病患者不良事件的预测因子。本综述主要介绍妊娠相关蛋白-A的生物学特性及其与心血管疾病以及易损斑块关系的研究进展,为临床诊断和治疗带来新的思路。     

动脉粥样硬化易损斑块的分子影像研究进展

动脉粥样硬化是心脑血管疾病最主要的病因,而其中易损斑块的突然破损所诱发的血小板聚集和血栓形成是引起脑卒中和急性心肌梗死的重要发病机制.如何更有效地早期诊断动脉粥样硬化的易损斑块是目前研究的热点.文章主要就近年来分子影像技术用于动脉粥样硬化易损斑块的评价研究进行综述.     

《PLoS综合》:血管内超高分辨光声显微系统研制成功

<正>中国科学院深圳先进技术研究院生物医学与健康工程研究所生物医学光学与分子影像研究室宋亮课题组携手相关单位,在国际上率先研制出成像分辨率高达19.6微米的血管内超高分辨光声显微成像系统,有望为急性心脑血管事件的介入诊断和治疗提供革新的技术手段。3月20日,相关研究成果发表在国际著名学术期刊《公共科学图书馆》(PLOS ONE)杂志上。急性心肌梗死、脑卒中等急性心脑血管事件是威胁人类健康的头号杀手,而近70%的急性心血管事件,是由于冠状动脉的易损斑块破裂形成     

脂蛋白相关磷脂酶A2对急性前循环脑梗死患者颈动脉斑块易损性的预测价值

目的:探讨脂蛋白相关磷脂酶A2(Lp-PLA2)对急性前循环脑梗死患者颈动脉斑块易损性的预测价值。方法:选取2015年9月至2017年3月我院收治的急性前循环脑梗死患者150例作为研究组,另选同期我院体检健康者100例作为对照组,检测两组血清Lp-PLA2、超敏C反应蛋白(hs-CRP)水平,并应用彩色多普勒超声检查研究组患者颈动脉粥样硬化情况,分析不同颈动脉粥样硬化情况以及不同病情患者血清Lp-PLA2、hs-CRP、颈动脉内膜-中层厚度(IMT),并分析血清Lp-PLA2对颈动脉斑块易损性的预测价值。结果:研究组血清Lp-PLA2、hs-CRP和IMT均显著高于对照组(P0.05)。易损斑块组、稳定斑块组、内膜增厚组血清Lp-PLA2、hs-CRP和IMT均显著高于内膜正常组,易损斑块组、稳定斑块组血清Lp-PLA2、hs-CRP和IMT均显著高于内膜增厚组(P0.05),易损斑块组血清Lp-PLA2、hs-CRP显著高于稳定斑块组(P0.05),而IMT比较无统计学差异(P0.05)。重度组、中度组脑梗死患者血清Lp-PLA2、hs-CRP和IMT均显著高于轻度组,重度组脑梗死患者血清Lp-PLA2、hs-CRP和IMT显著高于中度组(P0.05)。ROC曲线显示血清Lp-PLA2、hs-CRP对脑梗死患者颈动脉斑块易损性预测的曲线下面积(AUC)分别为0.809(95%CI:0.739-0.883)、0.598(95%CI:0.495-0.694),血清Lp-PLA2对脑梗死患者颈动脉斑块易损性的预测价值显著高于hs-CRP(P0.05)。结论:急性前循环脑梗死患者血清Lp-PLA2出现异常升高,其水平可以反映颈动脉斑块易损性,可为脑梗死诊断提供依据。     

IL-18、IL-10及其比值与冠状动脉粥样硬化斑块易损性研究进展

急性冠脉综合征主要是由于具有易损性的冠状动脉粥样硬化斑块发生破裂或蚀损,继发血栓形成,并引起具有严重危害的急性冠状动脉事件.炎症反应是影响冠状动脉粥样硬化斑块易损性的主要因素,参与反应的炎症因子是近年来研究的热点.有研究发现白细胞介素-18(IL-18)作为一个促炎症因子,会增加斑块的易损性,而白细胞介素-10(IL-10)作为主要的抗炎症因子,则具有抗动脉硬化及稳定粥样斑块的作用.IL-18/IL-10的比值代表了机体促炎性与抗炎性动态平衡的状态,其比值失衡可能是影响斑块易损性的重要因素.近来有研究认为,IL-18/IL-10的比值可作为急性冠脉综合征患者近期冠脉事件的预测因子.文章就近几年来有关IL-10、IL-18及其比值与冠状动脉粥样硬化斑块易损性的研究进展作一综述,以探讨其可能的临床意义.     

hs-CRP、D-二聚体和Lp-PLA2与冠心病患者冠状动脉粥样硬化易损斑块的相关性

目的:研究超敏C反应蛋白(hs-CRP)、D-二聚体和脂蛋白相关磷脂酶A2(Lp-PLA2)与冠心病患者冠状动脉粥样硬化易损斑块的相关性。方法:选择2014年1月~2016年12月在我院进行冠状动脉造影和血管内超声检查的患者106例,按照检查结果分为易损斑块组、稳定斑块组和对照组。检测和比较三组患者的血清hs-CRP、D-二聚体和Lp-PLA2水平,并采用Pearson相关分析探讨其与纤维帽厚度、斑块偏心指数和血管重构指数的相关性。结果:易损斑块组和稳定斑块组的血清hs-CRP、D-二聚体和Lp-PLA2水平明显高于对照组(P0.05),且易损斑块组的血清hs-CRP、D-二聚体和Lp-PLA2水平明显高于稳定斑块组(P0.05)。hs-CRP与纤维帽厚度呈负相关(r=-0.712,P0.05),与斑块偏心指数和血管重构指数呈正相关(r=0.813,0.756,P0.05);D-二聚体与纤维帽厚度呈负相关(r=-0.654,P0.05),与斑块偏心指数和血管重构指数呈正相关(r=0.912,0.853,P0.05);Lp-PLA2与纤维帽厚度呈负相关(r=-0.796,P0.05),与斑块偏心指数和血管重构指数呈正相关(r=0.836,0.729,P0.05)。结论:hs-CRP、D-二聚体和Lp-PLA2与冠心病患者冠状动脉粥样硬化易损斑块具有较高的相关性,可作为评估冠状动脉粥样斑块不稳定性的参考指标。     

宝石能谱CT 冠脉成像在隐匿型冠心病冠状动脉粥样斑块性质判断中的价值

目的:探讨宝石能谱CT冠脉成像在隐匿型冠心病冠状动脉粥样斑块性质判断中的价值,为临床隐匿型冠心病的诊断和治疗提供影像学参考依据。方法:选择2014年6月~2015年6月在我院诊断为心肌缺血且无临床症状的隐匿型冠心病患者共360例,所有入选患者均行宝石能谱CT冠脉成像检查,其中155例有冠状动脉狭窄,且伴有不同性质的粥样斑块。分析冠状动脉不同血管狭窄情况、斑块分型和斑块数目。结果:所有冠脉动脉狭窄均为轻度狭窄和中度狭窄,主要集中在左主干和左前降支,分别占35.48%和37.42%。硬斑块数目最多,占75.43%,其次为混合斑块和软斑块,分别占16.19%和8.38%。冠状动脉4支血管粥样斑块均为硬斑块者最多(29.03%)、硬斑块与软斑块同时存在者占29.03%、硬斑块与软斑块、混合斑块同时存在者占14.84%,未见单纯混合斑块或软斑块的患者。结论:隐匿型冠心病患者冠状动脉狭窄主要为轻、中度狭窄,冠状动脉斑块以硬斑块为主。宝石能谱CT冠脉成像能准确的判断隐匿型冠心病冠状动脉粥样斑块性质,值得临床推广借鉴。     

老年急性脑梗死患者外周血EMMPRIN表达与颈动脉易损斑块的相关性

目的:分析老年急性脑梗死(acute cerebral infarction,ACI)患者外周血血小板表面细胞外基质金属蛋白酶诱导因子(EMMPRIN)表达与颈动脉易损斑块的相关性。方法:收集2017年3月至2019年3月于我院收治的老年ACI患者作为研究对象,按照超声下颈动脉斑块的分类标准,将颈动脉斑块呈高回声受检者纳入稳定斑块组(n=41),斑块呈低回声或等回声的受检者则纳入易损斑块组(n=52)。应用logisitc回归模型,分析ACI患者颈动脉易损斑块的影响因素;采用Pearson相关分析,研究外周血单个核细胞EMMPRIN与各临床指标的相关性;采用受试者工作特征(ROC)曲线评价EMMPRIN诊断颈动脉易损斑块的准确性。结果:易损斑块组高脂血症、高血压病、2型糖尿病比例以及FPG、IL-6、IL-1β、MMP-9、MCP-1、TNF-α、LDL、EMMPRIN水平均高于稳定斑块组,组间差异显著(P0.05);易损斑块组HDL水平均低于稳定斑块组,组间差异显著(P0.05)。person相关分析结果显示,EMMPRIN与IL-6、IL-1β、MMP-9、TNF-α均呈正相关(r=0.348,0.374,0.418,0.427,P0.05)。logistic多因素回归分析显示,结果显示,高血压病、2型糖尿病、IL-1β、MMP-9、EMMPRIN均为颈动脉易损斑块的危险因素。EMMPRIN的AUC优于MMP-9、IL-1β(P=0.016,0.039,均P0.05)。结论:外周血血小板表面EMMPRIN水平可能与老年ACI患者颈动脉斑块稳定性有关,可作为辅助临床诊断颈动脉易损斑块的预警指标,对于ACI的发生、发展均具有重要的临床意义。     

Hcy, hs-CRP与急性脑梗死患者颈动脉粥样硬化关系的研究

目的:探讨急性脑梗死患者血清同型半胱氨酸(Hcy)、超敏C反应蛋白(hs-CRP)与颈动脉粥样硬化的相关性及临床意义。方法:收集确诊为急性脑梗死患者90例,对患者进行颈动脉超声检查,根据颈动脉狭窄程度将患者分成颈动脉内膜正常组、轻度狭窄组、中-重度狭窄组。比较三组患者斑块检出率、Hcy、hs-CRP水平和IMT厚度,同时对Hcy、hs-CRP与IMT进行相关性分析。结果:中-重度狭窄组斑块检出率为86.4%,显著高于轻度狭窄组和颈动脉内膜正常组(P0.05);颈动脉内膜正常组Hcy、hs-CRP水平以及IMT厚度均显著低于颈动脉轻度狭窄组、中-重度狭窄组(P0.05);hs-CRP与IMT呈正相关(r=0.71,P0.05);Hcy与IMT呈正相关(r=0.79,P0.05)。结论:血清Hcy和hs-CRP水平与颈动脉粥样硬化程度密切相关,Hcy、hs-CRP联合检测对急性脑梗死的早期诊断和预后有着重要临床意义。     

螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值

目的:探讨螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值。方法:选取2014年1月至2016年1月期间来我院就诊的60例急性脑梗死患者作为观察组,另选同期来我院就诊的非急性脑梗死患者60例作为对照组。两组患者均进行螺旋CT头颈部血管成像检查,比较两组患者的颈动脉狭窄程度及各段血管斑块分布情况,并根据检查结果评价螺旋CT头颈部血管成像对急性脑梗死患者颈动脉狭窄的诊断价值。结果:观察组轻度狭窄与中度狭窄检出率均显著高于对照组(P0.05),重度狭窄与闭塞检出率与对照组比较无统计学差异(P0.05),观察组总检出狭窄率高于对照组(P0.05)。观察组与对照组在颈动脉分叉处、颈总动脉、颈内动脉及颈外动脉均有斑块检出,观察组斑块总检出率为69.4%,显著高于对照组的41.2%(P0.05)。结论:临床上应用128层螺旋CT头颈部血管成像技术对急性脑梗死患者颈动脉狭窄情况可进行有效评估,该方法对患者轻、中度狭窄以及双侧颈动脉斑块检出率更高,在临床诊断及预后防治中具有应用推广价值。     

Imaging of coronary atherosclerosis and identification of the vulnerable plaque

Identification of the vulnerable plaque responsible for the occurrence of acute coronary syndromes and acute coronary death is a prerequisite for the stabilisation of this vulnerable plaque. Comprehensive coronary atherosclerosis imaging in clinical practice should involve visualisation of the entire coronary artery tree and characterisation of the plaque, including the three-dimensional morphology of the plaque, encroachment of the plaque on the vessel lumen, the major tissue components of the plaque, remodelling of the vessel and presence of inflammation.Obviously, no single diagnostic modality is available that provides such comprehensive imaging and unfortunately no diagnostic tool is available that unequivocally identifies the vulnerable plaque.The objective of this article is to discuss experience with currently available diagnostic modalities for coronary atherosclerosis imaging. In addition, a number of evolving techniques will be briefly discussed.     

斑点追踪技术对非ST 段抬高急性冠脉综合征的研究进展

非ST段抬高急性冠脉综合征(Non-ST segment elevation acute coronary syndrome,NSTE-ACS)是不稳定斑块基础上急性血栓形成,冠脉狭窄程度骤然加剧,冠脉血流减少导致心肌氧供应的直接减少为病理基础的一组临床综合征,好发于老年人,常累及多支血管,由于其心电图及常规超声心动图表现不典型,容易给临床带来困扰,斑点追踪成像(speckle tracking imaging,STI)无角度依赖性分别评价左室纵向、圆周、径向、扭转功能,为敏感评价左室功能早期改变提供了新的方法,本文对非ST段抬高急性冠脉综合征患者的临床特点以及斑点追踪技术的临床应用研究进展进行了综述。     

Echocardiographic assessment and percutaneous closure of multiple atrial septal defects

Percutaneous coronary intervention can be associated with distal embolization of thrombotic material causing myocardial necrosis and infarction. We discuss the role of intravascular imaging to guide the use of a distal protection device by describing the outcome of a young woman presenting with non-ST elevation myocardial infarction. Coronary angiography demonstrated an isolated minor stenosis in the proximal left anterior descending coronary artery with slight haziness beyond the lesion. Intravascular ultrasound confirmed an extensive thrombus overlying a bulky atherosclerotic plaque. A distal filter wire was therefore successfully used to reduce the risk of distal embolization. The use of intravascular ultrasound in patients presenting with acute coronary syndrome may reveal large thrombi that are difficult to image using conventional angiographic techniques. Intravascular ultrasound can therefore be used as a tool to select lesions requiring distal protection.     

Progressive epicardial coronary blood flow reduction fails to produce ST-segment depression at normal heart rates

ST-segment depression is commonly seen in patients with acute coronary syndromes. Most authors have attributed it to transient reductions in coronary blood flow due to nonocclusive thrombus formation on a disrupted atherosclerotic plaque and dynamic focal vasospasm at the site of coronary artery stenosis. However, ST-segment depression was never reproduced in classic animal models of coronary stenosis without the presence of tachycardia. We hypothesized that ST-segment depression occurring during acute coronary syndromes is not entirely explained by changes in epicardial coronary artery resistance and thus evaluated the effect of a slow, progressive epicardial coronary artery occlusion on the ECG and regional myocardial blood flow in anesthetized pigs. Slow, progressive occlusion over 72 min (SD 27) of the left anterior descending coronary artery in 20 anesthetized pigs led to a 90% decrease in coronary blood flow and the development of ST-segment elevation associated with homogeneous and transmural myocardial blood flow reductions, confirmed by microspheres and myocardial contrast echocardiography. ST-segment depression was not observed in any ECG lead before the development of ST-segment elevation. At normal heart rates, progressive epicardial stenosis of a coronary artery results in myocardial ischemia associated with homogeneous, transmural reduction in regional myocardial blood flow and ST-segment elevation, without preceding ST-segment depression. Thus, in coronary syndromes with ST-segment depression and predominant subendocardial ischemia, factors other than mere increases in epicardial coronary resistance must be invoked to explain the heterogeneous parietal distribution of flow and associated ECG changes.     

3D computational parametric analysis of eccentric atheroma plaque: influence of axial and circumferential residual stresses

Plaque rupture plays a role in the majority of acute coronary syndromes. Rupture has usually been associated with stress concentrations, which are mainly affected by the plaque geometry and the tissue properties. The aim of this study is to evaluate the influence of morphology on the risk of plaque rupture, including the main geometrical factors, and to assess the role of circumferential and axial residual stresses by means of a parametric 3D finite element model. For this purpose, a 3D parametric finite element model of the coronary artery with eccentric atheroma plaque was developed. Healthy (adventitia and media in areas without atheroma plaque) and diseased (fibrotic and lipidic) tissues were considered in the model. The geometrical parameters used to define and design the idealized coronary plaque anatomy were the lipid core length, the stenosis ratio, the fibrous cap thickness, and the lipid core ratio. Finally, residual stresses in longitudinal and circumferential directions were incorporated into the model to analyse the influence of the important mechanical factors in the vulnerability of the plaque. Viewing the results, we conclude that residual stresses should be considered in the modelling of this kind of problems since they cause a significant alteration of the vulnerable plaque region limits. The obtained results show that the fibrous cap thickness and the lipid core length, in combination with the lipid core width, appear to be the key morphological parameters that play a determinant role in the maximal principal stress (MPS). However, the stenosis ratio is found to not play a significant role in vulnerability related to the MPS. Plaque rupture should therefore be observed as a consequence, not only of the cap thickness, but as a combination of the stenosis ratio, the fibrous cap thickness and the lipid core dimensions.     

The emerging role of thrombus aspiration in contemporary percutaneous coronary intervention practice

Coronary atherosclerosis may lead towards thrombogenesis, usually triggered by rupture or erosion of a vulnerable epicardial coronary artery plaque. Most acute coronary syndromes are caused by ruptured atherosclerotic plaques with superimposed thrombus.     

Higher critical plaque wall stress in patients who died of coronary artery disease compared with those who died of other causes: A 3D FSI study based on ex vivo MRI of coronary plaques

Mechanical forces play an important role in the rupture of vulnerable plaques. This process is often associated with cardiovascular syndromes, such as heart attack and stroke. In this study, magnetic resonance imaging (MRI)-based models were used to investigate the association between plaque wall stress (PWS) and coronary artery disease (CAD).     

The roles of myeloperoxidase in coronary artery disease and its potential implication in plaque rupture

Atherosclerosis is the main pathophysiological process underlying coronary artery disease (CAD). Acute complications of atherosclerosis, such as myocardial infarction, are caused by the rupture of vulnerable atherosclerotic plaques, which are characterized by thin, highly inflamed, and collagen-poor fibrous caps. Several lines of evidence mechanistically link the heme peroxidase myeloperoxidase (MPO), inflammation as well as acute and chronic manifestations of atherosclerosis. MPO and MPO-derived oxidants have been shown to contribute to the formation of foam cells, endothelial dysfunction and apoptosis, the activation of latent matrix metalloproteinases, and the expression of tissue factor that can promote the development of vulnerable plaque. As such, detection, quantification and imaging of MPO mass and activity have become useful in cardiac risk stratification, both for disease assessment and in the identification of patients at risk of plaque rupture. This review summarizes the current knowledge about the role of MPO in CAD with a focus on its possible roles in plaque rupture and recent advances to quantify and image MPO in plasma and atherosclerotic plaques.     

Asymmetric dimethylarginine and long-term adverse cardiovascular events in patients with type 2 diabetes: relation with the glycemic control

Patients with type 2 diabetes are at a high risk for acute cardiovascular events, which usually arise from the rupture of a vulnerable coronary lesion characterized by specific morphological plaque features. Thus, the identification of vulnerable plaques is of utmost clinical importance in patients with type 2 diabetes. However, there is currently no scoring system available to identify vulnerable lesions based on plaque characteristics. Thus, we aimed to characterize the diagnostic value of optical coherence tomography (OCT) - derived lesion characteristics to quantify plaque vulnerability both as individual parameters and when combined to a score in patients with type 2 diabetes. OCT was performed in the coronary culprit lesions of 112 patients with type 2 diabetes. The score, which quantifies plaque vulnerability, was defined as the predicted probability that a lesion is the cause for an acute coronary syndrome (ACS) (vs. stable angina (SAP)) based on its specific plaque morphology. Multivariable logistic regression analysis demonstrated that plaque vulnerability was independently predicted by the minimal fibrous cap thickness overlying a lesion’s lipid core (odds ratio (OR) per 10 μm 0.478, p = 0.002), the medium lipid arc (OR per 90° 13.997, p < 0.001), the presence of macrophages (OR 4.797, p = 0.015) and the lipid plaque length (OR 1.290, p = 0.098). Receiver-operating-characteristics (ROC) analyses demonstrated that these parameters combined to a score demonstrate an excellent diagnostic efficiency to identify culprit lesions of patients with ACS (vs. SAP, AUC 0.90, 95% CI 0.84-0.96). This is the first study to present a score to quantify lesion vulnerability in patients with type 2 diabetes. This score may be a valuable adjunct in decision-making and useful in guiding coronary interventions.