Differences in intravascular ultrasound and histological findings in culprit coronary plaques between ST-segment elevation myocardial infarction and stable angina

A comprehensive evaluation of culprit coronary lesions may help to understand vulnerable plaques responsible for ST-segment elevation myocardial infarction (STEMI). We compared intravascular ultrasound (IVUS) and histological findings in culprit coronary plaques from 94 patients with STEMI (n = 54) or stable angina (n = 40). Tissue specimens were obtained by directional coronary atherectomy and IVUS was performed before percutaneous coronary intervention. IVUS and histological data were analyzed. Clinical characteristics were largely similar between the two groups. Plaque rupture and thrombi were more frequently found in the STEMI group than in the stable angina group. There were no significant differences between plaque types or proximal and distal reference measurements in the two groups. However, the site of minimal lumen area had a greater vessel area, remodeling index, and plaque burden with lesser lumen area in the STEMI group than in the stable angina group. Plaque areas immunopositive for CD68 and CD31 were significantly larger in the STEMI group, while the area immunopositive for α-smooth muscle actin was larger in the stable angina group. In conclusion, culprit lesions in STEMI patients showed a greater plaque burden, remodeling index, and more frequent thrombi with increased inflammation and neovascularization compared to the stable angina group, supporting the current concept of vulnerable plaques being responsible for STEMI.     

Expression of ADAMTS-2, -3, -13, and -14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina

ADAMTS (a disintegrin and metalloproteinase with thrombospondin type 1 motifs) proteases are emerging as key participants in the pathogenesis of vascular diseases. We studied the expression of ADAMTS-2, -3, -4 and -14 in the culprit plaques from patients presenting with acute myocardial infarction (AMI) versus stable angina. Tissue samples were gathered from 52 patients with AMI (n = 35) or stable angina (n = 17) who underwent directional coronary atherectomy. The specimens were stained with hematoxylin-eosin and analyzed immunohistochemically using antibodies specific to ADAMTS-2, -3, -13 and -14, and markers for endothelial cells, macrophages, and smooth muscle cells. Baseline characteristics of the groups were mostly similar. The proportion of smooth muscle α-actin-immunopositive area was smaller in the AMI group than in the stable angina group, but the areas immunopositive for CD31 or CD68 were higher in the AMI group. The relative areas immunopositive for ADAMTS-2, -3, and -13 in AMI were significantly larger than those in stable angina. However, the proportion of areas immunopositive for ADAMTS-14 did not differ between the two groups. Areas that stained for ADAMTS-2, -3, -13, and -14 largely overlapped with those positive for CD31 or CD68. The areas immunopositive for ADAMTS proteases were significantly correlated with CD31- or CD68-immunostained areas. In conclusions, ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina. These results support a role for these enzymes in the pathogenesis of AMI.     

Coronary artery disease: arterial remodelling and clinical presentation

OBJECTIVE—To investigate the hypothesis that in coronary artery disease large plaques in compensatorily enlarged segments are associated with acute coronary syndromes, whereas smaller plaques in shrunken segments are associated with stable angina pectoris.METHODS—Patients selected for percutaneous transluminal coronary angioplasty (PTCA) were divided into two groups, one with stable angina pectoris (stable group, n = 37) and one with unstable angina or postmyocardial infarction angina of the infarct related artery (unstable group, n = 32). In both groups, remodelling at the culprit lesion site was determined by intravascular ultrasound before the intervention. Remodelling was calculated as relative vessel area: [vessel area culprit lesion site ÷ mean vessel area of both proximal and distal reference sites] × 100%. Compensatory enlargement was defined as remodelling of ? 105%, whereas shrinkage was defined as remodelling of ? 95%.RESULTS—In the unstable group, the vessel area at the culprit lesion site was larger than in the stable group, at mean (SD) 18.1 (5.3) v 14.6 (5.4) mm² (p = 0.008). Lumen areas were similar. Consequently, plaque area and percentage remodelling were larger in the unstable group than in the stable group: mean (SD) 14.8 (4.8) v 11.6 (4.9) mm² (p = 0.009) and 112 (31)% v 95 (17)% (p = 0.005), respectively. Significantly more culprit lesion sites were classified as shrunken in the stable group (21/37) than in the unstable group (8/32; p = 0.014). On the other hand, more lesion sites were classified as enlarged in the unstable group (16/23) than in the stable group (8/37; p = 0.022).CONCLUSIONS—In patients selected for PTCA, the mode of remodelling is related to clinical presentation.     

Impact of counterbalance between macrophage migration inhibitory factor and its inhibitor Gremlin-1 in patients with coronary artery disease

Objective: Monocyte infiltration is a critical step in the pathophysiology of plaque instability in coronary artery disease (CAD). Macrophage migration inhibitory factor (MIF) is involved in atherosclerotic plaque progression and instability leading to intracoronary thrombosis. Gremlin-1 (Grem1) has been recently identified as endogenous inhibitor of MIF. To date there are no data on the clinical impact of this interaction in cardiovascular patients. Methods and results: Plasma levels of MIF and Grem1 were determined by enzyme-linked immunoassay in patients with acute coronary syndromes (ACS, n = 120; stable CAD, n = 166 and healthy control subjects, n = 25). MIF levels were significantly increased in ACS compared to stable CAD and healthy control (ACS: median 2.85; IQR 3.52 ng/ml; versus SAP: median 1.22; IQR 2.99 ng/ml; versus healthy control: median 0.10; IQR 0.09 ng/ml, p < 0.001). Grem1 levels were significantly higher in ACS and stable CAD patients compared to healthy control (ACS: median 211.00; IQR 130.47 ng/ml; SAP: median 220.20; IQR 120.93 ng/ml, versus healthy control: median 90.57; IQR 97.68 ng/ml, p < 0.001). Grem1/MIF ratio was independently associated with ACS, whereas the single parameters were not associated with the presence of ACS. Furthermore, Grem1/MIF ratio was associated with angiographic signs of intracoronary thrombi and severity of thrombus burden. Conclusion: These novel findings suggest a potential role of Grem1/MIF ratio to indicate acuity of CAD and the grade of plaque stability. Prospective angiographic cohort studies involving plaque imaging techniques are warranted to further characterize the prognostic role of this novel risk marker in CAD patients.     

Prediction of the no-reflow phenomenon during percutaneous coronary intervention using coronary computed tomography angiography

Coronary computed tomography angiography (CTA) can assess plaque characteristics and plaque size noninvasively. The purpose of this study was to investigate whether coronary CTA before percutaneous coronary intervention (PCI) can predict the no-reflow phenomenon during PCI. Seventy-eight patients [acute coronary syndrome (ACS) = 43, stable angina pectoris (SAP) = 35, male/female = 72/6, age: 65 ± 10 years] who underwent 16- or 64-slice CTA in the 4 weeks before PCI were enrolled. The low attenuation plaque size on CTA was compared between patients with (NR+) and without the no-reflow phenomenon (NR−). No-reflow phenomenon was observed in 11 patients, including 10 patients with ACS and 1 patient with SAP. Low attenuation plaque was detected in 9 (82%) NR(+) lesions and 35 (52%) NR(−) lesions. The length of low attenuation plaque was significantly longer in NR(+) than in NR(−) patients (9.0 ± 6.5 vs. 1.6 ± 2.7 mm, p < 0.0001). On step-wise regression analysis, ACS (p = 0.036, 95% CI = 0.009–0.258) and the presence of low attenuation plaque with a length >4.7 mm (p < 0.001, 95% CI = 0.447–0.778) were significant independent predictors of NR(−) no-reflow phenomenon. Low attenuation plaque with lesion length of >4.7 mm on coronary CTA and ACS were the significant predictors for the no-reflow phenomenon during PCI. Coronary CTA assessment before PCI would be useful to predict coronary events during PCI in advance.     

急性冠状动脉综合征患者不稳定性斑块的血管内超声

目的观察急性冠状动脉综合征患者不稳定性斑块的血管内超声特征.方法 36例急性冠状动脉综合征患者和20例稳定型心绞痛患者进行冠状动脉造影及血管内超声检查.应用血管内超声分别观察比较冠状动脉内斑块的性质,同时测量冠状动脉病变部位及其参考部位的血管外弹力膜面积、管腔面积、斑块面积及管腔面积狭窄率,并计算斑块的偏心指数及血管重构指数.结果急性冠状动脉综合征患者中脂质斑块占77.8%(28/36),其中10例发生斑块破裂及血栓形成;稳定型心绞痛患者主要为纤维性斑块及混合性斑块,脂质斑块仅占10%(2/20),无斑块破裂及血栓形成.两组斑块的特征包括偏心性、外弹力膜面积、斑块面积及管腔面积狭窄率具有显著性差异.不稳定性斑块呈现明显的正性重构,占72.2%(26/36),而稳定性斑块主要表现为负性重构,占75%(15/20).结论血管内超声能够准确地识别动脉粥样硬化不稳定性斑块,为早期临床发现不稳定性斑块并预测斑块破裂奠定了基础.     

Multislice computed tomographic characteristics of coronary lesions in acute coronary syndromes.

OBJECTIVES: To evaluate the feasibility of noninvasive assessment of the characteristics of disrupted atherosclerotic plaques, the authors interrogated the culprit lesions in acute coronary syndromes (ACS) by multislice computed tomography (CT). BACKGROUND: Disrupted atherosclerotic plaques responsible for ACS histopathologically demonstrate large lipid cores and positive vascular remodeling. It is expected that plaques vulnerable to rupture should bear similar imaging signatures by CT. METHODS: Either 0.5-mm x 16-slice or 64-slice CT was performed in 38 patients with ACS and compared with 33 patients with stable angina pectoris (SAP) before percutaneous coronary intervention. The coronary plaques in ACS and SAP were evaluated for the CT plaque characteristics, including vessel remodeling, consistency of noncalcified plaque (NCP <30 HU or 30 HU 相似文献   

Healed Culprit Plaques in Patients With Acute Coronary Syndromes

BackgroundHealed plaques, morphologically characterized by a layered phenotype, are frequently found in subjects with sudden cardiac death. However, in vivo data are lacking.ObjectivesThe purpose of this study was to determine the prevalence, morphological characteristics, and clinical significance of healed culprit plaques in patients with acute coronary syndromes (ACS) using optical coherence tomography (OCT).MethodsA total of 376 ACS patients (252 ST-segment elevation myocardial infarction [MI] and 124 non–ST-segment elevation acute coronary syndrome) who had undergone pre-intervention OCT imaging of the culprit lesion were enrolled. Patients were stratified according to the presence of layered phenotype, defined as layers of different optical density at OCT. Clinical and laboratory data, OCT characteristics, and 1-year outcome were compared between the 2 groups.ResultsAmong 376 patients, 108 (28.7%) healed plaques were identified. Hyperlipidemia, diabetes, and history of MI were more frequent in patients with healed plaques (44.4% vs. 33.2%; p = 0.041; 35.2% vs. 23.5%; p = 0.021; and 15.7% vs. 6.3%; p = 0.009, respectively). High-sensitivity C-reactive protein was significantly higher in patients with healed plaques (median 4.98 mg/l [interquartile range: 1.00 to 11.32 mg/l] vs. 3.00 mg/l [interquartile range: 0.30 to 10.15 mg/l]; p = 0.029). Plaque rupture (64.8% vs. 53.0%; p = 0.039), thin cap fibroatheroma (56.5% vs. 42.5%; p = 0.016), and macrophage accumulation (81.1% vs. 63.4%; p = 0.001) were common in the layered group. OCT also revealed greater area stenosis in plaques with layered phenotype (79.2 ± 9.5% vs. 74.3 ± 14.3%; p = 0.001). The incidence of major adverse cardiovascular events was similar between the 2 groups, except that the all-cause rehospitalization rate was higher among healed plaques (32.7% vs. 16.5%; p = 0.013).ConclusionsHealed plaques, a signature of prior plaque destabilization, were found at the culprit site in more than one-quarter of ACS patients. Such patients more frequently were diabetic, were hyperlipidemic, or had a history of MI. Healed plaques frequently showed OCT features of vulnerability with evidence of local and systemic inflammation. The combination of plaque vulnerability, local inflammation, and greater plaque burden in addition to systemic inflammation may outweigh the protective mechanism of plaque healing and predispose those plaques to develop occlusive thrombus.     

Recent activation of the plaque immune response in coronary lesions underlying acute coronary syndromes

Objective—To discriminate between chronic inflammation and acute activation of the plaque immune response in culprit lesions of patients with acute coronary syndromes.Design—Retrospective study.Setting—Tertiary referral centre.Subjects—71 patients having coronary atherectomy were classified according to their ischaemic syndrome: stable angina (n = 23); stabilised unstable angina (n = 18); refractory unstable angina (n = 11); and acute myocardial infarction (n = 19).Main outcome measures—Immunohistochemical measurement of interleukin 2 receptor (IL-2R) (CD25) positive cells expressed as a percentage of the total amount of (CD3 positive) T lymphocytes in frozen sections of atherectomy specimens.Results—The number of lesions containing IL-2R (CD25) positive T cells increased with severity of the ischaemic coronary syndrome (stable angina, 52%; stabilised unstable angina, 77.8%; refractory unstable angina, 90.9%; acute myocardial infarction, 89.4%). The percentage of activated T cells (CD25/CD3 ratios ×100) increased in lesions associated with refractory unstable angina (7.8%) and acute myocardial infarction (18.5%), compared with those in lesions associated with either chronic stable angina (2.2%) or stabilised unstable angina (3.3%).Conclusions—An increase in the percentage of IL-2R positive T lymphocytes in culprit lesions of patients with acute coronary syndromes indicates recent activation and amplification of the immune response within plaques. This may result in a burst of inflammatory products with tissue degrading and vasoactive properties and, hence, could initiate or accelerate the onset of an acute coronary event.     

High-Risk Plaque Detected on Coronary CT Angiography Predicts Acute Coronary Syndromes Independent of Significant Stenosis in Acute Chest Pain : Results From the ROMICAT-II Trial

Background

It is not known whether high-risk plaque, as detected by coronary computed tomography angiography (CTA), permits improved early diagnosis of acute coronary syndromes (ACS) independently to the presence of significant coronary artery disease (CAD) in patients with acute chest pain.

Objectives

The primary aim of this study was to determine whether high-risk plaque features, as detected by CTA in the emergency department (ED), may improve diagnostic certainty of ACS independently and incrementally to the presence of significant CAD and clinical risk assessment in patients with acute chest pain but without objective evidence of myocardial ischemia or myocardial infarction (MI).

Methods

We included patients randomized to the coronary CTA arm of the ROMICAT-II (Rule Out Myocardial Infarction/Ischemia Using Computer-Assisted Tomography II) trial. Readers assessed coronary CTA qualitatively for the presence of nonobstructive CAD (1% to 49% stenosis), significant CAD (≥50% or ≥70% stenosis), and the presence of at least 1 of the high-risk plaque features (positive remodeling, low <30 Hounsfield units plaque, napkin-ring sign, spotty calcium). In logistic regression analysis, we determined the association of high-risk plaque with ACS (MI or unstable angina pectoris) during the index hospitalization and whether this was independent of significant CAD and clinical risk assessment.

Results

Overall, 37 of 472 patients who underwent coronary CTA with diagnostic image quality (mean age 53.9 ± 8.0 years; 52.8% men) had ACS (7.8%; MI n = 5; unstable angina pectoris n = 32). CAD was present in 262 patients (55.5%; nonobstructive CAD in 217 patients [46.0%] and significant CAD with ≥50% stenosis in 45 patients [9.5%]). High-risk plaques were more frequent in patients with ACS and remained a significant predictor of ACS (odds ratio [OR]: 8.9; 95% CI: 1.8 to 43.3; p = 0.006) after adjustment for ≥50% stenosis (OR: 38.6; 95% CI: 14.2 to 104.7; p < 0.001) and clinical risk assessment (age, sex, number of cardiovascular risk factors). Similar results were observed after adjustment for ≥70% stenosis.

Conclusions

In patients presenting to the ED with acute chest pain but negative initial electrocardiogram and troponin, presence of high-risk plaques on coronary CTA increased the likelihood of ACS independent of significant CAD and clinical risk assessment (age, sex, and number of cardiovascular risk factors). (Multicenter Study to Rule Out Myocardial Infarction by Cardiac Computed Tomography [ROMICAT-II]; NCT01084239)     

Intravascular Polarimetry in Patients With Coronary Artery Disease

ObjectivesThe aims of this first-in-human pilot study of intravascular polarimetry were to investigate polarization properties of coronary plaques in patients and to examine the relationship of these features with established structural characteristics available to conventional optical frequency domain imaging (OFDI) and with clinical presentation.BackgroundPolarization-sensitive OFDI measures birefringence and depolarization of tissue together with conventional cross-sectional optical frequency domain images of subsurface microstructure.MethodsThirty patients undergoing polarization-sensitive OFDI (acute coronary syndrome, n = 12; stable angina pectoris, n = 18) participated in this study. Three hundred forty-two cross-sectional images evenly distributed along all imaged coronary arteries were classified into 1 of 7 plaque categories according to conventional OFDI. Polarization features averaged over the entire intimal area of each cross section were compared among plaque types and with structural parameters. Furthermore, the polarization properties in cross sections (n = 244) of the fibrous caps of acute coronary syndrome and stable angina pectoris culprit lesions were assessed and compared with structural features using a generalized linear model.ResultsThe median birefringence and depolarization showed statistically significant differences among plaque types (p < 0.001 for both, one-way analysis of variance). Depolarization differed significantly among individual plaque types (p < 0.05), except between normal arteries and fibrous plaques and between fibrofatty and fibrocalcified plaques. Caps of acute coronary syndrome lesions and ruptured caps exhibited lower birefringence than caps of stable angina pectoris lesions (p < 0.01). In addition to clinical presentation, cap birefringence was also associated with macrophage accumulation as assessed using normalized SD.ConclusionsIntravascular polarimetry provides quantitative metrics that help characterize coronary arterial tissues and may offer refined insight into coronary arterial atherosclerotic lesions in patients.     

Association between plasma inflammatory markers and morphology of coronary artery lesion in patients with coronary artery disease

The atherosclerotic plaque vulnerability may be related to inflammation,immunity,metabolism and blood clotting.One of the key factors affecting plaque stability is inflammatory reaction.This study was to investigate the relationship between vulnerability of coronary artery plaque evaluated with coronary angiography (CAG),intravascular ultrasound (IVUS) and the levels of plasma inflammatory markers.Methods Fifty-eight consecutive patients with acute coronary syndrome who had coronary lesion of a single vessel were divided into 3 groups based on angiographic morphology of the lesions:type Ⅰ lesion group (n =16),type Ⅱ lesion group (n =25) and type Ⅲ lesion group (n =17).The control group consisted of 17 patients with stable angina.Plasma levels of high sensitivity C reaction protein (hs-CRP),matrix metalloproteinase (MMP,including MMP-2 and MMP-9),CD40 ligand (CD40L) and pregnancy associated plasma protein-A (PAPP-A) were measured by ELISA.A subgroup of 28 patients (including 18 ACS patients and 10 stable angina control patients) who underwent IVUS study,were analyzed.Results The plasma levels of MMP-2,MMP-9 and PAPP-A in type Ⅱ lesion group were significantly higher than those in other groups (all P＜0.05).In type Ⅱ lesion group,linear correlation analyses showed significant positive correlation between levels of hs-CRP and MMP-2 (r=0.508);MMP-2 and MMP-9,CD40L,PAPP-A (r=0.647,0.704 and 0.751,respectively);MMP-9 and CD40L,PAPP-A (r=0.491 and 0.639,respectively);CD40L and PAPP-A (r=0.896).IVUS subgroup analysis showed that the area of plaques and plaque burden in culprit lesion,the incidence of high-risk plaques,remodeling index (RI) and positive remodeling percentage in ACS patients were significantly greater than those in control subgroup (P=0.000,0.037,0.028,0.015 and 0.040,respectively).Compared with control subgroup,the plasma levels of hs-CRP,MMP-2,MMP-9 and PAPP-A were markedly elevated (P=0.033,0.000,0.000 and 0.027,respectively).Conclusions CAG and IVUS combined with study on plasma levels of inflammation mediators are helpful in judging the vulnerability of coronary artery plaques.(J Geriatr Cardiol 2008;5:207-211)     

Distribution,frequency and clinical implications of napkin-ring sign assessed by multidetector computed tomography

BackgroundPlaque rupture and secondary thrombus formation play key roles in the onset of acute coronary syndrome (ACS). Plaques showing the napkin-ring sign in multidetector computed tomography (MDCT) have been reported as thin-cap fibroatheroma that is recognized as a precursor lesion for plaque rupture. The purpose of this study was to investigate distribution and frequency of napkin-ring sign and its relationship to features indicating coronary plaque vulnerability on MDCT in patients with coronary artery disease.MethodsWe enrolled 273 patients with ACS (n = 61) or stable angina pectoris (SAP, n = 212) who were assessed by MDCT. The definition of the napkin-ring sign was the presence of a ring of high attenuation and the CT attenuation of a ring presenting higher than those of the adjacent plaque and no greater than 130 HU.ResultsThe culprit plaques with the napkin-ring sign show higher remodeling index and lower CT attenuation (1.15 ± 0.12 vs. 1.02 ± 0.12, p < 0.01 and 39.9 ± 22.8 vs. 72.7 ± 26.6, p < 0.01, respectively). Napkin-ring sign at culprit lesions was more frequent in patients with ACS than those with SAP (49.0% vs. 11.2%, p < 0.01). Moreover, napkin-ring sign at non-culprit lesions was more frequently observed in ACS patients compared with SAP patients (12.7% vs. 2.8%, p < 0.01). The distribution of the napkin-ring sign in the right coronary arteries and left circumflex arteries of our population was relatively even, whereas the napkin-ring sign in the left anterior descending artery was common in the proximal sites (p < 0.01).ConclusionsThe napkin-ring sign assessed by MDCT represents similar clinical features of fibroatheroma. MDCT could contribute to the search for fibroatheroma.     

Increased expression of C-reactive protein and tissue factor in acute coronary syndrome lesions: Correlation with serum C-reactive protein, angioscopic findings, and modification by statins

BackgroundSerum C-reactive protein (CRP) is a strong risk predictor of cardiovascular events, and tissue factor (TF) plays a central role in thrombus formation of advanced atherosclerotic plaques. Aim of the present study was to quantify in situ CRP and TF in coronary atherectomy specimens associated with acute coronary syndromes (ACS) or stable angina (SA). In addition, the effect of statin treatment on both intimal determinants was analyzed.Methods and resultsSerial sections from atherectomy probes retrieved from coronary primary target lesions of 42 ACS and 70 SA patients were examined for CRP and TF expression using immunostaining. CRP and TF intimal expression was consistently higher in ACS lesions and a positive correlation between both determinants was detected. In both subgroups intimal staining intensity of CRP but not TF was strongly associated with serum CRP levels. Using angioscopy, complex plaques revealed a higher intimal CRP and TF expression than white/yellow plaques. Both CRP and TF were consistently lower expressed in target lesions of patients with pre-existing statin treatment.ConclusionsCRP and TF expression is markedly increased in plaques derived from patients with ACS as compared to SA patients. Statin treatment appears to reduce vascular expression of CRP and TF.     

Early changes in local hemostasis activation following percutaneous coronary intervention in stable angina patients: a comparison between drug-eluting and bare metal stents

Background Early change in local intracoronary hemostasis following drug-eluting (DES) and bare metal stent (BMS) implantation has never been assessed in stable angina patients. Methods Markers of local platelet activation (soluble glycoprotein V [sGPV] and P-Selectin [CD62P]), coagulation activation (tissue factor [TF], prothrombin fragments 1 + 2 [F1 + 2] and activated factor VII [FVIIa]) and fibrinolysis markers (D-dimers [DD], fibrinogen [FIB], tissue plasminogen activator [t-PA], and plasminogen activator inhibitor type-1 complexes [PAI-1]) were determined in 20 patients with stable angina who underwent percutaneous coronary intervention (PCI). All patients were pretreated with clopidogrel, aspirin, and enoxaparin. Systematic balloon predilation was performed before DES (9 patients) and BMS (11 patients) implantation. All blood samples were drawn 10–20 mm distal to the lesion site. Results No significant changes in levels of platelet activation markers occurred during PCI. There was a transient significant increase in TF (14%; P = 0.004), in F1 + 2 (40%; P = 0.001), and FVIIa (31%; P = 0.007) following angioplasty. Similarly, a significant 43% increase was observed in DD levels following balloon predilation, associated with an increase of 46%, 60%, and 70% in FIB, t-PA and PAI-1 levels, respectively (all P < 0.0001). All these markers returned to baseline values after stent implantation. No difference was observed between DES and BMS. Conclusions Early changes in local hemostasis activation following PCI, were related to balloon predilation. Neither DES nor BMS increased markers of platelet activation, coagulation, or fibrinolysis, under dual antiplatelet and anticoagulant pretreatment.     

Mitogen-activated protein kinases activation in T lymphocytes of patients with acute coronary syndromes

Current available biomarkers cannot identify myocardial ischemia without necrosis. To overcome this issue and to increase diagnostic power, we evaluated the activation of the three MAPK pathways, ERK1/2, JNK and p38, in T lymphocytes of patients with acute coronary syndromes (ACS). We included sixty consecutive patients affected by either unstable angina (UA, N = 22), Non- ST-segment elevation MI (NSTEMI, N = 19) or ST-segment elevation MI (STEMI, N = 19). Two separate groups of patients were matched as controls: healthy subjects (CTRL, N = 20) and patients with stable coronary artery disease (CAD, N = 21). MAPK activation in T lymphocytes, measured by phospho-ERK1/2, phospho-JNK and phospho-p38 levels, was assessed by flow cytometry analysis which revealed significantly increased phosphorylated levels of ERK1/2 in patients with UA, compared to controls. In UA patients no significant changes were detected for phospho-JNK compared to both control groups. NSTEMI and STEMI groups showed a statistically significant increase in both phospho-ERK1/2 and phospho-JNK, compared to control groups. All ACS groups demonstrated significantly increased phosphorylation of p38 compared to CTRL, but not CAD. ROC curves showed that a cut-off value of 22.5 intensity of fluorescence for phospho-ERK1/2 was able to significantly discriminate UA patients from patients with stable angina with 78% sensitivity and 90% specificity. Therefore, a differential MAPK activation in T lymphocytes denotes patients with ACS. Indeed, patients with unstable angina are identified with high specificity by activated ERK1/2 and normal JNK levels. These data could represent a valuable new molecular signature to be used as specific biomarkers for the diagnosis of unstable angina within ACS.     

急性冠脉综合征病变的血管内超声研究

目的 探讨急性冠脉综合征(ACS)冠状动脉粥样斑块病变的血管内超声(IVUS)特点.方法 应用IVUS观察35例稳定型心绞痛(SA)和49例急性冠脉综合征(包括急性心肌梗死和不稳定型心绞痛)患者冠脉病变处的粥样硬化斑块的特征.结果 ACS组患者冠脉病变处以软斑块为主69.4% (34/49),SA患者冠脉病变处以硬斑块为主77.1% ( 27/35),差异有统计学意义(P＜0.05),其中ACS组不稳定斑块和斑块破裂,血栓形成病变占总病变的57.2%,与SA组(8.6%)相比具有显著差异性(P＜0.01);同时两组患者斑块面积、斑块负荷、偏心指数相比差异亦具有显著性(P＜0.01);ACS患者主要以正性重构为主(59.2%),而SA患者主要以负性重构为主(57.1%),二者均有统计学差异(P＜0.01).结论 ACS组软斑块及斑块破裂、血栓形成、血管正性重构发生率明显高于SA组,IVUS检查是在体观察粥样斑块的良好手段,并可以指导治疗策略.     

Peri-Coronary Adipose Tissue Density Is Associated With 18F-Sodium Fluoride Coronary Uptake in Stable Patients With High-Risk Plaques

ObjectivesThis study aimed to assess the association between increased lesion peri-coronary adipose tissue (PCAT) density and coronary ¹⁸F-sodium fluoride (¹⁸F-NaF) uptake on positron emission tomography (PET) in stable patients with high-risk coronary plaques (HRPs) shown on coronary computed tomography angiography (CTA).BackgroundCoronary ¹⁸F-NaF uptake reflects the rate of calcification of coronary atherosclerotic plaque. Increased PCAT density is associated with vascular inflammation. Currently, the relationship between increased PCAT density and ¹⁸F-NaF uptake in stable patients with HRPs on coronary CTA has not been characterized.MethodsPatients who underwent coronary CTA were screened for HRP, which was defined by 3 concurrent plaque features: positive remodeling; low attenuation plaque (LAP) (<30 Hounsfield units [HU]) and spotty calcification; and obstructive coronary stenosis ≥50% (plaque volume >100 mm³). Patients with HRPs were recruited to undergo ¹⁸F-NaF PET/CT. In lesions with stenosis ≥25%, quantitative plaque analysis, mean PCAT density, maximal coronary motion−corrected ¹⁸F-NaF standard uptake values (SUVmax), and target-to-background ratios (TBR) were measured.ResultsForty-one patients (age 65 ± 6 years; 68% men) were recruited. Fifty-one lesions in 23 patients (56%) showed increased coronary ¹⁸F-NaF activity. Lesions with ¹⁸F-NaF uptake had higher surrounding PCAT density than those without ¹⁸F-NaF uptake (−73 HU; interquartile range −79 to −68 HU vs. −86 HU; interquartile range −94 to −80 HU; p < 0.001). ¹⁸F-NaF TBR and SUVmax were correlated with PCAT density (r = 0.63 and r = 0.68, respectively; all p < 0.001). On adjusted multiple regression analysis, increased lesion PCAT density and LAP volume were associated with ¹⁸F-NaF TBR (β = 0.25; 95% confidence interval: 0.17 to 0.34; p < 0.001 for PCAT, and β = 0.07; 95% confidence interval: 0.03 to 0.11; p = 0.002 for LAP).ConclusionsIn patients with HRP features on coronary CTA, increased density of PCAT was associated with focal ¹⁸F-NaF PET uptake. Simultaneous assessment of these imaging biomarkers by ¹⁸F-NaF PET and CTA might refine cardiovascular risk prediction in stable patients with HRP features.     

Differences in Culprit Lesions Between Premenopausal and Postmenopausal Women With Acute Coronary Syndrome: An Optical Coherence Tomography Study

BackgroundDifferences in culprit lesion characteristics remain unclear between premenopausal and postmenopausal women with acute coronary syndrome (ACS). Optical coherence tomography (OCT) enables high-resolution in vivo identification of plaques. We investigated potential differences in culprit lesions between premenopausal and postmenopausal women with ACS by means of OCT.MethodsWe included 191 ACS patients who had undergone preinterventional OCT and stratified them into 2 groups according to their menopausal status: premenopausal (n = 97) and postmenopausal (n = 94). The characteristics of culprit lesions were compared between the 2 groups.ResultsMultivessel lesions were more commonly noted on angiography in the postmenopausal group than in the premenopausal group (40.21% vs 72.34%; P < 0.0001). On OCT, the most common type of culprit plaque was the fibrous plaque in the premenopausal group and the lipid plaque in the postmenopausal group. Compared with the premenopausal group, plaque rupture was more common in the postmenopausal group (39.18% vs 55.32%; P = 0.0254); culprit lesions had more vulnerable features, including macrophage accumulation (58.76% vs 87.23%; P < 0.0001), microchannel (38.14% vs 84.04%; P < 0.0001), cholesterol crystals (30.93% vs 62.77%; P < 0.0001), lipid-rich plaque (32.99% vs 58.51%; P < 0.0001), thin-cap fibroatheroma (3.09% vs 21.28%; P = 0.0001), and calcium (20.62% vs 44.68%; P = 0.0004); maximum lipid arc was larger (121.06 ± 110.99° vs 220.12 ± 115.47°, P < 0.0001); and lipid length was longer (5.78 ± 5.29 mm vs 12.90 ± 8.97 mm; P < 0.0001).ConclusionsCompared with premenopausal women with ACS, postmenopausal women with ACS had more vulnerable culprit lesions. These finding suggest potential optimised lipid-lowering therapy for postmenopausal women with ACS.     

Multidetector computed tomography evaluation of coronary plaque morphology in patients with stable angina

The purpose of this study was to evaluate the morphology and composition of atherosclerotic coronary plaques in patients with stable coronary artery disease by 64-row multidetector computed tomography (CT) angiography. A total of 56 patients were divided into an ischemia-related (n = 31) and a nonischemia-related lesion group (n = 25) based on myocardial perfusion scintigraphy, invasive angiography, and 1-year clinical follow-up. The 56 lesions detected by CT imaging were analyzed; the severity of stenosis, the lesion length, CT attenuation value, and calcium deposition of the plaques were evaluated. Clinical characteristics and CT findings were compared using univariate and multivariate logistic regression analyses. Ischemia-related lesions exhibited a greater severity of coronary stenosis, were longer (17.8 ± 8.5 vs 9.1 ± 3.9 mm), and had a higher CT attenuation value (101.7 ± 36.7 vs 81.6 ± 32.6 HU) and larger calcium deposition. By univariate logistic analysis, severity of stenosis, lesion length, CT attenuation value, and calcium deposition were significantly associated with ischemia-related plaques. The odds ratio (OR) of these parameters was 6.874 (P = 0.007), 1.371 (P = 0.001), 1.018 (P = 0.044), and 5.400 (P = 0.004), respectively. By multivariate logistic analysis, the severity of stenosis and lesion length were significantly associated with ischemia-related plaques (OR 7.588, P = 0.036 and OR 1.365, P = 0.003, respectively). In conclusion, coronary CT angiography is useful for the identification of morphological differences between ischemia-related and nonischemia-related plaques in patients with stable coronary artery disease.