Thin Fibrous Cap Research Articles

Matrix Metalloproteinases and Vulnerable Atheromatous Plaque

Atherosclerotic coronary artery disease, the underlying basis for ischemic heart disease, is the leading cause of death and disability in the USA and recent trends indicate that coronary artery disease is also becoming a major public health problem in developing countries [1]. Atherosclerosis is a continuous process that is initiated early in life, which gradually progresses with potentially devastating consequences: atherosclerotic plaque rupture is the most common underlying pathological mechanism creating acute ischemic coronary syndromes [2]. This term refers to the process of disruption of the endothelial surface and the exposure of the underlying prothrombotic vessel wall to circulating platelets and coagulation factors. In order to identify the high-risk plaque we need to recognize its specific morphological and functional characteristics. The morphological characteristics have been identified in several human histopathological and in vivo studies, and include: 1) a large lipid core (≥40% plaque volume) composed of free cholesterol crystals, cholesterol esters, and oxidized lipids impregnated with tissue factor, 2) a thin fibrous cap depleted of smooth muscle cells and collagen, 3) an outward (positive) remodeling, 4) inflammatory cell infiltration of fibrous cap and adventitia (mostly monocyte- macrophages, activated T cells and mast cells), and 5) increased neovascularization. The terms vulnerable, unstable or 'high-risk' are now widely used to describe plaques that exhibit such features, irrespective of whether rupture of the fibrous cap is present [3].

EFFECT OF ETHYL ICOSAPENTATE THERAPY WITH ASSESSMENT BY OPTICAL COHERENCE TOMOGRAPHY STUDY IN LOW LDL-CHOLESTEROL PATIENTS WITH ACUTE CORONARY SYNDROME

Atheroma with thin-fibrous cap thickness <65 μm estimated by optical coherence tomography (OCT) is thought to be a precursor lesion of plaque rupture. The purpose of study was to examine whether ethyl icosapentate (EPA-E) may have the effect to increase in the fibrous-cap thickness similar to

Abstract 3565: Nox4 Overexpression is Associated with Thin Fibrous Cap in a Swine Model of Carotid Atherosclerosis

Purpose: The NADPH oxidases (Nox) are a family of reactive oxygen species generating enzymes, which play an important role in the pathophysiology of atherosclerosis. The relationship of Nox expression with carotid plaque vulnerability has not well been described. Vulnerable plaque with thin fibrous cap may be associated with the feature of distal emboli in a swine model of carotid atherosclerosis. The purpose of this study is to assess the association of Nox4 expression in vulnerable carotid plaque with thin fibrous cap in a swine model. Materials and Methods: Carotid atherosclerosis was induced in miniswines using the combination of partial ligation and high cholesterol diet, and a minimum 70% stenosis was confirmed by Doppler ultrasonography immediately post-ligation. Carotid artery sections were obtained for histopathological examination and immunohistochemical study for Nox4 at three months. Distal embolism was determined by the presence of atheroemboli in the ipsilateral rete mirabile. The atherosclerotic lesions of AHA stage type IV to VI were defined as vulnerable plaques. The association of distal embolism in the rete mirabile with vulnerable carotid plaque was analyzed. The association of Nox4 expression in the plaque with the morphological features of plaque vulnerability was analyzed. Results: One hundred ninety-one carotid segments from ten carotid artery models were assessed. One hundred two segments had vulnerable plaque. Vulnerable atherosclerotic plaques were found more frequently in the vessel wall proximal to the partial ligation than distal. Distal embolism was found in all 10 rete mirabilis, and deemed to be from the ipsilateral vulnerable carotid plaques. Areas positive for Nox4 tended to be greater in the plaques with the vulnerability features, including necrosis core, marked foam cells, plaque rupture, intraplaque hemorrhage and surface thrombus. The positive expression of Nox4 was associated with the feature of a large lipid core (p=0.035). Forty-eight segments were considered as thin fibrous cap plaques with the minimal thickness of fibrous cap less than 200 μ m. Areas positive for Nox4 were significantly greater in the plaque with thin fibrous cap than in the plaque with thick fibrous cap (p=0.005). On multivariate analysis, positive expression of Nox4 was an independent predictor of thin fibrous cap. Conclusion: Vulnerable carotid plaques with distal embolism were created in a swine model of carotid atherosclerosis. Increased expression of Nox 4 is associated with the feature of thin fibrous cap in vulnerable carotid plaques and may be used as a target for reducing the risk of distal embolism.

Near Infrared Spectroscopy

The pursuit to identify vulnerable plaque has been relentless, as it is responsible for major healthcare problems, such as sudden cardiac death and acute coronary syndromes, including acute myocardial infarction (AMI). Per definition, vulnerable plaque is plaque that is prone to rupture but has not yet ruptured.1 The features associated with vulnerable plaque include a large lipid core, thin fibrous cap overlying the lipid core, increased macrophage activity, positive remodeling, and increased vasa vasorum.2 Among these 5 components, the 2 most important ones are probably the large lipid core and thin fibrous cap. Article see p 55 Since 95% of ruptured fibrous caps are thinner than 65 μm, noninvasive diagnostic tests such as computed tomography and magnetic resonance do not have sufficient resolution to accurately measure this thin structure. Therefore, a number of intravascular diagnostic modalities have been extensively tested over the last decade3 (Table). Among those most widely tested are radiofrequency intravascular ultrasound, angioscopy, and optical coherence tomography. Recently, near infrared spectroscopy (NIRS) received US Food and Drug Administration approval. It is now being actively investigated. View this table: Table. Comparison of Invasive Diagnostic Modalities for Detection of Vulnerable Plaque Radiofrequency intravascular ultrasound was used in the PROSPECT trial4 and showed that plaque burden >70%, virtual histology-thin–cap fibroatheroma, and minimal luminal area ≤4.0 mm2 are factors for composite major adverse cardiac events during the 3-year follow-up period. Although the factors for future cardiac events were identified, all 3 predictors are related to plaque burden, …

Abstract 2286: Ultrasonographic And Pathological Measurement Of Fibrous Cap In Rupture-prone Carotid Plaques Using Advanced Ultrasound Technology

[Background and Purpose] In carotid stenosis, thin fibrous cap, as one of the characteristics of unstable plaques, have been thought to be an important risk factor for plaque rupture and acute cerebral ischemic events. A study reported there was good agreement between ultrasonographic and pathological fibrous cap thickness(FCT). The fibrous cap of ultrasound image in this study, however, was not measured at the same location in pathology. So, we precisely aligned ultrasonographic images with pathology in carotid plaques by advanced ultrasound with global position system (GPS)-like positon-sensing technology, and examined the characteristics of fibrous cap in rupture-prone plaques. [Methods and Results] 24 patients(symptomatic=18, asymptomatic=6) undergoing carotid endarterectomy for carotid stenosis between June 2010 and January 2011 were subjected in this study. We performed carotid ultrasound using a LOGIQ E9(GE Healthcare) within three days before carotid endarterectomy. Three-dimensinal images with the positonal information were obtained using an electromagnetic transmitter and sensors mounted on a linear probe. Endarterectomy specimens were cut every 3mm from carotid bifurcation in the short axis view. The three-dimensinal images alined with the specimens were extracted every 3mm of the same location in the short axis view. We measured maximal and minimal FCT in these ultrasonographic and pathological images. There was a positive relation(r=0.74) between fibrous cap thickness in pathology(maximal FCT =571μm[93 to 1062]) and ultrasound(maximal FCT =439μm[242 to 809]). Maximal FCT in pathology was significantly less in the pathologically ruptured plaques(n=16) than in the nonrupured plaques(n=8) (456μm VS 803μm, P&lt;0.05). In contrast, maximal FCT in ultrasound had no difference in the two groups(389μm VS 497μm, P=0.09). In pathology fibrous cap was ruptured in 16 patients(67%, minimal FCT=0μm), and thin, restored and sparse though nonruptured in other 5 patients(21%, minimal FCT=177μm[50 to 339]). At the same location, the fibrous cap of ultrasound image disappeared in all these 21 patients. The other 3 patients(13%) without plaque rupture showed thick fibrous cap in pathology(minimal FCT =301μm[279 to 325]) and ultrasound(minimal FCT =283μm[250 to 300]). [Conclusions] Using advanced ultrasound with GPS-like technology, we were able to examine the pathological characteristics of fibrous cap in ultrasound in detail. It is difficult to sort out preoperatively more pathologically unstable plaques only by measuring FCT in ultrasound. Ultrasonographic disappearance of fibrous cap is more significant sign of pathologically unstable plaques.

Abstract 2291: Enhanced Carotid Plaque On Contrast-enhanced Ultrasound Is Associated With Plaque Instability And Rupture

Background: Ischemic stroke is one of causes of atherosclerotic diseases, and is closely associated with vulnerable plaque at the origin of the internal carotid artery. Several studies have shown that neovascularization in atheromatous plaque serves as a reliable maker of plaque vulnerability.Contrast-enhanced ultrasound (CEUS) can demonstrate the presence of carotid intraplaque neovascularization. The aim of the present study was to investigate the histopathologic findings of enhanced carotid plaque on CEUS. Methods: We studied consecutive 18 patients (16 men, mean age 69.4 ± 6.7 years) who underwent carotid endarterectomy. Enhanced plaque was classified into two subgroups: a spotty pattern as moving bright spots within plaque ( Figure 1 A, Panel A); and a linear pattern, where enhanced lesions appeared as a line from intima into plaque ( Figure 1 B, Panel A). Sonazoid (Daiich-Sankyo, Tokyo, Japan), perflurobutane microbubbles, was used as the contrast agent. A bolus intravenous injection of Sonazoid (0.015 mL/kg body weight (0.12 μ L perflurobutane microbubble /kg body weight)) was performed via the peripheral venous line followed by a flush with 10 mL of normal saline. We investigated the association between enhanced plaque on CEUS and histopathologic findings. Results: CEUS revealed enhanced plaque in 11 (61.1%) of 18 patients. Only a spotty pattern (spotty subgroup) was observed in 5 patients, whereas both a spotty and linear pattern (linear subgroup) was observed in 6. The amount of neovascularization was larger in enhanced than in non-enhanced plaque (6.79 ± 5.17/2.5 mm 2 vs. 1.12 ± 0.90/2.5 mm 2 , P=0.001). Furthermore, the enhanced group had more macrophage aggregation (7.76 ± 3.70% vs. 4.23 ± 1.63%, P=0.030) and intraplaque hemorrhage (18.84 ± 14.88% vs. 5.52 ± 9.68%, P=0.013) compared with the non-enhanced group. Thin fibrous cap (&lt;200 μ m) was more frequent in enhanced than non-enhanced plaque (100% vs. 28.6%, P=0.002). All of the enhanced plaques with a linear pattern had fibrous cap rupture, but this was observed in only 20% of those with a spotty pattern (P=0.015, Figure 1 B, Panel B). Conclusions: Enhanced plaque on CEUS indicates vulnerable plaque. A linear pattern of enhanced plaque indicates plaque rupture. Enhanced plaque on CEUS should become a new surrogate marker of vulnerable carotid plaque.

Bare Metal Stent Thrombosis and In-Stent Neoatherosclerosis

Very late stent thrombosis (VLST) was reported to occur even in patients with bare metal stent (BMS) implantation, although the annual incidence of VLST after BMS was much lower than that after drug-eluting stent implantation. Pathophysiologic mechanisms of VLST after BMS implantation remain largely unknown. From September 2002 to February 2010, we identified 102 patients with definite stent thrombosis (ST) of BMS and 42 control patients with acute coronary syndrome (ACS) unrelated to ST who underwent thrombus aspiration with histopathologic evaluation. There were 40 patients with early ST (EST, within 30 days), 20 patients with late ST (LST, between 31-365 days), and 42 patients with VLST (>1 year). Evidence for fragments of atherosclerotic plaques, such as foamy macrophages, cholesterol crystals, and thin fibrous cap, was more commonly seen in patients with EST (23%) and VLST (31%), whereas these findings were rarely observed in patients with LST (10%). Atherosclerotic fragments were predominantly seen in patients who had EST within 7 days or VLST beyond 3 years. The aspirated thrombi harvested from patients with ST and those with ACS were histologically indistinguishable from each other. Eosinophils were very rarely observed. Plasma level of total cholesterol and triglyceride were significantly higher in VLST cases with atherosclerotic fragments as compared with those without. Fragments of atherosclerotic plaque were highly prevalent in patients with VLST beyond 3 years. Disruption of in-stent neoatherosclerosis could play an important role in the pathogenesis of VLST of BMS occurring beyond 3 years after implantation.

Validation of a New Animal Model of Vulnerable Plaques by Intravascular Optical Coherence TomographyIn Vivo

We aimed to establish a rabbit model of vulnerable plaques (VPs) with the morphology and component characteristics of human VPs and to evaluate the microstructural features of VPs in vivo using intravascular optical coherence tomography (OCT). Twelve rabbits underwent endothelial denudation of the carotid artery and consumed a 1% high-cholesterol diet (HCD). They were equally divided into two groups: group A (modified needle injury) and group B (balloon injury). OCT was undertaken thrice before injury as well as 1 h and 12 weeks after injury. The degree of acute artery injury after endothelial denudation was detected by OCT. Twelve weeks after injury, OCT showed that both groups generated VPs which had thin fibrous caps and a large lipid core, whereas plaques in group A had smaller lipid arcs (P < 0.0001). Histological findings demonstrated that a larger eccentricity index (EI) (P < 0.05) and greater infiltration of macrophages (P < 0.05) in group A than in group B. Qualitative and morphometric analyses of plaques showed a significant correlation between histological and OCT measurements. A combination of modified endothelial denudation and an HCD in rabbits produced more eccentric lesions similar to those seen in humans. These data suggest that OCT could be a useful tool for evaluation of the degree of injury and VPs in vivo.

Application of Optical Coherence Tomography in Percutaneous Coronary Intervention

Optical coherence tomography (OCT) is a high resolution imaging technique that offers microscopic visualization of the coronary artery. The fast scanning speed and simple imaging procedure of new-generation frequency-domain OCT make this technology easy to use in the clinical setting. The OCT examination is useful for guidance and risk stratification of percutaneous coronary intervention (PCI). OCT-derived thin-cap fibroatheroma, which is characterized by large lipid-core and thin fibrous cap <65 μm, is a predictor of peri-PCI complications, such as angiographic no-reflow, microvascular obstruction, and post-PCI cardiac troponin I elevation. Stent malapposition, tissue protrusion, and stent edge dissection are assessed in more detail by OCT than with conventional intravascular imaging modalities. Neointimal coverage at strut level assessed by OCT could be a surrogate endpoint for quickly scrutinizing safety after drug-eluting stent implantation. The OCT findings of in-stent neoatherosclerosis, such as lipid-rich neointima, microvascular proliferation, and neointimal plaque rupture, are associated with very late stent failure, including thrombosis and restenosis. With its excellent ability to assess coronary atherosclerosis and to guide PCI, OCT provides new insights into interventional cardiology.

Preface

The aim of the study was to determine the association of ultrasonic texture features (severity of stenosis, grey scale median, plaque area, juxtaluminal black area [JBA], and discrete white areas) previously shown to be independent predictors for stroke with established histologic features of plaque instability.A cross-sectional study was performed involving 70 patients scheduled for carotid endarterectomy. Before surgery, carotid plaque texture features were obtained with ultrasound after normalization using commercially available software (LifeQ Medical, Nicosia, Cyprus). After carotid endarterectomy, histologic features (number of macrophages [CD68 staining], severity of angiogenesis [CD31 staining], smooth muscle cell [SMC] numbers, size of lipid core, thickness of the fibrous cap, presence of intraplaque hemorrhage, plaque rupture, and instability) also were studied.Symptomatic (n = 20) and asymptomatic (n = 50) patients were comparable in terms of internal carotid stenosis (mean stenosis, 86%; range, 60%-99%) and prevalence of risk factors except for total cholesterol (which was higher in the symptomatic group; P = .023). A low grey scale median and the presence of discrete white areas were associated with an increased number of macrophages (P < .001 and P < .001, respectively), increased neovascularization (P = .019 and P < .001, respectively), larger lipid core (P = .001 and P = .025, respectively), intraplaque hemorrhage presence (P = .001 and P = .001, respectively), plaque rupture (P = .001 and P = .025, respectively), and a decreased number of SMCs (P = .003 and P = .003, respectively). The presence of JBA was associated with a decreased number of SMCs (P = .042), larger lipid core (P = .013), and plaque rupture (P = .002). The combination of a thin fibrous cap with either a large lipid core or plaque rupture was associated with the highest (65%) prevalence of a JBA. Plaque area was not associated with any of the histologic features. After adjusting statin therapy for symptoms, statins were associated with a decreased number of macrophages (P = .038), decreased neovascularization (P = .019), and an increased number of SMCs (P = .023).A number of ultrasonic texture features previously shown to be independent predictors of stroke have been found to have a strong association with established histologic features of plaque instability. This finding provides insight into the mechanism of ultrasonic texture features in stroke prediction and validates the use of ultrasound in stroke risk stratification.

Abstract 17948: In-vivo Visualization of Increased and Persistent Vascular Lipid Deposition by Nirs and Ivus Predicts Subsequent Development of High-Risk Atherosclerotic Lesions

Introduction: Thin-cap fibroatheromas are the pathologic cause of acute coronary syndromes and ischemic sudden death. Near infrared spectroscopy (NIRS) detects lipid concentration in the arterial wall and intravascular ultrasound (IVUS) identifies necrotic cores and vascular remodeling. We hypothesized that concurrent use of these two invasive technologies could predict development and progression of high-risk fibroatheromas as determined by histology. Methods: Multi-vessel coronary angiography, IVUS and NIRS were performed 3, 6 and 9 months (m) after induction of diabetes (DM) and hypercholesterolemia (HC) in 21 pigs. Five animals died of ischemic sudden death and 3 of other causes. The remaining animals were sacrificed at 9-m. Results: Longitudinal IVUS data demonstrated a progressive increase in plaque + media and necrotic core areas and positive remodeling. At 9-m NIRS positivity predicted the presence of TCFAs and ThFCAs (both p=0.0001 vs NIRS negative), greater plaque (p&lt;0.0001) and necrotic core (p&lt;0.0019) areas and thinner fibrous caps (p=0.04) by histology. Importantly, NIRS positive fibroatheromas possessed a higher number of activated macrophages (p=0.006), as well as greater number of proliferating (p=0.016) and apoptotic cells (p=0.04) in the fibrous cap. NIRS positivity also predicted greater necrotic core size on IVUS scan at the subsequent time point. Moreover, 88% of arterial segments which were NIRS positive at 3 and 6-m developed into a fibroatheroma at 9-m by histology compared to 35% of persistently NIRS negative segments (p&lt;0.01). Conclusion: Results from IVUS and NIRS predicted the subsequent development of high-risk coronary fibroatheromas with greater plaque and larger necrotic core areas possessing characteristics of increased plaque instability.

Abstract 17330: Relation Between Coronary Plaque Characteristics in Culprit Lesions and C-Reactive Protein Elevation after Percutaneous Coronary Intervention in Patients with Effort Angina Pectoris

Background: A significant increase in plasma C-reactive protein(CRP) after percutaneous coronary intervention(PCI) has been reported to be a predictor of long term cardiovascular events in patients with stable angina pectoris. The aim of this study was to investigate the relation between the plasma CRP before and after PCI and the coronary plaque characteristics in patients with effort angina pectoris. Methods: 54 patients with effort angina pectoris who underwent intravascular ultrasound(IVUS) and optical coherence tomography(OCT) before PCI were included. Patients were divided into a high increment in CRP one day after PCI(high-delta CRP) group(n=14, ≥3mg/l: 14.4±10.6mg/l) and a low-delta CRP group(n=40, &lt;3mg/l: 0.84±1.1mg/l). Arterial remodeling of culprit lesion was assessed by IVUS. OCT plaque characteristics for lipid content, thrombus and fibrous cap thickness were examined using previously validated criteria. In addition, the presence of lipid-laden intima with characterized a high signal band with attenuation and a diffuse border was evaluated. Results: Ruptured plaque was not observed. The thickness of the fibrous cap in the low-delta CRP group was significantly larger than that of high-delta CRP group(112.3±42.5μ m vs. 77.1±28.1μ m P&lt;0.01). And, lipid-laden intima was more frequently observed in high-delta CRP group than in the low -delta CRP group(84% vs. 25%, respectively; P&lt;0.05). Higher CRP values before PCI were observed in high-delta CRP group(2.9±2.9 mg/l vs. 1.1±1.4 mg/l, respectively; P&lt;0.05). Remodeling index, calcified and lipid plaque frequency and lipid profile were comparable between two groups. An increment of Troponin-I level after PCI had a tendency to be higher in high-delta CRP group than low-delta CRP group(2.75±3.39 ng/ml vs. 0.97±2.57 ng/ml, respectively; p=0.067). Conclusion: This result suggests that existence of thin fibrous cap with non-ruptured lipid plaque accelerates to inflammatory process in coronary atherosclerotic lesion by mechanical stress due to PCI and that OCT is useful for detecting the appearance of coronary plaque instability in patients with effort angina pectoris.

Abstract 8793: Impact of Cardiorespiratory Fitness on Characteristics of Coronary Plaque: Assessment Using Integrated Backscatter Intravascular Ultrasound and Optical Coherence Tomography

Background: Cardiorespiratory fitness (CRF) is a predicter for the future cardiovascular disease. Rupture of vulnerable plaque that often has a large lipid core with a thin fibrous cap results in acute coronary syndrome including sudden cardiac death. We hypothesized that preserved CRF is associated with low lipid composition and thick fibrous cap thickness of coronary plaques. Methods: Both integrated backscatter intravascular ultrasound (IB-IVUS) and optical coherence tomography (OCT) were performed for 77 non-culprit coronary plaques in 77 consecutive angina pectoris patients undergoing percutaneous coronary intervention (PCI). As an indicator of CRF of patient, percentage of achieved of predicted peak oxygen consumption (%PPeak Vo 2 ) calculated based on peak Vo 2 which were directly mesured using a cardiopulmonary exercise testing post PCI was adapted. Results: Patients were classified into two groups [those with preserved CRF (%PPeak Vo 2 &gt;82%) (group I) or others (group II)]. Coronary plaques in patients of group I had significantly smaller lipid volume, greater fibrous volume, and thicker fibrous cap thickness than those in group II (32±14% vs. 45±13%, p&lt;0.001; 57±11% vs. 49±11%, p&lt;0.001; and 177.7±20.9μ m vs. 143.7±36.9μ m, p&lt;0.001). After multivariate linear regression analysis, %PPeak Vo 2 had a significantly negative correlation with lipid volume and a positive correlation with fibrous volume and fibrous cap thickness (β=-0.418, p=0.001; β=0.361, p=0.006; and β=0.339, p=0.008). Conclusions: High %PPeak Vo 2 was associated with low lipid volume, high fibrous volume and thick fibrous cap thickness in coronary plaques. Those results may explain a decreased risk of cardiovascular events in patients with preserved CRF.

Pro-inflammatory effects of the mushroom Agaricus blazei and its consequences on atherosclerosis development

Extracts of the mushroom Agaricus blazei (A. blazei) have been described as possessing immunomodulatory and potentially cancer-protective activities. However, these effects of A. blazei as a functional food have not been fully investigated in vivo. Using apolipoprotein E-deficient (ApoE(-/-)) mice, an experimental model of atherosclerosis, we evaluated the effects of 6 or 12 weeks of A. blazei supplementation on the activation of immune cells in the spleen and blood and on the development of atherosclerosis. Food intake, weight gain, blood lipid profile, and glycemia were similar between the groups. To evaluate leukocyte homing and activation, mice were injected with (99m)Tc-radiolabeled leukocytes, which showed enhanced leukocyte migration to the spleen and heart of A. blazei-supplemented animals. Analysis of the spleen showed higher levels of activation of neutrophils, NKT cells, and monocytes as well as increased production of TNF-α and IFN-γ. Circulating NKT cells and monocytes were also more activated in the supplemented group. Atherosclerotic lesion areas were larger in the aorta of supplemented mice and exhibited increased numbers of macrophages and neutrophils and a thinner fibrous cap. A. blazei-induced transcriptional upregulation of molecules linked to macrophage activation (CD36, TLR4), neutrophil chemotaxy (CXCL1), leukocyte adhesion (VCAM-1), and plaque vulnerability (MMP9) were seen after 12 weeks of supplementation. This is the first in vivo study showing that the immunostimulatory effect of A. blazei has proatherogenic repercussions. A. blazei enhances local and systemic inflammation, upregulating pro-inflammatory molecules, and enhancing leukocyte homing to atherosclerosis sites without affecting the lipoprotein profile.

Subsequent silent plaque rupture of nonculprit lesion in a patient with acute myocardial infarction

The lesions responsible for acute coronary syndrome (ACS) are pathologically sudden ruptures of vulnerable plaques with superimposed thrombosis. Vulnerable plaques are generally characterized as those having a thin inflamed fibrous cap over a very large lipid core with activated macrophages near the fibrous cap [1]. An intravascular ultrasound (IVUS) report have suggested that the presence of positive vascular remodeling and hypoechoic regions corresponding to lipid rich tissue in coronary plaques were related to acute coronary events [2]. A ST-segment elevation myocardial infarction caused by plaque rupture was associated with a large degree of myocardial damage and poor functional recovery as compared with that without plaque rupture, even after successful primary angioplasty [3]. ACS patients may harbor multiple complex coronary plaques, which are associated with adverse clinical outcomes [4]. Plaque instability is thus not merely a local vascular accident but probably reflects more generalized pathophysiologic processeswith the potential to destabilize atherosclerotic plaques throughout the coronary tree [5]. Therefore, it is very important to detect silent plaque rupture, because detection of a rupture at a nonculprit site could indicate a plaque that is at high risk of thrombotic complication, and could be used as a prognostic indicator. Here, we present an interesting case of clinically silent nonculprit plaque rupture detected by serial preand post-rupture IVUS imaging.

Association of coronary plaque composition and arterial remodelling: A optical coherence tomography study

BackgroundConflicting data have been reported about the association between plaque composition and remodelling index (RI). The aim of this study is to evaluate the relationship between plaque morphology obtained by optical coherence tomography (OCT) and arterial remodelling. Methods and resultsOCT and intravascular ultrasound imaging pull back was performed at corresponding sites on 94 lesions in 47 patients. OCT plaque characteristics for lipid content, fibrous cap thickness, thin-cap fibroatheroma (TCFA), plaque rupture, thrombus, calcification and erosion were derived using validated criteria. Compared with intermediate/negative remodelling (RI<1.0), positive remodelling (RI>1.0) was associated with presence of higher lipid pool (2.86±0.42 vs. 2.20±0.78; p<0.001), thin fibrous cap (47.86±25.43μm vs. 74.41±32.41μm; p<0.001), TCFA>3mm (82.1% vs. 22.7%; p<0.0001), plaque rupture and thrombus (42.8% vs. 19.7%; p=0.024), and higher plaque burden (73.70 vs. 70.70; p=0.048). No difference was observed in the presence of calcification and plaque erosions. ConclusionsCoronary lesions with positive remodelling show higher incidences of vulnerable plaque and plaque rupture across the lesion length. This potentially explains the correlation between unstable coronary syndromes and positive remodelling.

Through IVUS study of characterised the relationship as stable angina (SA) and unstable angina (UA) patients

PurposeAs medical technology advances, the understanding of coronary heart disease from the previous clinical diagnosis, diagnostic ECG, ECG to diagnosis, then diagnostic coronary angiography (coronary angiography CAG), and then by...

The effect of statins on high-risk atherosclerotic plaque associated with low endothelial shear stress

Low endothelial shear stress (ESS) plays an important role in the progression and severity of atherosclerotic lesions. As 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) appear to stabilize plaque, it would be valuable to understand how statins affect the nature of lesions in the proatherogenic and proinflammatory environment of low ESS and the effect of statins on that atherosclerotic process. The purpose of this review is to summarize the relationship among low ESS, high-risk plaque and statins. Low ESS is a critically important determinant of plaque development and progression to high-risk plaques with large necrotic lipid core, intensive inflammation and thin fibrous cap. In addition to the proatherogenic phenotypic switching in areas of low ESS, local LDL cholesterol concentrations are also increased in areas of low ESS, which exacerbates the local atherogenic process. In experimental models, statins appear to reduce the inflammation in lesions associated with low ESS and reduce the atherosclerotic phenotype even in these high-risk prone vascular areas. The relationship between low ESS and statins has not been fully investigated, but the available data underscore the vasculoprotective effect of statins. Understanding the mechanisms whereby statins reduce the atherogenic and inflammatory phenotype resulting from a low ESS environment would provide new insights to design strategies to prevent regional formation of high-risk, inflamed plaques likely to rupture and cause an adverse clinical event.

Symptomatic and asymptomatic carotid artery plaque

Carotid atherosclerotic plaques represent both stable and unstable atheromatous lesions. Atherosclerotic plaques that are prone to rupture owing to their intrinsic composition such as a large lipid core, thin fibrous cap and intraplaque hemorrhage are associated with subsequent thromboembolic ischemic events. At least 15–20% of all ischemic strokes are attributable to carotid artery atherosclerosis. Characterization of plaques may enhance the understanding of natural history and ultimately the treatment of atherosclerotic disease. MRI of carotid plaque and embolic signals during transcranial Doppler have identified features beyond luminal stenosis that are predictive of future transient ischemic attacks and stroke. The value of specific therapies to prevent stroke in symptomatic and asymptomatic patients with severe carotid artery stenosis are the subject of current research and analysis of recently published clinical trials that are discussed in this article.

Complementary Value of Cardiac FDG PET and CT for the Characterization of Atherosclerotic Disease

For decades, the identification of significant luminal narrowing has been the hallmark to characterize the presence and extent of coronary artery disease. However, it is now known that characterizations of systemic atherosclerosis burden and inflammation, as well as the local quality of plaque composition and morphology, allow better characterization of coronary artery disease and thus may allow improved prediction of adverse cardiovascular events. Plaque characterized histologically as a thin-cap fibroatheroma (ie, an atheroma with a thin fibrous cap, an underlying lipid-rich necrotic core, and inflammatory activity) has been recognized as representing vulnerable or high-risk plaque. Positron emission tomography (PET) and cardiac computed tomography (CT) are noninvasive modalities that provide metabolic (PET) and morphologic (CT) information about atherosclerotic plaque. PET allows the quantification of the uptake of fluorine 18 fluorodeoxyglucose (FDG) within the arterial wall, which provides a measure of macrophage activity within atheromatous plaque. Coronary CT allows the depiction of plaque morphology and composition. Thus, integrated imaging with PET and CT (PET/CT) permits coregistration of FDG activity with the presence and morphology of plaque and may lead to improved characterization of vulnerable plaque or vulnerable patients, or both. This review details the methods and principles of cardiac FDG PET and coronary CT and provides an overview of the research, with an emphasis on the identification and characterization of vulnerable plaque.