Atherosclerotic Plaques In Coronary Arteries Research Articles

Photon counting spectral CT component analysis of coronary artery atherosclerotic plaque samples.

To evaluate the capabilities of photon counting spectral CT to differentiate components of coronary atherosclerotic plaque based on differences in spectral attenuation and iodine-based contrast agent concentration. 10 calcified and 13 lipid-rich non-calcified histologically demonstrated atheromatous plaques from post-mortem human coronary arteries were scanned with a photon counting spectral CT scanner. Individual photons were counted and classified in one of six energy bins from 25 to 70 keV. Based on a maximum likelihood approach, maps of photoelectric absorption (PA), Compton scattering (CS) and iodine concentration (IC) were reconstructed. Intensity measurements were performed on each map in the vessel wall, the surrounding perivascular fat and the lipid-rich and the calcified plaques. PA and CS values are expressed relative to pure water values. A comparison between these different elements was performed using Kruskal-Wallis tests with pairwise post hoc Mann-Whitney U-tests and Sidak p-value adjustments. RESULTS for vessel wall, surrounding perivascular fat and lipid-rich and calcified plaques were, respectively, 1.19 ± 0.09, 0.73 ± 0.05, 1.08 ± 0.14 and 17.79 ± 6.70 for PA; 0.96 ± 0.02, 0.83 ± 0.02, 0.91 ± 0.03 and 2.53 ± 0.63 for CS; and 83.3 ± 10.1, 37.6 ± 8.1, 55.2 ± 14.0 and 4.9 ± 20.0 mmol l(-1) for IC, with a significant difference between all tissues for PA, CS and IC (p < 0.012). This study demonstrates the capability of energy-sensitive photon counting spectral CT to differentiate between calcifications and iodine-infused regions of human coronary artery atherosclerotic plaque samples by analysing differences in spectral attenuation and iodine-based contrast agent concentration. Photon counting spectral CT is a promising technique to identify plaque components by analysing differences in iodine-based contrast agent concentration, photoelectric attenuation and Compton scattering.

Abstract 455: The Effects of Diet on Occlusive Coronary Artery Atherosclerosis, Thrombosis and Myocardial Infarction in SR-BI/LDL Receptor Double KO Mice

Objective: Deficiency of the HDL receptor, SR-BI, in apolipoprotein E knockout or hypomorphic mice respectively results in spontaneous or diet-inducible occlusive coronary artery atherosclerosis, myocardial infarction, and early death. Here, we examine the effects of SR-BI deficiency on cardiovascular phenotypes in LDLR knockout mice fed different atherogenic diets. Approach and Results SR-BI/LDLR double knockout and control LDLR knockout mice were fed diets containing different amounts of fat and cholesterol and which either lacked or contained 0.5% sodium cholate. Double knockout mice fed diets high in cholesterol exhibited significantly reduced survival compared to LDLR knockout mice fed the same diets. In addition to increased aortic sinus atherosclerosis, we observed significant coronary artery atherosclerosis in double knockout mice, and diet dependent accumulation of platelets in coronary artery atherosclerotic plaques. This was accompanied by substantial myocardial fibrosis in double knockout mice fed high cholesterol diets. Double knockout mice also exhibited higher circulating cytokine levels, monocytosis with increased proportions of monocytes expressing high levels of Ly6C, and higher adhesion molecule expression in coronary artery endothelial cells compared to control LDLR knockout mice. Conclusions: Diet accelerated atherosclerosis and occlusive, platelet rich coronary artery disease in SR-BI/LDLR dKO mice is affected by amounts of cholesterol and cholate in atherogenic diets, and is accompanied by increased expression of VCAM-1 and ICAM-1 in coronary arteries and increased Ly6C+ monocytes in circulation. The increased VCAM-1 and ICAM-1 in coronary artery endothelial cells in SR-BI-deficient mice likely explains their increased susceptibility to atherosclerosis in coronary arteries.

Prevalence and extent of atherosclerotic coronary artery disease and related outcome based on coronary computed tomographic angiography in asymptomatic elderly patients: retrospective cohort study

There is little data regarding coronary artery disease (CAD) and/or atherosclerotic plaques on coronary computed tomographic angiography (CCTA) among the elderly and its outcome, especially in asymptomatic patients. Using CCTA, we evaluated the prevalence and extent of CAD and/or atherosclerosis and related outcomes in asymptomatic elderly patients as compared with symptomatic elderly patients. The study included 1,196 consecutive patients aged 70 years or older who underwent CCTA over a 2-year period. Data were retrospectively evaluated for clinical cardiovascular risk factors with co-morbidities, and CCTA findings, including calcium scores, atherosclerotic plaques (number, plaque-segment score, plaque-extent score, and plaque-significant score) and presence of significant CAD. Follow-up data for active management and all-cause mortality after CCTA were collected for 2 years. Two-sided Student's t test for independent samples, Chi square contingency tables, and Kaplan-Meier survival curves were used for statistical analysis. Data for 454 asymptomatic and 742 symptomatic elderly patients were analyzed. The prevalence of significant CAD and the extent of atherosclerotic plaques did not differ between the two groups (all P > 0.05). Asymptomatic patients with significant CAD on CCTA, were less likely to receive active management (P < 0.001), which may be related to the higher death rate in this group (P = 0.012) than in the symptomatic patients with significant CAD. Overall, symptoms were not related to the presence of significant CAD or to the extent of atherosclerosis in these elderly patients. However, all-cause mortality was higher in the asymptomatic patients with significant CAD than in the symptomatic ones.

Mechanical properties of human atherosclerotic intima tissue

Progression and rupture of atherosclerotic plaques in coronary and carotid arteries are the key processes underlying myocardial infarctions and strokes. Biomechanical stress analyses to compute mechanical stresses in a plaque can potentially be used to assess plaque vulnerability. The stress analyses strongly rely on accurate representation of the mechanical properties of the plaque components.In this review, the composition of intima tissue and how this changes during plaque development is discussed from a mechanical perspective. The plaque classification scheme of the American Heart Association is reviewed and plaques originating from different vascular territories are compared.Thereafter, an overview of the experimental studies on tensile and compressive plaque intima properties are presented and the results are linked to the pathology of atherosclerotic plaques. This overview revealed a considerable variation within studies, and an enormous dispersion between studies.Finally, the implications of the dispersion in experimental data on the clinical applications of biomechanical plaque modeling are presented. Suggestions are made on mechanical testing protocol for plaque tissue and on using a standardized plaque classification scheme.This review identifies the current status of knowledge on plaque mechanical properties and the future steps required for a better understanding of the plaque type specific material properties. With this understanding, biomechanical plaque modeling may eventually provide essential support for clinical plaque risk stratification.

New era of evidence-based medicine with noninvasive imaging

In 2013, advances in noninvasive imaging methods pushed traditional boundaries in the detection, diagnosis, and functional assessment of coronary artery disease, atherosclerotic plaque, and myocardial function. We highlight five important studies that demonstrate how these developments are allowing medicine to become increasingly evidence-based and personalized.

Apelin: a potential marker of coronary artery stenosis and atherosclerotic plaque stability in ACS patients.

Apelin was shown to play an important role in atherosclerosis in mice. However, the involvement of apelin in atherosclerosis in humans has not been investigated. To characterize plasma apelin levels following acute coronary syndrome (ACS) and to examine their relationship with coronary stenosis and atherosclerotic plaque stability.The study enrolled 196 patients admitted with ACS, and another 171 outpatients with no coronary heart disease as control. Plasma concentrations of apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP), and matrix metalloproteinase-9 (MMP-9) were measured 2 hours and 6 months after admission, respectively. The severity of coronary artery stenosis of ACS patients was evaluated using the Gensini score. The stability and components of atherosclerotic plaque was assessed by intravascular ultrasound (IVUS). All statistical analyses were performed using SPSS version 16.0.Apelin concentration was reduced compared with healthy controls following ACS (0.54 ± 0.25 versus 3.22 ± 1.08 ng/mL, P < 0.001) and remained low to 6 months. The plasma level of apelin in the ACS group was negatively correlated with the Gensini score (r = -0.382, P = 0.009). Moreover, in the ACS patients, apelin levels were significantly lower in the group with the ruptured plaque than in those with the nonruptured plaque (0.42 ± 0.24 versus 0.68 ± 0.30 ng/mL, P = 0.042). Apelin levels were negatively correlated with plaque cross-sectional area (CSA) (r = -0.425, P = 0.018) and positively correlated with external elastic membrane (EEM) CSA (r = 0.311, P = 0.037). Plasma apelin levels were inversely correlated with the severity of coronary artery stenosis and positively related with the stability of atherosclerotic plaque in humans with ACS.

Elevated plasma IL-37, IL-18, and IL-18BP concentrations in patients with acute coronary syndrome.

Objective. More recently, evidence showed that the novel anti-inflammatory cytokine interleukin- (IL-) 37 was expressed in the foam-like cells of atherosclerotic coronary and carotid artery plaques, suggesting that IL-37 is involved in atherosclerosis-related diseases. However, the plasma levels of IL-37 in patients with acute coronary syndrome (ACS, including unstable angina pectoris and acute myocardial infarction) have yet to be investigated. Methods. Plasma IL-37, IL-18, and IL-18BP levels were measured in 50 patients with stable angina pectoris (SAP), 75 patients with unstable angina pectoris (UAP), 67 patients with acute myocardial infarction (AMI), and 65 control patients. Results. The plasma IL-37, IL-18, and IL-18BP levels were significantly increased in ACS patients compared to SAP and control patients. A correlation analysis showed that the plasma biomarker levels were positively correlated with each other and with the levels of C-reactive protein (CRP), N-terminal probrain natriuretic peptide (NT-proBNP), and left ventricular end-diastolic dimension (LVEDD) but negatively correlated with left ventricular ejection fraction (LVEF). Furthermore, the plasma IL-37, IL-18, and IL-18BP had no correlation with the severity of the coronary artery stenosis. Conclusions. The results indicate that the plasma IL-37 levels are associated with the onset of ACS.

Risk Factors for Coronary Artery Diseases: A Study Among Patients With Ischemic Heart Disease in India (Kerala)

Summary Coronary artery disease (CAD) is a condition that develops due to accumulation of atherosclerotic plaque in the epicardial coronary arteries, leading to myocardial ischemia. It is the leading cause of death worldwide and is a common complex disease. A study was carried out in a group of 496 patients with acute coronary syndrome or with angiographic or stress test evidence for coronary artery disease, admitted to the Department of Cardiology at Lourdes Heart Institute and Neuro Centre during the period June-August 2012. The risk factors studied were hypertension, diabetes mellitus, dyslipidemia, body mass index, smoking and family history of CAD. The results demonstrated that in both males and females of the Indian population studies, diabetes and dyslipidemia were major risk factors for CAD, while hypertension was not a major risk factor. Therefore, early detection and treatment of diabetes mellitus and dyslipidemia play a vital role in prevention of CAD in Indian population.

Pattern of instent neointimal formation compared to native atherosclerosis in the coronary bifurcation lesions: volumetric intravascular ultrasound analysis

Background No clinical study has systematically analyzed and compared circumferential neointimal and plaque distribution of stent neointimal proliferation and in native atherosclerotic plaques. This study aimed to investigate and compare the pattern of instent neointimal formation and native atherosclerosis in the coronary bifurcation lesions by volumetric analysis using systematic intravascular ultrasound (IVUS). Methods We examined bifurcation lesions in native coronary artery (plaque group, n=102) and stented bifurcations at 9-month follow-up (neointima group, n=51) using volumetric IVUS analysis of both the main vessel (MV) and side branch (SB). Three 5-mm segments were analyzed; the proximal MV (MVp), distal MV (MVd) and SB ostium (SBo). For each segment, volumetric analysis was performed in each of four quadrants (divided according to the branch takeoff and the geometric center of the lumen); carinal, epicardial, abcarinal, and myocardial. The eccentricity index was defined as the ratio of the abcarinal plaque (or neointimal) volume to the carinal plaque (or neointimal) volume. Results The plaque distribution differed significantly between the four quadrants, with the largest in the abcarinal quadrant, followed by the myocardial, epicardial, and carinal quadrants. The distribution of neointima was similar in the MV, but the four quadrants in the SB did not differ significantly. The eccentricity indices of both the MVd (P &lt;0.001) and SBo (P=0.001) were significantly higher for the plaque group than the neointima group. Conclusions The distribution of neointimal proliferation seems to have a similar pattern to that of atherosclerotic plaque in native coronary arteries, particularly in the main vessel, but the trend is less prominent.

Twinkle, Twinkle, Little Plaque

At high resolution, atherosclerotic plaques in coronary arteries show their microcalcifications.

Measurement of Circumferential Strain Distribution in Human Coronary Arteries with Atherosclerotic Plaque

Rupture of atherosclerotic plaque in coronary artery causes serious results. Since heterogeneously distributed plaque may cause local stress concentration, the local strain in circumferential direction of the coronary artery with atherosclerosis was investigated. For eight specimens from four human atherosclerotic coronary arteries, four needles were stuck into each the specimen at equal intervals on their circumference. Specimens were pressurized and local circumferential length was calculated from movement of the needles observed from longitudinal direction. For each specimen, pressure strain elastic modulus Ep, stiffness parameter β, and incremental elastic modulus Einc were calculated. Local circumferential strain was calculated by referring to circumferential length at no-stress state. Total thickness Ttotal, plaque thickness Tplaque, medial and adventitial wall thickness Twall, and area fraction of plaque Aplaque were also measured in histological sections. Ep and β obtained in the present study were almost comparable to those of nonatherosclerotic human coronary arteries in previous studies. Local strains were different even in a circumference. The local strain at 80 mmHg ε80 correlated significantly with Twall (r = 0.48, p < 0.05), while ε80 had insignificant correlation with Tplaque, Ttotal, and Aplaque. Coefficient of variance of local Twall decreased with the increase in the pressure. These results indicate that mechanical properties of human atherosclerotic coronary arteries are heterogeneously distributed in circumferential direction, plaque has insignificant effect to their mechanical properties, and Twall becomes more uniform at physiological state than at no-stress state. These dada may be useful to simulate stress distribution in atherosclerotic coronary artery.

The challenges presented by decomposition

A feature of forensic practice that is often remarked uponby non-pathologists is the requirement to sometimesundertake examinations of bodies that have undergoneconsiderable changes due to decomposition. The value ofsuch an exercise is sometimes questioned. The followingeditorial reviews issues that may arise in the postmortemevaluation of such cases based on studies and observationsthat the authors have undertaken and made over time.Decomposition refers to the variety of processes ofdegradation that commence as soon as an organism hasdied. The combined effects of putrefaction from bacterialovergrowth, and autolysis from tissue self-digestion, resultin a predictable sequence of events commencing withvenous marbling and blistering of the skin, followed bypurging of fluids through the mouth and nose, gaseousdistention of subcutaneous tissues and body cavities, andinsect colonization. Under specific circumstances lesscommon changes such as mummification or adipocere(‘‘grave wax’’) formation occur [1, 2].Death scene evaluations may be more complicated whendecomposition is present as it may be a marker for socialisolation and domestic disorder. This is best demonstratedby the Diogenes syndrome, where elderly reclusive indi-viduals living in squalor may not be found for some timeafter their deaths [3]. Lesions caused by the postmortemactivity of both domestic and nondomestic animals livingin the house may be found [4], and inexperienced sceneexaminers may conclude that purging of reddish fluid fromthe mouth and nose represents bleeding from an assault.Determining the time of death cannot be done with anyprecision, although entomological examination of insectsand the temperature of maggot masses may provide someguide to this [1, 2]. Stiffening of the limbs from subcuta-neous gas accumulation, so-called ‘‘putrefactive rigormortis’’, should not be misinterpreted as true rigor due toATP depletion [5].Decomposition also complicates autopsy evaluations bydistorting and changing tissue morphology. Tissues andorgans may be absent in advanced cases, and dissectionsare often more difficult to perform as the normal anatomyhas either been considerably modified or disguised. Putre-fied and liquefied fat may make tissues and floors slipperycreating a potentially dangerous work environment. Thismay be particularly so in temporary mortuaries used fordisaster victim identification, as proper cleaning facilitiesmay not be available.Despite marked tissue changes, determination of thecause and manner of death has been shown to be achiev-able [6], although cases were not stratified according to thedegree of decomposition in this retrospective study. Theexact effect of decompositional changes on particular tis-sues is also not always known and it may be possible thatlesions such as non-calcific, grumous coronary artery ath-erosclerotic plaques may liquefy and so disappear by thetime that the arteries are being examined at autopsy. If thisis the case, then determining the degree of antemortemcoronary artery stenosis may simply not be possible.Sometimes even the finding of coronary arteries in adecomposed heart may be a challenge. On occasion,

Subcellular localization of tissue factor and human coronary artery smooth muscle cell migration

Tissue factor (TF) is the most relevant physiological trigger of thrombosis. Additionally TF is a transmembrane receptor with cell signaling functions. The aim of this study was to investigate TF subcellular localization, function and signaling in human coronary artery smooth muscle cell migration. Coronary arteries and primary cultures of vascular smooth muscle cells (HVSMC) were obtained from human explanted hearts. Wound repair and Boyden chamber assays were used to measure migration in vitro. TF-pro-coagulant activity (TF-PCA) was measured in extracted cellular membranes. Analysis of TF distribution was performed by confocal microscopy. A nucleofector device was used for TF and protease activated receptor 2 (PAR2) silencing. mRNA levels were analyzed by RT-PCR. In migrating HVSMC TF translocates to the leading edge of the cells showing an intense patch-like staining in the lamellipodia. In the migrating front TF colocalizes with filamin (FLN) in the polarized lipid rafts. TF-PCA was increased in migrating cells. Silencing of the TF gene inhibits RSK-induced FLN-Ser-2152 phosphorylation, down-regulates CDC42, RhoA, and Rac1 protein expression and significantly inhibits cell migration. Silencing PAR2 also inhibits cell migration; however, silencing both TF and PAR2 induces a significantly higher effect on migration. Smooth muscle cells expressing TF have been identified in non-lipid-rich human coronary artery atherosclerotic plaques. TF translocates to the cell front in association with cytoskeleton proteins and regulates HVSMC migration by mechanisms dependent and independent of factor (F)VIIa/PAR2. These results extend the functional role of TF to smooth muscle cell trafficking in vessel wall remodeling.

Effect of magnetic field on temperature distribution of atherosclerotic plaques in coronary artery under pulsatile blood flow condition

Temperature heterogeneity in plaque containing inflammatory cells can cause thermal stress, and speeds up plaque growth or rupture process. Activated inflammatory cells embedded in plaques release heat while the plaque is cooled by blood flow. In the present work, arterial wall temperature distribution of atherosclerotic Right Coronary in the presence of external uniform and multi-directional magnetic field is investigated by numerical methods. The magnetic field is applied in both x and y directions. An advanced coupled FEM–FVM algorithm is used to determine temperature distribution inside the artery. Transient Navier–Stokes and energy equations in 2D idealized arterial model of a bending artery coupled with Maxwell's equations are discretized using the Finite-Volume Method and solved by SIMPLE algorithm in curvilinear coordinate to analyze pulsatile blood flow, whereas the transient heat conduction equation in the plaque is solved simultaneously with these equations using Finite-Element Method. The plaque temperature, Nusselt Number and heat flux at the plaque/lumen interface is obtained for various moments of cardiac cycle and different states of magnetic field to investigate influence of produced electromagnetic force on the cooling effect of blood. It is observed that how magnetic field modifies the temperature heterogeneity of plaque and decreases probability of rupture of Atherosclerotic plaque.

Guest Editorial Cardiovascular Health Informatics: Risk Screening and Intervention

Despite enormous efforts to prevent cardiovascular disease (CVD) in the past, it remains the leading cause of death in most countries worldwide. Around two-thirds of these deaths are due to acute events, which frequently occur suddenly and are often fatal before medical care can be given. New strategies for screening and early intervening CVD, in addition to the conventional methods, are therefore needed in order to provide personalized and pervasive healthcare. In this special issue, selected emerging technologies in health informatics for screening and intervening CVDs are reported. These papers include reviews or original contributions on 1) new potential genetic biomarkers for screening CVD outcomes and high-throughput techniques for mining genomic data; 2) new imaging techniques for obtaining faster and higher resolution images of cardiovascular imaging biomarkers such as the cardiac chambers and atherosclerotic plaques in coronary arteries, as well as possible automatic segmentation, identification, or fusion algorithms; 3) new physiological biomarkers and novel wearable and home healthcare technologies for monitoring them in daily lives; 4) new personalized prediction models of plaque formation and progression or CVD outcomes; and 5) quantifiable indices and wearable systems to measure them for early intervention of CVD through lifestyle changes. It is hoped that the proposed technologies and systems covered in this special issue can result in improved CVD management and treatment at the point of need, offering a better quality of life to the patient.

Non–ST-Segment Elevation Acute Coronary Syndromes

Non–ST-segment elevation (NSTE) acute coronary syndromes (ACS), encompassing NSTE myocardial infarction (NSTEMI) and unstable angina, lack the declarative electrocardiographic findings that readily identify patients with STEMI, yet comprise >70% of all ACS.1–3 Unlike STEMI patients who receive uniform treatment to restore flow in an occluded artery, NSTE-ACS patients (who often present first to an emergency department [ED]) have varying degrees of coronary obstruction, undergo more heterogeneous management, and have worse long-term outcomes.2, 4 Despite guidelines, there remains inconsistent use of routinely advocated medical therapies and invasive evaluation5 that reflect uncertainty in initial evaluation. Greater age and comorbidities plus varied coronary artery disease (CAD) severity further complicate decision making. In addition, although cardiogenic shock, heart failure, and arrhythmias may be less than in STEMI, NSTE-ACS patients suffer more recurrent events and worse long-term outcomes.1 As our understanding of NSTE-ACS pathophysiology has grown, several noninvasive imaging techniques have emerged that offer high-resolution characterization of relevant markers of pathophysiology such as coronary atherosclerotic plaque and salvageable myocardium. Incorporating such techniques into evaluating the ED patient with suspected or established NSTE-ACS promises improved outcomes by demonstrating patient-specific, mechanistically based targets for therapy. This review summarizes NSTE-ACS, current imaging approaches, and emerging imaging advances to improve diagnosis, treatment, and outcomes. NSTE-ACS is most commonly caused by disruption of a coronary artery atherosclerotic plaque, with myocardial ischemia and injury often resulting from partial or intermittent occlusion along the ischemic cascade.6 Other causes beyond the focus of this work include embolism and revascularization.7 Events in the coronary and downstream myocyte together offer targets for imaging in NSTE-ACS. ### Events in the Coronary Artery Coronary plaque formation has been well underway before NSTE-ACS presentation.8 The plaque prone to cause ACS has a thin fibrous cap, large lipid pool, and is susceptible to disruption via inflammation, metalloproteinases, …

Estudo iWONDER (Imaging WhOle vessel coroNary tree with intravascular ultrasounD and iMap® in patiEnts with acute myocaRdial infarction): racional e desenho do estudo

BACKGROUND: Intravascular ultrasound (IVUS) provides a sensitive and reproducible measurement of coronary artery dimensions, atherosclerotic plaque, and arterial lumen. Advances in IVUS technology now allow the characterization of the composition and morphology of atherosclerotic plaques. Although previous studies have reported data using IVUS radiofrequency analysis, the use of a new modality (iMap®, Boston Scientific, Santa Clara, USA) of atherosclerotic plaque characterization is very little known. Our objective is to analyze the morphological, phenotypic and tissue characteristics of culprit and non-culprit atherosclerotic plaques determined by angiography in patients undergoing coronary angiography due to acute myocardial infarction (AMI). METHODS: Prospective, cross-sectional, single center study (Hospital Sao Paulo - Escola Paulista de Medicina - Universidade Federal de Sao Paulo/UNIFESP, Sao Paulo, SP, Brazil). Fifty patients will be selected for ultrasound analysis according to the following inclusion criteria: age < 75 years, non-ST-segment elevation AMI or recent ST-segment elevation AMI, with or without previous fribrinolytic agents. CONCLUSIONS: The present study is aimed at obtaining morphological, phenotypic and tissue characteristics of the atherosclerotic plate using an imaging modality not extensively evaluated in patients with AMI.

Angiogenesis in Vulnerable Atherosclerotic Plaques in Apparently Healthy Human Hearts

Background Angiogenesis or neovascularization involves the formation of new blood vessels in the adjacency of preexisting vessels . This vascular proliferation is prevalent in various clinical circumstances, such as atherosclerosis. Microvessels in coronary artery atherosclerotic plaques may contribute to plaque instability. Objectives To correlate the presence of angiogenesis in atherosclerotic plaques with the criteria of vulnerable plaque used by the American Heart Association (AHA). Ma terial and Methods A total of 121 hearts from non-diabetic and apparently healthy transplant donors older than 40 years were selected. The coronary arteries were examined and all areas of cross-sectional luminal narrowing underwent histological, immunohistochemical and morphometric studies. We used a semi-quantitative score (scale 0-3) for identification of angiogenesis. Univariate and multivariate logistic regression analysis was performed to identify angiogenesis-related risk factors. Results We found 143 high-risk lesions (AHA type IV, V and VI) in the left anterior descending coronary artery (46.3%), in the circumflex coronary artery (28.9%) and in the right coronary artery (43%). Angiogenesis had a statistically significant association with the severity of vascular occlusion, inflammatory cell infiltration, the presence of a lipid core, fibrosis and periarteritis. The history of HT was associated with angiogenesis only in lesions of the LAD artery. According to the AHA classification we detected angiogenesis in one lesion Type II; five in plaques Type III; 21 in lesions Type IV; 22 in Type V; and 7 in plaques Type VI. Conclusions Angiogenesis in vulnerable plaques was associated with the severity of vascular occlusion, inflammatory cell infiltration, fibrosis and the presence of a lipid core, HT in lesions of the LAD. There was no association between plaque hemorrhage or calcification, suggesting that angiogenesis may anticipate plaque rupture.

Classification of Human Coronary Atherosclerotic Plaques Using Ex Vivo High-Resolution Multicontrast-Weighted MRI Compared With Histopathology

The objective of our study was to evaluate the feasibility of ex vivo high-resolution multicontrast-weighted MRI to accurately classify human coronary atherosclerotic plaques according to the American Heart Association classification. Thirteen human cadaver heart specimens were imaged using high-resolution multicontrast-weighted MR technique (T1-weighted, proton density-weighted, and T2-weighted). All MR images were matched with histopathologic sections according to the landmark of the bifurcation of the left main coronary artery. The sensitivity and specificity of MRI for the classification of plaques were determined, and Cohen's kappa analysis was applied to evaluate the agreement between MRI and histopathology in the classification of atherosclerotic plaques. One hundred eleven MR cross-sectional images obtained perpendicular to the long axis of the proximal left anterior descending artery were successfully matched with the histopathologic sections. For the classification of plaques, the sensitivity and specificity of MRI were as follows: type I-II (near normal), 60% and 100%; type III (focal lipid pool), 80% and 100%; type IV-V (lipid, necrosis, fibrosis), 96.2% and 88.2%; type VI (hemorrhage), 100% and 99.0%; type VII (calcification), 93% and 100%; and type VIII (fibrosis without lipid core), 100% and 99.1%, respectively. Isointensity, which indicates lipid composition on histopathology, was detected on MRI in 48.8% of calcified plaques. Agreement between MRI and histopathology for plaque classification was 0.86 (p < 0.001). Ex vivo high-resolution multicontrast-weighted MRI can accurately classify advanced atherosclerotic plaques in human coronary arteries.

High Platelet Reactivity on Clopidogrel Therapy Correlates With Increased Coronary Atherosclerosis and Calcification: A Volumetric Intravascular Ultrasound Study

This study sought to evaluate the relationship between platelet reactivity and atherosclerotic burden in patients undergoing percutaneous coronary intervention (PCI) with pre-intervention volumetric intravascular ultrasound (IVUS) imaging. Atherosclerosis progresses by the pathologic sequence of subclinical plaque rupture, thrombosis, and healing. In this setting, increased platelet reactivity may lead to more extensive arterial thrombosis at the time of plaque rupture, leading to a more rapid progression of the disease. Alternatively, abnormal vessel wall biology with advanced atherosclerosis is known to enhance platelet reactivity. Therefore, it is possible that by either mechanism, increased platelet reactivity may be associated with greater atherosclerotic burden. This study included patients who underwent PCI with pre-intervention IVUS imaging and platelet reactivity functional assay (P2Y(12) reaction units) performed >16 h after PCI, after the stabilization of clopidogrel therapy (administered before PCI). Platelet reactivity >230 P2Y(12) reaction units defined high on-treatment platelet reactivity (HPR). Among 335 patients (mean age 65.0 years, 71% men), there were 109 patients with HPR (32.5%) and 226 without HPR (67.5%), with HPR being associated with diabetes and chronic renal insufficiency. By IVUS analysis, patients with HPR had significantly greater target lesion calcium lengths, calcium arcs, and calcium indexes. Furthermore, patients with HPR tended to have longer lesions and greater volumetric dimensions, indicating higher plaque volume, larger total vessel volume, and also greater luminal volume, despite similar plaque burden. By multivariate analysis controlling for baseline clinical variables, HPR was the single consistent predictor of all IVUS parameters examined, including plaque volume, calcium length, and calcium arc. Increased platelet reactivity on clopidogrel treatment, defined as >230 P2Y(12) reaction units, is associated with greater coronary artery atherosclerotic disease burden and plaque calcification.