Features Of Plaque Vulnerability Research Articles

Co-localization of plaque macrophages with calcification is associated with a more vulnerable plaque phenotype and a greater calcification burden in coronary target segments as determined by OCT.

BackgroundThe presence of plaque macrophages and microcalcifications are acknowledged features of plaque vulnerability. Experimental data suggest that microcalcifications promote inflammation and macrophages foster microcalcifications. However, co-localization of plaque macrophages and calcification (ColocCaMa) in coronary segments and its impact on plaque phenotype and lesion vulnerability is unexplored.MethodsPlaque morphology including ColocCaMa of calcified coronary target segments in patients with stable coronary artery disease (n = 116) was analyzed using optical coherence tomography (OCT) prior to coronary intervention. Therefore we considered macrophages co-localized with calcification if their distance in an OCT frame was <100μm and OCT-defined microcalcifications with a calcium arc <22.5°.ResultsColocCaMa was present in 29/116(25.0%) coronary segments. Calcium burden was greater (calcium volume index:1731±1421°*mm vs. 963±984°*mm, p = 0.002) and calcifications were more superficial (minimal thickness of the fibrous cap overlying the calcification 35±37μm vs. 64±72μm, p = 0.005) in the presence of ColocCaMa. Segments with ColocCaMa demonstrated a higher incidence of newly suggested features of plaque vulnerability, with a 3.5-fold higher number of OCT-defined microcalcifications (0.7±1.0 vs. 0.2±0.6, p = 0.022) and a 6.7-fold higher incidence of plaque inflammation (macrophage volume index:148.7±248.3°*mm vs. 22.2±57.4°*mm, p<0.001). Clinically, intima–media thickness (IMT) in carotid arteries was increased in patients with ColocCaMa (1.02±0.30mm vs. 0.85±0.18, p = 0.021).In a multivariate model, IMT (OR1.76 for 100μm, 95%CI 1.16–2.65, p = 0.007), HDL-cholesterol (OR0.36 for 10mg/dl, 95%CI 0.16–0.84, p = 0.017), calcium volume index (OR1.07 for 100°*mm, 95%CI 1.00–1.14, p = 0.049), macrophage volume index (OR5.77 for 100°*mm, 95%CI 2.04–16.3, p = 0.001) and minimal luminal area (OR3.41, 95%CI 1.49–7.78, p = 0.004) were independent predictors of ColocCaMa.ConclusionPlaque macrophages co-localize with calcifications in coronary target segments and this is associated with high-risk morphological features including microcalcifications and macrophage infiltration as well as with greater calcification burden. Our data may add to the understanding of the relationship between plaque macrophages, vascular calcification and their clinical impact.

TCT-268 Five-year clinical outcomes of patients with OCT-detected features of vulnerable plaque in intermediate grade coronary stenoses proven insignificant by FFR

The purpose of this study is to determine the relationship between optical coherence tomography (OCT) detected features of vulnerable plaque morphology and the risk of adverse events among patients with angiography detected intermediate grade coronary lesions proven insignificant by fractional flow

TCT-423 Incidence and prognostic impact of the calcified nodule in coronary artery disease patients on hemodialysis

Coronary artery calcification is frequently observed in coronary artery disease (CAD) patients with end-stage renal disease (ESRD). Calcified nodule (CN) is recognized as one of the vulnerable plaque characteristics responsible for acute coronary syndrome (ACS) or sudden cardiac death. Although CN

Vascular Smooth Muscle-Specific Progerin Expression Accelerates Atherosclerosis and Death in a Mouse Model of Hutchinson-Gilford Progeria Syndrome.

Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). Patients who have HGPS exhibit ubiquitous progerin expression, accelerated aging and atherosclerosis, and die in their early teens, mainly of myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part, because of the lack of appropriate animal models. We generated an atherosclerosis-prone model of HGPS by crossing apolipoprotein E-deficient (Apoe-/-) mice with LmnaG609G/G609G mice ubiquitously expressing progerin. To induce progerin expression specifically in macrophages or vascular smooth muscle cells (VSMCs), we crossed Apoe-/-LmnaLCS/LCS mice with LysMCre and SM22αCre mice, respectively. Progerin expression was evaluated by polymerase chain reaction and immunofluorescence. Cardiovascular alterations were determined by immunofluorescence and histology in male mice fed normal chow or a high-fat diet. In vivo low-density lipoprotein retention was assessed by intravenous injection of fluorescently labeled human low-density lipoprotein. Cardiac electric defects were evaluated by electrocardiography. Apoe-/-LmnaG609G/G609G mice with ubiquitous progerin expression exhibited a premature aging phenotype that included failure to thrive and shortened survival. In addition, high-fat diet-fed Apoe-/-LmnaG609G/G609G mice developed a severe vascular pathology, including medial VSMC loss and lipid retention, adventitial fibrosis, and accelerated atherosclerosis, thus resembling most aspects of cardiovascular disease observed in patients with HGPS. The same vascular alterations were also observed in Apoe-/-LmnaLCS/LCSSM22αCre mice expressing progerin specifically in VSMCs, but not in Apoe-/-LmnaLCS/LCSLysMCre mice with macrophage-specific progerin expression. Moreover, Apoe-/-LmnaLCS/LCSSM22αCre mice had a shortened lifespan despite the lack of any overt aging phenotype. Aortas of ubiquitously and VSMC-specific progerin-expressing mice exhibited increased retention of fluorescently labeled human low-density lipoprotein, and atheromata in both models showed vulnerable plaque features. Immunohistopathological examination indicated that Apoe-/-LmnaLCS/LCSSM22αCre mice, unlike Apoe-/-LmnaG609G/G609G mice, die of atherosclerosis-related causes. We have generated the first mouse model of progerin-induced atherosclerosis acceleration, and demonstrate that restricting progerin expression to VSMCs is sufficient to accelerate atherosclerosis, trigger plaque vulnerability, and reduce lifespan. Our results identify progerin-induced VSMC death as a major factor triggering atherosclerosis and premature death in HGPS.

No Association between Thrombin Generation and Intra-Plaque Haemorrhage in Symptomatic Carotid Atherosclerotic Plaques: The Plaque at RISK (PARISK) Study.

Carotid atherosclerosis is an important cause of stroke. Intra-plaque haemorrhage (IPH) on magnetic resonance imaging (MRI) increases stroke risk. Development of IPH is only partly understood. Thrombin is an essential enzyme in haemostasis. Experimental animal studies have shown conflicting results on the relation between thrombin and plaque vulnerability. We hypothesize that decreased thrombin generation (TG) is associated with IPH and plaque vulnerability. This article investigates whether TG is associated with IPH and other features of plaque vulnerability in stroke patients. Recently symptomatic stroke patients underwent carotid MRI and blood sampling. MRI plaque features include plaque burden, presence of IPH, amount of lipid-rich necrotic core (LRNC), calcified tissue and fibrous tissue (% of total wall volume). TG was assessed in platelet-poor plasma and expressed as: peak height (PH) and endogenous thrombin potential (ETP). MR images could be analysed in 224 patients. Blood samples were available in 161 of 224 patients. Binary multivariate logistic and linear regression were used to investigate the association between TG and MRI plaque features. IPH and LRNC were present in 65 (40%) and 102 (63%) of plaques. There were no significant associations between TG and IPH; PH odds ratio (OR) = 1, 95% confidence interval (CI): 0.76 to 1.45 and ETP OR = 1, 95% CI: 0.73 to 1.37. After correction for age, sex and hypercholesterolaemia, the association was weak but non-significant; PH: OR = 0.76, 95% CI: 0.52 to 1.10 and ETP: OR = 0.73, 95% CI: 0.53 to 1.37. Features of carotid plaque on MRI show no significant association with TG in stroke patients. Systemic TG does not seem to be an important factor in IPH development.

In vivo vulnerability grading system of plaques causing acute coronary syndromes: An intravascular imaging study

BackgroundAutopsy studies shed light on the interplay between fatal acute coronary syndromes (ACS) and features of plaque vulnerability. This is a prospective pilot study designed for generating a new in vivo imaging grading system of plaque vulnerability. MethodsWe studied 87 coronary vessels in 63 consecutive patients: 48 with Acute Coronary Syndrome (ACS) and 15 with stable coronary artery disease using IntraVascular-Ultrasound Near-Infrared-Spectroscopy (IVUS-NIRS) and Optical Coherence Tomography (OCT). We identified 99 lesions: 21 were the ACS culprit lesions (18 ulcerations and 3 with intact fibrous cap), 78 were non-culprit lesions including plaques located in the same ACS culprit vessel (N12), plaques located in a non-culprit vessel in patients with ACS (28) and target lesions of stable patients (N 38). A second analysis focused on lipid plaques, comparing the 18 ACS culprit ulcerated lesions and the 55 non-culprit lesions. ResultsThe co-presence of the following three features of vulnerability [Minimal Luminal Area (MLA) <4 mm2, Fibrous Cap Thickness (FCT) < 75 μm and superficial macrophages] was by far more frequent in ACS culprit lesions than in controls (OR 40.6 for all lesions and OR 45.7 for ulcerated culprit lesions only). The triple-feature OCT grading identified vulnerable plaques with a much higher accuracy than that obtained applying each single feature of vulnerability. ConclusionsThe co-presence of the 3 OCT features of vulnerability (MLA < 4 mm2, FCT < 75 μm and superficial macrophages) identifies culprit ACS lesions with a very high odd ratio. This finding could set the basis for a new OCT vulnerability grading system including superficial macrophages.

Invited commentary

This report represents a thorough analysis of the search for associations between plasma renin or aldosterone levels and excised carotid artery plaque characteristics and composition and includes evaluation of many important intraplaque inflammatory mediators. Because activation of the renin-angiotensin system has been previously described to be associated with an increase in coronary and cerebrovascular events, it seemed logical to assume that these levels should correlate with the atherosclerotic plaque. Failure to find such a relationship was unexpected, which implies that the mechanism for the clinical outcomes is unrelated to acceleration of plaque lesion growth or plaque destabilization. Interestingly, a higher incidence of the composite of subsequent major clinical cardiovascular events was noted to be associated with higher levels of renin and aldosterone, although a history of prior cardiac disease at baseline was also higher among these patients. Nonetheless, the association of subsequent cardiovascular events did reflect greater numbers of adverse cerebrovascular and peripheral vascular episodes in addition to cardiac events. In attempting to understand the findings presented, it must be noted that plasma samples were obtained at only one point during the lifetime of the atherosclerotic process. Were the mature plaques derived from arteries that may have long since become activated by the renin-angiotensin system and no longer were dependent on it for continued activity, with the effect of renin and aldosterone most critical in the early stages of lesion development? Alternatively, although exclusion of patients using angiotensin-converting enzyme inhibitors in this real-life population would have severely limited the sample set size available for analysis, such inhibition may still compromise the ability to interpret these results, even if use of this drug class did not appear to affect the results of preliminary Cox regression analysis. Certainly, use of these inhibitors has been associated with reductions in cardiovascular events.1Yusuf S. Sleight P. Pogue J. Bosch J. Davies R. Dagenais G. Heart Outcomes Prevention Evaluation Study InvestigatorsEffects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients.N Engl J Med. 2000; 342: 145-153Crossref PubMed Scopus (8167) Google Scholar Could it be that elevated renin and aldosterone levels have, in fact, no causal role, but rather serve merely as markers of an as yet undiscovered mechanism of plaque destabilization? Whatever the case, atherosclerosis remains a complex process, resistant to complete explanation despite the laudable efforts of committed researchers such as Dr Hillaert and her colleagues. The opinions or views expressed in this commentary are those of the authors and do not necessarily reflect the opinions or recommendations of the Journal of Vascular Surgery or the Society for Vascular Surgery. Renin and aldosterone are not associated with vulnerable plaque characteristics in patients with carotid artery diseaseJournal of Vascular SurgeryVol. 68Issue 1PreviewThe renin-angiotensin-aldosterone system is increasingly being recognized to play an important role in the development and clinical course of cardiovascular diseases. Renin-angiotensin-aldosterone system activation is associated with clinical outcome in various populations of cardiovascular patients, such as patients with coronary artery, peripheral artery, and cerebrovascular disease. In this study, we investigated the associations between plasma renin and aldosterone concentrations and atherosclerotic plaque characteristics and secondary vascular events in patients undergoing carotid endarterectomy. Full-Text PDF Open Archive

Morphological Features and Plaque Composition in Culprit Atheromatous Plaques of Patients with Acute Coronary Syndromes

Abstract Background: The independent role of each plaque feature in relation to plaque vulnerability is still the subject of ongoing research. This study aimed to compare the morphologic characteristics of vulnerable atheromatous coronary plaques with the ones of stable, non-vulnerable plaques, and in plaques with different locations in the coronary tree, in order to identify the most relevant imaging-based biomarkers associated with coronary plaque vulnerability. Material and methods: This was a prospective observational, non-randomized study that included 50 patients with unstable angina who underwent computed tomography angiography for assessment of the entire coronary artery tree followed by complex morphologic analysis of all lesions, divided into two groups: group 1 – 25 patients with vulnerable plaque (VP) and group 2 – 25 age- and gender-matched patients with non-vulnerable plaque (NVP). Results: Lesions with a stenosis degree &gt;70% were significantly longer than those with a stenosis degree &lt;70% (8.27 ± 2.74 mm vs. 5.56 ± 4.11 mm, p = 0.04). VP presented significantly higher values of plaque thickness (p = 0.0005), plaque burden (p = 0.0004), and higher total plaque volume (p = 0.0005) than NVP. The remodeling index was not significantly different between the groups (p = 0.6), but the eccentricity index was (0.24 ± 0.14 compared to 0.14 ± 0.17, p = 0.023). Linear regression analysis revealed a significant correlation between plaque burden and plaque components in VP (r = 0.76, p &lt;0.0001 for necrotic core; r = 0.62, p = 0.0008 for fibro-fatty tissue; and r = 0.5, p = 0.01 for fibrotic tissue volume). Culprit plaques located in the right coronary artery presented significantly larger plaque burden volumes (91.17 ± 4.88 mm3 vs. 83.35 ± 8.47 mm3, p = 0.04), larger volumes of necrotic core (82.03 ± 47.85 mm3 vs. 45.84 ± 43.72 mm3, p = 0.02) and fibrofatty tissue (53.23 ± 31.92 mm3 vs. 23.76 ± 20.90 mm3, p = 0.02) than the ones situated in the left coronary artery. Conclusions: VPs from the culprit lesions exhibit a different phenotype than non-vulnerable ones, and vulnerability features are present in a significantly larger extent in VPs from the right coronary artery as compared to those from the left coronary artery.

Plasma trimethylamine N-oxide is associated with vulnerable plaque characteristics in CAD patients as assessed by optical coherence tomography

BackgroundPlaque vulnerability indicates the risk of a cardiovascular event. In the present study, we sought to analyze the relationship between trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, and vulnerable plaque characteristics in patients with coronary artery disease (CAD). MethodsOne hundred eighty non-culprit plaques from 90 patients with ACS or with stable angina were assessed by optical coherence tomography (OCT). The plasma TMAO levels were measured using rapid resolution liquid chromatography quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS). ResultsPatients were divided into two groups (high TMAO group and low TMAO group) according to the median plasma TMAO level (114.73 μg/L). The non-culprit plaques in the high TMAO group exhibited a thinner fibrous cap thickness (FCT) (65.97 ± 25.89 vs. 93.0 ± 28.28 μm, P < 0.001), higher frequency of microvessels (75.6% vs. 31.1%, P < 0.001, per-patient) and increased incidence of thin-cap fibroatheroma (TCFA) (69.2% vs. 18.4%, P < 0.001, per-patient) compared with the low TMAO group. Moreover, the level of TMAO was negatively associated with FCT (r = −0.418, P < 0.001). Furthermore, multivariate regression analysis results showed that TMAO (OR: 7.455, 95% CI: 2.753–20.189, P < 0.001) had a significant association with TCFA, with a cut-off point of 118.34 μg/L, specificity of 72.6% and sensitivity of 79.5% in predicting the prevalence of TCFA. ConclusionsIn conclusion, these findings suggest that the level of TMAO is significantly correlated with the incidence of TCFA. New biomarkers acquired through non-invasive means, such as TMAO, offer the potential to improve risk stratification and clinical management in patients with CAD.

Hyperintense Plaque on Intracranial Vessel Wall Magnetic Resonance Imaging as a Predictor of Artery-to-Artery Embolic Infarction.

The aim of the present study was to investigate atherosclerotic plaque characteristics in patients with artery-to-artery (A-to-A) embolic infarction by whole-brain high-resolution magnetic resonance imaging. Seventy-four patients (mean age, 54.7±12.1 years; 59 men) with recent stroke in the territory of middle cerebral artery because of intracranial atherosclerotic disease were prospectively enrolled. Whole-brain high-resolution magnetic resonance imaging was performed in all the patients both precontrast and postcontrast administration by using a 3-dimensional T1-weighted vessel wall magnetic resonance imaging technique known as inversion-recovery prepared sampling perfection with application-optimized contrast using different flip angle evolutions. Patients were divided into A-to-A embolic infarction and non-A-to-A embolic infarction groups based on diffusion-weighted imaging findings. The characteristics of the intracranial atherosclerotic plaques were compared between groups. A total of 74 intracranial atherosclerotic plaques were analyzed (36 in A-to-A embolism group and 38 in non-A-to-A embolism group). Hyperintense plaques (HIPs) were more frequently observed in A-to-A embolism group (75.0% versus 21.1%; P<0.001). Eighteen of the 27 HIPs (66.7%) demonstrated hyperintense spots or areas located adjacent to the lumen versus 9 HIPs (33.3%) located within the plaque in A-to-A embolism group. Furthermore, a higher prevalence of plaque surface irregularity was also observed in A-to-A embolism group (41.7% versus 18.4%; P=0.029). Logistic regression analysis showed that HIP was the most powerful independent predictor of A-to-A embolic infarction (P<0.001), with the odds ratio of 11.2 (95% confidence interval, 3.5-36.2). A-to-A embolic infarction has distinct vulnerable plaque characteristics compared with non-A-to-A embolic infarction. HIP and plaque surface irregularity may predict A-to-A embolic infarction.

Renin and aldosterone are not associated with vulnerable plaque characteristics in patients with carotid artery disease

BackgroundThe renin-angiotensin-aldosterone system is increasingly being recognized to play an important role in the development and clinical course of cardiovascular diseases. Renin-angiotensin-aldosterone system activation is associated with clinical outcome in various populations of cardiovascular patients, such as patients with coronary artery, peripheral artery, and cerebrovascular disease. In this study, we investigated the associations between plasma renin and aldosterone concentrations and atherosclerotic plaque characteristics and secondary vascular events in patients undergoing carotid endarterectomy. Methods and ResultsBaseline plasma renin and aldosterone concentrations from 506 subjects undergoing carotid endarterectomy (mean age, 67 ± 9 years; 65% male) were correlated with histopathologic characteristics and inflammatory protein concentrations of the excised atherosclerotic plaque. Ordinal logistic regression (for ordinal outcome parameters) or linear regression (for linear outcome) analysis did not show a statistically significant relationship between plasma renin or aldosterone concentrations and plaque fat, thrombus, calcifications, collagen, smooth muscle cells, or macrophage content. Neither could any association be found with intraplaque inflammatory mediators. During a median follow-up of 3 years, 102 (20%) patients experienced a major secondary vascular event (composite of stroke, myocardial infarction, leg amputation, vascular death, or coronary revascularization or peripheral intervention). In multivariable Cox regression analysis, including both renin and aldosterone, baseline renin concentrations were associated with the occurrence of secondary events. ConclusionsIn patients with established atherosclerotic disease undergoing carotid endarterectomy, plasma renin and aldosterone concentrations were not associated with atherosclerotic plaque characteristics. Plasma renin concentration was positively associated with the occurrence of major secondary vascular events.

MOLECULAR IMAGING OF CORONARY ATHEROSCLEROSIS: QUANTIFICATION AND REPRODUCIBILITY OF CORONARY 18F-FLUORIDE POSITRON EMISSION TOMOGRAPHY

Microcalcification is a key feature of vulnerable plaque. 18F-fluoride is a highly sensitive positron emission tomography tracer that binds to microcalcification and combined with computed tomography angiography (PET-CT) enables simultaneous anatomical and metabolic imaging that non-invasively

FRACTIONAL FLOW RESERVE BUT NOT INSTANTANEOUS WAVE-FREE RATIO DETECTS PLAQUE VULNERABILITY

Background: Fractional fow reserve (FFR) is, next to lesion severity, affected by plaque vulnerability as assessed by coronary computed tomography angiography (CCTA) and associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator free assessment with iFR is associated with plaque stability similarly as FFR. The current substudy of the PACIFIC trial explores the impact of CCTA derived unfavorable plaque features on both hyperemic and non-hyperemic fow indices in order to detect vulnerable plaques. Methods: Of 119 patients (62% men, age 58 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice CCTA to assess stenosis severity and plaque features (positive remodeling (PR), low attenuation plaque (LAP), spotty calcifcation (SC) and napkin ring sign (NRS)), as well as intracoronary pressure measurements (FFR, iFR, resting Pd/Pa and pressure ratio during adenosine within the wave-free period (iFRa)). CCTA derived plaque characteristics were related to these invasive pressure measurements. Results: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was signifcantly associated with impaired FFR, iFR, resting Pd/Pa and iFRa. Multivariable analysis revealed that PR and LAP were independently related to an impaired FFR (p = 0.006 and p = 0.038, respectively) and iFRa (p = 0.005 and p = 0.027, respectively), next to stenosis severity (p <0.001 for all). Conversely, these adverse plaque characteristics were not related to the vasodilator free parameters iFR and Pd/Pa. Conclusion: CCTA derived vulnerable plaque characteristics are associated with detrimental hyperemic fow indices as assessed with FFR and iFRa, but not with non-hyperemic indices as defined by iFR and resting Pd/Pa. These findings suggest that induction of hyperemia is mandatory to reveal plaque vulnerability during hemodynamic interrogation of a coronary artery.

Fibronectin Containing Extra Domain A Induces Plaque Destabilization in the Innominate Artery of Aged Apolipoprotein E-Deficient Mice.

Fibronectin containing extra domain A (Fn-EDA) is an endogenous ligand of TLR4 (toll-like receptor 4) and is abundant in the extracellular matrix of advanced atherosclerotic lesions in human and mice. Irrespective of sex, deletion of Fn-EDA reduces early atherosclerosis in apolipoprotein E-deficient (Apoe-/-) mice. However, the contribution of Fn-EDA in advanced atherosclerosis remains poorly characterized. We determined the contribution of Fn-EDA in advanced atherosclerotic lesions of aged (1-year-old) Apoe-/- mice. Plaque composition was determined in the innominate artery, a plaque instability site that is known to mimic several histological features of vulnerable human plaques. Female Apoe-/-, Fn-EDA-/-Apoe-/-, TLR4-/-Apoe-/-, and Fn-EDA-/-TLR4-/-Apoe-/- mice were fed a high-fat Western diet for 44 weeks. Fn-EDA-/-Apoe-/- mice exhibited reduced plaque size characterized by smaller necrotic cores, thick fibrous caps containing abundant vascular smooth muscle cells and collagen, reduced CD68/MMP9 (matrix metalloproteinase 9)-positive content, less accumulation of MMP-cleaved extracellular matrix aggrecan, and decreased vascular smooth muscle cell and macrophage apoptosis (P<0.05 versus Apoe-/- mice). Together these findings suggest that Fn-EDA induces plaque destabilization. Deletion of TLR4 reduced histological features of plaque instability in Apoe-/- mice but did not further reduce features of plaque destabilization in Fn-EDA-/-Apoe-/- mice, suggesting that TLR4 may contribute to Fn-EDA-induced plaque destabilization. Fn-EDA potentiated TLR4-dependent MMP9 expression in bone marrow-derived macrophages, suggesting that macrophage TLR4 may contribute to Fn-EDA-mediated plaque instability. Fn-EDA induces histological features of plaque instability in established lesions of aged Apoe-/- mice. The abundance of Fn-EDA in advanced atherosclerotic lesions may increase the risk of plaque destabilization.

Differences in the CT findings between vulnerable plaque and culprit lesions in acute coronary syndrome

BackgroundThe CT finding of “vulnerable plaque” is widely regarded as similar to that of a culprit lesion in an acute coronary syndrome (ACS). However, this hypothesis may not be accurate, since “vulnerable plaques” may substantially change their morphology when they rupture to cause an ACS. MethodsWe retrospectively evaluated coronary CT angiography data sets of 25 patients with ACS who had vulnerable (n = 10) or culprit plaques (n = 15). We analyzed CT features including positive remodeling (PR), low attenuation plaque (LAP), the napkin ring sign (NRS), degree of stenosis (normal, <50%, 50–99%, 100%), and myocardial hypoperfusion in the left ventricle. ResultsThere was no difference in the prevalence of PR, NRS, or LAP between vulnerable and culprit plaques. In contrast, a majority (80%, 8/10) of vulnerable plaques were associated with <50% luminal stenosis while total occlusion was identified in 47% (7/15) of culprit plaques (p = .037). In all patients with occlusion, myocardial hypoperfusion was demonstrated in the corresponding arterial territory on CT. ConclusionCT features of vulnerable and culprit plaques differ in cases with thrombotic occlusion reflecting dynamic plaque changes related to the episode of ACS.

Type 2 diabetes mellitus is associated with a lower fibrous cap thickness but has no impact on calcification morphology: an intracoronary optical coherence tomography study

BackgroundPatients with type 2 diabetes (T2DM) are at high risk for cardiovascular events, which usually arise from the rupture of a vulnerable coronary plaque. The minimal fibrous cap thickness (FCT) overlying a necrotic lipid core is an established predictor for plaque rupture. Recently, coronary calcification has emerged as a relevant feature of plaque vulnerability. However, the impact of T2DM on these morphological plaque parameters is largely unexplored. Therefore, this study aimed to compare differences of coronary plaque morphology in patients with and without T2DM with a particular focus on coronary calcification.MethodsIn 91 patients (T2DM = 56, non-T2DM = 35) with 105 coronary de novo lesions (T2DM = 56, non-T2DM = 49) plaque morphology and calcification were analyzed using optical coherence tomography (OCT) prior to coronary intervention.ResultsPatients with T2DM had a lower minimal FCT (80.4 ± 27.0 µm vs. 106.8 ± 27.8 µm, p < 0.001) and a higher percent area stenosis (77.9 ± 8.1% vs. 71.7 ± 11.2%, p = 0.001) compared to non-diabetic subjects. However, patients with and without T2DM had a similar total number of calcifications (4.0 ± 2.6 vs. 4.2 ± 3.1, p = ns) and no significant difference was detected in the number of micro- (0.34 ± 0.79 vs. 0.31 ± 0.71), spotty (2.11 ± 1.77 vs. 2.37 ± 1.89) or macro-calcifications (1.55 ± 1.13 vs. 1.53 ± 0.71, all p = ns). The mean calcium arc (82.3 ± 44.8° vs. 73.7 ± 31.6), the mean thickness of calcification (0.54 ± 0.13 mm vs. 0.51 ± 0.15 mm), the mean calcified area (0.99 ± 0.72 mm2 vs. 0.78 ± 0.49 mm2), the mean depth of calcification (172 ± 192 μm vs. 160 ± 76 μm) and the cap thickness overlying the calcification (50 ± 71 μm vs. 62 ± 61 μm) did not differ between the diabetic and non-diabetic groups (all p = ns).ConclusionT2DM has an impact on the minimal FCT of the coronary target lesion, but not on localization, size, shape or extent of calcification. Thus, the minimal FCT overlying the necrotic lipid core but not calcification is likely to contribute to the increased plaque vulnerability observed in patients with T2DM.

Letter by Chung and Kim Regarding Article, “Head-to-Head Comparison of Inflammation and Neovascularization in Human Carotid Plaques: Implications for the Imaging of Vulnerable Plaques”

We read with interest the recent published article by Demeure et al1 on the comparison of inflammation and neovascularization in carotid plaques. The authors had reported that inflammation and intraplaque neovascularization (IPN) confirmed by contrast echocardiography, known as 2 features of plaque vulnerability, were not systemically associated in carotid plaque. Furthermore, the presence of IPN was not related with patients’ symptoms, whereas inflammation was associated. In their study, intensity of contrast enhancement was highly correlated with the amount of neovessels confirmed by histology, which means imaging study was well validated. Inflammation and angiogenesis influence …

Ischemic Stroke Patients Demonstrate Increased Carotid Plaque Microvasculature Compared to (Ocular) Transient Ischemic Attack Patients

Background: Patients with a recent ischemic stroke have a higher risk of recurrent stroke compared to (ocular) transient ischemic attack (TIA) patients. Plaque microvasculature is considered as a feature of plaque vulnerability and can be quantified with carotid dynamic contrast-enhanced MRI (DCE-MRI). The purpose of this cross-sectional study was to explore the association between plaque microvasculature and the type of recent cerebrovascular events in symptomatic patients with mild-to-moderate carotid stenosis. Methods: A total of 87 symptomatic patients with a recent stroke (n = 35) or (ocular) TIA (n = 52) underwent carotid DCE-MRI examination. Plaque microvasculature was studied in the vessel wall and adventitia using DCE-MRI and the pharmacokinetic modeling parameter K^trans. Statistical analysis was performed with logistic regression, correcting for associated clinical risk factors. Results: The 75th percentile adventitial (OR 1.97, 95% CI 1.18-3.29) K^trans was significantly associated with a recent ischemic stroke compared to (ocular) TIA in multivariate analysis, while clinical risk factors were not significantly associated with the type of event. Conclusions: This study indicates a positive association of leaky plaque microvasculature with a recent ischemic stroke compared to (ocular) TIA. Prospective longitudinal studies are needed to investigate whether K^trans or other plaque characteristics may serve as an imaging marker for predicting (the type of) future cerebrovascular events.

Intracoronary Shear Stress and CT Characteristics of Vulnerable Coronary Plaques

Abstract Vulnerable coronary plaques are associated with a significant risk for rupture, and the ability to detect their characteristic features is of extreme importance, as timely detection of rupture-prone plaques could lead to the appropriate initiation of adequate therapeutic measures and prevent the evolution to an acute coronary event. The most common features of vulnerability in coronary plaques are represented by the presence of low density atheroma, a thin fibrous cap, spotty calcifications, and positive remodeling. However, there is still a huge amount of information to be learned about the role of local forces, represented by the shear stress, on the plaque vulnerability. This clinical update aims to present the most recent advances in the field of knowledge regarding the relation between shear stress and plaque vulnerability, starting from the hypothesis that shear stress significantly correlates with the CT features of plaque vulnerability and can represent a new marker of vulnerability in coronary artery plaques.

PH-Sensitive polymer-gold nanohybrid system for antitumor drug delivery and CT imaging

A high r1 relaxivity manganese–gadolinium nanocolloid (αvβ3-MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12 months using a clinical MRI scanner (3 T). 3D mapping of neovasculature signal intensity revealed the spatial coherence and intensity of plaque angiogenic expansion, which may, with other high risk MR bioindicators, help identify high-risk patients with moderate (40% to 60%) vascular stenosis. Microscopy confirmed the predominant media and plaque distribution of fluorescent αvβ3-MnOL-Gd NC, mirroring the MR data. An expected close spatial association of αvβ3-integrin neovasculature and macrophages was noted, particularly within plaque shoulder regions. Manganese oleate bioelimination occurred via the biliary system into feces. Gd-DOTA was eliminated through the bile–fecal and renal excretion routes. αvβ3-MnOL-Gd NC offers an effective vehicle for T1w neovascular imaging in atherosclerosis.Cerebrovascular accidents are a leading cause of mortality and morbidity worldwide. The acute formation of thrombus following atherosclerotic plaque rupture has been well recognized as the etiology of stroke. The authors studied microanatomical features of vulnerable atherosclerotic plaque in this article, in an attempt to identify those with high risk of rupture. Gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) was developed as a novel contrast agent for MRI. They show that this agent is effective in providing neovascular imaging.