Minimum Fibrous Cap Thickness Research Articles

NecroX-7 reduces necrotic core formation in atherosclerotic plaques of Apoe knockout mice

Background and aimsA large necrotic core is a key feature of atherosclerotic plaque instability. Necrotic cellular debris accumulates in the lipid-rich core and promotes inflammation, destabilization and ultimately rupture of the plaque. Although the role of necrosis in atherosclerosis is rather clear-cut, not many strategies have been performed up till now to specifically target plaque necrosis. In the present study, we tested the plaque stabilizing potential of NecroX-7, a novel compound with antioxidative and anti-necrotic properties. MethodsMale apolipoprotein E (Apoe) knockout mice were treated with NecroX-7 (30 mg/kg) or vehicle, 3 times per week, via intraperitoneal injections for 16 weeks. Meanwhile, mice were fed a western-type diet to induce plaque formation. ResultsNecroX-7 reduced total plaque burden in the thoracic aorta as compared to vehicle-treated mice, without affecting total plasma cholesterol. Plaques in the aortic root of NecroX-7-treated mice showed a significant decrease in necrotic core area, 8-oxodG, iNOS and MMP13 expression, while collagen content and minimum fibrous cap thickness were increased. Moreover, NecroX-7 treatment reduced the expression of multiple inflammation markers such as TNFα, IL1β, iNOS, HMGB1 and RAGE in a NF-κB-dependent manner. In vitro, NecroX-7 prevented tert-butyl hydroperoxide (tBHP)-induced mitochondrial ROS formation, necrosis, iNOS expression and HMGB1 release in primary macrophages. ConclusionsNecroX-7 improves features of plaque stability in Apoe knockout mice by reducing necrotic core formation, oxidative stress and inflammation, and by increasing collagen deposition and fibrous cap thickness. Therefore, NecroX-7 could be a promising pleiotropic drug for the treatment of atherosclerosis.

Optical coherence tomography imaging of coronary atherosclerosis is affected by intraobserver and interobserver variability.

Optical coherence tomography (OCT) has emerged as a novel imaging modality that allows plaque classification through identification of features including lipid, calcification and fibrous cap. However, subtle changes in light attenuation as the optical beam traverses the plaque in vivo are challenging to interpret and data on strength of observer agreement are minimal. Thus, we sought to assess both the intra and interobserver variability for plaque composition/classification using OCT. OCT imaging was performed in 50 patients prior to percutaneous coronary intervention. Analysis was performed offline by two independent, experienced OCT operators. Target lesion luminal dimensions and plaque composition were assessed at minimal luminal area (MLA) and at five 1-mm longitudinal intervals proximal and distal to the MLA. An OCT thin-capped fibroatheroma (OCT-TCFA) was defined as greater than 90 degree lipid arc with minimal fibrous cap thickness less than 0.85 μm. Overall, 540 frames of OCT were included and exceptional consistency was seen for all measures of luminal geometry [all intraclass correlation coefficients (ICC) >0.97, P < 0.001]. Intraobserver agreements for calcification and lipid arc were strong (both ICC >0.84, P < 0.001), whereas interobserver agreement was higher for calcium (ICC 0.76) than lipid (ICC 0.69). Interobserver agreement of minimal fibrous cap thickness was moderate (ICC 0.52, 95% confidence interval 0.45-0.58, P < 0.001], but improved as cap thickness decreased. Overall, intra and interobserver agreements for OCT-defined plaque classification were strong (K = 0.86 and 0.71, respectively). Luminal dimensions and plaque compositional features identified by OCT are minimally affected by observer variability, permitting dependable plaque classification.

Morphologic Features of Carotid Plaque Rupture Assessed by Optical Coherence Tomography.

Rupture of the plaque fibrous cap and subsequent thrombosis are the major causes of stroke. This study evaluated morphologic features of plaque rupture in the carotid artery by using optical coherence tomography in vivo. Thirty-six carotid plaques with high-grade stenosis were prospectively imaged by optical coherence tomography. "Plaque rupture" was defined as a plaque containing a cavity that had overlying residual fibrous caps. The fibrous cap thickness was measured at its thinnest part for both ruptured and nonruptured plaques. The distance between the minimum fibrous cap thickness site and the bifurcation point was also measured. Optical coherence tomography identified 24 ruptured and 12 nonruptured plaques. Multiple ruptures were observed in 9 (38%) patients: Six patients had 2 ruptures in the same plaque, 2 patients had 3 ruptures in the same plaque, and 1 patient had 5 ruptures in the same plaque. Most (84%) of the fibrous cap disruptions were identified at the plaque shoulder and near the bifurcation point (within a 4.2-mm distance). The median thinnest cap thickness was 80 μm (interquartile range, 70-100 μm), and 95% of ruptured plaques had fibrous caps of <130 μm. Receiver operating characteristic analysis revealed that a fibrous cap thickness of <130 μm was the critical threshold value for plaque rupture in the carotid artery. Plaque rupture was common in high-grade stenosis and was located at the shoulder of the carotid plaque close to the bifurcation. A cap thickness of <130 μm was the threshold for plaque rupture in the carotid artery.

A computer-simulation study on the effects of MRI voxel dimensions on carotid plaque lipid-core and fibrous cap segmentation and stress modeling.

BackgroundThe benefits of a decreased slice thickness and/or in-plane voxel size in carotid MRI for atherosclerotic plaque component quantification accuracy and biomechanical peak cap stress analysis have not yet been investigated in detail because of practical limitations.MethodsIn order to provide a methodology that allows such an investigation in detail, numerical simulations of a T1-weighted, contrast-enhanced, 2D MRI sequence were employed. Both the slice thickness (2 mm, 1 mm, and 0.5 mm) and the in plane acquired voxel size (0.62x0.62 mm2 and 0.31x0.31 mm2) were varied. This virtual MRI approach was applied to 8 histology-based 3D patient carotid atherosclerotic plaque models.ResultsA decreased slice thickness did not result in major improvements in lumen, vessel wall, and lipid-rich necrotic core size measurements. At 0.62x0.62 mm2 in-plane, only a 0.5 mm slice thickness resulted in improved minimum fibrous cap thickness measurements (a 2–3 fold reduction in measurement error) and only marginally improved peak cap stress computations. Acquiring voxels of 0.31x0.31 mm2 in-plane, however, led to either similar or significantly larger improvements in plaque component quantification and computed peak cap stress.ConclusionsThis study provides evidence that for currently-used 2D carotid MRI protocols, a decreased slice thickness might not be more beneficial for plaque measurement accuracy than a decreased in-plane voxel size. The MRI simulations performed indicate that not a reduced slice thickness (i.e. more isotropic imaging), but the acquisition of anisotropic voxels with a relatively smaller in-plane voxel size could improve carotid plaque quantification and computed peak cap stress accuracy.

A score to quantify coronary plaque vulnerability in high-risk patients with type 2 diabetes: an optical coherence tomography study.

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

Optical coherence tomography derived differences of plaque characteristics in coronary culprit lesions between type 2 diabetic patients with and without acute coronary syndrome

To compare optical coherence tomography (OCT)-derived plaque characteristics of coronary target lesions between diabetic patients with acute coronary syndrome (ACS) versus stable angina pectoris (SAP). In vivo assessment of plaque composition of coronary culprit lesions in a cardiovascular high-risk population with diabetes mellitus is incompletely elucidated. 102 diabetic patients with coronary de novo lesions were enrolled and categorized into an ACS-group (40 patients) and a SAP-group (62 patients) according to their clinical presentation. Assessment of clinical data, angiographic, and OCT imaging including the analysis of plaque composition and lipid content of the target lesions were performed prior to percutaneous coronary intervention and compared between the two groups. Plaque characteristics of patients in the ACS-group compared with the SAP-group showed a higher incidence of lipid-rich plaque [33 (82.5%) vs. 25 (40.3%)], thin-capped fibroatheroma [29 (72.5%) vs. 10 (16.1%)], macrophage infiltration [32 (80.0%) vs. 21 (33.9%)], thrombus [23 (57.5%) vs. 2 (3.2%)], and plaque rupture [27 (67.5%) vs. 2 (3.2%)] (all P < 0.001). Moreover, there was a wider lipid arc (174.5 ± 33.8° vs. 122.9 ± 43.9°), a longer lipid plaque length (6.52 ± 2.04 mm vs. 3.73 ± 2.16 mm), a greater lipid volume index (1117.2 ± 349.9 vs. 504.8 ± 379.3), and a smaller minimal fibrous cap thickness (51.52 ± 9.14 µm vs. 80.33 ± 26.71 µm) within lipid-rich lesions of ACS patients (all P < 0.001). Diabetic patients with ACS exhibit more vulnerable plaque features in coronary culprit lesions compared with diabetic patients with SAP. This may provide rationale for a specific therapeutic strategy either by pharmacological plaque stabilization or coronary intervention in any lesion with vulnerable plaque morphology in patients with diabetes.

Incidence, Predictors, Morphological Characteristics, and Clinical Outcomes of Stent Edge Dissections Detected by Optical Coherence Tomography

This study sought to investigate the frequency, predictors, and detailed qualitative and quantitative assessment of optical coherence tomography (OCT)-detected stent edge dissections. Its impact on subsequent management and clinical outcomes were also investigated. OCT is a high-resolution imaging modality that can lead to more frequent recognition and accurate assessment of vascular injuries during percutaneous coronary intervention (PCI). From September 2010 to June 2011, all patients with OCT post-PCI were enrolled. Edge dissections were defined as disruptions of the arterial lumen surface in both the 5-mm distal and proximal stent edges. Qualitative and quantitative analyses of all edges were performed at 0.2-mm intervals. In total, 395 edges (249 lesions in 230 patients) were analyzed. The overall incidence of OCT-detected edge dissection was 37.8%, and most (84%) were not apparent on angiography. Independent predictors for OCT-detected dissections were presence of atherosclerotic plaque at stent edges, calcification angle, minimum fibrous cap thickness, thin-cap fibroatheromas, stent/lumen eccentricity, and vessel overstretching. Mean dissection length measured 2.04 ± 1.60 mm, 96.2% appeared as flaps, and 52.8% extended beyond the intima/atheroma layer. Additional stenting was performed in 22.6% of all dissections, which were longer, had bigger dimensions, and promoted deeper vascular injury. The 12-month major adverse cardiac event rate was similar between patients with (7.95%) and without (5.69%, p= 0.581) dissections. High rates of stent edge dissections were detected by OCT, usually related to the presence of atherosclerosis at stent edges and to PCI technique. Detailed OCT assessment of dissectionseverity was possible and affected the subsequent management of this complication. Non-flow-limiting, small, and superficial dissections left untreated proved benign.

Plaque vulnerability of coronary artery lesions is related to left ventricular dilatation as determined by optical coherence tomography and cardiac magnetic resonance imaging in patients with type 2 diabetes

BackgroundPatients with type 2 diabetes are at increased risk for both, left ventricular (LV)-dilatation and myocardial infarction (MI) following the rupture of a vulnerable plaque. This study investigated the to date incompletely understood relationship between plaque vulnerability and LV-dilatation using optical coherence tomography (OCT) and cardiac magnetic resonance imaging (CMR) in patients with type 2 diabetes and stable coronary artery disease.MethodsCMR was performed in 58 patients with type 2 diabetes, in which 81 coronary lesions were investigated using OCT.ResultsA decreased minimal fibrous cap thickness (FCT) of coronary lesions was associated with an increase of several CMR-derived parameters including LV-end diastolic volume (LVEDV, r = 0.521, p < 0.001), LV-end diastolic diameter (r = 0.502, p < 0.001) and LV-end systolic volume (r = 0.467, p = 0.001). Similar results were obtained for mean FCT.Furthermore, patients with dilated versus non-dilated LV differed significantly in several cardiovascular risk factors including previous MI (47.1% vs. 14.6%, p = 0.009), HDL-cholesterol (40.35 ± 5.57 mg/dl vs. 45.20 ± 10.79 mg/dl, p = 0.029) and smoking (82.4% vs. 51.2%, p = 0.027). However, minimal FCT is associated to LV-dilatation independent of previous MIs (odds ratio 0.679, p = 0.022).Receiver-operating curve analysis demonstrated that CMR-derived LVEDV predicts plaque vulnerability with low-moderate diagnostic efficiency (area under the curve 0.699) and considerate specificity (83.3%) at the optimal cut-off value (159.0 ml).ConclusionThese data suggest that vulnerability of coronary lesions is associated with LV-dilatation in high risk patients with type 2 diabetes. CMR may be a useful adjunct to the risk-stratification in this population. Future studies are warranted to investigate potential mechanisms linking plaque vulnerability and LV-dilatation.

Relationship between optical coherence tomography derived intraluminal and intramural criteria and haemodynamic relevance as determined by fractional flow reserve in intermediate coronary stenoses of patients with type 2 diabetes

BackgroundThe relationship between functional relevance and optical coherence tomography (OCT)-derived measurements of coronary lesions is incompletely understood and of critical importance, particularly in cardiovascular high-risk patients with type 2 diabetes.ObjectiveTo...

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.

The impact of epicardial fat volume on coronary plaque vulnerability: insight from optical coherence tomography analysis

Epicardial fat volume (EFV) has been implicated in coronary artery disease. Relationship between EFV and coronary plaque vulnerability has not been elucidated. The aim of this study was to investigate the association of EFV with coronary plaque vulnerability by using optical coherence tomography (OCT). We enrolled 117 patients who underwent multislice computed tomography (MSCT) and OCT. EFV was quantified on MSCT. Patients were categorized according to tertiles of EFV: low tertile, EFV < 104.1 cm(3); mid-tertile, 104.1 cm(3)≤ EFV ≤ 130.7 cm(3); high tertile, EFV > 130.7 cm(3). A total of 180 vessels and 221 plaques were assessed with OCT to detect a thin-capped fibroatheroma (TCFA). TCFA was defined as a plaque with necrotic lipid pools ≥ 2 quadrants and minimum fibrous cap thickness measuring <65 μm. Patients with low computed tomographic attenuation and positive remodelling were frequently observed and patients with OCT-derived TCFA were more common in the high tertile EFV. EFV was associated with a maximal lipid arc (103.4 ± 28.2 cm(3) in 0 quadrant, 120.2 ± 35.2 cm(3) in 1-2 quadrants, and 131.5 ± 41.1 cm(3) in >2 quadrants; P= 0.01) and inversely correlated with a minimum fibrous cap thickness of the patients (r = -0.400, P<0.01). In multivariate analysis, the high tertile of EFV remained an independent predictor for patients with OCT-derived TCFA [odds ratio (OR) 2.92; 95% confidence interval (CI) 1.13-7.55; P= 0.027] and acute coronary syndrome (ACS) patients (OR 2.89; 95% CI 1.14-7.29; P= 0.025). EFV was associated with coronary plaque vulnerability and high EFV was an independent predictor of ACS in patients with coronary artery disease.

Dynamic Nature of Coronary Plaques and Clinical Outcomes in Diabetic Patients: Is Change in Itself Bad?

We evaluated the geographic distribution of thin-cap fibroatheromas (TCFAs) in the coronary arteries using optical coherence tomography (OCT), a high-resolution imaging modality.Plaque rupture is the most frequent cause of acute myocardial infarction (AMI). It has been recognized that TCFA is the primary plaque type at the site of plaque rupture.We performed 3-vessel OCT examinations in 55 patients: 35 AMI and 20 stable angina pectoris patients. The criteria for TCFA in an OCT image was a lipid-rich plaque with fibrotic cap thickness <65 μm. The distance between each TCFA location and the respective coronary artery ostium was measured with motorized OCT imaging pullback. The total length of all 3 coronary arteries imaged by OCT pullbacks was 82 ± 21 mm in the left anterior descending coronary artery (LAD), 67 ± 26 mm in the left circumflex coronary artery (LCx), and 104 ± 32 mm in the right coronary artery (RCA).OCT detected 94 TCFAs in 165 coronary arteries. The minimum fibrous-cap thickness of TCFAs was 57.4 ± 5.4 μm in AMI patients, and 55.9 ± 7.3 μm in stable angina pectoris patients (p = 0.4). Of the total of 94 TCFAs, 28 were detected in the LAD, 18 in the LCx, and 48 in the RCA. Most LAD TCFAs were located between 0 and 30 mm from the LAD ostium (76%). Conversely, LCx and RCA TCFAs were evenly distributed throughout the entire coronary length. The clustering of the TCFAs was similar in culprit segments as compared with nonculprit segments. In AMI patients, most LAD TCFAs were distributed near side branches, mainly positioned opposite the side branch bifurcation.Three-vessel OCT imaging showed that TCFAs tend to cluster in predictable spots within the proximal segment of the LAD, but develop relatively evenly in the LCx and RCA arteries.

Pathological characterization of yellow and white plaques under angioscopy

Recently it has been reported that the lipid core area and the fibrous cap thickness cannot be deduced from the stenotic ratio. However, there is no comparative study between yellow and white plaques. This study assessed the precise characterization of yellow and white plaques using angioscopy. We observed 198 segments of coronary from autopsy artery using angioscopy, then 46 yellow plaque lesions and 61 white plaque lesions of atheroma were excised and prepared for pathological examination. The stenotic ratio, the plaque area (PA), the lipid core size as a percentage of total vessel area (%C), and the minimum fibrous cap thickness (FCt) were measured and compared between yellow and white plaque groups. In this study, the stenotic ratio and the PA were significantly larger in the white plaque group (p<.001). The FCt was significantly thinner in the yellow plaque group (58±18 µm vs. 648±356 µm p<.0001). There was no correlation between the stenotic ratio and the %C in the whole cases (r=.22). Although it was the same in the white plaque group (r=.13), significant correlation between them was shown in the yellow plaque group (r=.64). No significant correlation was observed between the stenotic ratio and the FCt in each plaque group. We concluded that a yellow plaque with moderate stenosis could be diagnosed as a vulnerable plaque by the combination of coronary angiography and angioscopy.

In-vivo detection of the frequency and distribution of thin-cap fibroatheroma and ruptured plaques in patients with coronary artery disease

The purpose of this study was to assess the prevalence and to quantify the thin-cap fibroatheroma (TCFA) and ruptured plaques in patients with coronary artery disease using optical coherence tomography (OCT). TCFA lesions are the most prevalent precursors of plaque rupture, and are responsible for acute coronary syndromes (ACS). There are limited data regarding the frequency and distribution of TCFA in diseased coronary arteries. Coronary artery OCT was performed in 78 vessels in 47 patients, with stable angina (SA) or ACS. OCT plaque characteristics were derived using criteria that had been validated earlier. TCFA was defined as rich in lipid (two or more quadrants) with thin fibrous cap (<65 μm). Comparison was made between SA and unstable angina, and culprit and nonculprit vessels. There was a higher incidence of TCFA and plaque rupture (65 vs. 24%, P=0.003, and 40 vs. 15%, P=0.04) in ACS patients. This was reflected in a higher lipid pool (2.66 vs. 2.26 quadrants, P=0.04) and minimum fibrous cap thickness (52 vs. 74 μm, P=0.001) in ACS patients. The mean numbers of TCFA (2.5) were similar in patients with SA and ACS. However, the maximal length of TCFA (2.63 vs. 5.54 mm, P=0.026) and plaque rupture sites (P=0.046) were higher in ACS vessels. No relationship was found between baseline characteristics and TCFA incidence and plaque rupture. We identified ACS (P=0.002), higher mean lipid pool (P=0.002), longer TCFA length (P=0.007) and higher number of TCFA (P=0.02) as predictors of plaque rupture sites. In this in-vivo study, we identified a higher incidence of longer TCFAs and plaque rupture sites associated with ACS.

Association of the platelet GPIIb/IIIa polymorphism with atherosclerotic plaque morphology: The Atherosclerosis Risk in Communities (ARIC) Study

Objectives Platelet activation and aggregation play an important role in the pathogenesis of cardiovascular disease. We examined the association of a single nucleotide polymorphism (SNP) in the GPIIIa platelet glycoprotein (Leu33Pro) with carotid artery plaque morphology and with expression of platelet markers using data from the Atherosclerosis Risk in Communities (ARIC) Carotid MRI study.Methods The study sample consisted of 1202 Caucasian members of the ARIC study cohort recruited in 2004–2005 to participate in the Carotid MRI Substudy under stratified sampling based on maximum carotid artery wall thickness. The Leu33Pro polymorphism was identified as SNP rs5918 in the ITGB3 gene. Plaque visualization was accomplished with contrast enhanced MRI examination of the thickest segment of the carotid artery. Expression of platelet markers was measured using fasting whole blood flow cytometry.Results This cross-sectional analysis based on age and gender adjusted weighted linear regression models suggests that those homozygous for the Leu33Pro risk allele (C) have decreased mean and minimum fibrous cap thickness. We did not observe differences in plaque lipid volume or maximum carotid artery wall thickness across SNP rs5918 genotypes. Carriers of the Leu33Pro polymorphism, as compared to major allele homozygotes, had greater percent of platelets expressing P-selectin, a platelet glycoprotein indicating activation status. Prevalent coronary heart disease did not affect estimates of fibrous cap thickness or of platelet activation.Conclusion Our results suggest that individuals with Leu33Pro polymorphism of the GPIIIa glycoprotein may be predisposed to increased risk of atherosclerotic plaque rupture.

Relationship between circulating levels of RANTES (regulated on activation, normal T-cell expressed, and secreted) and carotid plaque characteristics: the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study

To assess the relationship between regulated on activation, normal T-cell expressed and secreted (RANTES) and carotid atherosclerotic plaque burden and plaque characteristics. Gadolinium-enhanced magnetic resonance imaging (MRI) of the carotid artery was performed in 1901 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Wall thickness and volume, lipid-core volume, and fibrous cap thickness (by MRI) and plasma RANTES levels (by ELISA) were measured. Regression analysis was performed to study the associations between MRI variables and RANTES. Among 1769 inclusive participants, multivariable regression analysis revealed that total wall volume [beta-coefficient (β) = 0.09, P = 0.008], maximum wall thickness (β = 0.08, P = 0.01), vessel wall area (β = 0.07, P = 0.02), mean minimum fibrous cap thickness (β = 0.11, P = 0.03), and high-sensitivity C-reactive protein (β = 0.09, P = 0.01) were positively associated with RANTES. Total lipid-core volume showed positive association in unadjusted models (β = 0.18, P = 0.02), but not in fully adjusted models (β = 0.13, P = 0.09). RANTES levels were highest in Caucasian females followed by Caucasian males, African-American females, and African-American males (P < 0.0001). Statin use attenuated the relationship between RANTES and measures of plaque burden. Positive associations between RANTES and carotid wall thickness and lipid-core volume (in univariate analysis) suggest that higher RANTES levels may be associated with extent of carotid atherosclerosis and high-risk plaques. Associations between fibrous cap thickness and RANTES likely reflect the lower reliability estimate for fibrous cap measurements compared with wall volume or lipid-core volume measurements. Statin use may modify the association between RANTES and carotid atherosclerosis. Furthermore, RANTES levels vary by race.

037 In vivo detection of frequency and distribution of thin cap fibroatheroma ANA ruptured plaques in patients with coronary artery disease: a optical coherence tomography study

Objectives The purpose of this study was to assess the prevalence and quantify the Thin- cap fibroatheroma (TCFA) and ruptured plaques in patients with coronary artery disease using optical coherence tomography (OCT). Background TCFA lesions are the most prevalent precursor of plaque rupture, and responsible for acute coronary syndromes. There is limited data regarding the frequency and distribution of TCFA in diseased coronary arteries. Methods Coronary artery OCT was performed in 78 vessels in (47 patients), with stable angina (SA) or acute coronary syndrome (ACS). OCT plaque characteristics were derived using previously validated criteria. TCFA was defined as lipid rich (two or more quadrants) with thin fibrous cap ( Results There was a higher incidence of TCFA and plaque rupture (65% vs 24%, p=0.003, and 40% vs 15%, p=0.04) in ACS patients. This was reflected in higher lipid pool (2.66 vs 2.26 quadrants, p=0.04) and minimum fibrous cap thickness (52 μm vs 74 μm, p=0.001) in ACS patients. The mean numbers of TCFA (2.5) were similar in patients with SA and ACS. However, the maximal length of TCFA (2.63 mm vs 5.54 mm, p=0.026), and plaque rupture sites (p=0.046) were higher in ACS vessels. No relation ship was found between baseline characteristics and TCFA incidences and plaque rupture. We identified ACS (p=0.002), higher mean lipid pool (p=0.002), longer TCFA length (p=0.007), and higher number TCFA (p=0.02) as predictors of plaque rupture sites. Conclusions In this in vivo study, we identified higher incidences of longer length TCFAs and plaque rupture sites associated with ACS.

Arterial Luminal Curvature and Fibrous-Cap Thickness Affect Critical Stress Conditions Within Atherosclerotic Plaque: An In Vivo MRI-Based 2D Finite-Element Study

High mechanical stress in atherosclerotic plaques at vulnerable sites, called critical stress, contributes to plaque rupture. The site of minimum fibrous cap (FC) thickness (FC(MIN)) and plaque shoulder are well-documented vulnerable sites. The inherent weakness of the FC material at the thinnest point increases the stress, making it vulnerable, and it is the big curvature of the lumen contour over FC which may result in increased plaque stress. We aimed to assess critical stresses at FC(MIN) and the maximum lumen curvature over FC (LC(MAX)) and quantify the difference to see which vulnerable site had the highest critical stress and was, therefore, at highest risk of rupture. One hundred patients underwent high resolution carotid magnetic resonance (MR) imaging. We used 352 MR slices with delineated atherosclerotic components for the simulation study. Stresses at all the integral nodes along the lumen surface were calculated using the finite-element method. FC(MIN) and LC(MAX) were identified, and critical stresses at these sites were assessed and compared. Critical stress at FC(MIN) was significantly lower than that at LC(MAX) (median: 121.55kPa; inter quartile range (IQR)=[60.70-180.32]kPa vs. 150.80kPa; IQR=[91.39-235.75]kPa, p<0.0001). If critical stress at FC(MIN) was only used, then the stress condition of 238 of 352 MR slices would be underestimated, while if the critical stress at LC(MAX) only was used, then 112 out of 352 would be underestimated. Stress analysis at FC(MIN) and LC(MAX) should be used for a refined mechanical risk assessment of atherosclerotic plaques, since material failure at either site may result in rupture.

OCT Assessment of Thin-Cap Fibroatheroma Distribution in Native Coronary Arteries

We evaluated the geographic distribution of thin-cap fibroatheromas (TCFAs) in the coronary arteries using optical coherence tomography (OCT), a high-resolution imaging modality. Plaque rupture is the most frequent cause of acute myocardial infarction (AMI). It has been recognized that TCFA is the primary plaque type at the site of plaque rupture. We performed 3-vessel OCT examinations in 55 patients: 35 AMI and 20 stable angina pectoris patients. The criteria for TCFA in an OCT image was a lipid-rich plaque with fibrotic cap thickness <65 microm. The distance between each TCFA location and the respective coronary artery ostium was measured with motorized OCT imaging pullback. The total length of all 3 coronary arteries imaged by OCT pullbacks was 82 +/- 21 mm in the left anterior descending coronary artery (LAD), 67 +/- 26 mm in the left circumflex coronary artery (LCx), and 104 +/- 32 mm in the right coronary artery (RCA). OCT detected 94 TCFAs in 165 coronary arteries. The minimum fibrous-cap thickness of TCFAs was 57.4 +/- 5.4 microm in AMI patients, and 55.9 +/- 7.3 microm in stable angina pectoris patients (p = 0.4). Of the total of 94 TCFAs, 28 were detected in the LAD, 18 in the LCx, and 48 in the RCA. Most LAD TCFAs were located between 0 and 30 mm from the LAD ostium (76%). Conversely, LCx and RCA TCFAs were evenly distributed throughout the entire coronary length. The clustering of the TCFAs was similar in culprit segments as compared with nonculprit segments. In AMI patients, most LAD TCFAs were distributed near side branches, mainly positioned opposite the side branch bifurcation. Three-vessel OCT imaging showed that TCFAs tend to cluster in predictable spots within the proximal segment of the LAD, but develop relatively evenly in the LCx and RCA arteries.

Abstract 5337: Morphological Characteristics of the Culprit Lesion Correlate With the Angiographic Flow Grade Following Thrombolysis in Myocardial Infarction. An Optical Coherence Tomography Study

Background: Intravenous thrombolysis fails to restore blood flow in a significant percentage of patients with ST-elevation myocardial infarction (STEMI). It remains unknown, whether certain morphological characteristics of the culprit lesion (CL) can predict the success of thrombolysis. We hypothesized that the thickness of the fibrous cap and the incidence of plaque rupture at the CL, as measured by Optical Coherence Tomography (OCT), may correlate with the outcome of thrombolysis. Methods: We prospectively enrolled 55 consecutive patients with STEMI that were treated with thrombolysis 6 hours from symptom onset. All patients underwent coronary angiography within 24 hours from thrombolysis. We estimated TIMI flow grade and the corrected TIMI frame count (CTFC) for patients with TIMI flow II or III. In target vessels with TIMI flow grade ≤1 aspiration thrombectomy was performed. We then acquired OCT images from the CL. We measured the fibrous cap thickness (FCT) at the thinnest part overlying a lipid pool, the lipid content (in quadrants) and the incidence of plaque rupture, which was defined as the presence of fibrous-cap discontinuity. Results: Of the total study population, 15 patients had TIMI flow 0 or I, 15 had TIMI flow II, and 25 had TIMI flow III. The number of lipid quadrants was greater in patients with TIMI flow 0-I than in patients with TIMI flow II and III (median 4, (range 1) vs. median 3 (range 2) vs. median 2 (range 1), p&lt;0.001). The culprit lesion of the patients with TIMI flow 0 or I was more often characterized by a ruptured plaque compared to those with TIMI flow II and III (n=13 (86.67%) for TIMI 0–1, n=8 (53.33%) for TIMI II and n=6 (24%) for TIMI III, p&lt;0.001). For patients with TIMI 0 and I, minimum FCT was 41±7 μ m, for patients with TIMI II 55±23 μ m and for those with TIMI III 87±26 μ m (p&lt;0.001). In patients with TIMI flow II or III, a correlation was found between CTFC and the minimal cap thickness (r=−0.423, p=0.006). Conclusion: In patients with STEMI, TIMI flow III following thrombolysis is associated with greater fibrous cap thickness, reduced lipid content and reduced incidence of plaque rupture in the CL. This study suggests that specific morphological features of the CL correlate with the flow grade following thrombolytic therapy in patients with STEMI.