Plaque Cross-sectional Area Research Articles

Beneficial effects of flavonoids on animal models of atherosclerosis: A systematic review and meta-analysis

Atherosclerosis is the main cause of cardiovascular diseases that seriously endanger human health. The existing treatment drugs are effective, but they have some side effects. Accumulating evidence suggests that flavonoids have attracted wide attention due to their multiple cardioprotective effects and fewer side effects. PubMed, Web of Science database, Embase, and Cochrane Library were searched for studies evaluating the effects of flavonoids against atherosclerosis. 119 studies published from August 1954 to April 2023 were included. Random-effects models were performed for synthesis. Compared with the control group, flavonoids significantly reduced longitudinal and cross-sectional plaque area. The findings indicated that flavonoids significantly reduced the concentrations of serum TC, TG, and LDL-C and increased serum HDL-C concentrations. Besides, flavonoids reduced the levels of circulating pro-inflammatory factors, including TNF-α, IL-1β, and IL-6, and increased the serum IL-10 level. This study provides evidence for the potential cardiovascular benefits of flavonoids.

Tanshinone IIA Alleviates Atherosclerosis Through Inhibition of NF-κB and PPARα/ABCA1 Signaling Pathways

This study evaluated the role and underlying mechanisms of Tanshinone IIA (Tan IIA) in atherosclerosis. C57BL mice (control group) and ApoE mice (model group) were administered a conventional and high-fat diet for 20 weeks. The Tan IIA group was obtained by administering a high-fat diet plus 8 weeks of Tan IIA to other mice for 20 weeks, followed by oil red O staining and lipid examination. RAW264.7 cells were transfected with PPARα siRNA+Tan IIA to measure their expression. The results showed little change in body weight between the three groups (P < 0.05). Liver index was significantly increased in the model and Tan IIA groups (P <0.05). Atherosclerotic plaques, plaque cross-sectional area, human oxidized low-density lipoprotein (ox-LDL), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels, p-NF-κB, p-IKKα, P-Ikkα/β, TNF-α and IL-1β levels were significantly increased in the model group and decreased in the Tan IIA group (P < 0.05). We also noted a decrease in PPARα, PGC-1α and ABCA1 in the model group and an increase in the Tan IIA group. NF-κB expression was increased in the nucleus and decreased in the cytoplasm in the model group, which was reversed by Tan IIA treatment. Tan IIA significantly reduced ox-LDL, LDL-C and TG levels, plaque size and plaque cross-sectional area in atherosclerosis. Tan IIA effectively inhibited NF-κB, activated the PPARα/ABCA1 signalling pathway, and reduce inflammatory pathways, thereby improving lipid deposition and acting as an anti-atherosclerotic agent.

Association of Lipoprotein (a) With Coronary-Computed Tomography Angiography-Assessed High-Risk Coronary Disease Attributes and Cardiovascular Outcomes.

Lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular events. This study evaluated the relationship between Lp(a) and high-risk attributes by coronary computed tomography angiography as well as their prognostic value. Lp(a) and coronary computed tomography angiography from 377 consecutive patients at Zhongshan Hospital (Shanghai, China) were evaluated. High-risk attributes were defined as high-risk morphological attributes (low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimum lumen area <4 mm2, or plaque burden [ratio between cross-sectional plaque area at the site of maximum stenosis and cross-sectional vessel area] ≥70%); inflammatory attribute represented by fat attenuation index; high-risk physiological attributes [lesion-specific ischemia defined by fractional flow reserve by coronary computed tomography angiography ≤0.8, physiologic diffuseness defined by fractional flow reserve by coronary computed tomography angiography pullback pressure gradient]. Total plaque volume in mm3 was also quantified. Quintiles or binary classification of Lp(a) levels were used to evaluate its relationships with plaque features and clinical outcomes with ANOVA, Cox models, and log-rank tests, as appropriate. The major adverse cardiovascular event included cardiovascular death, nonfatal myocardial infarction, and target vessel revascularization. Lp(a) was significantly associated with total plaque volume (P=0.004), fat attenuation index (P=0.031), and fractional flow reserve by coronary computed tomography angiography pullback pressure gradient (P=0.038). Patients with a high Lp(a) level had a higher total plaque volume (393.3 mm3 versus 293.9 mm3, P<0.001), lower pullback pressure gradient (0.62 versus 0.69, P=0.023), higher fat attenuation index (-70.5HU versus -73.9HU, P=0.004), and higher incidence of major adverse cardiovascular event (14.5% versus 6.3%, adjusted hazard ratio: 2.52, 95% CI: 1.12-5.63, P=0.025). In a 4-group classification according to Lp(a) and high-risk attributes, patients with high Lp(a) and ≥3 high-risk attributes had the highest risk of major adverse cardiovascular event (25.9%; overall P<0.001). Causal mediation analysis revealed that around 40% of the prognostic effect of Lp(a) was mediated by high-risk attributes. Lp(a) level is associated with coronary computed tomography angiography high-risk characteristics, including morphologic, physiologic, and inflammatory attributes as well as major adverse cardiovascular event. This effect is partly mediated by inflammation and vulnerable plaque. URL: https://www. gov; Unique identifier: NCT05323227.

Quantitative plaque characterisation and association with acute coronary syndrome on medium to long term follow up: insights from computed tomography coronary angiography.

BackgroundComputed tomography coronary angiography (CTCA) is an established imaging modality widely used for diagnosing coronary artery stenosis with expanding potential for comprehensive assessment of coronary artery disease (CAD). Lesion-based analyses of high-risk plaques (HRP) on CTCA may aid further in prognostication presenting with stable chest pain. We conduct qualitative and quantitative assessments to identify HRPs that are associated with acute coronary syndrome (ACS) on a medium to long term follow-up.MethodsRetrospective cohort study of patients who underwent CTCA for suspected CAD. Obstructive stenosis (OS) is defined as ≥50% and the presence of HRP and its constituents: positive-remodelling (PR), low-attenuation-plaque (LAP; <56 HU), very-low-attenuation-plaque (vLAP; <30 HU) and spotty-calcification (SC) were recorded. A cross-sectional quantitative analysis of HRP was performed at the site of minimum-luminal-area (MLA). The primary endpoint was fatal or non-fatal ACS on follow-up.ResultsA total of 1,257 patients were included (mean age 61±14 years old and 51% male) with a median follow-up of 7.24 years (interquartile range 5.5 to 7.7 years). The occurrence of ACS was significantly higher in HRP (+) patients compared to HRP (−) patients and patients with no plaques (20.5% vs. 1.6% vs. 0.4%, log-rank test P<0.001). ACS was more frequent in HRP (+)/OS (+) patients (20.7%) compared to HRP (+)/OS (−) patients (8.6%), HRP (−)/OS (+) patients (1.8%) and HRP (−)/OS (−) patients (1.0%). OS, cross-sectional plaque area (PA) and the presence of vLAP identified those HRP lesions that were more likely to cause future ACS. Cross-sectional LAP area (<56 HU) in HRP lesions added incremental prognostic value to OS in predicting ACS (P=0.008).ConclusionsThe presence of OS and the LAP area at the site of MLA identify the HRP lesions that have the greatest association with development of future ACS.

Symptomatic vs. Asymptomatic 20-40% Internal Carotid Artery Stenosis: Does the Plaque Size Matter?

Background: Around 9–15% of ischemic strokes are related to internal carotid artery (ICA)-stenosis ≥50%. However, the extent to which ICA-stenosis <50% causes ischemic cerebrovascular events is uncertain. We examined the relation between plaque cross-sectional area and length and the risk of ischemic stroke or TIA among patients with ICA-stenosis of 20–40%.Methods: We retrospectively identified patients admitted to the Department of Neurology, University Hospital of Würzburg, from January 2011 until September 2016 with ischemic stroke or TIA and concomitant ICA-stenosis of 20–40%, either symptomatic or asymptomatic. Plaque length and cross-sectional area were assessed on ultrasound scans.Results: We identified 41 patients with ischemic stroke or TIA and ICA-stenosis of 20–40%; 14 symptomatic and 27 asymptomatic. The plaque cross-sectional area was significantly larger among symptomatic than asymptomatic ICA-stenosis; median values (IQR) were 0.45 (0.21–0.69) cm2 and 0.27 (0.21–0.38) cm2, p = 0.03, respectively. A plaque cross-sectional area ≥0.36 cm2 had a sensitivity of 71% and a specificity of 76% for symptomatic compared with asymptomatic ICA-stenosis. In a sex-adjusted multivariate logistic regression, a plaque cross-sectional area ≥0.36 cm2 and a plaque length ≥1.65 cm were associated with an OR (95% CI) of 5.54 (1.2–25.6), p = 0.028 and 1.78 (0.36–8.73), p = 0.48, respectively, for symptomatic ICA-stenosis.Conclusion: Large plaques might increase the risk of ischemic stroke or TIA among patients with low-grade ICA-stenosis of 20–40%. Sufficiently powered prospective longitudinal cohort studies are needed to definitively test the stroke risk stratification value of carotid plaque length and cross-sectional area in the setting of current optimal medical treatment.

Neprilysin Inhibitor\u2013Angiotensin II Receptor Blocker Combination Therapy (Sacubitril/valsartan) Suppresses Atherosclerotic Plaque Formation and Inhibits Inflammation in Apolipoprotein E- Deficient Mice

We assessed the effects of the sacubitril/valsartan combination drug (LCZ696), in comparison to valsartan alone, on the progression of atherosclerotic plaque formation and inflammatory gene expression in apolipoprotein E- deficient mice (apoE−/− mice). Seventy-two apoE−/− mice were fed a western diet and a constrictive silastic tube was used to elicit carotid lesion formation. The animals were separated into a control group, a valsartan group or an LCZ696 group (n = 24 in each group). Plaques in the carotid artery were harvested 12 weeks later for histological examination. The levels of pro-inflammatory genes in the plasma and lesions were detected using real-time PCR and ELISA. Valsartan or LCZ696 treatment remarkably inhibited the expression of pro-inflammatory genes, including interleukin-6, matrix metalloproteinase-8 and monocyte chemotactic protein-1, in comparison with the control group. Meanwhile, both valsartan and LCZ696 suppressed the formation of atherosclerotic plaques by decreasing plaque lipid content and cross-sectional plaque area and increasing the content of plaque collagen and fibrous cap thickness. In particular, LCZ696 performed the best in suppressing atherosclerosis and inhibiting the level of pro-inflammatory genes. LCZ696 significantly ameliorated atherosclerosis and inflammation in apoE−/− mice compared with valsartan.

Effects of Combination of Ezetimibe and Rosuvastatin on Coronary Artery Plaque in Patients with Coronary Heart Disease

In approximately 80% of cardiovascular disease-related deaths, patients suffer from coronary atherosclerotic heart disease. Ezetimibe is the first intestinal cholesterol absorption inhibitor. Its combination with statins for treating coronary atherosclerotic heart disease has attracted attention worldwide. The study group comprised 106 patients with coronary atherosclerotic heart disease and hyperlipidaemia. Each was randomly assigned to one of two groups: (1) Ezetimibe (10mg, once a night) plus rosuvastatin (10mg, once a night) (n=55) or (2) Rosuvastatin alone (10mg, once a night) (n=51). The primary endpoint was new or recurrent myocardial infarction, unstable angina pectoris, cardiac death, and stroke. Blood lipid, high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and matrix metalloproteinase-9 (MMP-9) levels were measured before treatment and at one, six and 12 months after treatment. Coronary plaque size and compositional changes were determined using intravascular ultrasonography. The combination of ezetimibe plus rosuvastatin decreased total cholesterol, low-density lipoprotein cholesterol, hsCRP, IL-6, and MMP-9 levels at six and 12 months after treatment. Statistical significance was detected between two groups. At 12 months, the plaque burden, plaque cross-sectional area, and percentage of necrotic plaque composition were significantly lower in the combination group than in rosuvastatin alone group (P<0.05). And compared with rosuvastatin alone group, the primary endpoint decreased more effectively in combination group. The combination of ezetimibe and rosuvastatin apparently diminishes lipid levels and plaque burden and improves plaque stability, which may be associated with the potent inhibitory effects of ezetimibe and rosuvastatin on inflammatory cytokines.

Impact of Remnant Lipoprotein on Coronary Plaque Components.

Intravascular ultrasound (IVUS) is a useful modality for visualizing atherosclerotic lesions in coronary arteries, not only for the degree of arterial luminal stenosis but also for the plaque composition within the vessel walls. We aimed to determine the relationship between the clinical parameters and coronary plaque characteristics evaluated by IVUS in patients with stable angina under medical treatment. Plaque measurements within the coronary arteries were collected by coronary angiography and iMAP-IVUS in 40 men with stable angina. The serum remnant-like cholesterol (RemL-C) was measured using homogeneous assays and serum adiponectin and omentin-1 levels were measured by enzyme-linked immunosorbent assays. The iMAP-IVUS analysis of the coronary arteries demonstrated that the plaque cross-sectional area (CSA) was 11.0±3.5 mm(2). Plaque CSA positively correlated with body mass index and negatively correlated with the serum adiponectin levels. Both areal and volumetric analyses of the plaque characteristics demonstrated that the serum RemL-C level was a positive determinant for %Necrosis and the negative determinant for %Fibrosis of the plaques. Neither serum high-density lipoprotein cholesterol nor low-density lipoprotein cholesterol levels correlated with the proportion of any plaque components. Additionally, the RemL-C/triglyceride ratio positively correlated with %Lipid significantly in the areal analysis. Elevation of the serum RemL-C levels in the patients with stable angina may link to coronary plaque vulnerability, which is characterized by high necrotic and low fibrotic components.

Clinical validation of a novel software for quantitative analysis of coronary intravascular ultrasound.

CAAS IntraVascular (CAAS-IV) is a recently released software that provides options for sophisticated quantitative coronary ultrasound (QCU) analysis. The aim of this study was to validate CAAS-IV for QCU in diseased human coronaries. Ten preprocedural and 5 postprocedural IVUS studies were derived from daily practice. Intraobserver, interobserver, intersoftware (CAAS-IV vs. Curad) and interplatform (CAAS-IV vs. Volcano console) variability were assessed for cross-sectional area (CSA) measurements. Interobserver and intersoftware comparisons were made for volume measurements. Measurements of lumen, EEM, plaque and stent CSA demonstrated small differences in the intraobserver (0.0±3.7%, -0.7±2.8%, -0.5±7.0% and -0.9±3.4%), interobserver (0.1±4.4%, 0.1±3.4%, -0.5±8.2% and -0.8±4.3%), intersoftware (-0.3±4.5%, 0.2±2.4%, 0.4±6.8% and -0.5±3.2%) and interplatform (0.7±7.9%, 0.9±4.0%, -1.1±12%, -1.8±3.6%) comparisons. For lumen, EEM, plaque and stent volume, the interobserver (-2.1±9.3%, 0.9±5.6%, 3.4±7.2% and -0.2±3.6%) and intersoftware (-2.2±6.2%, -2.6±6.1%, -2.7±12% and -4.1±3.2%) differences were substantially larger. Excluding large side-branches and calcifications, post-hoc measurements of lumen, EEM, plaque and stent volume showed small differences in the interobserver (-0.3±3.2%, 0.9±2.4%, 2.9±4.4% and -1.3±1.8%) and intersoftware (0.5±2.5%, -1.2±1.7%, -3.4±5.1% and -1.5±2.2%) comparisons. Analysis time for entire pullbacks was reduced by 19.2 [14.9-30.0]% using CAAS-IV (p<0.01). CAAS-IV demonstrated reliable QCU with excellent agreement with previously validated software and the IVUS imaging console. Precision and reproducibility of measurements were high, proving CAAS-IV to be a valid option for QCU analysis in clinical practice and research. Interactive contour editing reduced analysis time by 20%.

Compensatory enlargement of the left main coronary artery

Glagov proposed that remodeling delayed development of significant coronary artery stenoses until plaque occupied, on average, 40% of arterial area (40% plaque burden). The aim of the current study was to confirm the previously proposed concept of coronary remodeling as first described by Glagov who studied postmortem left main coronary arteries (LMCAs). Using the in-vivo intravascular ultrasound data from the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, we evaluated 552 LMCAs in 552 patients. External elastic membrane cross-sectional areas (CSAs) increased in proportion to the increase in plaque and media CSAs (r=0.61, P<0.0001), especially when the plaque burden was 20% or lower (r=0.88, P<0.0001). For more advanced atherosclerosis (>40% plaque burden), there was an inverse relationship between lumen CSA and plaque burden (r=-0.57, P<0.0001), whereas this relationship was weak in the presence of less than 40% plaque burden. The frequency of virtual histology derived thin-cap fibroatheroma increased with increasing plaque burden. In contrast, the frequency of pathological intimal thickening decreased. The previously proposed remodeling concept of Glagov was validated in vivo in the PROSPECT study patients. In addition, the present study suggested that plaque phenotype worsened with increasing LMCA plaque growth.

Thalidomide influences atherogenesis in aortas of ApoE−/−/LDLR−/− double knockout mice: a nano-CT study

Plaque progression in atherosclerosis is closely connected to angiogenesis due to vasa vasorum (VV) growth. Objective of this study was to determine the unknown long-term effect of thalidomide on adventitial VV neovascularization and plaque progression using nano-focussed computed tomography (nano-CT). Proliferation and migration assays in human coronary artery endothelial cells (HCAEC) measured number of viable cells after incubation with thalidomide. Male ApoE−/−/LDLR−/− (AL) mice (n = 5) received a thalidomide containing western diet (WD) over 29 weeks. Another five male AL mice (WD without thalidomide) served as control group. Descending aortas were scanned with nano-CT at (1.5 μm)3 isotropic voxel size. Number and area of adventitial VV as well as plaque cross sectional area were measured. Results were complemented by histology. Thalidomide inhibited proliferation and migration of HCAEC dose-dependently. VV neovascularization decreased in number per cross section (7.66 ± 0.301 vs. 8.62 ± 0.164, p < 0.001) and in cross sectional area (0.0183 ± 0.0011 vs. 0.0238 ± 0.0008 mm2, p < 0.001). Cross sectional area of plaque decreased significantly when treated with thalidomide (0.57 ± 0.0187 vs. 0.803 ± 0.0148 mm2, p < 0.001). Nano-CT imaging revealed a reduced plaque growth and VV neovascularization after long-term application of thalidomide. Therefore, nano-CT can be considered as a new method to detect therapeutic effects in experimental models of atherosclerosis.

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.

Comparative analysis of lumen enlargement mechanisms achieved with the bifurcation dedicated BiOSS® stent versus classical coronary stent implantations by means of provisional side branch stenting strategy: an intravascular ultrasound study

The aim of this study was to analyze the mechanisms of lumen enlargement in bifurcation lesions, as assessed by intravascular ultrasound (IVUS), after percutaneous treatment with classic provisional “T” stenting with conventional drug-eluting stents (DES) versus bifurcation dedicated BiOSS® (Balton, Warsaw, Poland) stent. In this prospective study between Jan and Dec/11, 32 patients with single de novo coronary bifurcation lesions suitable for treatment with BiOSS stents were randomized (1:1). IVUS method included pre- and post-procedure analysis in the parent vessel. Vessel, lumen and plaque cross-sectional areas were determined at the target lesion [minimum lumen area (MLA) site], proximal limb, distal limb, and “window”—defined as the segment between the carina (flow divider) and the vessel wall at the level of the side branch inflow. All lesions were treated with provisional approach and only 1 case in BiOSS group had a stent implanted in the side branch. Angiographic and IVUS results including MLA at the target site and proximal/distal references were similar. However, mean window length—largest diameter within the window, was similar at baseline, but BiOSS measured significantly longer at postprocedure (2.21 ± 0.37 vs. 1.76 ± 0.52 mm, p = 0.01). In addition, the magnitude of changes in vessel (27 ± 24 % vs. 9 ± 10 %, p = 0.01) and plaque (2 ± 26 % vs. −2 ± 26 %, p = 0.02) areas at the window were significantly different for DES versus BiOSS groups, respectively. The contribution of vessel extension for lumen enlargement represented 54 versus 43 %, 130 versus 46 %, 98 versus 80 % and 51 versus 19 % of the result achieved at the proximal limb, window, distal limb and MLA sites for DES versus BiOSS, respectively; as for plaque re-distribution, results were 36 versus 57 %, −30 versus 54 %, 2 versus 20 %, and 49 versus 81 %, at the proximal limb, window, distal limb and MLA sites, respectively. These results suggest different mechanisms of lumen enlargement comparing conventional DES versus BiOSS dedicated bifurcation stent, which can impact side branch compromise during procedure.

Comparison of quantitative measurements between two different intravascular ultrasound systems: In vitro and in vivo studies

BackgroundAlthough intravascular ultrasound (IVUS) allows for precise measurements of coronary artery dimension, variability in quantitative measurements among currently available different IVUS systems is unknown. The aim of study was to compare two different IVUS catheters and consoles to verify their accuracy and compatibility. Methods(1) In vitro study: IVUS imaging was performed in a concentric cylindrical phantom with 6 sections of known, cross-sectional diameter ranging from 3.0 to 8.0mm. The minimum lumen diameter (MLD) and lumen cross sectional area (CSA) were measured and compared. (2) In vivo study: IVUS imaging was performed in 69 coronary arterial segments from 20 patients. The external elastic membrane cross sectional area (EEM-CSA), lumen CSA, and plaque plus media (P+M) CSA were measured and compared between the two IVUS systems. Results(1) In vitro study: MLD and lumen CSA obtained by the two IVUS systems correlated well with the actual values. (2) In vivo study: EEM-, lumen and P+M CSA obtained by the two IVUS systems showed good correlations (R2=0.973, p<0.0001; R2=0.938, p<0.0001; R2=0.949, p<0.0001, respectively). ConclusionsQuantitative measurements by 2 different, currently available IVUS systems were accurate and comparable. These results suggest that the 2 different IVUS catheters/systems may be alternatively used during clinical studies assessing coronary arterial size.

Variability and accuracy of coronary CT angiography including use of iterative reconstruction algorithms for plaque burden assessment as compared with intravascular ultrasound—an ex vivo study

To systematically assess inter-technique and inter-/intra-reader variability of coronary CT angiography (CTA) to measure plaque burden compared with intravascular ultrasound (IVUS) and to determine whether iterative reconstruction algorithms affect variability. IVUS and CTA data were acquired from nine human coronary arteries ex vivo. CT images were reconstructed using filtered back projection (FBPR) and iterative reconstruction algorithms: adaptive-statistical (ASIR) and model-based (MBIR). After co-registration of 284 cross-sections between IVUS and CTA, two readers manually delineated the cross-sectional plaque area in all images presented in random order. Average plaque burden by IVUS was 63.7 ± 10.7% and correlated significantly with all CTA measurements (r = 0.45-0.52; P < 0.001), while CTA overestimated the burden by 10 ± 10%. There were no significant differences among FBPR, ASIR and MBIR (P > 0.05). Increased overestimation was associated with smaller plaques, eccentricity and calcification (P < 0.001). Reproducibility of plaque burden by CTA and IVUS datasets was excellent with a low mean intra-/inter-reader variability of <1/<4% for CTA and <0.5/<1% for IVUS respectively (P < 0.05) with no significant difference between CT reconstruction algorithms (P > 0.05). In ex vivo coronary arteries, plaque burden by coronary CTA had extremely low inter-/intra-reader variability and correlated significantly with IVUS measurements. Accuracy as well as reader reliability were independent of CT image reconstruction algorithm. • IVUS is deemed the gold standard in-vivo coronary plaque assessment • But coronary CT angiography findings correlate strongly with IVUS results • Coronary CT angiography now allows plaque quantification close to IVUS • Iterative image reconstruction algorithms do not alter accuracy or reproducibility • Plaque quantification is more challenging in smaller eccentric calcified lesions.

The quantification of vitamin D receptors in coronary arteries and their association with atherosclerosis

ObjectiveThe activated vitamin D receptor (VDR) may have an important role in vascular health. The objective of this study was to determine whether there is an association between the expression of VDRs in coronary arteries and the extent of diet-induced atherosclerosis. MethodsUtilizing a cohort of 39 postmenopausal female cynomolgus monkeys with varying stages of atherosclerosis, histologic sections of the left anterior descending artery (LAD) were analyzed for plaque cross-sectional area, plaque thickness, and VDR quantity using immunohistochemical H-score analysis. The quantities of VDRs were analyzed as a continuous variable and were divided at the median intimal H-score into high vs. low groupings. ResultsIn the LAD, a significant negative correlation was observed between the quantity of VDR and plaque size (both cross-sectional area [p<0.001] and plaque thickness [p<0.001]). Monkeys in the low VDR group had a significantly greater cross-sectional plaque area (1.2mm2) and greater plaque thickness (0.3mm) than those in the high VDR group (0.4mm2, p=0.005; 0.1mm, p=0.003, respectively). ConclusionsLower concentrations of VDRs in a main coronary artery were associated with greater atherosclerotic plaque size in postmenopausal female monkeys. Given that coronary artery atherosclerosis is a major cause of coronary heart disease in postmenopausal women, further research to ascertain the relationship between VDRs and atherosclerosis is warranted.

Hyperinsulinemia Does Not Change Atherosclerosis Development in Apolipoprotein E Null Mice

To determine the contribution of hyperinsulinemia to atherosclerosis development. Apolipoprotein E (Apoe) null mice that had knockout of a single allele of the insulin receptor (Insr) gene were compared with littermate Apoe null mice with intact insulin receptors. Plasma insulin levels in Insr haploinsufficient/Apoe null mice were 50% higher in the fasting state and up to 69% higher during a glucose tolerance test, but glucose tolerance was not different in the 2 groups. C-peptide levels, insulin sensitivity, and postreceptor insulin signaling in muscle, liver, fat, and aorta were not different between groups, whereas disappearance in plasma of an injected insulin analog was delayed in Insr haploinsufficient/Apoe null mice, indicating that impaired insulin clearance was the primary cause of hyperinsulinemia. No differences were observed in plasma lipids or blood pressure. Despite the hyperinsulinemia, atherosclerotic lesion size was not different between the 2 groups at time points up to 52 weeks of age when measured as en face lesion area in the aorta, cross-sectional plaque area in the aortic sinus, and cholesterol abundance in the brachiocephalic artery. Hyperinsulinemia, without substantial vascular or whole-body insulin resistance and without changes in plasma lipids or blood pressure, does not change susceptibility to atherosclerosis.

Plaque Characteristics of Thin-Cap Fibroatheroma Evaluated by OCT and IVUS

The purpose of this study was to assess plaque characteristics of optical coherence tomography (OCT)-derived thin-cap fibroatheroma (TCFA) by integrated backscatter intravascular ultrasound (IB-IVUS). Radiofrequency signal-derived IVUS tissue characterization technology has become clinically available and provided objective and quantitative plaque characteristics of the coronary vessel wall. Integrated backscatter IVUS is one of the tissue characterization methods that can possibly provide quantitative plaque characteristics of the OCT-derived TCFA. Eighty-one coronary lesions with plaque burden >40% were selected and analyzed with both IB-IVUS and OCT. The OCT-derived TCFA was defined as a presence of thin fibrous cap (<65 μm) overlying a signal-poor lesion with diffuse border representing a lipid-rich plaque. By conventional gray-scale IVUS, external elastic membrane (EEM) cross-sectional area (CSA), lumen CSA, plaque plus media (P+M) CSA, plaque burden and remodeling index were measured. By IB-IVUS, plaque characteristics were further classified as fibrosis, dense fibrosis, calcification, or lipid pool. Optical coherence tomography identified 40 TCFAs (49%) and 41 non-TCFAs. The EEM CSA, P+M CSA, plaque burden, and remodeling index were significantly larger in OCT-derived TCFA than non-TCFA. By IB-IVUS, percentage lipid pool area (= lipid pool area/P+M CSA × 100) was significantly higher (62.4 ± 12.8% vs. 38.4 ± 13.1%, p<0.0001) and percentage fibrosis area (= fibrosis area/P+M CSA × 100) was significantly lower (34.6 ± 11.4% vs. 50.5 ± 8.7%, p<0.0001) in OCT-derived TCFA than non-TCFA. By receiver-operator characteristic curve analysis, percentage lipid pool area ≥55%, percentage fibrosis area ≤41%, and remodeling index ≥1.0 were predictors of OCT-derived TCFA. The OCT-derived TCFA had larger plaque burden and positive remodeling with predominant lipid component and less fibrous plaque assessed by IB-IVUS.

Assessment of coronary stenosis, plaque burden and remodeling by multidetector computed tomography in patients referred for suspected coronary artery disease

To compare multidetector computed tomography (MDCT) with intravascular ultrasound (IVUS) and invasive quantitative coronary angiography (QCA) for assessment of coronary lesions in patients referred for suspected coronary artery disease (CAD). We studied 57 patients (48 men; mean age: 63 ± 10 years) who underwent 64-slice MDCT because of atypical chest pain, stable angina, or ECG abnormalities and were diagnosed with CAD. All patients subsequently underwent QCA and IVUS. We analyzed 102 coronary lesions using the three techniques. Measurements of luminal area stenosis and cross-sectional area by MDCT (72.9 ± 7.0% and 4.5 ± 1.8 mm, respectively) were in good agreement with those by IVUS [72.7 ± 6.7% and 4.5 ± 1.6 mm, respectively; Lin's concordance correlation coefficient r = 0.847; 95% confidence interval (CI) = 0.792-0.902 and r = 0.931; 95% CI = 0.906-0.956, respectively] but not QCA (r = 0.115; 95% CI = 0.040-0.189 and r = 0.433; 95% CI = 0.291-0.576, respectively). Plaque cross-sectional area and plaque volume measured by MDCT (12.4 ± 3.8 mm and 104.7 ± 52.8 microl, respectively) were in good agreement with those by IVUS (12.2 ± 3.7 mm and 102.8 ± 54.1 microl; r = 0.913; 95% CI = 0.880-0.945 and r = 0.979; 95% CI = 0.969-0.990, respectively). Remodeling index measurements by MDCT (1.22 ± 0.22) were in good agreement with those by IVUS (r = 0.876; 95% CI = 0.831-0.922). Positive remodeling occurred in 63% of stenoses. MDCT allows accurate noninvasive assessment of coronary stenosis, plaque burden and remodeling in patients referred for suspected CAD. Positive remodeling is a frequent finding in stable lesions.

A Selective Matrix Metalloproteinase-12 Inhibitor Retards Atherosclerotic Plaque Development in Apolipoprotein E–Knockout Mice

Matrix metalloproteinase (MMP)-12 has been implicated in plaque progression and instability and is also amenable to selective inhibition. In this study, we investigated the influence of a greater than 10-fold selective synthetic MMP-12 inhibitor on plaque progression in the apolipoprotein E knockout mouse model of atherosclerosis. A phosphinic peptide (RXP470.1) that is a potent, selective murine MMP-12 inhibitor significantly reduced atherosclerotic plaque cross-sectional area by approximately 50% at 4 different vascular sites in male and female apolipoprotein E knockout mice fed a Western diet. Furthermore, RXP470.1 treatment resulted in less complex plaques with increased smooth muscle cell:macrophage ratio, less macrophage apoptosis, increased cap thickness, smaller necrotic cores, and decreased incidence of calcification. Additional in vitro and in vivo findings indicate that attenuated monocyte/macrophage invasion and reduced macrophage apoptosis probably underlie the beneficial effects observed on atherosclerotic plaque progression with MMP-12 inhibitor treatment. Our data demonstrate that a selective MMP-12 inhibitor retards atherosclerosis development and results in a more fibrous plaque phenotype in mice. Our study provides proof of principle to motivate translational work on MMP-12 inhibitor therapy in humans.