Atherosclerotic Plaque Phenotype Research Articles

Association of Circulating Autophagy Proteins ATG5 and Beclin 1 with Acute Myocardial Infarction in a Case-Control Study

Introduction: Acute myocardial infarction (AMI) is a main contributor of sudden cardiac death worldwide. The discovery of new biomarkers that can improve AMI risk prediction meets a major clinical need for the identification of high-risk patients and the tailoring of medical treatment. Previously, we reported that autophagy a highly conserved catabolic mechanism for intracellular degradation of cellular components is involved in atherosclerotic plaque phenotype and cardiac pathological remodeling. The crucial role of autophagy in the normal and diseased heart has been well described, and its activation functions as a pro-survival process in response to myocardial ischemia. However, autophagy is dysregulated in ischemia/reperfusion injury, thus promoting necrotic or apoptotic cardiac cell death. Very few studies have focused on the plasma levels of autophagy markers in cardiovascular disease patients, even though they could be companion biomarkers of AMI injury. The aims of the present study were to evaluate (1) whether variations in plasma levels of two key autophagy regulators autophagy-related gene 5 (ATG5) and Beclin 1 (the mammalian yeast ortholog Atg6/Vps30) are associated with AMI and (2) their potential for predicting AMI risk. Methods: The case-control study population included AMI patients (n = 100) and control subjects (n = 99) at high cardiovascular risk but without known coronary disease. Plasma levels of ATG5 and Beclin 1 were measured in the whole population study by enzyme-linked immunosorbent assay. Results: Multivariate analyses adjusted on common cardiovascular factors and medical treatments, and receiver operating characteristic curves demonstrated that ATG5 and Beclin 1 levels were inversely associated with AMI and provided original biomarkers for AMI risk prediction. Conclusion: Plasma levels of autophagy regulators ATG5 and Beclin 1 represent relevant candidate biomarkers associated with AMI.

Differential Proteoglycan Expression in Atherosclerosis Alters Platelet Adhesion and Activation.

Proteoglycans are differentially expressed in different atherosclerotic plaque phenotypes, with biglycan and decorin characteristic of ruptured plaques and versican and hyaluronan more prominent in eroded plaques. Following plaque disruption, the exposure of extracellular matrix (ECM) proteins triggers platelet adhesion and thrombus formation. In this study, the impact of differential plaque composition on platelet function and thrombus formation was investigated. Platelet adhesion, activation and thrombus formation under different shear stress conditions were assessed in response to individual proteoglycans and composites representing different plaque phenotypes. The results demonstrated that all the proteoglycans tested mediated platelet adhesion but not platelet activation, and the extent of adhesion observed was significantly lower than that observed with type I and type III collagens. Thrombus formation upon the rupture and erosion ECM composites was significantly reduced (p < 0.05) compared to relevant collagen alone, indicating that proteoglycans negatively regulate platelet collagen responses. This was supported by results demonstrating that the addition of soluble biglycan or decorin to whole blood markedly reduced thrombus formation on type I collagen (p < 0.05). Interestingly, thrombus formation upon the erosion composite displayed aspirin sensitivity, whereas the rupture composite was intensive to aspirin, having implications for current antiplatelet therapy regimes. In conclusion, differential platelet responses and antiplatelet efficacy are observed on ECM composites phenotypic of plaque rupture and erosion. Proteoglycans inhibit thrombus formation and may offer a novel plaque-specific approach to limit arterial thrombosis.

Influence of intracoronary hemodynamic forces on atherosclerotic plaque phenotypes

Background and aimsCoronary hemodynamics impact coronary plaque progression and destabilization. The aim of the present study was to establish the association between focal vs. diffuse intracoronary pressure gradients and wall shear stress (WSS) patterns with atherosclerotic plaque composition. MethodsProspective, international, single-arm study of patients with chronic coronary syndromes and hemodynamic significant lesions (fractional flow reserve [FFR] ≤ 0.80). Motorized FFR pullback pressure gradient (PPG), optical coherence tomography (OCT), and time-average WSS (TAWSS) and topological shear variation index (TSVI) derived from three-dimensional angiography were obtained. ResultsOne hundred five vessels (median FFR 0.70 [Interquartile range (IQR) 0.56–0.77]) had combined PPG and WSS analyses. TSVI was correlated with PPG (r = 0.47, [95% Confidence Interval (95% CI) 0.30–0.65], p < 0.001). Vessels with a focal CAD (PPG above the median value of 0.67) had significantly higher TAWSS (14.8 [IQR 8.6–24.3] vs. 7.03 [4.8–11.7] Pa, p < 0.001) and TSVI (163.9 [117.6–249.2] vs. 76.8 [23.1–140.9] m−1, p < 0.001). In the 51 vessels with baseline OCT, TSVI was associated with plaque rupture (OR 1.01 [1.00–1.02], p = 0.024), PPG with the extension of lipids (OR 7.78 [6.19–9.77], p = 0.003), with the presence of thin-cap fibroatheroma (OR 2.85 [1.11–7.83], p = 0.024) and plaque rupture (OR 4.94 [1.82 to 13.47], p = 0.002). ConclusionsFocal and diffuse coronary artery disease, defined using coronary physiology, are associated with differential WSS profiles. Pullback pressure gradients and WSS profiles are associated with atherosclerotic plaque phenotypes. Focal disease (as identified by high PPG) and high TSVI are associated with high-risk plaque features. Clinical trial registrationhttps://clinicaltrials,gov/ct2/show/NCT03782688

Influence of LGALS3 Gene Polymorphism as A Potential Predictor for Cardiopathy Complication of Type 2 Diabetes Mellitus

Galectin-3(Gal-3) belongs to lectins family binding β-galactoside that have at least one of the carbohydrate recognition domains (CRDs) in their own structure, which located on chromosome 14 (14q22.3).Gal-3Plays an important role in modulating cardiac inflammation and fibrosis. Therefore, LGALS3 gene, encoding galectin-3 protein, which considered promising candidate for the genetic study of cardiovascular diseases (CVDs),and evaluating the association between LGALS3 gene polymorphisms and the susceptibility and prognosis of myocardial infarction(MI) .Gal-is a pleiotropic molecule expressed on the cell membrane, within the cytoplasm or the nucleus. It has been proposed to function as a mediator of inflammation, fibrosis, cell adhesion, apoptosis, and chemotaxis. It is highly expressed in macrophages within and atherosclerotic plaques.galectin-3 can mediate production of profibrotic factors and collagen accumulation in a variety of diseases. The role of galectIn-3 in regulating macrophage invasion and consequent modulation of atherosclerotic plaque phenotype. Finally, the current study concluded that the amount of LGALS-3 gene expression is related to rs4652 SNP variant in patients with MI due toT2D complications.

Coronary Atherosclerosis Phenotypes in Focal and Diffuse Disease

BackgroundThe interplay between coronary hemodynamics and plaque characteristics remains poorly understood. ObjectivesThe aim of this study was to compare atherosclerotic plaque phenotypes between focal and diffuse coronary artery disease (CAD) defined by coronary hemodynamics. MethodsThis multicenter, prospective, single-arm study was conducted in 5 countries. Patients with functionally significant lesions based on an invasive fractional flow reserve ≤0.80 were included. Plaque analysis was performed by using coronary computed tomography angiography and optical coherence tomography. CAD patterns were assessed using motorized fractional flow reserve pullbacks and quantified by pullback pressure gradient (PPG). Focal and diffuse CAD was defined according to the median PPG value. ResultsA total of 117 patients (120 vessels) were included. The median PPG was 0.66 (IQR: 0.54-0.75). According to coronary computed tomography angiography analysis, plaque burden was higher in patients with focal CAD (87% ± 8% focal vs 82% ± 10% diffuse; P = 0.003). Calcifications were significantly more prevalent in patients with diffuse CAD (Agatston score per vessel: 51 [IQR: 11-204] focal vs 158 [IQR: 52-341] diffuse; P = 0.024). According to optical coherence tomography analysis, patients with focal CAD had a significantly higher prevalence of circumferential lipid-rich plaque (37% focal vs 4% diffuse; P = 0.001) and thin-cap fibroatheroma (TCFA) (47% focal vs 10% diffuse; P = 0.002). Focal disease defined by PPG predicted the presence of TCFA with an area under the curve of 0.73 (95% CI: 0.58-0.87). ConclusionsAtherosclerotic plaque phenotypes associate with intracoronary hemodynamics. Focal CAD had a higher plaque burden and was predominantly lipid-rich with a high prevalence of TCFA, whereas calcifications were more prevalent in diffuse CAD. (Precise Percutaneous Coronary Intervention Plan [P3]; NCT03782688)

Effects of intensive lipid lowering compared with moderate-intensity lipid lowering on coronary atherosclerotic plaque phenotype and major adverse cardiovascular events in adults with low to intermediate 10-year ASCVD risk (ILLUMINATION study): protocol for a multicentre, open-label, blinded-endpoint, randomised controlled trial

IntroductionCurrent guidelines recommend moderate-intensity lipid lowering (low-density lipoprotein cholesterol, LDL-C of <2.6 mmol/L or 30%–49% reduction from the baseline) for patients with intermediate 10-year atherosclerotic cardiovascular disease (ASCVD) risk. The...

Peroxisome proliferator-activated receptor δ improves the features of atherosclerotic plaque vulnerability by regulating smooth muscle cell phenotypic switching.

Vascular smooth muscle cells (SMCs) undergo phenotypic switching during sustained inflammation, contributing to an unfavourable atherosclerotic plaque phenotype. PPARδ plays an important role in regulating SMC functions; however, its role in atherosclerotic plaque vulnerability remains unclear. Here, we explored the pathological roles of PPARδ in atherosclerotic plaque vulnerability in severe atherosclerosis and elucidated the underlying mechanisms. Plasma levels of PPARδ were measured in patients with acute coronary syndrome (ACS) and stable angina (SA). SMC contractile and synthetic phenotypic markers, endoplasmic reticulum (ER) stress, and features of atherosclerotic plaque vulnerability were analysed for the brachiocephalic artery of apolipoprotein E-knockout (ApoE-/- ) mice, fed a high-cholesterol diet (HCD) and treated with or without the PPARδ agonist GW501516. In vitro, the role of PPARδ was elucidated using human aortic SMCs (HASMCs). Patients with ACS had significantly lower plasma PPARδ levels than those with SA. GW501516 reduced atherosclerotic plaque vulnerability, a synthetic SMC phenotype, ER stress markers, and NLRP3 inflammasome expression in HCD-fed ApoE-/- mice. ER stress suppressed PPARδ expression in HASMCs. PPARδ activation inhibited ER stress-induced synthetic phenotype development, ER stress-NLRP3 inflammasome axis activation and matrix metalloproteinase 2 (MMP2) expression in HASMCs. PPARδ inhibited NFκB signalling and alleviated ER stress-induced SMC phenotypic switching. Low plasma PPARδ levels may be associated with atherosclerotic plaque vulnerability. Our findings provide new insights into the mechanisms underlying the protective effect of PPARδ on SMC phenotypic switching and improvement the features of atherosclerotic plaque vulnerability.

SGLT2-inhibitors effects on the coronary fibrous cap thickness and MACEs in diabetic patients with inducible myocardial ischemia and multi vessels non-obstructive coronary artery stenosis

BackgroundSodium–glucose transporter 2 inhibitors (SGLT2-I) could modulate atherosclerotic plaque progression, via down-regulation of inflammatory burden, and lead to reduction of major adverse cardiovascular events (MACEs) in type 2 diabetes mellitus (T2DM) patients with ischemic heart disease (IHD). T2DM patients with multivessel non-obstructive coronary stenosis (Mv-NOCS) have over-inflammation and over-lipids’ plaque accumulation. This could reduce fibrous cap thickness (FCT), favoring plaque rupture and MACEs. Despite this, there is not conclusive data about the effects of SGLT2-I on atherosclerotic plaque phenotype and MACEs in Mv-NOCS patients with T2DM. Thus, in the current study, we evaluated SGLT2-I effects on Mv-NOCS patients with T2DM in terms of FCT increase, reduction of systemic and coronary plaque inflammation, and MACEs at 1 year of follow-up.MethodsIn a multi-center study, we evaluated 369 T2DM patients with Mv-NOCS divided in 258 (69.9%) patients that did not receive the SGLT2-I therapy (Non-SGLT2-I users), and 111 (30.1%) patients that were treated with SGLT2-I therapy (SGLT2-I users) after percutaneous coronary intervention (PCI) and optical coherence tomography (OCT) evaluation. As the primary study endpoint, we evaluated the effects of SGLT2-I on FCT changes at 1 year of follow-up. As secondary endpoints, we evaluated at baseline and at 12 months follow-up the inflammatory systemic and plaque burden and rate of MACEs, and predictors of MACE through multivariable analysis.ResultsAt 6 and 12 months of follow-up, SGLT2-I users vs. Non-SGLT2-I users showed lower body mass index (BMI), glycemia, glycated hemoglobin, B-type natriuretic peptide, and inflammatory cells/molecules values (p < 0.05). SGLT2-I users vs. Non-SGLT2-I users, as evaluated by OCT, evidenced the highest values of minimum FCT, and lowest values of lipid arc degree and macrophage grade (p < 0.05). At the follow-up end, SGLT2-I users vs. Non-SGLT2-I users had a lower rate of MACEs [n 12 (10.8%) vs. n 57 (22.1%); p < 0.05]. Finally, Hb1Ac values (1.930, [CI 95%: 1.149–2.176]), macrophage grade (1.188, [CI 95%: 1.073–1.315]), and SGLT2-I therapy (0.342, [CI 95%: 0.180–0.651]) were independent predictors of MACEs at 1 year of follow-up.ConclusionsSGLT2-I therapy may reduce about 65% the risk to have MACEs at 1 year of follow-up, via ameliorative effects on glucose homeostasis, and by the reduction of systemic inflammatory burden, and local effects on the atherosclerotic plaque inflammation, lipids’ deposit, and FCT in Mv-NOCS patients with T2DM.

Intracoronary Imaging of Coronary Atherosclerotic Plaque: From Assessment of Pathophysiological Mechanisms to Therapeutic Implication

Atherosclerotic cardiovascular disease is the leading cause of morbidity and mortality worldwide. Several cardiovascular risk factors are implicated in atherosclerotic plaque promotion and progression and are responsible for the clinical manifestations of coronary artery disease (CAD), ranging from chronic to acute coronary syndromes and sudden coronary death. The advent of intravascular imaging (IVI), including intravascular ultrasound, optical coherence tomography and near-infrared diffuse reflectance spectroscopy has significantly improved the comprehension of CAD pathophysiology and has strengthened the prognostic relevance of coronary plaque morphology assessment. Indeed, several atherosclerotic plaque phenotype and mechanisms of plaque destabilization have been recognized with different natural history and prognosis. Finally, IVI demonstrated benefits of secondary prevention therapies, such as lipid-lowering and anti-inflammatory agents. The purpose of this review is to shed light on the principles and properties of available IVI modalities along with their prognostic significance.

Current Applications and New Perspectives in Optical Coherence Tomography (OCT) Coronary Atherosclerotic Plaque Assessment: From PCI Optimization to Pharmacological Treatment Guidance

Since its ability to precisely characterized atherosclerotic plaque phenotypes, to tailor stent implantation, as well as to guide both complex percutaneous coronary interventions (PCI) and invasive diagnostic work-ups (e.g., spontaneous coronary dissections or myocardial infarction with non-obstructive arteries), the adoption of optical coherence tomography (OCT) was raised in the past decades in order to provide complementary information to the traditional angiography and to overcome its limitations. However, the impact of OCT on daily clinical practice is currently modest, firstly because of the lack of both standardized algorithms of PCI guidance and data from prospective clinical trials. Therefore, the aim of our narrative review is to provide a comprehensive overview of the basic OCT interpretation, to summarize the evidence supporting the OCT guidance procedures and applications, to discuss its current limitations, and to highlight the knowledge gaps that need to be filled with more robust evidence.

Association of immunoglobulin G N-glycosylation with carotid atherosclerotic plaque phenotypes and actual clinical cardiovascular events: a study protocol for a longitudinal prospective cohort study

IntroductionImmune-inflammatory response plays a key role in the pathogenesis of atherosclerosis. IgG N-glycosylation is reported to be associated with the 10-year atherosclerotic cardiovascular disease risk score and subclinical atherosclerosis. However,...

Melanocortin 1 Receptor Deficiency in Hematopoietic Cells Promotes the Expansion of Inflammatory Leukocytes in Atherosclerotic Mice.

Melanocortin receptor 1 (MC1-R) is expressed in leukocytes, where it mediates anti-inflammatory actions. We have previously observed that global deficiency of MC1-R signaling perturbs cholesterol homeostasis, increases arterial leukocyte accumulation and accelerates atherosclerosis in apolipoprotein E knockout (Apoe-/-) mice. Since various cell types besides leukocytes express MC1-R, we aimed at investigating the specific contribution of leukocyte MC1-R to the development of atherosclerosis. For this purpose, male Apoe-/- mice were irradiated, received bone marrow from either female Apoe-/- mice or MC1-R deficient Apoe-/- mice (Apoe-/- Mc1re/e) and were analyzed for tissue leukocyte profiles and atherosclerotic plaque phenotype. Hematopoietic MC1-R deficiency significantly elevated total leukocyte counts in the blood, bone marrow and spleen, an effect that was amplified by feeding mice a cholesterol-rich diet. The increased leukocyte counts were largely attributable to expanded lymphocyte populations, particularly CD4+ T cells. Furthermore, the number of monocytes was elevated in Apoe-/- Mc1re/e chimeric mice and it paralleled an increase in hematopoietic stem cell count in the bone marrow. Despite robust leukocytosis, atherosclerotic plaque size and composition as well as arterial leukocyte counts were unaffected by MC1-R deficiency. To address this discrepancy, we performed an in vivo homing assay and found that MC1-R deficient CD4+ T cells and monocytes were preferentially entering the spleen rather than homing in peri-aortic lymph nodes. This was mechanistically associated with compromised chemokine receptor 5 (CCR5)-dependent migration of CD4+ T cells and a defect in the recycling capacity of CCR5. Finally, our data demonstrate for the first time that CD4+ T cells also express MC1-R. In conclusion, MC1-R regulates hematopoietic stem cell proliferation and tissue leukocyte counts but its deficiency in leukocytes impairs cell migration via a CCR5-dependent mechanism.

SUR1-E1506K mutation impairs glucose tolerance and promotes vulnerable atherosclerotic plaque phenotype in hypercholesterolemic mice.

Background and aimsDiabetes is a major risk factor of atherosclerosis and its complications. The loss-of-function mutation E1506K in the sulfonylurea receptor 1 (SUR1-E1506K) induces hyperinsulinemia in infancy, leading to impaired glucose tolerance and increased risk of type 2 diabetes. In this study, we investigate the effect of SUR1-E1506K mutation on atherogenesis in hypercholesterolemic LDLR-/- mice.MethodsSUR1-E1506K mutated mice were cross-bred with LDLR-/- mice (SUR1Δ/LDLR-/-), 6 months old mice were fed a western-diet (WD) for 6 months to induce advanced atherosclerotic plaques. At the age of 12 months, atherosclerosis and plaque morphology were analyzed and mRNA gene expression were measured from aortic sections and macrophages. Glucose metabolism was characterized before and after WD. Results were compared to age-matched LDLR-/- mice.ResultsAdvanced atherosclerotic plaques did not differ in size between the two strains. However, in SUR1Δ/LDLR-/- mice, plaque necrotic area was increased and smooth muscle cell number was reduced, resulting in higher plaque vulnerability index in SUR1Δ/LDLR-/- mice compared to LDLR-/- mice. SUR1Δ/LDLR-/- mice exhibited impaired glucose tolerance and elevated fasting glucose after WD. The positive staining area of IL-1β and NLRP3 inflammasome were increased in aortic sections in SUR1Δ/LDLR-/- mice compared to LDLR-/- mice, and IL-18 plasma level was elevated in SUR1Δ/LDLR-/- mice. Finally, the mRNA expression of IL-1β and IL-18 were increased in SUR1Δ/LDLR-/- bone marrow derived macrophages in comparison to LDLR-/- macrophages in response to LPS.ConclusionsSUR1-E1506K mutation impairs glucose tolerance and increases arterial inflammation, which promotes a vulnerable atherosclerotic plaque phenotype in LDLR-/- mice.

Histone deacetylase 9 promotes endothelial-mesenchymal transition and an unfavorable atherosclerotic plaque phenotype.

Endothelial-mesenchymal transition (EndMT) is associated with various cardiovascular diseases and in particular with atherosclerosis and plaque instability. However, the molecular pathways that govern EndMT are poorly defined. Specifically, the role of epigenetic factors and histone deacetylases (HDACs) in controlling EndMT and the atherosclerotic plaque phenotype remains unclear. Here, we identified histone deacetylation, specifically that mediated by HDAC9 (a class IIa HDAC), as playing an important role in both EndMT and atherosclerosis. Using in vitro models, we found class IIa HDAC inhibition sustained the expression of endothelial proteins and mitigated the increase in mesenchymal proteins, effectively blocking EndMT. Similarly, ex vivo genetic knockout of Hdac9 in endothelial cells prevented EndMT and preserved a more endothelial-like phenotype. In vivo, atherosclerosis-prone mice with endothelial-specific Hdac9 knockout showed reduced EndMT and significantly reduced plaque area. Furthermore, these mice displayed a more favorable plaque phenotype, with reduced plaque lipid content and increased fibrous cap thickness. Together, these findings indicate that HDAC9 contributes to vascular pathology by promoting EndMT. Our study provides evidence for a pathological link among EndMT, HDAC9, and atherosclerosis and suggests that targeting of HDAC9 may be beneficial for plaque stabilization or slowing the progression of atherosclerotic disease.

Phenotyping carotid endarterectomy plaques of patients with elevated levels of lipoprotein(A)

Background and Aims: Elevated lipoprotein(a) [Lp(a)] levels have been demonstrated to be a causal risk factor for the development of cardiovascular disease. While previous studies have shown the atherogenicity of Lp(a) on monocyte activation and migration as well by activation of the vessel wall, the atherosclerotic plaque phenotype of individuals with elevated Lp(a) levels have not been studied up till now.

The Emerging Role of CT-Based Imaging in Adipose Tissue and Coronary Inflammation.

A large body of evidence arising from recent randomized clinical trials demonstrate the association of vascular inflammatory mediators with coronary artery disease (CAD). Vascular inflammation localized in the coronary arteries leads to an increased risk of CAD-related events, and produces unique biological alterations to local cardiac adipose tissue depots. Coronary computed tomography angiography (CTA) provides a means of mapping inflammatory changes to both epicardial adipose tissue (EAT) and pericoronary adipose tissue (PCAT) as independent markers of coronary risk. Radiodensity or attenuation of PCAT on coronary CTA, notably, provides indirect quantification of coronary inflammation and is emerging as a promising non-invasive imaging implement. An increasing number of observational studies have shown robust associations between PCAT attenuation and major coronary events, including acute coronary syndrome, and ‘vulnerable’ atherosclerotic plaque phenotypes that are associated with an increased risk of the said events. This review outlines the biological characteristics of both EAT and PCAT and provides an overview of the current literature on PCAT attenuation as a surrogate marker of coronary inflammation.

Common Genetic Variation in MC4R Does Not Affect Atherosclerotic Plaque Phenotypes and Cardiovascular Disease Outcomes.

We analyzed the effects of the common BMI-increasing melanocortin 4 receptor (MC4R) rs17782313-C allele with a minor allele frequency of 0.22–0.25 on (1) cardiovascular disease outcomes in two large population-based cohorts (Copenhagen City Heart Study and Copenhagen General Population Study, n = 106,018; and UK Biobank, n = 357,426) and additionally in an elderly population at risk for cardiovascular disease (n = 5241), and on (2) atherosclerotic plaque phenotypes in samples of patients who underwent endarterectomy (n = 1439). Using regression models, we additionally analyzed whether potential associations were modified by sex or explained by changes in body mass index. We confirmed the BMI-increasing effects of +0.22 kg/m2 per additional copy of the C allele (p < 0.001). However, we found no evidence for an association of common MC4R genetic variation with coronary artery disease (HR 1.03; 95% CI 0.99, 1.07), ischemic vascular disease (HR 1.00; 95% CI 0.98, 1.03), myocardial infarction (HR 1.01; 95% CI 0.94, 1.08 and 1.02; 0.98, 1.07) or stroke (HR 0.93; 95% CI 0.85, 1.01), nor with any atherosclerotic plaque phenotype. Thus, common MC4R genetic variation, despite increasing BMI, does not affect cardiovascular disease risk in the general population or in populations at risk for cardiovascular disease.

Mitochondrial quality control is altered in ATG7-deficient vascular smooth muscle cells and linked to unstable atherosclerotic plaque phenotype

Mitochondrial quality control is altered in ATG7-deficient vascular smooth muscle cells and linked to unstable atherosclerotic plaque phenotype

P977 CT phenotype of high-risk atherosclerotic plaques causing an acute coronary syndrome compared to silent vulnerable plaques

Abstract Funding Acknowledgements PlaqueImage.- research grant no. 103544/2016, contract number 26/01.09.2016 - Background Previous studies demonstrated that plaque morphology has a crucial role in the development of an acute coronary syndrome (ACS). However, not all vulnerable coronary plaques produce an ACS and the prediction power of various vulnerability features to predict an acute coronary event in a close future, has not been elucidated so far. Objective We aimed to use multi-slice computed tomography angiography (CTA) for assessment of morphological characteristics of culprit lesions producing an ACS in the next several months after CT assessment, in comparison with morphological characteristics of unstable coronary atherosclerotic plaques which did not trigger an ACS. Material and methods We analyzed 40 patients in whom CTA revealed presence of unstable coronary lesions, exhibiting at least one marker of vulnerability: napkin ring sign (NRS), spotty calcium (SC), positive remodeling (PR) or presence of low attenuation plaque (LAP), divided in 2 groups: group 1 - 20 patients who developed an ACS in the next 6 months following CTA examination, and group 2 – 20 patients matched for age, gender and risk factors, who did not present any cardiovascular event 6 month after CTA assessment. Post-processing of multi-slice CTA images was performed in order to assess morphological characteristics and CT-derived markers of atherosclerotic plaque instability. Results Similar mean values of plaque length (17.1 +/- 5.9 mm vs 16.9 +/- 3.4 mm; p = 0.6) and total atheroma volume (188.1 +/- 104.7 mm3vs 186.4 +/- 90.7 mm3; p = 0.8) were obtained for both groups. The mean number of vulnerability markers was 1.6 in group 1 vs 1.2 in group 2 (p = 0.07). However, atherosclerotic lesions in patients from group 1 presented significantly higher values of lipid-rich atheroma (9.8 +/- 10.8 mm3vs 2.6 +/- 1.0 mm3; p = 0.01) and remodeling index (1.14 +/- 0.3 in group 1 vs 0.89 +/- 0.19 in group 2, p = 0.04). At the same time, atheromatous plaques in patients who developed an ACS during the 6-months follow-up showed in a significantly higher proportion LAP (45% in group vs 10% in group 2, p = 0.03) and PR (15%in group 1 versus 5% in group 2, p = 0.04), but not NRS (30% vs 25%, p = ns) or SC (65% vs 40%, p = 0.2). Conclusions Atherosclerotic plaques producing an ACS exhibit a different phenotype than unstable plaques that remain silent. The CTA profile of atheromatous plaques producing an ACS includes the presence of low attenuation, positive remodeling, higher RI and lipid-rich atheroma. Presence of these features in high-risk coronary plaques identifies very high risk patients, who can benefit from adapted therapeutic strategy in order to prevent the development of an ACS.

Carotid Plaque Morphology is Similar in Patients with Reduced and Normal Renal Function.

Background:Chronic Kidney Disease (CKD) is associated with an increased risk for cardiovascular events such as stroke. However, it is still unclear if decreased kidney function is associated with a vulnerable atherosclerotic plaque phenotype. To explore if renal function was associated with carotid plaque vulnerability we analyzed carotid plaques obtained at surgery from the Carotid Plaque Imaging Project (CPIP).Methods:Patients were enrolled through the CPIP cohort. The indication for surgery was plaques with stenosis >70%, associated with ipsilateral symptoms or plaques with stenosis >80% not associated with symptoms. Transversal sections from the most stenotic plaque region were analyzed for connective tissue, calcium, lipids, macrophages, intraplaque hemorrhage, and smooth muscle cells. Homogenates were analyzed for collagen and elastin.Results:Carotid endarterectomy specimens from 379 patients were obtained. The median GFR was 73 ml/min/1.73 m2. Plaque characteristics showed no significant association with eGFR, neither when eGFR was divided in CKD groups nor when eGFR was handled as a continuous variable and adjusting for other known risk factors (ie, age, diabetes, hypertension, and smoking).Conclusions:The higher risk of cardiovascular disease such as stroke in CKD is not associated with increased plaque vulnerability and other factors have to be sought.