Plaque Composition Research Articles

Increased Macrophage-Specific Arterial Infiltration Relates to Noncalcified Plaque and Systemic Immune Activation in People With Human Immunodeficiency Virus.

Persistent immune activation is thought to contribute to heightened atherosclerotic cardiovascular disease (ASCVD) risk among people with human immunodeficiency virus (PWH). Participants (≥18 years) with or without human immunodeficiency virus (HIV) and without history of clinical ASCVD were enrolled. We hypothesized that increased macrophage-specific arterial infiltration would relate to plaque composition and systemic immune activation among PWH. We applied a novel targeted molecular imaging approach (technetium-99m [99mTc]-tilmanocept single photon emission computed tomography [SPECT]/CT) and comprehensive immune phenotyping. Aortic 99mTc-tilmanocept uptake was significantly higher among PWH (n = 20) than participants without HIV (n = 10) with similar 10-year ASCVD risk (P = .02). Among PWH, but not among participants without HIV, noncalcified aortic plaque volume related directly to aortic 99mTc-tilmanocept uptake at different uptake thresholds. An interaction (P = .001) was seen between HIV status and noncalcified plaque volume, but not calcified plaque (P = .83). Systemic levels of caspase-1 (P = .004), CD14-CD16+ (nonclassical/patrolling/homing) monocytes (P = .0004) and CD8+ T cells (P = .005) related positively and CD4+/CD8+ T-cell ratio (P = .02) inversely to aortic 99mTc-tilmanocept uptake volume. Macrophage-specific arterial infiltration was higher among PWH and related to noncalcified aortic plaque volume only among PWH. Key systemic markers of immune activation relating to macrophage-specific arterial infiltration may contribute to heightened ASCVD risk among PWH. NCT02542371.

The role of cardiac computed tomography in predicting adverse coronary events.

Cardiac computed tomography (CCT) is now considered a first-line diagnostic test for suspected coronary artery disease (CAD) providing a non-invasive, qualitative, and quantitative assessment of the coronary arteries and pericoronary regions. CCT assesses vascular calcification and coronary lumen narrowing, measures total plaque burden, identifies plaque composition and high-risk plaque features and can even assist with hemodynamic evaluation of coronary lesions. Recent research focuses on computing coronary endothelial shear stress, a potent modulator in the development and progression of atherosclerosis, as well as differentiating an inflammatory from a non-inflammatory pericoronary artery environment using the simple measurement of pericoronary fat attenuation index. In the present review, we discuss the role of the above in the diagnosis of coronary atherosclerosis and the prediction of adverse cardiovascular events. Additionally, we review the current limitations of cardiac computed tomography as an imaging modality and highlight how rapid technological advancements can boost its capacity in predicting cardiovascular risk and guiding clinical decision-making.

Association between myocardial ischemia and plaque characteristics in chronic total occlusion

BackgroundMyocardial ischemia varies in chronic total occlusion (CTO) despite the occluded artery. We analyzed whether it is associated with the plaque characteristics of the occluded segment. MethodsWe retrospectively enrolled 100 patients with CTO who underwent myocardial perfusion single-photon emission computed tomography (SPECT) and coronary computed tomography angiography (CCTA) within 2 months. CTO-related ischemia was classified as moderate to severe (summed difference score [SDS] of the CTO territory ≥ 5) or mild or none (SDS < 5) on SPECT. Using CCTA, the atherosclerotic plaques of the occluded segment were subdivided into low-density (− 100-30 HU), intermediate-density (31-350 HU), and high-density (351-1000 HU) plaques. The plaque composition was compared according to the severity of CTO-related ischemia. ResultsModerate-to-severe CTO-related ischemia (n = 23) showed significantly higher proportion of intermediate-density plaques (72.4% vs. 64.0%), intermediate/low-density (7.10 vs. 3.65) and intermediate-to-high/low-density (7.78 vs. 3.80) plaque ratios, frequent shorter occlusion (30% vs. 6%), and lower volume (26.5 mm3 vs. 58.8 mm3) and proportion (11.4% vs. 20.8%) of low-density plaques. Multivariable analysis revealed significant associations between higher proportion of intermediate-density plaques and moderate-to-severe CTO-related ischemia, independent of occlusion length. ConclusionHigher proportion of intermediate-density plaques in the occluded segment was associated with the moderate-to-severe CTO-related ischemia.

Serial Changes in Coronary Plaque Formation Using CT Angiography in Patients Undergoing PCSK9-Inhibitor Therapy With 1-year Follow-up.

Previous studies have shown positive effects of intensive low-density lipoprotein (LDL)-lowering therapy on atheroma volume using invasive intravascular ultrasound. This study describes the changes in coronary plaque composition on coronary computed tomography angiography in patients treated with proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors. In this prospective study, coronary plaques were analyzed using third-generation dual-source computed tomography before and after 1 year of PCSK9-inhibitor treatment. Plaque markers included total plaque volume (TPV), calcified plaque volume (CPV), noncalcified plaque volume (NCPV), lumen volume and vessel volume (VV), minimal luminal area (MLA), minimal lumen diameter (MLD), corrected coronary opacification, eccentricity, remodeling index, and functional plaque parameters. Primary endpoint was defined as change in TPV; the secondary endpoint was TPV or CPV regression or nominal change in plaque parameters. We analyzed 74 coronary plaques in 23 patients (60±9y, 65% male). After 1 year of PCSK9-inhibitor treatment, LDL was reduced from 148 to 66mg/dL ( P <0.0001). Significant changes were found for VV (196 to 215mm 3 , P =0.0340), MLA (3.1 to 2.6mm 2 , P =0.0413), and MLD (1.7 to 1.4mm, P =0.0048). TPV, CPV, NCPV, lumen volume, and functional plaque parameters did not change significantly ( P >0.05). Coronary artery plaque analysis by coronary computed tomography angiography highlights that LDL lowering therapy affects plaque composition. The primary endpoint of TPV change was not reached; however, VV, MLA, and MLD changed significantly.

Imaging diagnosis and research progress of carotid plaque vulnerability.

Ischemic stroke (IS) exhibits a high disability rate, mortality, and recurrence rate, imposing a serious threat to human survival and health. Its occurrence is affected by various factors. Although the previous research has demonstrated that the occurrence of IS is mainly associated with lumen stenosis caused by carotid atherosclerotic plaque (AP), recent studies have revealed that many patients will still suffer from IS even with mild carotid artery lumen stenosis. Blood supply disturbance causes 10% of IS to the corresponding cerebral blood supply area caused by carotid vulnerable plaque. Thrombus blockage of distal branch vessels caused by rupture of vulnerable carotid plaque is the main cause of ischemic stroke. Therefore, how to accurately evaluate vulnerable plaque and intervene as soon as possible is a problem that needs to be solved in clinic. The vulnerability of plaque is determined by its internal components, including thin and incomplete fibrous cap, necrotic lipid core, intra-plaque hemorrhage, intra-plaque neovascularization, and ulcerative plaque formation. The development of imaging technology enables the routine detection of AP vulnerability. By analyzing the pathological changes, characteristics, and formation mechanism of carotid plaque vulnerability, this article aims to explore the modern imaging methods which can be used to identify plaque composition and plaque vulnerability to provide a reference basis for disease diagnosis and differential diagnosis.

Colchicine Impacts Leukocyte Trafficking in Atherosclerosis and Reduces Vascular Inflammation.

BackgroundInflammation strongly contributes to atherosclerosis initiation and progression. Consequently, recent clinical trials pharmacologically targeted vascular inflammation to decrease the incidence of atherosclerosis-related complications. Colchicine, a microtubule inhibitor with anti-inflammatory properties, reduced cardiovascular events in patients with recent acute coronary syndrome and chronic coronary disease. However, the biological basis of these observations remains elusive. We sought to explore the mechanism by which colchicine beneficially alters the course of atherosclerosis.Methods and ResultsIn mice with early atherosclerosis (Apoe-/- mice on a high cholesterol diet for 8 weeks), we found that colchicine treatment (0.25 mg/kg bodyweight once daily over four weeks) reduced numbers of neutrophils, inflammatory monocytes and macrophages inside atherosclerotic aortas using flow cytometry and immunohistochemistry. Consequently, colchicine treatment resulted in a less inflammatory plaque composition and reduced plaque size. We next investigated how colchicine prevented plaque leukocyte expansion and found that colchicine treatment mitigated recruitment of blood neutrophils and inflammatory monocytes to plaques as revealed by adoptive transfer experiments. Causally, we found that colchicine reduced levels of both leukocyte adhesion molecules and receptors for leukocyte chemoattractants on blood neutrophils and monocytes. Further experiments showed that colchicine treatment reduced vascular inflammation also in post-myocardial infarction accelerated atherosclerosis through similar mechanisms as documented in early atherosclerosis. When we examined whether colchicine also decreased numbers of macrophages inside atherosclerotic plaques by impacting monocyte/macrophage transitioning or in-situ proliferation of macrophages, we report that colchicine treatment did not influence macrophage precursor differentiation or macrophage proliferation using cell culture experiments with bone marrow derived macrophages.ConclusionsOur data reveal that colchicine prevents expansion of plaque inflammatory leukocytes through lowering recruitment of blood myeloid cells to plaques. These data provide novel mechanistic clues on the beneficial effects of colchicine in the treatment of atherosclerosis and may inform future anti-inflammatory interventions in patients at risk.

515 Lower Extremity Atherosclerotic Plaque Burden And Composition Can Be Assessed Via CT Angiography With High Inter-reader Reproducibility

Introduction: Anatomical assessment of peripheral artery disease (PAD) with CT angiography (CTA) allows for plaque burden and composition analysis; establishing a reproducible analysis of this data will allow for evaluation of its clinical significance. In this study we establish inter-reader reproducibility of lower extremity CTA analysis for atherosclerotic plaque burden and composition.

514 Usefulness And Clinical Implications Of Plaque Analysis And Pfai For The Evaluation Of Cardiovascular Risk

Introduction: Clinical evidence has emphasized importance of coronary plaques’ characteristics, rather than lumen stenosis’ severity for outcome of cardiovascular events. Coronary Computed Tomographic angiography (CCTA) represents a non-invasive approach to assess plaques. Aim of the study was to compare clinical characteristics and outcomes (death, hospital admissions for percutaneous angioplasty or by-pass procedures) of patients with different plaques composition. Findings were also compared with patients without significant coronary heart disease (CAD).

Salivary and Dental Plaque Composition in Disabled Children Who Require Home Care: A Cross-sectional Investigation.

ABSTRACTAims:The purpose of this study was to compare salivary and dental plaque (DP) composition between disabled children who require home care (DCHC) and a control group (CG) and to correlate it with oral and systemic health factors.Materials and Methods:This cross-sectional study included 15 DCHC and 15 healthy children (aged between 4 and 10 years). The caregivers answered a questionnaire on disease diagnosis, medical history, dental history, and oral hygiene routine. In addition to clinical examination, saliva and DP samples were collected and analyzed using attenuated total reflection-Fourier transform infrared spectroscopy. Data were collected between January and December 2019. Student’s t and Kendall correlation tests were used.Results:Calculus (46.7%), bleeding on toothbrushing (53.3%), and gingival hyperplasia (40.0%) were prevalent in DCHC. The saliva of DCHC presented a higher amount of lipids and collagen and a lower amount of carbohydrates than that of the CG (P < 0.05). DP components were similar in DCHC and CG.Conclusion:DCHC presented oral comorbidities and changes in salivary composition, compared with the CG.

Carotid Plaque Characteristics Predict Recurrent Ischemic Stroke and TIA: The PARISK (Plaque At RISK) Study

BackgroundPatients with symptomatic carotid stenosis are at high risk for recurrent stroke. The decision for carotid endarterectomy currently mainly relies on degree of stenosis (cutoff value >50% or 70%). Nevertheless, also, patients with mild-to-moderate stenosis still have a considerable recurrent stroke risk. Increasing evidence suggests that carotid plaque composition rather than degree of stenosis determines plaque vulnerability; however, it remains unclear whether this also provides additional information to improve clinical decision making. ObjectivesThe PARISK (Plaque At RISK) study aimed to improve the identification of patients at increased risk of recurrent ischemic stroke using multimodality carotid imaging. MethodsThe authors included 244 patients (71% men; mean age, 68 years) with a recent symptomatic mild-to-moderate carotid stenosis in a prospective multicenter cohort study. Magnetic resonance imaging (carotid and brain) and computed tomography angiography (carotid) were performed at baseline and after 2 years. The clinical endpoint was a recurrent ipsilateral ischemic stroke or transient ischemic attack (TIA). Cox proportional hazards models were used to assess whether intraplaque hemorrhage (IPH), ulceration, proportion of calcifications, and total plaque volume in ipsilateral carotid plaques were associated with the endpoint. Next, the authors investigated the predictive performance of these imaging biomarkers by adding these markers (separately and simultaneously) to the ECST (European Carotid Surgery Trial) risk score. ResultsDuring 5.1 years follow-up, 37 patients reached the clinical endpoint. IPH presence and total plaque volume were associated with recurrent ipsilateral ischemic stroke or TIA (HR: 2.12 [95% CI: 1.02-4.44] for IPH; HR: 1.07 [95% CI: 1.00-1.15] for total plaque volume per 100 µL increase). Ulcerations and proportion of calcifications were not statistically significant determinants. Addition of IPH and total plaque volume to the ECST risk score improved the model performance (C-statistics increased from 0.67 to 0.75-0.78). ConclusionsIPH and total plaque volume are independent risk factors for recurrent ipsilateral ischemic stroke or TIA in patients with mild-to-moderate carotid stenosis. These plaque characteristics improve current decision making. Validation studies to implement plaque characteristics in clinical scoring tools are needed. (PARISK: Validation of Imaging Techniques [PARISK]; NCT01208025)

Added Value of CCTA-Derived Features to Predict MACEs in Stable Patients Undergoing Coronary Computed Tomography.

Clinical evidence has emphasized the importance of coronary plaques’ characteristics, rather than lumen stenosis, for the outcome of cardiovascular events. Coronary computed tomographic angiography (CCTA) has a well-established role as a non-invasive tool for assessing plaques. The aim of this study was to compare clinical characteristics and CCTA-derived information of stable patients with non-severe plaques in predicting major adverse cardiac events (MACEs) during follow-up. We retrospectively selected 371 patients (64% male) who underwent CCTA in our center from March 2016 to January 2021 with Coronary Artery Disease—Reporting and Data System (CAD-RADS) 0 to 3. Of those, 198 patients (53% male) had CAD-RADS 0 to 1. Among them, 183 (49%) had normal pericoronary fat attenuation index (pFAI), while 15 (60% male) had pFAI ≥ 70.1 Hounsfield unit (HU). The remaining 173 patients (76% male) had CAD-RADS 2 to 3 and were divided into patients with at least one low attenuation plaque (LAP) and patients without LAPs (n-LAP). Compared to n-LAP, patients with LAPs had higher pFAI (p = 0.005) and had more plaques than patients with n-LAP. Presence of LAPs was significantly higher in elderly (p < 0.001), males (p < 0.001) and patients with traditional risk factors (hypertension p = 0.0001, hyperlipemia p = 0.0003, smoking p = 0.0003, diabetes p = <0.0001, familiarity p = 0.0007). Among patients with CAD-RADS 0 to 1, the ones with pFAI ≥ 70.1 HU were more often hyperlipidemic (p = 0.05) and smokers (p = 0.007). Follow-up (25,4 months, range: 17.6–39.2 months) demonstrated that LAP and pFAI ≥ 70.1 significantly and independently (p = 0.04) predisposed to outcomes (overall mortality and interventional procedures). There is an added value of CCTA-derived features in stratifying cardiovascular risk in low- to intermediate-risk patients with non-severe, non-calcified coronary plaques. This is of utmost clinical relevance as it is possible to identify a subset of patients with increased risk who need strengthening in therapeutic management and closer follow-up even in the absence of severe CAD. Further studies are needed to evaluate the effect of medical treatments on pericoronary inflammation and plaque composition.

The oral microbiome analysis reveals the similarities and differences between periodontitis and Crohn's disease-associated periodontitis

Patients with Crohn's disease (CD) have higher incidences of oral diseases such as dental caries and periodontitis than healthy people. Studies indicate that the interaction between gut and oral microbiota is an important factor. To compare the composition and diversity of the oral microbiome in periodontitis and CD-associated periodontitis, subgingival plaque and saliva samples from patients with these diseases were collected for 16S rRNA gene sequencing analyses. In CD-associated periodontitis, the subgingival plaque had greater microbial diversity than saliva. Subgingival plaque had decreased abundances of Firmicutes, Streptococcus, and Haemophilus and increased abundances of Bacteroidetes, Actinomyces, Treponema_2, Capnocytophaga, and Porphyromonas relative to saliva. The microbial composition in subgingival plaque was similar between the two diseases. Both red complex (Porphyromonas, Tannerella, and Treponema) and orange complex (Fusobacteria) bacteria were abundant in periodontitis subgingival plaque, while orange complex bacteria (Prevotella_2 and Prevotella) were abundant in CD-associated periodontitis subgingival plaque. Pocket depth was significantly positively correlated with multiple periodontal pathogens, including Porphyromonas, Tannerella, and Treponema. This study reveals the similarities and differences in the oral microbiome between periodontitis and CD-associated periodontitis, which provides a foundation to further explore the associations between CD and periodontitis.

CT angiography-based radiomics as a tool for carotid plaque characterization: a pilot study.

Radiomics is a quantitative method able to analyze a high-throughput extraction of minable imaging features. Herein, we aim to develop a CT angiography-based radiomics analysis and machine learning model for carotid plaques to discriminate vulnerable from no vulnerable plaques. Thirty consecutive patients with carotid atherosclerosis were enrolled in this pilot study. At surgery, a binary classification of plaques was adopted ("hard" vs "soft"). Feature extraction was performed using the R software package Moddicom. Pairwise feature interdependencies were evaluated using the Spearman rank correlation coefficient. A univariate analysis was performed to assess the association between each feature and the plaque classification and chose top-ranked features. The feature predictive value was investigated using binary logistic regression. A stepwise backward elimination procedure was performed to minimize the Akaike information criterion (AIC). The final significant features were used to build the models for binary classification of carotid plaques, including logistic regression (LR), support vector machine (SVM), and classification and regression tree analysis (CART). All models were cross-validated using fivefold cross validation. Class-specific accuracy, precision, recall and F-measure evaluation metrics were used to quantify classifier output quality. A total of 230 radiomics features were extracted from each plaque. Pairwise Spearman correlation between features reported a high level of correlations, with more than 80% correlating with at least one other feature at |ρ|> 0.8. After a stepwise backward elimination procedure, the entropy and volume features were found to be the most significantly associated with the two plaque groups (p < 0.001), with AUCs of 0.92 and 0.96, respectively. The best performance was registered by the SVM classifier with the RBF kernel, with accuracy, precision, recall and F-score equal to 86.7, 92.9, 81.3 and 86.7%, respectively. The CART classification tree model for the entropy and volume features model achieved 86.7% well-classified plaques and an AUC of 0.987. This pilot study highlighted the potential of CTA-based radiomics and machine learning to discriminate plaque composition. This new approach has the potential to provide a reliable method to improve risk stratification in patients with carotid atherosclerosis.

436-P: Reducing Autoinflammation: The Impact of T-Cell Deficiency on Atherosclerosis

Type 1 diabetes (T1D) , a prototypic autoimmune disease, creates several serious complications of which atherosclerosis is the major co-morbid condition. Atherosclerosis is defined by arterial plaque deposition due to coagulation blood products, lipid deposition, and inflammation. The latter has been known for more than a decade but only recently have inflammatory mediators proven to be a beneficial target once traditional treatment has been exhausted. T-cell mediators associated with the CD40-CD154 inflammatory dyad are found in autoimmune diseases such as T1D and rheumatoid arthritis and may be a cause of the added atherosclerotic risk which these disease states maintain. This study seeks to explore the role of T cells in atherogenesis through the use of pro-atherogenic ApoE-/- mice bred to create T cell deficiency (ApoE-/- TCRα-/-) for analysis of the overall effect of T cells in atherogenesis. Mice are sacrificed at 8 months of age and dissected to obtain the aortas and hearts. The aorta is used for en-face Sudan IV staining analysis while serial aortic valve cross sections are used to characterize the lesion in terms of area and content. Analyses of aortic valve cross sections (A-D) and whole aortas (E-F) of this novel model not only demonstrated a significant reduction in overall plaque, but also revealed a change in plaque composition due to T cell deficiency. Future aims are to define the specific subset of pathogenic T cells. Disclosure A.J.Shepherd: None. M.Yussman: None. D.H.Wagner: Other Relationship; Op-T, LLC. G.M.Vaitaitis: None. Funding National Institutes of Health (4R42DK115296-02)

Association between Bone Mineral Density and Coronary Atherosclerotic Plaque According to Plaque Composition: Registry for the Women Health Cohort for Bone, Breast, and Coronary Artery Disease Study.

BackgroundAlthough biological links are unclear, low bone density and atherosclerosis are inversely associated. This study evaluated the association between bone mineral density (BMD) and coronary computed tomographic angiography (CCTA) findings, including coronary artery calcification (CAC) score and the presence, extent, and composition of coronary atherosclerotic plaque (CAP) in asymptomatic women.MethodsA symptomatic women aged ≥40 years (N=2, 100; median age, 52 years; range, 40–80 years) were selected from a retrospective observational cohort and stratified into normal, osteopenia, and osteoporosis groups according to BMD T-score grades. We evaluated CAC score and assessed the presence, extent, and stenosis severity of CAP on CCTA. Additionally, CAP was categorized as calcified, mixed, or non-calcified according to calcified component valiums (>130 Hounsfield units).ResultsOsteopenia and osteoporosis were found in 28.8% and 5.3% of participants, respectively. CAC score and CAC severity significantly increased with decreased BMD grades (from normal to osteoporosis). The presence of CAP (overall, 15.6%; normal, 12.6%; osteopenia, 20.2%; osteoporosis, 28.8%; P<0.001) and number of segments with CAP significantly increased with decreased BMD grades. Furthermore, the number of segments with calcified or mixed plaques, excluding non-calcified plaques, increased with decreased BMD grades. Although most associations were attenuated or disappeared after adjusting for age and other covariates, calcified plaques showed a strong and age-independent association with BMD grades.ConclusionsThe presence and severity of CAC and CAP were significantly associated with BMD severity in asymptomatic women, particularly for the presence of calcified plaques. Further studies are required to determine the association between vascular calcification and bone health status.

Efficacy and Underlying Mechanism of Berberine Against Atherosclerosis: A Meta-Analysis in Preclinical Animal Studies.

Atherosclerosis is the primary cause of many cardiovascular diseases, and an increasing number of studies have shown that berberine could delay plaque formation and development. Therefore, we aimed to evaluate its effects and explore its mechanisms in this meta-analysis. We searched PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and VIP databases for original preclinical studies to conduct meta-analysis. Twelve articles (16 studies; 312 ApoE -/- mice) were included, and all the studies scored 3-5 points according to SYRCLE's risk of bias tool. Berberine could significantly decrease plaque area and plaque macrophage content (plaque area, SMD = -2.02, 95% CI: -2.80 to -1.24, P = 0.000; plaque macrophage content, SMD = -4.28, 95% CI: -7.67 to -0.88, P = 0.013); lower the levels of TC, triglyceride, and low-density lipoprotein (TC, SMD = -1.47, 95% CI: -2.20 to -0.74, P = 0.000; triglyceride, SMD = -0.77, 95% CI: -1.21 to -0.33, P = 0.000; low-density lipoprotein, SMD = -0.61, 95% CI: -1.11 to -0.11, P = 0.000), and change the secretion of inflammatory cytokines (IL-1β, SMD = -2.29, 95% CI: -3.40 to -1.18, P = 0.000; interleukin-6, SMD = -1.48, 95% CI: -2.11 to -0.85, P = 0.008; tumor necrosis factor-α, SMD = -1.98, 95% CI: -3.01 to -0.94, P = 0.000; interleukin-10, SMD = 1.78, 95% CI: 0.76 to 2.80, P = 0.015), but there were no significant differences in high-density lipoprotein levels and plaque lipid content (high-density lipoprotein, SMD = 0.02, 95% CI: -0.35 to 0.40, P = 0.021; plaque lipid content, SMD = -6.85, 95% CI: -21.09 to 7.39, P = 0.007). The results were robust across a range of sensitivity analyses. Therefore, the results indicate that berberine is a promising drug for the treatment of atherosclerosis through regulating lipid metabolism, inflammation, and plaque composition. However, some potential mechanisms remain to be further elucidated.

Zinc Fertilizers Modified the Formation and Properties of Iron Plaque and Arsenic Accumulation in Rice (Oryza sativa L.) in a Life Cycle Study.

This study examined the effect of three forms of zinc fertilizers on arsenic (As) accumulation and speciation in rice tissues over the life cycle of this cereal crop in a paddy soil. The formation and properties of iron plaque on rice roots at the maximum tillering stage and the mature stage were also determined. Elevated As at 5 mg/kg markedly lowered the rice yield by 86%; however, 100 mg/kg Zn fertilizers significantly increased the rice yield by 354-686%, regardless of the Zn form. Interestingly, only Zn2+ significantly lowered the total As in rice grains by 17% to 3.5 mg/kg and As(III) by 64% to around 0.5 mg/kg. Zinc amendments substantially hindered and, in the case of zinc oxide bulk particles (ZnOBPs), fully prevented the crystallization of iron oxides (Fe3O4 and Fe2O3) and silicon oxide (SiO2) and altered the composition of iron plaques on rice roots. SiO2 was first reported to be a significant component of iron plaque. Overall, ZnOBPs, ZnO nanoparticles, and Zn2+ displayed significant yet distinctive effects on the properties of iron plaque and As accumulation in rice grains, providing a fresh perspective on the potentially unintended consequences of different Zn fertilizers on food safety.

OP0136 SERUM CHOLESTEROL LOADING CAPACITY ON MACROPHAGES AND INTERACTIONS WITH TREATMENTS ON CORONARY ATHEROSCLEROSIS BURDEN AND EVENT RISK IN RHEUMATOID ARTHRITIS

BackgroundCholesterol loading capacity (CLC) describes the ability of serum to deliver cholesterol to cells. It is linked to foam cell formation, a pivotal step in atherosclerotic plaque development. Rheumatoid arthritis (RA) serum promoted foam cell formation significantly more than control serum. Likewise, RA patients display greater plaque burden and higher-risk features than non-RA controls. bDMARDs and statins lower cardiovascular risk by reducing new coronary plaque formation, promoting regression, altering the composition and stabilizing prevalent atherosclerotic lesions.ObjectivesTo evaluate the associations between CLC, coronary plaque burden and cardiovascular event risk in patients with RA. We further explored the conditioning effects of RA treatments on these relationships.Methods140 patients underwent coronary CT angiography for atherosclerosis evaluation and were prospectively followed for cardiovascular events over 6.0±2.4 years. Coronary artery calcium score (CAC), number of segments with plaque (segment involvement score [SIS]) and plaque composition were assessed. CLC was the macrophage cholesterol content, measured by fluorometric assay, after a 24-hour incubation with whole serum. Robust linear regression examined the effects of CLC and the interaction between CLC and bDMARD use on SIS and CAC. Negative binomial regression evaluated CLC and CLC × bDMARD interaction effects on number of high-risk (low-attenuation) plaques. With data discretized into 1-month intervals, weighted pooled logistic regression models with robust variance estimation evaluated CLC and time-varying bDMARD use as predictors of event risk, and the effect of CLC × time-varying bDMARD use on risk. Stabilized inverse probability of treatment and censoring weights were estimated as a function of ASCVD risk, SIS, RA duration, and baseline and time-varying CRP and statin use.ResultsMean (SD) CLC was 12.67 (2.83) μg/mg protein. In analyses adjusting for ASCVD score, HDL, prednisone and statin use, CLC (per 1-SD unit) was not related to SIS (β -0.05 [95%CI -1.19,0.09]), number of high-risk plaques (rate ratio [RR] 1.20 [95%CI 0.80-1.80]) or ln-transformed CAC (β 0.017 [95%CI -0.133,0.147]). However, in analyses stratified by baseline bDMARD use, CLC (per 1-SD unit) was positively related to number of high-risk plaques (RR 2.14 [95%CI 1.04-4.40]) and ln-transformed CAC (β 0.21 [95%CI 0.01-0.41]) among bDMARD-naïve individuals (Figure 1). In addition, CLC inversely associated with SIS (per SD increment; β -0.16 [95%CI -0.32, -0.01]) only in bDMARD-treated patients. Baseline statin use did not significantly modify the effect of CLC on coronary plaque (not shown). CLC associated with cardiovascular event risk (per SD increment; adjusted odds ratio 2.02 [95%CI 1.27-3.50], p=0.011) covarying for ASCVD score and time-varying bDMARD use. The CLC × time-varying bDMARD use interaction also predicted event risk (p =0.010); current bDMARD use associated with lower event risk at higher (1 SD above the mean) CLC levels (p=0.037) but not average or lower (1 SD below the mean) CLC levels (p=0.064 and 0.756, respectively).ConclusionCLC associated with greater CAC score and high-risk plaque burden in bDMARD-naïve RA patients and lower total plaque burden in bDMARD-treated patients at baseline. CLC also predicted long-term cardiovascular risk and its effect was mitigated by bDMARD use.Disclosure of InterestsGeorge Karpouzas Speakers bureau: Sanofi-Genzyme-Regeneron, Janssen, Bristol-Meyer-Squibb, Consultant of: Sanofi-Genzyme-Regeneron, Janssen, Bristol-Meyer-Squibb, Grant/research support from: Pfizer, Bianca Papotti: None declared, Sarah Ormseth: None declared, Marcella Palumbo: None declared, Elizabeth Hernandez: None declared, Cinzia Marchi: None declared, Francesca Zimetti: None declared, Matthew Budoff Consultant of: Pfizer, Nicoletta Ronda: None declared

C47 CORO–CT PLAQUE ANALYSIS IN ASSESSMENT OF CARDIOVASCULAR RISK

Abstract Background Computed tomographic (CT) coronary angiography represents a non–invasive approach to assess plaque characteristics that provides information to change treatment of coronary artery disease (CAD) and to asses risk stratification. Purpose Analyze the differences in plaque composition between patients with different plaque features: soft unstable plaques, hard stable plaques and no plaques; identify whether there is a relationship between the plaque density and the pericoronary fat attenuation index (pFAI). Materials and methods: 372 patients retrospectively analyzed who underwent CTCA for exclusion of CAD. They were divided into three groups: 37 (10%) patients with high attenuated plaques (&amp;gt; 60HU), 137 (37%)with low attenuated plaques (&amp;lt;29 HU and a volume of at least 15 mm3 and/or 30–59 HU with a volume greater than 52 mm3) and 198 (53%) patients without significant CAD. For each patients we collected clinical, radiological and follow–up data. Results and Discussion Low–attenuated plaques are significantly associated with older age, male sex, dyslipidemia and diabetes mellitus (p &amp;lt; 0.001). Higher values of pFAI were more present in patients with soft plaques than in those with stable plaques and without plaques (p = 0.005). It was also found that soft plaques were present in more CA segments compared to stable plaques. Overall volume of soft plaque appears greater than hard plaques and mainly localized in the anterior descendant coronary artery with higher stenosis values (p &amp;lt; 0.001). Presence of plaques with soft or high–risk features predisposes significantly and independently (p &amp;lt; 0.001) to a composite outcome (death, in–hospital admissions for percutaneous angioplasty or by–pass procedures) at the follow up. Conclusions Coronary plaque analysis showed a good correlation between high–risk plaques and pFAI, supporting the hypothesis that the presence of high–risk plaques can be correlated to inflammatory burden. Furthermore, the presence of high risk plaques predispose to death or hospitalization for coronary intervention.

2D-perfusion angiography for intra-procedural endovascular treatment response assessment in chronic mesenteric ischemia: a feasibility study

BackgroundEndovascular revascularization has become the first-line treatment of chronic mesenteric ischemia (CMI). The qualitative visual analysis of digital subtraction angiography (DSA) is dependent on observer experience and prone to interpretation errors. We evaluate the feasibility of 2D-Perfusion Angiography (2D-PA) for objective, quantitative treatment response assessment in CMI.Methods49 revascularizations in 39 patients with imaging based evidence of mesenteric vascular occlusive disease and clinical signs of CMI were included in this retrospective study. To assess perfusion changes by 2D-PA, DSA-series were post-processed using a dedicated, commercially available software. Regions of interest (ROI) were placed in the pre- and post-stenotic artery segment. In aorto-ostial disease, the inflow ROI was positioned at the mesenteric artery orifice. The ratios outflow to inflow ROI for peak density (PD), time to peak and area-under-the-curve (AUC) were computed and compared pre- and post-interventionally. We graded motion artifacts by means of a four-point scale. Feasibility of 2D-PA and changes of flow parameters were evaluated.ResultsMotion artifacts due to a mobile vessel location beneath the diaphragm or within the mesenteric root, branch vessel superimposition and inadequate contrast enhancement at the inflow ROI during manually conducted DSA-series via selective catheters owing to steep vessel angulation, necessitated exclusion of 26 measurements from quantitative flow evaluation. The feasibility rate was 47%. In 23 technically feasible assessments, PDoutflow/PDinflow increased by 65% (p < 0.001) and AUCoutflow/AUCinflow increased by 85% (p < 0.001). The time to peak density values in the outflow ROI accelerated only minimally without reaching statistical significance. Age, BMI, target vessel (celiac trunk, SMA or IMA), stenosis location (ostial or truncal), calcification severity, plaque composition or the presence of a complex stenosis did not reach statistical significance in their distribution among the feasible and non-feasible group (p > 0.05). ConclusionsCompared to other vascular territories and indications, the feasibility of 2D-PA in mesenteric revascularization for CMI was limited. Unfavorable anatomic conditions contributed to a high rate of inconclusive 2D-PA results.