European Atherosclerosis Journal <p><em>European Atherosclerosis Journal</em> is an international, peer-reviewed, fully open access, four-monthly journal covering all topics within atherosclerosis and cardiovascular disease areas.</p> <p><em>European Atherosclerosis Journal</em> is the official journal of SITeCS (Società Italiana di Terapia Clinica e Sperimentale - Italian Society for Experimental and Clinical Therapeutics).</p> <p><em>European Atherosclerosis Journal</em> aims to publish high quality research and follows strict rules to assess originality and best practices for authorship and disclosure of potential conflicts of interest.</p> en-US <p>For commercial re-use, please contact the Editorial Office</p> [email protected] (Editorial Office) [email protected] (Editorial Office) Tue, 30 Apr 2024 00:00:00 +0000 OJS 60 BPIFB4 protein and monocytes phenotyping: a preclinical asset for marking the frailty condition <p style="font-weight: 400;"> Advanced age impacts on frequency and phenotype of immune cells as monocytes and macrophages. In this context, BPIFB4, a host defense protein with an immunomodulatory activity, has been found to be protective in healthy long living individuals in whom monocytes and macrophages have a favorable redistribution and phenotype. Thus, the aim of this study is to investigate the correlation between BPIFB4 levels in recruited frail subjects and both their frailty assessment/health status and monocytic profile.<br />In this study, both a group of 40 frail individuals and 20 aged-matched healthy volunteers were recruited. Participants were subjected to standardized questionnaires to assess frailty risk, routine clinical examinations and blood test, monocytes extraction with next immunophenotypic FACS analysis.<br />Overall, 70% of the frailty cohort has mild frailty, 25.5% has moderate frailty, and 5% has severe frailty. Compared to healthy controls, frail subjects show lower levels of circulating BPIFB4 that inversely correlate with the relative risk index for hypertension and cardiovascular disease. Flow cytometry results indicate total circulating monocyte frequency is reduced in frail subjects as compared to healthy controls. Considering monocytes’ subsets, CD14++CD16–classical monocytes and non-classical CD14+CD16++monocytes were significantly increased in frail people compared to old controls, whereas intermediate CD14++CD16+monocytes were reduced. Moreover, also the M2/M1 monocytic balance is altered in frailty condition compared to old volunteers. No relationship between BPIFB4 plasma levels and monocytes’subsets was found. Our findings highlight BPIFB4 protein has a potential prognostic value for marking the frailty condition.</p> Elena Ciaglia, Silvana Mirella Aliberti, Francesco Montella, Valentina Lopardo, Albino Carrizzo, Paola Di Pietro, Cristina Basile, Anna Maciag, Maria Consiglia Calabrese, Mario Capunzo, Carmine Vecchione, Annibale Alessandro Puca Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Effect of anti-PCSK9 drugs on the association of PCSK9 to LDL <p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a protein that is known to interact with the LDL receptor, thereby promoting its degradation and blunting the uptake of LDL from the circulation. In this context, anti-PCSK9 monoclonal antibodies (mAbs) and siRNAs have been approved for the treatment of hypercholesterolaemia. Previous studies have shown that a significant proportion of circulating PCSK9 is associated with LDL. The aim of our research is to investigate the effect of mAbs and siRNA on the association of PCSK9 protein with LDL. In this study, 10 statin-intolerant patients received treatment with anti-PCSK9 mAbs or siRNA, in addition to therapy with a low-dose statin and ezetimibe. Their plasma samples were analysed before and after 1, 3, and 6/9 months of treatment. The results showed that both the monoclonal antibodies and inclisiran reduced LDL-C levels by 50% to 60%. LDL-C levels decreased from 92±28 mg/dL to 44±26 mg/dL after siRNA treatment and reached 97±9, 27±10, 32±14, and 23±10 mg/dL after mAbs therapy. The circulating PCSK9 level decreased by 70% after the first siRNA injection, while it increased 10-fold after mAbs therapy. Regardless of treatment, the percentage of PCSK9 bound to LDL did not vary from baseline and remained constant during the treatment period. Whether this is of physiological relevance remains to be addressed.</p> Sara Matteucci, Valentina Pravatà, Francesco Maria Esposito, Angela Pirillo, Liliana Grigore, Alberico Luigi Catapano Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Spring Meeting of the Young Researchers of SID, SIIA, SIMI, SIPREC, SISA <p>The IX Spring Meeting of Young Researchers of the Italian Society of Diabetology (SID), the Italian Society of Arterial Hypertension (SIIA), the Italian Society of Internal Medicine (SIMI), the Italian Society of Cardiovascular Prevention (SIPREC) and the Italian Society for the Study of Atherosclerosis (SISA), entitled “Research drives us crazy”, was held in Rimini on February 25-27, 2024. The Congress was organized by young researchers from the aforementioned scientific societies working in the cardiometabolic field. The Congress hosted five sessions promoted by the five societies, addressing hot topics in the prevention and treatment of cardiometabolic diseases. <br>More than one hundred young researchers had the opportunity to discuss their scientific work in dedicated oral and poster sessions. In this conference report, we offer an overview of the key topics covered in the presentations at the meeting.</p> Vanessa Bianconi, Damiano D’Ardes, Rosa Lombardi, Alessandro Maloberti, Francesco Spannella, Valeria Visco, Luca D’Onofrio, Carla Greco, Giovanna Gallo, Chiara Pavanello Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Determinants of early subclinical systolic dysfunction in patients with type 2 diabetes <p>Aim. Type 2 Diabetes (DM2) is a risk factor for the development of heart failure (HF). Global longitudinal strain (GLS) is more sensitive than ejection fraction (EF) in diagnosing subclinical left ventricular systolic dysfunction (LVSD). Metabolic-associated fatty live disease has been involved in the development of subclinical LVSD-GLS. However, determinants of subclinical LVSD-GLS in DM2 remain poorly known. Our aim was to identify variables associated with altered GLS values in a cohort of DM2 individuals without heart disease and with normal EF.<br>Methods. The study was performed on DM2 patients (n=150) recruited in the TESEO cohort study with available data on GLS (Speckle Tracking Echocardiography, Epiq CVx Philips), hepatic steatosis (CAP), and liver stiffness (LS) (Fibroscan). Subjects with symptomatic HF, cardiovascular disease (CVD), other heart diseases, EF&lt;50%, eGFR&lt;30 ml/min/1.73m2, alcohol abuse, non-metabolic liver disease, and hepatic cirrhosis were excluded. Multiple regression and logistic regression analyses were used to identify GLS determinants and variables associated with subclinical LVSD-GLS (GLS≥-18%).<br>Results. Recruited subjects (age 61.39±7.89 years, male 57.3%) had a short DM2 duration (3.93±5.06 years) and good metabolic control (HbA1c 6.57%±1.00). Subclinical LVSD-GLS was present in 20% of subjects. Patients with LVSD-GLS had significantly higher LS values (5.77±1.75 vs 4.94±1.25, p=0.003). In multivariate regression analysis, LS values were a significant determinant of GLS, independent of age, waist circumference, diabetes duration, blood pressure, and e’ lateral. In logistic regression analysis, LS was associate with a 61% (95% CI 1.15-2,25) increased OR of LVSD-GLS independent of age, gender, WC, diabetes duration, blood pressure, ACR, LVH, and e’ lateral.<br>Conclusions. This study demonstrated that LS is independently associated with LVSD-GLS in DM2 patients with normal HF and without CVD. Abnormal LS values may identify a subgroup of DM2 patients at higher risk of symptomatic HF, who may benefit from closer clinical and echocardiographic monitoring.</p> Andrea Gaido, Marta Avataneo, Francesca Arietti, Matteo Bellettini, Alessandro Andreis, Gianpaolo Caviglia, Elisabetta Bugianesi, Federica Barutta, Arianna Ferro, Guglielmo Beccuti, Gabriella Gruden Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Real-world evidence evaluation of LDL-C among hospitalized patients: a population-based observational study in the timeframe 2021-2022 <p>Aims. European registries and retrospective cohorts highlighted the lack of low-density lipoprotein-cholesterol (LDL-C) goal achievement in many very high-risk patients. Hospitalized patients are often frail, and frailty is associated with all-cause mortality and cardiovascular mortality. Aim of this study is to evaluate LDL-C levels in a Real-World setting of inpatients, identify cardiovascular risk categories and highlight treatment gaps in the implementation of LDL-C control. <br>Methods. This retrospective, observational study included all the adult patients admitted at an Italian hospital between 2021-2022 and with LDL-C values available during hospitalization. Disease-related real-world data were collected from Hospital Information Systems using automated data extraction strategies and through the implementation of a patient-centered data repository (the Dyslipidemia Data Mart). Assessment of cardiovascular risk profiles, LDL-C target achievement according to the 2019 ESC/EAS guidelines and lipid-lowering therapies (LLT) use were performed.<br>Results. 13,834 patients were included: 17.15%, 13.72%, 16.82% and 49.76% were low (L), moderate (M), high (H) and very high-risk (VH) patients, respectively. The percentage of in-target patients was progressively lower moving towards worse categories (78.79% in L, 58.38% in M, 33.3% in H and 21.37% in VH). Among LLT treated patients in VH category, in-target are 28.48%; 47.6.% in H, 69.12% in M and 68.47% in L. The impact of monotherapies and combination therapies on target achievement was also analyzed. <br>Conclusions. This study depicts LDL-C control among an entire population of inpatients, highlighting relevant gaps especially in VH category. Future efforts must aim to reduce the cardiovascular risk of these subjects.</p> Umberto Capece, Chiara Iacomini, Teresa Mezza, Alfredo Cesario, Carlotta Masciocchi, Cassandra Morciano, Shawn Gugliandolo, Stefano Patarnello, Andrea Giaccari, Nicoletta Di Giorgi Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Using AI to identify left ventricular ejection fraction from the ECG: The SOLOMAX (SOciaL NetwOrk of MedicAl Experiences) project <p>Aim: The interest in machine learning-based algorithms in the cardiovascular field is rapidly growing, especially for diagnostic and prognostic purposes. Recent evidence has demonstrated that certain electrocardiographic (ECG) parameters are predominantly associated with systolic function, estimated as left ventricular ejection fraction (LVEF) by echocardiography, albeit with still relatively low accuracy.<br>Consequently, this study aims to develop an AI-based model capable of predicting LVEF from ECG data in an Italian population.<br>Methods: Within the SOLOMAX project, we collected paired ECG-Echocardiography exams from 105 patients (64.82±16.02y;62.86%male). Precisely, we excluded patients with atrial fibrillation at the time of the ECG, PMK or electrostimulated rhythm, valve prostheses, previous cardiac surgery, O2 therapy or COPD, previous ablation or invasive electrophysiology procedures, currently hospitalized for Takotsubo or ACS, heart failure exacerbation, inotropic therapy, ACS over the last 3 months. We recorded anthropometric, clinical, biochemical, ECG, and Echocardiography parameters. The collected data was studied using AI-based techniques to create a new model to predict LVEF from ECG. Using an approach based on evolutionary algorithms, genetic programming was used. This approach solves a symbolic regression problem through genetic algorithms and provides a mathematical model of the relationship between ECG parameters and LVEF. The formula obtained was then used to build a simple explainable classifier, which provides a global interpretation of the link between ECG parameters and LVEF.<br>Results: The performance of the proposed approach and the reliability of the results were assessed using the k-fold cross-validation method and by estimating standard metrics derived from the confusion matrix associated with a binary classifier, that is, accuracy, sensitivity, specificity, precision, and F-Measure. The proposed approach consistently demonstrated its ability to distinguish patients with preserved LVEF from those with reduced LVEF. Each metric averaged across all experiments scored approximately 95%. Furthermore, in the expression generated by the AI model, the axes of the P, QRS, and T waves play a prominent role, as they are likely to provide a better interpretation of the three-dimensional cardiac geometry and, consequently, cardiac function.<br>Conclusions: AI applied to ECG data can be used to create cost-effective diagnostic and predictive tools for assessing LVEF. Indeed, the obtained formula highlights the relationship between ECG parameters and LVEF, as well as its complexity, which can aid in detecting heart diseases.</p> Alfonso Ferrara, Valeria Visco, Antonio Robustelli, Francesco Loria, Antonella Rispoli, Andrea Martorella, Albino Carrizzo, Alessia Bramanti, Gianni D’Angelo, Carmine Vecchione, Michele Ciccarelli Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Metabolic dysfunction-associated steatotic liver disease in people with HIV is associated with lower BMI and more liver fibrosis compared to the uninfected population <p>Aim: People with HIV (PWH) are at high risk of metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the presence of hepatic steatosis plus any among overweight, diabetes, hypertension, or dyslipidemia. There are limited data whether MASLD in PWH differs in clinical presentation from MASLD in the uninfected population. Aim: to compare the severity of metabolic and hepatic dysfunction between MASLD patients with and without HIV. <br>Methods: 212 consecutive HIV mono-infected patients with MASLD at McGill University in Montreal were compared to a sex and age matched MASLD HIV negative control group at Policlinico Hospital in Milan. Fibroscan with controlled attenuation parameter (CAP) was used to define MASLD (CAP≥248 dB/m), severe MASLD (CAP&gt;280 dB/m), and significant liver fibrosis (liver stiffness measurement&gt;7.0 kPa). <br>Results: PWH with MASLD presented lower median BMI (28[25-31] vs 29[27-32] Kg/m2, p=0.002) and lower prevalence of obesity (26% vs 44%, p&lt;0.001) compared to MASLD uninfected patients, along with a lower prevalence of hypertension (21% vs 38%, p&lt;0.001). The prevalence of dyslipidemia (41% vs 26%, p&lt;0.001), hypertriglyceridemia (26% vs 9%, p&lt;0.001) and low HDL cholesterol (34% vs 15%, p&lt;0.001) was higher in MASLD patients with vs without HIV. No difference in cardiovascular events and diabetes prevalence was observed between the two groups. Regarding liver disease, PWH with MASLD had lower prevalence of severe MASLD (54% vs 74% p&lt;0.001) but higher prevalence of significant liver fibrosis (15 vs 7%, p=0.03) compared to MASLD uninfected patients. After adjustment, HIV positivity was an independent factor associated with significant liver fibrosis (figure).<br>Conclusions: Despite having lower BMI, PWH with MASLD have a more severe hepatic presentation and atherogenic lipid profile than MASLD uninfected patients. HIV positivity seems to be independently associated with significant liver fibrosis. Screening and follow-up for MASLD and liver fibrosis is recommended in PWH, even if they are lean.</p> Felice Cinque, Rosa Lombardi, Jaqueline Currà, Floriana Santomenna, Dana Kablawi, Annalisa Cespiati, Luca Marchesi, Erika Fatta, Cristina Bertelli, Giovanna Oberti, Giuseppina Pisano, Thierry Fotsing Tadjo, Wesal Elgretli, Bertrand Lebouché, Marc Deschenes, Anna Ludovica Fracanzani, Giada Sebastiani Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 The aging of neutrophils is actively involved in the metabolic consequences of high fat diet <p>Aim: The epigenetic modifications induced by High Fat Diets (HFDs) in long-living hematopoietic cells have been well described, but whether they affect the “aging” of neutrophils, characterized by far shorter half-life, is less clear. Neutrophils "age" through a reciprocal regulation of CXCR4, promoting a "fresh" status when leaving the BM, and CXCR2, accelerating their aging in the circulation. We study whether derailed aging exacerbates the metabolic and inflammatory consequences of HFD.<br>Methods: We immunophenotyped neutrophils and characterized the metabolic responses in physiology (wild-type mice, WT) and in mice with either constitutively aged neutrophils (MRP8 driven conditional deletion of CXCR4; herein CXCR4fl/flCre+) or with constitutively fresh neutrophils (MRP8 driven conditional deletion of CXCR2; CXCR2fl/flCre+), following 20 weeks of HFD feeding (45% Kcal from fat).<br>Results: CXCR4fl/flCre+ mice display higher plasma triglycerides levels versus WT, despite comparable glucose levels, when monitored during standard feeding. This metabolic difference was exacerbated by feeding mice a HFD for 20 weeks. Indeed, despite a comparable gluco-metabolic profile between CXCR4fl/flCre+ and WT mice, liver damage was increased in CXCR4fl/flCre+, linked to the higher accumulation of CXCR4fl/flCre+ neutrophils in the liver after 20 weeks and two hours after intragastric gavage with olive oil versus fasting. As this finding was not observed after 20 weeks of standard fat diet, these results suggest that HFD feeding redirects aged neutrophil to the liver, resulting in enriched oxidative metabolism and NETosis- and inflammation-related pathways in the liver of CXCR4fl/flCre+ mice.<br>Conversely, CXCR2fl/flCre+ mice were protected from obesity and insulin resistance, exhibiting a proresolutive phenotype.<br>In humans, increased plasma levels of Cxcl1 (ligand of CXCR2) correlated with visceral obesity and metabolic syndrome.<br>Conclusions: Neutrophil aging might contribute to the cardio-metabolic consequences of HFD. This aging could represent a new therapeutic target beyond the current anti-inflammatory therapies approved for the treatment of cardiovascular diseases.</p> Anna Parolini, Andrea Baragetti, Lorenzo Da Dalt, Annalisa Moregola, Ottavia Terenghi, Monika Svecla, Patrizia Uboldi, Giuseppe Danilo Norata Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Transcriptional regulation of Hexokinase-2 by BRD4 drives perivascular adipose tissue meta-inflammation in cardiometabolic disease <p>Aim: To investigate BRD4-related transcriptional programmes in mouse and human models of cardiometabolic disease.<br>Methods: Small arteries (0.1-0.3 mm) dissected from visceral fat biopsies from healthy subjects (n=16) and patients with obesity and hypertension (n=16) were mounted on a pressurized myograph to assess the acute ex-vivo effects of BRD4 inhibition on vascular function. Vasorelaxation to acetylcholine and acetylcholine+L-NAME was evaluated, in the presence or in the absence of perivascular adipose tissue (PVAT), at baseline and after incubation with the BRD4 inhibitor RVX-208 and with selective anti-inflammatory and anti-metabolic drugs. A cardiometabolic mouse (high-fat diet+L-NAME supplementation) was orally administered RVX-208 (150 mg/kg) to test in vivo effect of chronic BRD4 inhibition. ROS and nitric oxide were assessed by confocal microscopy; protein and gene expression by Western blot and qPCR. Transcriptional changes upon BRD4 inhibition were investigated by a custom PCR array, confirmed by ChIP, and characterised by metabolomics, lipidomics and mitochondrial swelling.<br>Results: Endothelial-dependent vasorelaxation and vascular and perivascular TNF-alpha, IL-1beta, IL-6 were altered in cardiometabolic patients and mice. RVX-208 substantially attenuated ex-vivo vascular dysfunction, with an impact greater than anti-IL-1beta, anti-IL-6 receptor and anti-TNF-alpha. The effect was more pronounced in vessels with intact PVAT, suggesting a restoration of the PVAT anti-contractile phenotype. Gene expression profiling in PVAT unveiled hexokinase-2 (HK2) - a glycolytic enzyme implicated in mitochondrial dysfunction and inflammation - as the top downregulated gene by RVX-208 treatment. Increased binding of BRD4 to HK2 promoter in PVAT samples from cardiometabolic mice was confirmed by ChIP assays. Metabolomics assays further validated the findings by demonstrating a glycolytic shift in PVAT under disease conditions. Finally, ex vivo selective inhibition of HK2 rescued vascular dysfunction.<br>Conclusion: Targeting the deleterious BRD4-HK2 interplay restores cardiometabolic vascular dysfunction via reversal of the PVAT meta-inflammatory shift, highlighting a novel potential target to fight cardiometabolic pandemics.</p> Alessandro Mengozzi, Sarah Costantino, Alessia Mongelli, Emiliano Duranti, Shafeeq A. Mohammed, Era Gorica, Marialucia Telesca, Silvia Armenia, Federica Cappelli, Christian M. Matter, Stefano Taddei, Stefano Masi, Frank Ruschitzka, Agostino Virdis, Francesco Paneni Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Extracellular vesicles characterization in patients with hypertrophic cardiomyopathy <p>Background: Hypertrophic cardiomyopathy (HCM) is diagnosed according to the presence of morphological and functional traits of the heart, often in the presence of genetic mutations. A specific biomarker assessing the aetiopathology of this condition is lacking. Extracellular vesicles (EVs), small particles released by all cells into biological fluids, hold promise as diagnostic and prognostic tools for cardiac diseases. We aim at characterising plasma-derived EVs isolated from 18 consecutive HCM patients and 13 healthy volunteers (CTR). <br>Methods: HCM underwent echocardiographic assessment and genetic testing evaluating 200 genes (NGS). EVs were isolated via ultracentrifugation from platelet-free plasma. Quantitative and qualitative assessments of EVs were performed by nanoparticle tracking analysis and transmission electron microscopy. FACS analysis was used to characterize EV subpopulations. Data are expressed as median and interquartile ranges. <br>Results: Most patients were male (70.8% HCM and 54% CTR) with a median age of 61 (52.5-71) years (HCM) and 47 (44-52) (CTR). Missense mutations in the MYH7 gene were the most found in HCM. The median maximum wall thickness in HCM was 16 mm (15-19) vs 8 mm (7-9) in CTR. No differences were found in EV concentrations between HCM and CTR, respectively, 3.6*109 EV/ml/cell count (2*109-5*109) and 5*10⁹ EV/ml/cell count (4*109-6*109). However, EV concentration was positively associated with the sudden cardiac death risk score in HCM (r= 0.63). Among the EVs positive for CFSE (a specific dye for EVs), those released from platelets, progenitor endothelial cells and neutrophils were increased in HCM patients vs CTR, respectively, by 1.7-, 1.5- and 1.1-fold. A strong negative association (r= -0.74) was found between progenitor endothelial cell-derived EVs and the E/E’ ratio of diastolic function, a strong predictor of first cardiac events.<br>Conclusions: HCM patients present a peculiar phenotypic pattern of EVs that associates which diastolic function and sudden cardiac death.</p> Alessandra Rizzuto, Chiara Macchi, Andrea Faggiano, Margherita Calcagnino, Michele Baroni, Eleonora Gnan, Stefania Paganini, Ilaria Giusti, Vincenza Dolo, Alberto Corsini, Stefano Carugo, Massimiliano Ruscica Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Definition of the metabolic pattern of ANGPTL3 deficient mice on a chow diet and under dysmetabolic conditions <p>Aim: ANGPTL3 controls lipid and lipoprotein metabolism through lipoprotein lipase and endothelial lipase inhibition and the prevention of lipoprotein-derived triglycerides hydrolyzation.<br>Here we present the metabolic profile of ANGPTL3 deficient mice in physiology and during the development of metabolic disorders.<br>Methods: Angptl3 KO mice (C57BL6/J background) and their littermate controls (wild-type, WT) were fed a chow and a High Fat Diet (HFD, 60%kcal from lipids) for 16 weeks.<br>During the diet protocol, changes in lipids and lipoprotein profile, under fast, fed, and fast-refeed setting were assessed. The metabolic phenotype was assessed, with a Glucose Tolerance Test (GTT) and an Insulin Tolerance Test (ITT); the lipids absorption profile was assessed with an Oral Lipid Tolerance Test (OLTT).<br>Results: ANGPTL3 KO mice fed ad libitum a chow diet are hypolipidemic (plasma triglycerides levels: 42,42±8,80 mg/dL in ANGPTL3 KO mice compared to 122,02±55,09 mg/dL in WT mice; plasma cholesterol levels: 44,00±9,11 mg/dL in ANGPTL3 KO mice compared to 76,51±15,87 mg/dL in WT mice). <br>After 16h fasting, ANGPTL3 KO mice on a chow diet are hypolipidemic and display small lipoproteins less rich in cholesterol and triglycerides, as established in humans, and the same holds true for mice fed a HFD diet. <br>On HFD, ANGPTL3 KO mice gain less body weight, suggesting an improved metabolic profile compared to WT animals. <br>The hypolipidemia is conserved during all the timepoints of OLTT, both in mice on chow or HFD, suggesting a different lipid management; in spite, no significant differences in the circulating glycaemia has been proved with a GTT after 16h of fasting; likewise, a similar sensitivity to insulin has been outlined with an ITT after 4h of fasting.<br>Conclusions: This metabolic profiling of ANGPTL3 KO mice on chow diet or HFD highlights that these mice are hypolipidemic and may have beneficial metabolic features compared to controls.</p> Ottavia Terenghi , Lorenzo Da Dalt, Francesca Fantini, Annalisa Moregola, Fabrizia Bonacina, Patrizia Uboldi, Giuseppe Danilo Norata Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Cholesterol esterification is hampered in alzheimer’s disease and cholesteryl esters composition is consequently altered <p>Introduction and Aim: Several epidemiological studies indicate a strong inverse association between the risk of developing Alzheimer’s disease (AD) and plasma HDL-C levels. The mechanism by which plasma HDL influence the pathogenesis and progression of AD is still unsolved and since cholesterol esterification is a crucial step in HDL metabolism it could be involved. The purpose of this study was to evaluate cholesterol esterification and HDL subclasses in plasma and cerebrospinal fluid (CSF) of Alzheimer’s Disease (AD) patients. <br>Methods: The study enrolled 70 AD patients and 74 cognitively-normal controls comparable for age and sex. Lipids and lipoprotein profile, cholesterol esterification, and cholesterol efflux capacity (CEC) were evaluated in plasma and CSF using assays set for measurement in plasma, which were appropriately modified for CSF. <br>Results: AD patients have normal plasma lipids, but significantly reduced unesterified cholesterol and unesterified/total cholesterol ratio. Lecithin:cholesterol acyltransferase (LCAT) activity and cholesterol esterification rate (CER), two measures of the efficiency of the esterification process, were reduced by 29% and 16%, respectively, in plasma of AD patients. Plasma HDL subclass distribution in AD patients was comparable to that of controls, but the content of small discoidal preβ-HDL particles was significantly reduced. In agreement with the reduced preβ-HDL particles, cholesterol efflux capacity mediated by the transporters ABCA1 and ABCG1 was reduced in AD patients’ plasma. The CSF unesterified to total cholesterol ratio was increased in AD patients, and CSF CER and CEC from astrocytes were significantly reduced in AD patients. In the AD group, a significant positive correlation was observed between plasma unesterified cholesterol and unesterified/total cholesterol ratio with Aβ1-42 CSF content.<br>Conclusions: Taken together data indicate that cholesterol esterification is hampered in plasma and CSF of AD patients, and that plasma cholesterol esterification biomarkers (unesterified cholesterol and unesterified/total cholesterol ratio) are significantly associated to disease biomarkers (i.e., CSF Aβ1-42).</p> Marta Turri, Elisa Conti, Chiara Pavanello, Francesco Gastoldi, Marcella Palumbo, Franco Bernini, Vittoria Aprea, Francesca Re, Alberto Barbiroli, Davide Emide, Daniela Galimberti, Lucio Tremolizzo, Francesca Zimetti, Laura Calabresi Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Cardiovascular risk prediction - now and the future <p>Current cardiovascular risk estimation systems that estimate 10-year risk based on cohort studies starting at around age 40 have probably reached their limits based on current methods.<br>The challenges are to develop new systems that will permit personalised risk estimation earlier in life with better estimates of true lifetime risk and likely treatment benefits. We outline approaches to address these issues.</p> Ian M Graham Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000 Role of nuclear medicine assessing patients with suspected coronary artery disease <p>Nuclear medicine is a critical component in the field of cardiology as it provides diagnostic and prognostic insights that are essential for the effective management of heart disease. <br>Both single photon emission computed tomography (SPECT) and positron emission tomography (PET) play a significant role in assessing the likelihood of ischemic heart disease based on pre-test probabilities. Both SPECT and PET should be integrated into the clinical pathway according to the patient’s individual risk profile, symptoms, and initial test results. The guidelines recommend using these imaging modalities to refine risk stratification, particularly in intermediate-risk patients, and to guide further invasive diagnostic or therapeutic procedures based on the imaging findings.</p> Roberto F.E. Pedretti, Luca Genovese, Luca Alberti, Alessandro Cecilia, Martina Cellamare, Matteo Crippa, Gianmarco Dacquino, Aurora Danza, Matteo Della Torre, Federico Ferrari Bravo, Giuseppe Galati, Francesco Torlone, Simona Sarzi Braga Copyright (c) 2024 European Atherosclerosis Journal Tue, 30 Apr 2024 00:00:00 +0000