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Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Commission in the H2020 program: Project SMARTool, "Simulation Modeling of coronary ARTery disease: a tool for clinical decision support—SMARTool" Background and aims The coexistence of elevated plasma triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) may contribute to the residual cardiometabolic risk of coronary artery disease (CAD) independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) absolute plasma levels [1]. Aim of this study is to assess whether a high TG/HDL-C ratio is characterized by a specific lipidomics signature in statin users and its relationship with the coronary risk score defined by coronary computed tomography angiography (CTA). Methods TG/HDL-C ratio was calculated in 132 patients (68.8±7.7 years, 85 males) with suspected or known CAD referred to coronary CTA and receiving statins treatment in the last 6.3 ± 1.4 years before enrolment. Patients were grouped according to TG/HDL-C ratio quartiles: IQ (≤1.694), IIQ (1.695-2.399), IIIQ (2.400-3.281), and IVQ (>3.282). Coronary CTA exams were analysed according to the modified 17-segment American Heart Association classification [2] and interpretable segments were visually assessed for degree of stenosis and plaque composition. A comprehensive coronary risk score (CTA score) [3], previously validated as predictor of adverse outcome, was calculated in each patient. Except for subjects with normal arteries (CTA score = 0), all patients were classified into 3 groups of CTA score severity:  low (score < 5), intermediate (score 5-20) and high (score > 20) risk [4]. Patient-specific plasma targeted lipidomics was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). This approach allowed to quantify 69 circulating lipids encompassing six lipid classes (triacylglycerol [TG], phosphatidylcholine [PC], phosphatidylethanolamine [PE], ceramide [Cer], sphingomyelin [SM], cholesterol ester [CE]). Differential analysis was performed using TG/HDL-C and CTA score annotation. Results 18 altered lipid species in the group with higher TG/HDL-C ratio were also altered in the group with higher CTA risk score. This common set of lipids is composed of CE(16:0), CE(18:0), PC(38:2), 8 SM [SM(34:2), SM(38:2), SM(41:2), SM(41:1), SM(42:4), SM(42:3), SM(42:1), SM(43:3)], TG(52:1) and 6 PE [PE(34:0), PE(34:1), PE(34:2), PE(36:1), PE(36:2), PE(36:3)], and represents the lipidomics signature associating elevated plasma TG/HDL-C ratio with high CTA risk score in statin users. Conclusion In patients with stable CAD under statin treatment, a specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters and sphingomyelins and increased levels of triacylglicerols and phosphatidylethanolamines, is associated with high TG/HDL-C ratio and high CTA score. This specific lipidomic signature identifies patients with higher residual cardiometabolic and coronary risk, not tackled by current lipid lowering therapy, unveiling possible new molecular targets of treatment. Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Background. Inflammation is a critical process contributing to heart failure (HF).We hypothesized that IL-33/ST2 pathway, a new mechanism regulated during cardiac stress, may be involved in the functional worsening of end-stage HF patients, candidates for left ventricular assist device (LVAD) implantation, and potentially responsible for their outcome. Methods. IL-33, ST2, and conventional cytokines (IL-6, IL-8, and TNF-α) were determined in cardiac biopsies and plasma of 22 patients submitted to LVAD implantation (pre-LVAD) and compared with (1) control stable chronic HF patients on medical therapy at the moment of heart transplantation without prior circulatory support (HT); (2) patients supported by LVAD at the moment of LVAD weaning (post- LVAD). Results. Cardiac expression of ST2/IL-33 and cytokines was lower in the pre-LVADthan in theHT group. LVADdetermined an increase of inflammatory mediators comparable to levels of the HT group. Only ST2 correlated with outcome indices after LVAD implantation. Conclusions. IL-33/ST2 and traditional cytokines were involved in decline of cardiac function of ESHF patients as well as in hemodynamic recovery induced by LVAD. IL-33/ST2 pathway was also associated to severity of clinical course.Thus, a better understanding of inflammation is the key to achieving more favorable outcome by new specific therapies. [ABSTRACT FROM AUTHOR]

We examined the intestinal delivery of conjugated linoleic acids (CLA) given in their triacylglycerol form in the mesenteric lymph of rats. Emulsions containing a mixture of the trilinolein/triester of CLA (9:1) and a tri-[1-(14)C]-linoleyl-sn-glycerol tracer were administered by force-feeding. Lymph was collected over two time periods (0-6 and 6-24 h), and the apparent recovery of CLA was determined relative to that of [1-(14)C]-18:2(n-6). A mixture of CLA-triester/trilinolein (1:9), trilinolein or CLA-triester was separately subjected to pancreatic lipase hydrolysis in vitro to determine whether the lymphatic recovery of CLA was correlated with the initial step of digestion. Lymphatic recovery of CLA was similar to that of 18:2(n-6) (95.6+/-9.0% of the linoleic acid recovery), and isomer repartition was similar in lymph and in the oil fed, indicating that all the CLA isomers were equally absorbed by the enterocytes. Unexpectedly, the in vitro release of CLA into the absorbable forms (free fatty acids and 2-monoacyl-sn-glycerol) was consistently lower than that of 18:2(n-6). Moreover, the 9c, 11t-isomer of CLA was also released faster into the absorbable forms than its 10t,12c homolog (P = 0.05). We cannot ascribe a distinct cellular accumulation or a difference in the biological effects of different CLA isomers on the ground of a selective intestinal absorbability. Also, the physiological conditions prevailing in vivo in the digestive tract are likely to overcome the relative resistance of CLA ester bonds to pancreatic lipase hydrolysis and allow a lymphatic recovery of CLA similar to that of linoleic acid. [ABSTRACT FROM AUTHOR]

Cross-linguistic similarities and differences in early lexical and grammatical development are reported for 1001 English-speaking children and 386 Italian-speaking children between 1;6 and 2;6. Parents completed the English or Italian versions of the MacArthur Communicative Development Inventory: Words and Sentences, a parent report instrument that provides information about vocabulary size, vocabulary composition and grammatical complexity across this age range. The onset and subsequent growth of nouns, predicates, function words and social terms proved to be quite similar in both languages. No support was found for the prediction that verbs would emerge earlier in Italian, although Italians did produce a higher proportion of social terms, and there were small but intriguing differences in the shape of the growth curve for grammatical function words. A strikingly similar nonlinear relationship between grammatical complexity and vocabulary size was observed in both languages, and examination of the order in which function words are acquired also yielded more similarities than differences. However, a comparison of the longest sentences reported for a subset of children demonstrates large cross-linguistic differences in the amount of morphology that has been acquired in children matched for vocabulary size. Discussion revolves around the interplay between language-specific variations in the input to young children, and universal cognitive and social constraints on language development. [ABSTRACT FROM AUTHOR]

The present study examines the suggestion that in the absence of adequate bile and pancreatic juice, which support the absorption from the gut of long-chain fatty acidsinto lymph, the fatty acids are absorbed directly into the portal blood. Oleic acid (18:l) partitioning between lymph and portal blood was investigated in intact and bile- and pancreatic juice-diverted rats. In a first set of experiments, 18: 1 absorption from the gut into lymph and blood was studied by continuous recovery of the mesenteric lymph for 6 h and mesenteric portal venous blood for 1 h. In a second set of experiments, esterification processes were investigated by study of the mucosal distribution of labelled lipids and by mono- and diacylglycerol acyltransferase (EC 2.3.1.22 and EC 2.3.1.20 respectively) specific activities. In the bile- and pancreatic juice-diverted rats the absorption of labelled 18:l into lymph was significantly reduced during the first 3 h of intraluminal infusion of this substrate. In such rats a compensatory absorption of labelled 18: 1 into mesenteric portal blood was not observed. At 6 h after micellar lipid- mixture infusion, the overload of lipids both in free form and as triacylglycerols persisting in the mucosa paralleled the lower acyltransferase specific activities observed in bile- and pancreatic juice-diverted rats. These studies demonstrate the absence of a previously proposed compensatory absorption of 18: 1 into portal blood when absorption into lymph is impaired by an inadequate supply of bile and pancreatic juice. [ABSTRACT FROM PUBLISHER]

These studies were designed to investigate the lymph absorption of a lipid emulsion in rats prefed different long-term high-fat diets. Particular emphasis was placed on the consequences of endogenous fatty acid alteration on the lymph recovery of two labeled fatty acids. Male Wistar rats were fed a standard diet (LF) containing 3.5 g/100 g fat or high-fat diets containing 15 g/100 g sunflower oil (HSFO), menhaden oil (HMO) or medium-chain triglyceride oil (HMCT) for 4 wk. The lymph was collected for 3 h before and after the intraduodenal infusion of a 90 micromol lipid emulsion (30 micromol monopalmitin, 30 micromol oleic acid, 25 micromol linoleic acid, 5 micromol arachidonic acid) labeled with [3H] oleic (OA) and [14C] arachidonic (AA) acids. The [3H] OA and [14C] AA lymph recoveries were measured and the lymph samples were tested for fatty acid, phospholipid and triglyceride content. Prefeeding an HSFO or HMO diet led to a 65 or 32% greater total lymph fatty acid output, respectively, compared with rats prefed the LF diet. In rats prefed both the HSFO and HMO diets, lymph fatty acid characteristics provided evidence of a dilution of exogenous fatty acids coming from the emulsion by endogenous fatty acids. In rats prefed the HMCT diet, the total lymph fatty acid output after the infusion of the lipid emulsion was not greater than that of starved rats. Nevertheless, 27% [3H] OA and 21% [14C] AA were recovered in the lymph, suggesting a limited dilution of exogenous fatty acids by endogenous fatty acids. In rats prefed the HMCT diet, some exogenous long-chain fatty acids must have been transported by the portal vein in response to low biliary phopholipid production, as indicated by the proportions of [3H] OA and [14C] AA taken up by the mucosa and not recovered in the lymph. Thus we demonstrated that during absorption of a single long-chain fatty acid meal a dilution of exogenous fatty acids by endogenous fatty acids occurred. The nature and the quantity of these endogenous fatty acids could alter the absorption efficiency of long-chain fatty acids by the lymphatic pathway and modify the fatty acid characteristics of lymph lipoprotein. [ABSTRACT FROM AUTHOR]

An abstract of the article "Heat Shock Protein 72 in Heart Failure," by C. Caselli and colleagues is presented.

An abstract of the article "Circulating Antibodies to Heat Shock Protein 65 in Patients With Heart Failure," by D. Giannessi and colleagues is presented.

An abstract of the study "Circulating antibodies to heat shock proteins and biomarkers in patients with heart failure," by D. Giannessi and colleagues is presented.

Aims: To date, no studies have investigated the association between lipid species and coronary plaque changes over time, quantitatively assessed by serial imaging. We aimed to prospectively determine the association between lipid species quantified by a plasma lipidomic analysis and coronary plaque changes according to composition assessed by a quantitative serial analysis of coronary computed tomography angiography (CTA)., Methods and Results: Patients with suspected coronary artery disease (CAD) undergoing baseline coronary CTA were prospectively enrolled by seven EU centres in the SMARTool study and submitted to clinical, molecular, and coronary CTA re-evaluation at follow-up (an inter-scan period of 6.39 ± 1.17 years). Out of 202 patients who were analysed in the SMARTool main clinical study, a lipidomic analysis was performed in 154 patients before the baseline coronary CTA, and this group was included in the present study. A quantitative CTA analysis was performed by using a separate core laboratory blinded from clinical data. In the univariable analysis, it was found that no lipid species were significantly associated with annual total and calcified plaque changes. After adjusting for clinical variables at baseline and statin use, it was found that three lipid species were significantly associated with non-calcified plaque progression. In detail, cholesteryl ester(20:3), sphingomyelin (SM)(40:3), and SM(41:1) were found to be positively related to non-calcified plaque progression (Bonferroni-adjusted P-values = 0.005, 0.016, and 0.004, respectively)., Conclusion: The current study showed an independent relationship between specific lipid species determined by a plasma lipidomic analysis and non-calcified coronary plaque progression assessed by a serial, quantitative coronary CTA analysis., Competing Interests: Conflict of interest: A.S. received fees for consultancy or lectures from Abbot, Amgen, Astra Zeneca, Bayer, Boehringer Ingelheim, and Pfizer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Cardiometabolic risk factors, including high fasting plasma glucose (hFPG), are emerging prognostic determinants in patients with coronary artery disease (CAD) or heart failure (HF). Coronary microvascular dysfunction might be a comprehensive risk predictor in these patients. The purpose of this study was to assess whether hFPG and global myocardial blood flow (MBF) reserve measured by positron emission tomography (PET), expressing global coronary function, predict long-term prognosis beyond other risk factors and presence of obstructive CAD or left ventricular (LV) dysfunction associated with HF. We retrospectively collected long-term follow-up data in 103 patients (mean age 61 ± 10 years, 74 males) with stable chest pain or dyspnoea who underwent cardiac PET/computerized tomography and coronary angiography. Disease phenotypes included obstructive CAD (35%), LV dysfunction without obstructive CAD (43%), or none (22%). At multivariable logistic regression analysis, MBF reserve lower than the median value (OR 1.8, 95% CI 1.5-2.2) was significantly associated with male gender (OR 3.45, 95% CI 1.21-9.83) and hFPG (OR 3.87, 95% CI 1.17-12.84) among all risk factors. In a median follow-up of 10.9 years (interquartile range 7.8-13.9), 39 patients (37.8%) died (13.6% cardiac death). At multivariable Cox analyses including all risk factors and disease phenotypes, age (HR 1.07, 95% CI 1.02-1.12), hFPG (HR 2.18, 95% CI 1.02-4.63), and depressed MBF reserve (HR 4.47, 95% CI 1.96-10.18) were independent predictors of death (global χ 2 37.41, P = 0.0004). These results suggest a strong long-term prognostic role of hFPG and depressed MBF reserve in a high-risk population of patients with a high prevalence of obstructive CAD or HF., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: We assessed whether combinations of cardiometabolic risk factors independently predict coronary plaque progression (PP) and major adverse cardiovascular events in patients with stable coronary artery disease., Methods: Patients with known or suspected stable coronary artery disease (60.9±9.3 years, 55.4% male) undergoing serial coronary computed tomography angiographies (≥2 years apart), with clinical characterization and follow-up (N=1200), were analyzed from the PARADIGM study (Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging). Plaque volumes measured in coronary segments (≥2 mm in diameter) were summed to provide whole heart plaque volume (mm 3 ) and percent atheroma volume (plaque volume/vessel volume×100; %) per patient at baseline and follow-up. Rapid PP was defined as a percent atheroma volume increase of ≥1.0%/y. Major adverse cardiovascular events included nonfatal myocardial infarction, death, and unplanned coronary revascularization., Results: In an interscan period of 3.2 years (interquartile range, 1.9), rapid PP occurred in 341 patients (28%). At multivariable analysis, the combination of cardiometabolic risk factors defined as metabolic syndrome predicted rapid PP (odds ratio, 1.51 [95% CI, 1.12-2.03]; P =0.007) together with older age, smoking habits, and baseline percent atheroma volume. Among single cardiometabolic variables, high fasting plasma glucose (diabetes or fasting plasma glucose >100 mg/dL) and low HDL-C (high-density lipoprotein cholesterol; <40 mg/dL in males and <50 mg/dL in females) were independently associated with rapid PP, in particular when combined (odds ratio, 2.37 [95% CI, 1.56-3.61]; P <0.001). In a follow-up of 8.23 years (interquartile range, 5.92-9.53), major adverse cardiovascular events occurred in 201 patients (17%). At multivariable Cox analysis, the combination of high fasting plasma glucose with high systemic blood pressure (treated hypertension or systemic blood pressure >130/85 mm Hg) was an independent predictor of events (hazard ratio, 1.79 [95% CI, 1.10-2.90]; P =0.018) together with family history, baseline percent atheroma volume, and rapid PP., Conclusions: In patients with stable coronary artery disease, the combination of hyperglycemia with low HDL-C is associated with rapid PP independently of other risk factors, baseline plaque burden, and treatment. The combination of hyperglycemia with high systemic blood pressure independently predicts the worse outcome beyond PP., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02803411., Competing Interests: Dr Chang receives funding from the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT (grant No. 2012027176). Dr Min receives funding from GE Healthcare and serves on the scientific advisory board of Arineta and GE Healthcare. Dr Min also has an equity interest in and is an employee of Cleerly Inc. The other authors report no conflicts.

Background: The endothelial nitric oxide synthase (eNOS) gene deficiency is known to cause impaired coronary vasodilating capability in animal models. In the general clinical population, the eNOS gene polymorphisms, able to affect eNOS activity, were associated with cardiometabolic risk features and prevalence of coronary artery disease (CAD)., Aim: To investigate the association of eNOS Glu298Asp gene polymorphism, cardiometabolic profile, obstructive CAD and inducible myocardial ischemia in patients with suspected stable CAD., Methods: A total of 506 patients (314 males; mean age 62 ± 9 years) referred for suspected CAD was enrolled. Among these, 325 patients underwent stress ECG or cardiac imaging to assess the presence of inducible myocardial ischemia and 436 patients underwent non-invasive computerized tomography or invasive coronary angiography to assess the presence of obstructive CAD. Clinical characteristics and blood samples were collected for each patient., Results: In the whole population, 49.6% of patients were homozygous for the Glu298 genotype (Glu/Glu), 40.9% heterozygotes (Glu/Asp) and 9.5% homozygous for the 298Asp genotype (Asp/Asp). Obstructive CAD was documented in 178/436 (40.8%) patients undergoing coronary angiography while myocardial ischemia in 160/325 (49.2%) patients undergoing stress testing. Patients with eNOS Asp genotype (Glu/Asp + Asp/Asp) had no significant differences in clinical risk factors and in circulating markers. Independent predictors of obstructive CAD were age, gender, obesity, and low HDL-C. Independent predictors of myocardial ischemia were gender, obesity, low HDL-C and Asp genotype. In the subpopulation in which both stress tests and coronary angiography were performed, the Asp genotype remained associated with increased myocardial ischemia risk after adjustment for obstructive CAD., Conclusion: In this population, low-HDL cholesterol was the only cardiometabolic risk determinant of obstructive CAD. The eNOS Glu298Asp gene polymorphism was significantly associated with inducible myocardial ischemia independently of other risk factors and presence of obstructive CAD., (© 2024. The Author(s).)

The cardiac troponin complex (cTn) is a regulatory component of sarcomere. cTn consists of three subunits: cardiac troponin C (cTnC), which confers Ca 2+ sensitivity to muscle; cTnI, which inhibits the interaction of cross-bridge of myosin with thin filament during diastole; and cTnT, which has multiple roles in sarcomere, such as promoting the link between the cTnI-cTnC complex and tropomyosin within the thin filament and influencing Ca 2+ sensitivity of cTn and force development during contraction. Conditions that interfere with interactions within cTn and/or other thin filament proteins can be key factors in the regulation of cardiac contraction. These conditions include alterations in myofilament Ca 2+ sensitivity, direct changes in cTn function, and triggering downstream events that lead to adverse cardiac remodeling and impairment of heart function. This review describes gene expression and post-translational modifications of cTn as well as the conditions that can adversely affect the delicate balance among the components of cTn, thereby promoting contractile dysfunction., Competing Interests: The authors declare there are no competing interests., (© 2024 The Authors. Publishing services by Elsevier B.V. on behalf of KeAi Communications Co., Ltd.)

Background: Ventricular assist device (VAD) implant represents a therapeutic option for pediatric patients with end-stage heart failure (HF). Heart unloading by VAD can modify several molecular pathways underlying cardiac function in HF. Among them, the potential role of microRNA (miRNAs) in response to VAD implant is emerging. This study was aimed at investigating in HF pediatric patients the effect of VAD-modified miRNAs on the adiponectin (ADPN) system, known to exert cardioprotective actions., Methods: ADPN was measured in plasma samples obtained from HF children, before and 1 month after VAD implant, and from healthy control children. miRNA profile and molecules belonging to ADPN system were determined in cardiac biopsies collected at the time of VAD implantation (pre-VAD) and at the moment of heart transplant (post-VAD). An in vitro study using HL-1 cell line was performed to verify the regulatory role of the VAD-modified miRNA on the ADPN system., Results: VAD implant did not affect circulating and cardiac levels of ADPN, but increased the cardiac mRNA expression of ADPN receptors, including AdipoR1, AdipoR2, and T-cad. AdipoR2 and T-cad were inversely related to the VAD-modified miRNA levels. The in vitro study confirmed the regulatory role of miR-1246 and miR-199b-5p on AdipoR2, and of miR-199b-5p on T-cad., Conclusions: These data suggest that VAD treatment could regulate the expression of the cardioprotective ADPN system by epigenetic mediators, suggesting that miRNAs have a potential role as therapeutic targets to improve cardiac function in HF pediatric patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This study was supported partially by grants from the projects SensorART-A Remote Controlled Sensorized ARTificial Heart Enabling Patients Empowerment and New Therapy Approaches (FP7-ICT-2009 Project, Grant Agreement 24863)., (© 2024 International Society for Heart and Lung Transplantation.)

The cardiac troponins (cTns), cardiac troponin C (cTnC), cTnT, and cTnI are key elements of myocardial apparatus, fixed as protein complex on the thin filament of sarcomere and are involved in the regulation of excitation-contraction coupling of cardiomyocytes in the presence of Ca 2+ . Circulating cTnT and cTnI (cTns) increase following cardiac tissue necrosis, and they are consolidated biomarkers of acute myocardial infarction (AMI). However, the use of high sensitivity (hs)-immunoassay tests for cTnT and cTnI has made it possible to identify a multitude of other clinical conditions associated with increased circulating levels of cTns. cTns can be measured also in the peripheral circulation of healthy subjects or athletes, suggesting that different mechanisms are involved in the release of cTns in the blood independently of cardiac cell necrosis. In this review, the molecular/cellular mechanisms involved in cTns release in blood and the exploitation of cTnI and cTnT as biomarkers of cardiac adverse events, in addition to cardiac necrosis, are discussed., (© 2022 International Union of Biochemistry and Molecular Biology.)

The transcriptional profile of adrenomedullin (AM), a new metastasis-related factor involved in hepatocellular carcinoma (HCC), and its specific receptors (CLR, RAMP1, RAMP3) were evaluated in liver tissues of HCV-positive HCC subjects undergoing liver transplantation (LR) and in donors (LD). AM and its specific receptor expression were also assessed in extracellular vesicles (EVs) secreted by tumorigenic (HepG2) and non-tumorigenic (WRL68) cells by Real-Time PCR. AM expression resulted significantly elevated in LR concerning LD (p = 0.0038) and, for the first time, significantly higher levels in HCC patients as a function of clinical severity (MELD score), were observed. RAMP3 and CLR expression increased in LR as a function of clinical severity while RAMP1 decreased. Positive correlations were found among AM, its receptors, and apoptotic markers. No AM mRNA expression difference was observed between HepG2 and WRL68 EVs. RAMP1 and RAMP3 resulted lower in HepG2 concerning WRL68 while significantly higher levels were observed for CLR. While results at tissue level characterize AM as a regulator of carcinogenesis-tumor progression, those obtained in EVs do not indicate AM as a target candidate, neither as a pathological biomarker nor as a marker involved in cancer therapy., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background and Aims: Coronary atherosclerosis is a chronic non-resolving inflammatory process wherein the interaction of innate immune cells and platelets plays a major role. Circulating neutrophils, in particular, adhere to the activated endothelium and migrate into the vascular wall, promoting monocyte recruitment and influencing plaque phenotype and stability at all stages of its evolution. We aimed to evaluate, by flow cytometry, if blood neutrophil number and phenotype-including their phenotypic relationships with platelets, monocytes and lymphocytes-have an association with lipid-rich necrotic core volume (LRNCV), a generic index of coronary plaque vulnerability, in a group of stable patients with chronic coronary syndrome (CCS)., Methods: In 55 patients, (68.53 ± 1.07 years of age, mean ± SEM; 71% male), the total LRNCV in each subject was assessed by a quantitative analysis of all coronary plaques detected by computed tomography coronary angiography (CTCA) and was normalized to the total plaque volume. The expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1, CXCR4 and CD41a cell surface markers was quantified by flow cytometry. Adhesion molecules, cytokines and chemokines, as well as MMP9 plasma levels, were measured by ELISA., Results: On a per-patient basis, LRNCV values were positively associated, by a multiple regression analysis, with the neutrophil count ( n° /µL) ( p = 0.02), neutrophil/lymphocyte ratio ( p = 0.007), neutrophil/platelet ratio ( p = 0.01), neutrophil RFI CD11b expression ( p = 0.02) and neutrophil-platelet adhesion index ( p = 0.01). Significantly positive multiple regression associations of LRNCV values with phenotypic ratios between neutrophil RFI CD11b expression and several lymphocyte and monocyte surface markers were also observed. In the bivariate correlation analysis, a significantly positive association was found between RFI values of neutrophil-CD41a+ complexes and neutrophil RFI CD11b expression ( p < 0.0001)., Conclusions: These preliminary findings suggest that a sustained increase in circulating neutrophils, together with the up-regulation of the integrin/activation membrane neutrophil marker CD11b may contribute, through the progressive intra-plaque accumulation of necrotic/apoptotic cells exceeding the efferocytosis/anti-inflammatory capacity of infiltrating macrophages and lymphocytes, to the relative enlargement of the lipid-rich necrotic core volume of coronary plaques in stable CAD patients, thus increasing their individual risk of acute complication.