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Abstract Background The GLP-1 receptor agonist liraglutide is used to treat hyperglycemia in type 2 diabetes but is also known to induce weight loss, preserve the beta cell and reduce cardiovascular risk. The mechanisms underlying these effects are however still not completely known. Herein we explore the effect of liraglutide on markers of immune cell activity in a population of obese individuals with prediabetes or newly diagnosed type 2 diabetes mellitus. Method Plasma levels of the monocyte/macrophage markers, soluble (s)CD163 and sCD14, the neutrophil markers myeloperoxidase (MPO) and neutrophil gelatinase‐associated lipocalin (NGAL),the T-cell markers sCD25 and T-cell immunoglobulin mucin domain-3 (sTIM-3) and the inflammatory marker TNF superfamily (TNFSF) member 14 (LIGHT/TNFSF14) were measured by enzyme-linked immunosorbent assays in obese individuals with prediabetes or diabetes diagnosed within the last 12 months, prior to and after comparable weight loss achieved with lifestyle changes (n = 20) or liraglutide treatment (n = 20), and in healthy subjects (n = 13). Results At baseline, plasma levels of the macrophage marker sCD163, and the inflammatory marker LIGHT were higher in cases as compared to controls. Plasma levels of sCD14, NGAL, sTIM-3 and sCD25 did not differ at baseline between patients and controls. After weight reduction following lifestyle intervention or liraglutide treatment, sCD163 decreased significantly in the liraglutide group vs. lifestyle (between-group difference p = 0.023, adjusted for visceral adipose tissue and triglycerides basal values). MPO and LIGHT decreased significantly only in the liraglutide group (between group difference not significant). Plasma levels of MPO and in particular sCD163 correlated with markers of metabolic dysfunction and inflammation. After weight loss, only sCD163 showed a trend for decreased levels during OGTT, both in the whole cohort as in those of liraglutide vs lifestyle group. Conclusion Weight loss following treatment with liraglutide was associated with reduced circulating levels of sCD163 when compared to the same extent of weight loss after lifestyle changes. This might contribute to reduced cardiometabolic risk in individuals receiving treatment with liraglutide.

Cardiovascular disease (CVD) remains the leading cause of death worldwide. The risk of a cardiovascular (CV) event is not static and increases along a continuum, making identification and management complex.Aspirin has been the cornerstone of antiplatelet therapy in CV risk reduction and remains the only antiplatelet agent with current guideline recommendations throughout the CV risk continuum. In light of recent trials, the role of aspirin in CVD prevention in asymptomatic patients has been downgraded in clinical guidelines. However, a substantial proportion of asymptomatic patients have underlying conditions, such as advanced subclinical atherosclerosis that are associated with high CV risk. Advanced subclinical atherosclerosis has not been extensively investigated in patients in clinical trials but in the absence of significant bleeding risks, patients with subclinical atherosclerosis may particularly benefit from preventive aspirin therapy.Recent studies and clinical guidelines support the need for a personalized treatment approach for these patients, balancing their risk of future CV events against their relative bleeding risk. In this commentary, we first discussed various tools and strategies currently available for assessing CV and bleeding risks; we then provided two hypothetical cases to outline how these tools can be implemented for optimal management of patients with no prior CV events who, nonetheless, are susceptible to CVD.The first case details a young and apparently healthy patient with underlying advanced subclinical atherosclerosis; whereas the second case describes a patient with recently diagnosed type 2 diabetes mellitus who is at higher risk of CVD than their non-diabetic counterparts. For both cases, we considered patient clinical characteristics, CV and bleeding risks, as well as other risk factors to evaluate the appropriate treatment strategy and determine whether patients would obtain a net clinical benefit from low-dose aspirin therapy. These cases can serve as examples to guide clinical decision-making on the use of low-dose aspirin for primary CVD prevention and improve CVD management via a personalized approach.

Background Coronary artery calcium testing using noncontrast cardiac computed tomography is a guideline‐indicated test to help refine eligibility for aspirin in primary prevention. However, access to cardiac computed tomography remains limited, with carotid ultrasound used much more often internationally. We sought to update the role of aspirin allocation in primary prevention as a function of subclinical carotid atherosclerosis. Methods and Results The study included 11 379 participants from the MESA (Multi‐Ethnic Study of Atherosclerosis) and ARIC (Atherosclerosis Risk in Communities) studies. A harmonized carotid plaque score (range, 0–6) was derived using the number of anatomic sites with plaque from the left and right common, bifurcation, and internal carotid artery on ultrasound. The 5‐year number needed to treat and number needed to harm as a function of the carotid plaque score were calculated by applying a 12% relative risk reduction in atherosclerotic cardiovascular disease (ASCVD) events and 42% relative increase in major bleeding events related to aspirin use, respectively. The mean age was 57 years, 57% were women, 23% were Black, and the median 10‐year ASCVD risk was 12.8%. The 5‐year incidence rates (per 1000 person‐years) were 5.5 (4.9–6.2) for ASCVD and 1.8 (1.5–2.2) for major bleeding events. The overall 5‐year number needed to treat with aspirin was 306 but was 2‐fold lower for individuals with carotid plaque versus those without carotid plaque (212 versus 448). The 5‐year number needed to treat was less than the 5‐year number needed to harm when the carotid plaque score was ≥2 for individuals with ASCVD risk 5% to 20%, whereas the presence of any carotid plaque demarcated a favorable risk–benefit for individuals with ASCVD risk >20%. Conclusions Quantification of subclinical carotid atherosclerosis can help improve the allocation of aspirin therapy.

Background: Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin. Methods: PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included. Results: DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69–0.87]; p

Type 2 diabetes is a key player in atherothrombosis. Inflammation participates in metabolic homeostasis interacting with adipose tissue-specific macrophages. Platelets appear as addresses and players carrying and transducing metabolic derangement into vascular injury. AGE-RAGE pathway is recognized as the driver of metabolic memory. Human platelets have insulin receptors that participate in the regulation of platelet function and platelets are potential sites of insulin resistance. The present mini-review addresses key pathophysiological aspects including i) the role of inflammation in the pathogenesis of diabetes; ii) platelets as inflammatory cells; iii) the involvement on inflammation in the interindividual variability in aspirin response. Taken together, these aspects may contribute to expand knowledge about the link between the extent of inflammation, platelet activation and turnover, and interindividual variability in the development of atherothrombosis and its prevention, in a view of precision medicine.

Traditionally, guidelines divide patients into primary and secondary prevention for atherosclerotic cardiovascular disease (ASCVD) risk management. However, the modern understanding of the biological progression of atherosclerosis is inconsistent with this binary approach. Therefore, a new approach demonstrating both atherosclerosis and ASCVD risk as a continuum is needed to give clinicians a framework for better matching risk and intensity of therapy. Advances in coronary imaging have most clearly brought this problem into view, as for example coronary artery calcium (CAC) scoring has shown that some individuals in the primary prevention have equal or higher ASCVD risk as certain subgroups in secondary prevention. This article introduces “advanced subclinical atherosclerosis” as a new and distinct clinical group that sits between the traditional groups of primary and secondary prevention. Importantly, this article also introduces a new graphic to visualize this intermediate population that is explicitly based on plaque burden. The aim of the graphic is both to educate and to allow for better identification of a patient's cardiovascular risk and guide more effective risk-based management.

Abstract The 7th Cardiovascular Outcome Trial (CVOT) Summit on Cardiovascular, Renal, and Glycemic Outcomes, was held virtually on November 18–19, 2021. Pursuing the tradition of the previous summits, this reference congress served as a platform for in-depth discussion and exchange on recently completed CVOTs. This year’s focus was placed on the outcomes of EMPEROR-Preserved, FIGARO-DKD, AMPLITUDE-O, SURPASS 1–5, and STEP 1–5. Trial implications for diabetes and obesity management and the impact on new treatment algorithms were highlighted for endocrinologists, diabetologists, cardiologists, nephrologists, and general practitioners. Discussions evolved from outcome trials using SGLT2 inhibitors as therapy for heart failure, to CVOTs with nonsteroidal mineralocorticoid receptor antagonists and GLP-1 receptor agonists. Furthermore, trials for glycemic and overweight/obesity management, challenges in diabetes management in COVID-19, and novel guidelines and treatment strategies were discussed. Trial registration The 8th Cardiovascular Outcome Trial Summit will be held virtually on November 10–11, 2022 ( http://www.cvot.org )

Abstract Background Soluble suppression of tumorigenesis-2 (sST2) and galectin (Gal)-3 are two biomarkers related to inflammation, metabolic disturbances and to myocardial fibrosis that characterize several cardiac pathological conditions. Increased circulating levels of these molecules have been associated with risk of cardiovascular death. Treatment with liraglutide, a glucagon-like peptide 1 analog, is associated with weight loss, improved glycemic control, and reduced cardiovascular risk. We wanted to assess (I) potential differences between subjects with prediabetes or type 2 diabetes mellitus (T2DM) and healthy controls in sST2 and Gal-3 circulating levels, and their relationship with glycemic control and markers of beta cell function and myocardial injury; (II) whether liraglutide treatment modulates these markers in subjects with prediabetes or early T2DM independently of weight loss; (III) whether baseline levels of any of these two molecules may predict the response to liraglutide treatment. Methods Forty metformin-treated obese subjects (BMI ≥ 30) with prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) or both (n = 23)] or newly diagnosed T2DM (n = 17), were randomized to liraglutide or lifestyle counseling until achieving a comparable weight loss (7% of initial body weight). Thirteen subjects were enrolled as healthy controls for baseline sST2 and Gal-3 levels. Results Baseline sST2 levels were comparable between controls and obese patients (p = 0.79) whereas Gal-3 levels were significantly higher in patients as compared to controls (p

The most recent primary cardiovascular disease (CVD) prevention clinical guidelines used in Europe, Italy, the USA, China, and South Korea differ in aspects of their approach to CVD risk assessment and reduction. Low dose aspirin use is recommended in certain high-risk patients by most but not all the countries. Assessment of traditional risk factors and which prediction models are commonly used differ between countries. The assessments and tools may not, however, identify all patients at high risk but without manifest CVD. The use of coronary artery calcium (CAC) score to guide decisions regarding primary prevention aspirin therapy is recommended only by the US primary prevention guidelines and the 2021 European Society of Cardiology guidelines. A more consistent and comprehensive global approach to CVD risk estimation in individual patients could help to personalize primary CVD prevention. Wider detection of subclinical atherosclerosis, together with structured assessment and effective mitigation of bleeding risk, may appropriately target patients likely to gain net benefit from low dose aspirin therapy.

Abstract Background With aging of the population, screening and prevention health programs for blood donors will increasingly be a priority. We aimed at: assessing the 10 year-cardiovascular disease (CVD) risk in blood donors, according to Italian CUORE risk score (CRS); determining the association of homocysteine (Hcy), lipoprotein (Lp)(a) and socio-demographic or lifestyle variables with estimated 10-year CVD risk. Methods Between June 2015 and July 2017, 1,447 (61.2% men) unselected blood donors (aged 18–69 years) were enrolled at the Blood Transfusion Service of the Pescara General Hospital, Italy. The project entailed evaluation of unalterable (age and gender) and modifiable CV risk factors (total cholesterol, HDL, LDL, triglycerides, fasting glucose, smoking, hypertension). The educational attainment, socio-demographic and lifestyle behavior information were obtained through a structured self-report questionnaire, and Health-related quality of life (HRQoL) through the Short Form Survey (SF-12). Plasma Hcy and Lp(a) were determined in the fasting state. Results A CRS within the moderate-high risk range was reported in 21.7% donors. Multivariate logistic regression, after adjustment for clinical and demographic variables, showed that Hcy [OR (95% CI): 1.09 (1.04–1.13); p 30 mg/dL in 22.4% of the examined population, but without any significant correlation with CRS. Conclusions Our study highlights a previously unappreciated need for CV risk assessment in blood donors, which may include evaluation of educational attainment as a non-traditional risk marker.