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The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and volume homeostasis, promoting critical structural changes in every component of the cardiovascular system, including the heart and blood vessels. Consequently, the RAAS is a crucial therapeutic target for several chronic diseases of the cardiovascular system, spanning from arterial hypertension (AH) to heart failure (HF). AH represents a leading risk factor for the development of symptomatic HF, particularly with left ventricle (LV) preserved ejection fraction (HFpEF). LV diastolic dysfunction and cardiac remodelling are the first discernible manifestations of heart disease in patients with AH. Typically, AH develops many years before the diagnosis of overt HF, providing a therapeutic target for preventive strategies. Treatment of AH is based on different classes of antihypertensive drugs, which show differences in their capacity to prevent the evolution towards HF. The blockers of the RAAS are effective drugs to treat AH and prevent HF with reduced ejection fraction (HFrEF), but the evidence of the potential benefits in patients with HFpEF remains limited. In this review, the authors summarise data from several clinical trials of HFpEF and HFrEF, focusing on the mechanisms leading the transition from AH to HF and late complications.

Among patients with heart failure and a reduced ejection fraction, those who received the SGLT2 inhibitor empagliflozin had a significantly lower incidence of cardiovascular death or hospitalization for heart failure than those who received placebo.

Background Sodium-glucose cotransporter-2 inhibitors reduce blood pressure (BP) and renal and cardiovascular events in patients with type 2 diabetes through not fully elucidated mechanisms. Aim of this study was to investigate whether dapagliflozin is able to acutely modify systemic and renal vascular function, as well as putative mechanisms. Methods Neuro-hormonal and vascular variables, together with 24 h diuresis, urinary sodium, glucose, isoprostanes and free-water clearance were assessed before and after a 2-day treatment with dapagliflozin 10 mg QD in sixteen type 2 diabetic patients; data were compared with those obtained in ten patients treated with hydrochlorothiazide 12.5 mg QD. Brachial artery endothelium-dependent and independent vasodilation (by flow-mediated dilation) and pulse wave velocity were assessed. Renal resistive index was obtained at rest and after glyceryl trinitrate administration. Differences were analysed by repeated measures ANOVA, considering treatment as between factor and time as within factor; Bonferroni post hoc comparison test was also used. Results Dapagliflozin decreased systolic BP and induced an increase in 24 h diuresis to a similar extent of hydrochlorothiazide; 24 h urinary glucose and serum magnesium were also increased. 24 h urinary sodium and fasting blood glucose were unchanged. Oxidative stress was reduced, as by a decline in urinary isoprostanes. Flow-mediated dilation was significantly increased (2.8 ± 2.2 to 4.0 ± 2.1%, p < 0.05), and pulse-wave-velocity was reduced (10.1 ± 1.6 to 8.9 ± 1.6 m/s, p < 0.05), even after correction for mean BP. Renal resistive index was reduced (0.62 ± 0.04 to 0.59 ± 0.05, p < 0.05). These vascular modifications were not observed in hydrochlorothiazide-treated individuals. Conclusions An acute treatment with dapagliflozin significantly improves systemic endothelial function, arterial stiffness and renal resistive index; this effect is independent of changes in BP and occurs in the presence of stable natriuresis, suggesting a fast, direct beneficial effect on the vasculature, possibly mediated by oxidative stress reduction.

Endothelial Dysfunction as a Target for Prevention of Cardiovascular Disease Daniele Versari , MD , Elena Daghini , MD , Agostino Virdis , MD , Lorenzo Ghiadoni , MD, PHD and Stefano Taddei , MD From the Department of Internal Medicine, University of Pisa, Pisa, Italy. Corresponding author: Stefano Taddei, s.taddei{at}med.unipi.it . The endothelium, once considered a mere selectively permeable barrier between the bloodstream and the outer vascular wall, is now recognized to be a crucial homeostatic organ, fundamental for the regulation of the vascular tone and structure. Indeed, endothelial cells are able to synthesize and secrete a broad spectrum of anti-atherosclerotic substances, the most characterized of which is nitric oxide (NO), a gas that is generated from the metabolism of l -arginine by endothelial NO synthase (eNOS), constitutively expressed in endothelial cells ( 1 ). Under physiologic conditions, endothelial stimulation induces the production and release of NO, which diffuses to surrounding tissue and cells and exerts its cardiovascular protective role by relaxing media-smooth muscle cells, preventing leukocyte adhesion and migration into the arterial wall, muscle cell proliferation, platelet adhesion and aggregation, and adhesion molecule expression ( 1 , 2 ). In disease conditions, including the presence of cardiovascular risk factors, the endothelium undergoes functional and structural alterations, thus losing its protective role and becoming a proatherosclerotic structure ( 1 ). In the earliest stages, the principal endothelial alteration is merely functional and addressed as “endothelial dysfunction.” The fundamental feature of this condition is the impaired NO bioavailability. This can be the consequence of either a reduced production by eNOS or, more frequently, of an increased breakdown by reactive oxygen species (ROS) ( 1 , 2 ). In the presence of impaired NO bioavailability, the endothelium implements various physiological pathways in the attempt to compensate for NO deficiency. For instance, endothelium-dependent vasodilation is warranted, although impaired, also in the presence of cardiovascular risk factors by the production and release of endothelium-derived vasodilators other than NO, such as prostanoids and other endothelium-derived hyperpolarizing factors. Along with NO deficiency, a dysfunctioning endothelium also becomes the source of other substances and mediators that are detrimental to the arterial wall, including endothelin-1, tromboxane A … [Full Text of this Article]

The validation of HF radar systems remains an area with significant scope for advancement, particularly in terms of linking data quality with system operational parameters, fully utilizing the potential of redundant data (e.g., overlapping radial measurements), and accurately capturing the spatiotemporal variability observed by independent devices, such as drifters. In this study, we conducted a large-scale Lagrangian measurement campaign in the Tuscan Archipelago, aimed at validating surface current data from the HF radar network. This radar network, a recent addition to the area, monitors an oceanographic region critical to Mediterranean dynamics. The validation was executed using different approaches: a Eulerian method, comparing the radial velocities measured by radar with drifter-derived velocities along radial directions; a Lagrangian method, contrasting the observed drifter trajectories with the synthetic virtual trajectories generated from radar-based flow fields; and radar-to-radar comparisons with the concurrent utilization of two radars in same point. Through fine-tuning of the quality control parameters and an analysis of the impact of different thresholds of such parameters, we assessed the radar’s ability to capture dynamic processes, identifying both strengths and limitations. Our results not only confirm the utility of HF radar in coastal monitoring but also provide a basis for improving calibration strategies, ultimately supporting more accurate, high-resolution radar observations in complex marine environments.

IntroductionPostprandial hypoglycemia (PPHG) is a well-known complication after bariatric surgery (BS). However, it is not known whether PPHG affects weight loss after BS.AimsTo assess the impact of PPHG on weight loss after BS in subjects without and with type 2 diabetes mellitus (T2D).MethodsData from 338 subjects who had undergone gastric bypass (RYGB) or sleeve gastrectomy (LSG) and were followed up for at least 2 years were analyzed. At each follow-up visit, the patient’s anthropometric and biochemical characteristics were recorded and the Edinburgh Questionnaire was performed to evaluate the presence of PPHG symptoms.ResultsBefore surgery: younger age and lower BMI predicted PPHG after BS (p = 0.02 and p = 0.0008, respectively). Also, the baseline OGTT indicated that subjects who developed PPHG had an earlier glucose peak and more often had low glucose levels at 2 h compared with the no-PPHG group (p = 0.03 and p = 0.004, respectively). After surgery: Mild-to-moderate PPHG occurred equally after RYGB and LSG (38% vs 25%, p = ns when accounting for confounders), and in T2D who achieved remission and those who did not (29.5% vs 28.6%, ns). At the 2-year follow-up, occurrence of PPHG was independently associated with smaller weight loss (p = 0.0006).ConclusionsMild-to-moderate PPHG is a frequent complication after bariatric surgery and results in smaller weight loss after 2 years. Age, baseline BMI, and an earlier glucose peak during OGTT predict PPHG after bariatric surgery.

Background Mitochondrial dysfunction is a hallmark of cardiometabolic diseases. Circulating mitochondrial DNA (mtDNA) profiles could refine risk stratification, but current methods do not account for different fractions of circulating mtDNA. We investigated whether patients with type 2 diabetes and/or heart failure (HF) have a specific signature of the total circulating mtDNA profile, including intracellular and cell-free fractions. Methods We performed a complete clinical assessment, including blood tests, 12-lead ECG and ultrasound at rest and during cardiopulmonary exercise. Ultrasound congestion was defined at rest as inferior vena cava of ≥ 21 mm, lung B-lines ≥ 4, or discontinuous renal venous flow. In fasting whole blood and plasma samples collected at rest, we simultaneously measured the copy number of the cellular and cell-free components of mtDNA by real-time quantitative polymerase chain reaction (qPCR) using custom standards. We calculated the ratio of cell mtDNA to cell-free mtDNA as an index of mitochondrial efficiency. Results We enrolled 120 consecutive patients: 50 (42%) with HF and preserved ejection fraction (HFpEF), 40 (33%) with HF and reduced ejection fraction (HFrEF) and 30 (25%) at risk of developing HF; 42/120 (35%) had diabetes. Cell-free mtDNA was increased in patients with HF (with higher levels in HFrEF than HFpEF) and those with diabetes. Cell-free mtDNA was also higher in patients with systemic inflammation (expressed by high-sensitivity C-reactive protein [hs-CRP] ≥ 0.2 mg/dL with neutrophil-lymphocyte ratio [NLR] > 3) and more ultrasound signs of congestion. The cell/cell-free mtDNA ratio showed opposite trends (all p  < 0.05), but there were no significant differences in cell mtDNA. Cell-free mtDNA and mtDNA ratio independently predicted the presence of ≥ 2 ultrasound signs of congestion and effort intolerance (peak oxygen consumption < 16 mL/kg/min) at ROC analysis and using multivariable regressions after adjustment for age, sex, hs-CRP, NLR, high-sensitivity Troponin T and NT-proBNP. Conclusions Patients with HF and diabetes have an altered circulating mtDNA signature characterised by higher cell-free mtDNA and lower mtDNA ratio, whereas cellular mtDNA remains unaffected. Cell-free mtDNA and mtDNA ratio are associated with impaired response to exercise, higher systemic inflammation and increased congestion. Circulating mitochondrial profile could be a new biomarker of mitochondrial status in cardiometabolic diseases. Graphical abstract

Overweight and obesity are major risk factors for heart failure (HF), contributing to its development through metabolic, neurohormonal, haemodynamic, and inflammatory alterations. While overweight/obesity increases the risk of developing HF, its impact on patient outcomes remains complex. The “obesity paradox” suggests that a higher BMI may be associated with improved survival in patients with established HF. However, recent GLP-1 receptor agonist (GLP-1 RA) trials suggest that intentional weight loss positively influences outcomes in overweight/obese patients with HF. This seemingly contradictory evidence highlights the need for a deeper understanding of the mechanisms linking adiposity to HF outcomes. A more precise characterization of adiposity phenotypes using alternative and accurate measures of pathological fat accumulation is crucial in identifying individuals who may benefit most from anti-obesity treatments. In this context, recent research underscores the role of epicardial adipose tissue (EAT) in HF pathophysiology, as it directly influences cardiac function and structure through inflammatory, metabolic, and mechanical effects. This narrative review summarises current evidence on the impact of weight loss on HF outcomes, focusing on recent GLP-1 RA trial results. Additionally, it highlights epidemiological and molecular data supporting EAT as a novel adiposity measure that might allow refining patient selection for pharmacological weight-loss treatments. Finally, it emphasizes the need for future research to identify causal pathways linking alternative measures of visceral fat accumulation to HF outcomes. These efforts will be essential in optimizing the benefits of novel weight-loss treatments, ensuring effective and individualized therapeutic strategies for overweight or obese patients with HF. Graphical abstract

This data descriptor presents the HF radar and drifter datasets, along with the methods used to process and apply them in a previously published study on the validation of surface current measurements in a region characterized by highly variable coastal dynamics. The data were collected in the framework of a large-scale Lagrangian experiment, which included extensive drifter deployment and the generation of virtual trajectories based on HF radar-derived flow fields. Both Eulerian and Lagrangian approaches were used to assess radar performance through correlation and RMSE metrics, with additional refinement achieved via Kriging interpolation. The validation results, published in Remote Sensing, demonstrated good agreement between HF radar and drifter observations, particularly when quality control parameters were optimized. The datasets and associated methodologies described here support ongoing efforts to enhance HF radar tuning strategies and improve surface current monitoring in complex marine environments.

The Mediterranean Sea is greatly affected by marine litter. In this area, research on the impact of plastic debris (including microplastics) on biota, particularly large filter-feeding species such as the fin whale (Balaenoptera physalus), is still in its infancy. We investigated the possible overlap between microplastic, mesoplastic and macrolitter accumulation areas and the fin whale feeding grounds in in a pelagic Specially Protected Area of Mediterranean Importance (SPAMI): the Pelagos Sanctuary. Models of ocean circulation and fin whale potential habitat were merged to compare marine litter accumulation with the presence of whales. Additionally, field data on microplastics, mesoplastics and macrolitter abundance and cetacean presence were simultaneously collected. The resulting data were compared, as a multi-layer, with the simulated distribution of plastic concentration and the whale habitat model. These data showed a high occurrence of microplastics (mean: 0.082 items/m2, STD ± 0.079 items/m2) spatial distribution agreed with our modelling results. Areas with high microplastic density significantly overlapped with areas of high macroplastic density. The most abundant polymer detected in all the sampling sites was polyethylene (PE), suggesting fragmentation of larger packaging items as the primary source. To our knowledge, this is the first study in the Pelagos Sanctuary in which the simulated microplastic distribution has been confirmed by field observations. The overlap between the fin whale feeding habitat and the microplastic hot spots is an important contribution for risk assessment of fin whale exposure to microplastics.