Explore the vast range of titles available.

Background Epicardial adipose tissue (EAT) plays an important role in cardiometabolic risk. EAT is a modifiable risk factor and could be a potential therapeutic target for drugs that already show cardiovascular benefits . The aim of this study is to evaluate the effect of cardiometabolic drugs on EAT reduction. Methods A detailed search related to the effect on EAT reduction due to cardiometabolic drugs, such as glucagon-like peptide-1 receptor agonist (GLP-1 RA), sodium-glucose cotransporter-2 inhibitors (SGLT2-i), and statins was conducted according to PRISMA guidelines. Eighteen studies enrolling 1064 patients were included in the qualitative and quantitative analyses. Results All three analyzed drug classes, in particular GLP-1 RA, show a significant effect on EAT reduction (GLP-1 RA standardize mean difference (SMD) = − 1.005; p < 0.001; SGLT2-i SMD = − 0.552; p < 0.001, and statin SMD = − 0.195; p < 0.001). The sensitivity analysis showed that cardiometabolic drugs strongly benefit EAT thickness reduction, measured by ultrasound (overall SMD of − 0.663; 95%CI − 0.79, − 0.52; p < 0.001). Meta-regression analysis revealed younger age and higher BMI as significant effect modifiers of the association between cardiometabolic drugs and EAT reduction for both composite effect and effect on EAT thickness, (age Z: 3.99; p < 0.001 and Z: 1.97; p = 0.001, respectively; BMI Z: − 4.40; p < 0.001 and Z: − 2.85; p = 0.004, respectively). Conclusions Cardiometabolic drugs show a significant beneficial effect on EAT reduction. GLP-1 RA was more effective than SGLT2-i, while statins had a rather mild effect. We believe that the most effective treatment with these drugs should target younger patients with high BMI. Graphical Abstract

Diabetes mellitus (DM) is one of the most common and costly disorders that affect humans around the world. Recently, clinicians and scientists have focused their studies on the effects of glycemic variability (GV), which is especially associated with cardiovascular diseases. In healthy subjects, glycemia is a very stable parameter, while in poorly controlled DM patients, it oscillates greatly throughout the day and between days. Clinically, GV could be measured by different parameters, but there are no guidelines on standardized assessment. Nonetheless, DM patients with high GV experience worse cardiovascular disease outcomes. In vitro and in vivo studies showed that high GV causes several detrimental effects, such as increased oxidative stress, inflammation, and apoptosis linked to endothelial dysfunction. However, the evidence that treating GV is beneficial is still scanty. Clinical trials aiming to improve the diagnostic and prognostic accuracy of GV measurements correlated with cardiovascular outcomes are needed. The present review aims to evaluate the clinical link between high GV and cardiovascular diseases, taking into account the underlined biological mechanisms. A clear view of this challenge may be useful to standardize the clinical evaluation and to better identify treatments and strategies to counteract this DM aspect.

BackgroundFibrocalcific aortic valve sclerosis (AVSc), the earliest manifestation of aortic stenosis (AS), is increasingly recognised as a marker of systemic vascular damage and adverse cardiovascular outcomes. While a subset of AVSc patients progresses to AS, reported rates vary widely. We conducted a systematic review and meta-analysis to better define the natural history of AVSc progression.MethodsFollowing Preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines, we searched PubMed, Scopus and Web of Science through July 2025 for observational studies reporting AS development in AVSc patients. Primary outcomes were progression to any degree of AS and to severe AS. Pooled event rates were calculated using a random-effects model. Heterogeneity and publication bias were assessed using standard statistical methods. Meta-regression explored associations with clinical and demographic variables.ResultsEight studies (n=12 388 patients) reported on the progression of AVSc patients to any AS stage, and nine studies (n=19 486 patients) on the progression to severe AS. Over a median follow-up of 4.0 years, 14.1% of AVSc patients progressed to any AS stage (effect size: 0.14; 95% CI 0.02 to 0.53), and 2.0% to severe AS (effect size: 0.02; 95% CI 0.003 to 0.094). Heterogeneity was high, but no publication bias was detected. Meta-regression found no significant predictors of progression.ConclusionsApproximately one in six AVSc patients progresses to AS within 4 years, and 2% develop a severe disease. These findings underscore the importance of structured echocardiographic surveillance and support AVSc as a clinically relevant marker of systemic cardiovascular risk.

Background Aortic valve stenosis (AS) is a progressive valvular disease characterized by fibrocalcific remodeling of the aortic valve leaflets, contributing to significant cardiovascular morbidity and mortality. While valve calcification has been extensively studied, the relationship between valve fibrosis, lipoprotein(a) [Lp(a)], systemic inflammation, sex differences, and valve morphology remains less explored. Methods We prospectively enrolled 45 patients with severe AS undergoing preoperative echocardiography and contrast-enhanced cardiac computed tomography (CT) at Centro Cardiologico Monzino. Aortic valve calcium and fibrosis volumes were quantified using threshold-based segmentation on CT images. Lp(a) was measured by ELISA, while a multiplex Luminex assay measured a panel of 44 cytokines. Patients were stratified by Lp(a) levels (≤ 50 vs. > 50 mg/dL), sex, and valve morphology (bicuspid vs. tricuspid) to explore associations with the fibrocalcific components of stenotic aortic valves. Results The median Lp(a) level was 34.4 mg/dL (12.6; 93.4). No significant differences in valvular calcium load were observed between low and high Lp(a) groups. However, a modest increase in fibrotic volume was noted in patients with elevated Lp(a), particularly among men ( p  = 0.075). Several cytokines, including IL-1RA, IL-8, and TGF-α in men, and EGF, GM-CSF, IP-10, and IL-10 in women, were positively correlated with calcium burden. Fibrotic volume was associated with elevated eotaxin and PDGF-AA levels, with sex-specific patterns. Patients with bicuspid valve exhibited higher fibrocalcific volumes but lower circulating levels of several cytokines compared to patients with tricuspid valve morphology. Conclusions In patients with severe AS, circulating cytokine profiles show sex- and valve-morphology-specific associations with the fibrocalcific composition of the valve. However, Lp(a) was not associated with valvular calcification, and any relationship with fibrosis appeared at most modest, more evident in men. These results support the relevance of inflammatory profiling in assessing AS pathophysiology. Graphical abstract

Human aging is a complex phenomenon characterized by a wide spectrum of biological changes which impact on behavioral and social aspects. Age-related changes are accompanied by a decline in biological function and increased vulnerability leading to frailty, thereby advanced age is identified among the major risk factors of the main chronic human diseases. Aging is characterized by a state of chronic low-grade inflammation, also referred as inflammaging. It recognizes a multifactorial pathogenesis with a prominent role of the innate immune system activation, resulting in tissue degeneration and contributing to adverse outcomes. It is widely recognized that inflammation plays a central role in the development and progression of numerous chronic and cardiovascular diseases. In particular, low-grade inflammation, through an increased risk of atherosclerosis and insulin resistance, promote cardiovascular diseases in the elderly. Low-grade inflammation is also promoted by visceral adiposity, whose accumulation is paralleled by an increased inflammatory status. Aging is associated to increase in epicardial adipose tissue (EAT), the visceral fat depot of the heart. Structural and functional changes in EAT have been shown to be associated with several heart diseases, including coronary artery disease, aortic stenosis, atrial fibrillation, and heart failure. EAT increase is associated with a greater production and secretion of pro-inflammatory mediators and neuro-hormones, so that thickened EAT can pathologically influence, in a paracrine and vasocrine manner, the structure and function of the heart and is associated to a worse cardiovascular outcome. In this review, we will discuss the evidence underlying the interplay between inflammaging, EAT accumulation and cardiovascular diseases. We will examine and discuss the importance of EAT quantification, its characteristics and changes with age and its clinical implication.

Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder associated with various complications, including cardiovascular diseases. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) have emerged as novel therapeutic agents for T2DM, primarily aiming to reduce blood glucose levels. However, recent investigations have unveiled their multifaceted effects, extending beyond their glucose-lowering effect. SGLT2i operate by inhibiting the SGLT2 receptor in the kidneys, facilitating the excretion of glucose through urine, leading to reduced blood glucose levels, while GLP1-RA mimic the action of the GLP1 hormone, stimulating glucose-dependent insulin secretion from pancreatic islets. Both SGLT2i and GLP1-RA have shown remarkable benefits in reducing major cardiovascular events in patients with and without T2DM. This comprehensive review explores the expanding horizons of SGLT2i and GLP1-RA in improving cardiovascular health. It delves into the latest research, highlighting the effects of these drugs on heart physiology and metabolism. By elucidating their diverse mechanisms of action and emerging evidence, this review aims to recapitulate the potential of SGLT2i and GLP1-RA as therapeutic options for cardiovascular health beyond their traditional role in managing T2DM.

Thoracic aortic aneurysm (TAA) that progress to acute aortic dissection is often fatal and there is no pharmacological treatment that can reduce TAA progression. We aim to evaluate statins' effects on TAA growth rate and outcomes using a meta-analysis approach. A detailed search related to the effects of statins on TAA was conducted according to PRISMA guidelines. The analyses of statins' effects on TAA growth rate were performed on 4 studies (n = 1850), while the impact on outcomes was evaluated on 3 studies (n = 2,867). Patients under statin treatment showed a reduced TAA growth rate (difference in means = -0.36 cm/year; 95%CI: -0.64, -0.08; = 0.013) when compared to controls, patients not taking statins. Regarding the outcomes (death, dissection, or rupture of the aorta, and the need for operative repair), statins exhibited a protective effect reducing the number of events (log odds ratio = -0.56; 95%CI: -1.06, -0.05; = 0.030). , the anti-fibrotic effect of atorvastatin was tested on vascular smooth muscle cells (VMSC) isolated from patients with TAA. Our results highlighted that, in transforming growth factor beta 1 (TGF-β1) pro-fibrotic condition, VSMC expressed a significant lower amount of collagen type I alpha 1 chain (COL1A1) when treated with atorvastatin (untreated = +2.66 ± 0.23 fold-change vs. treated = +1.63 ± 0.09 fold-change; = 0.014). Statins show a protective effect on TAA growth rate and adverse outcomes in patients with TAA, possibly via their anti-fibrotic properties on VSMC. Given the current lack of effective drug treatments for TAA, we believe our findings highlight the need for more in-depth research to explore the potential benefits of statins in this context.

Aortic stenosis (AS) is the most common valve disorder characterized by fibro-calcific remodeling of leaflets. Recent evidence indicated that there is a sex-related difference in AS development and progression. Fibrotic remodeling is peculiar in women's aortic valves, while men's leaflets are more calcified. Our study aimed to assess aortic valve fibrosis (AVF) in a severe AS cohort using non-invasive diagnostic tools and determine whether sex-specific pathological pathways and cell types are associated with severe AS. We have included 28 men and 28 women matched for age with severe AS who underwent echocardiography and cardiac contrast-enhanced computed tomography (CT) before intervention. The calcium and fibrosis volumes were assessed and quantified using the ImageJ thresholding method, indexed calcium and fibrosis volume were calculated by dividing the volume by the aortic annular area. For a deeper understanding of molecular mechanisms characterizing AS disorder, differentially expressed genes and functional inferences between women and men's aortic valves were carried out on a publicly available microarray-based gene expression dataset (GSE102249). Cell types enrichment analysis in stenotic aortic valve tissues was used to reconstruct the sex-specific cellular composition of stenotic aortic valves. In agreement with the literature, our CT quantifications showed that women had significantly lower aortic valve calcium content compared to men, while fibrotic tissue composition was significantly higher in women than men. The expression profiles of human stenotic aortic valves confirm sex-dependent processes. Pro-fibrotic processes were prevalent in women, while pro-inflammatory ones, linked to the immune response system, were enhanced in men. Cell-type enrichment analysis showed that mesenchymal cells were over-represented in AS valves of women, whereas signatures for monocytes, macrophages, T and B cells were enriched men ones. Our data provide the basis that the fibro-calcific process of the aortic valve is sex-specific, both at gene expression and cell type level. The quantification of aortic valve fibrosis by CT could make it possible to perform population-based studies and non-invasive assessment of novel therapies to reduce or halt sex-related calcific aortic valve stenosis (CAVS) progression, acting in an optimal window of opportunity early in the course of the disease.

Background: Ageing is a significant risk factor for carotid atherosclerosis, affecting over a billion people worldwide. Carotid intima-media thickness (cIMT) is a surrogate marker for cardiovascular disease (CVD) risk, with age- and sex-related differences in levels and progression. The onset of clinical manifestations of CVD in women is delayed by about 10 years compared to men. The present study aims to evaluate whether subclinical atherosclerosis is the same disease in men and women or two pathologies with a possible different etiology. For this purpose, we analyzed the differences in cIMT, the impact of patient characteristics, and the influence of age on cIMT in men and women. Methods: A systematic search related to cIMT measured by an ultrasound and gender-specific differences was conducted according to the PRISMA 2020 guidelines. Ninety studies, enrolling 165,551 subjects (76,955 men and 88,553 women), were included in the quantitative synthesis. Results: We found that men compared to women had greater common cIMT, (standardized mean difference (SMD) = 0.506, p < 0.03; I2: 98.2, p < 0.0001), greater bifurcation IMT (SMD = 1.056, p = 0.022; I2: 99.9%, p < 0.001), and higher internal cIMT (SMD = 1.124, p = 0.017; I2: 99.9%, p < 0.001). The study did not reveal any association between cardiovascular risk factors and differences in cIMT between men and women. A virtual analysis revealed that age-related cIMT is equal between sexes but postponed by 10 years in women. Conclusions: This study showed that classical risk factors for CVD have a comparable effect on cIMT in men and women. While subclinical atherosclerotic disease, as assessed by cIMT, is essentially identical in the two sexes, it manifests itself by about 10 years later in women.

Genetic testing is essential for disease screening, diagnosis, prognosis, and pharmacotherapy guidance. Oxford Nanopore Technologies (ONT) offers a cost-effective platform for long-read sequencing, yet its routine use in clinical diagnostics remains under evaluation. We tested different nanopore sequencing pipelines aimed at accurately detecting single-nucleotide variants (SNV) in a gene locus spanning ⁓25 kb. As a proof of concept, was selected for its relevance to cardiovascular disease and suitable sequence structure. Twelve subjects were analyzed using different sequencing flow cells, basecalling models, and SNV calling algorithms. Sanger sequencing served as the reference for performance validation. Sequencing throughput per flow cell was also estimated. The combination of super high accuracy (SUP) basecalling with Longshot variant calling demonstrated the highest performance across flow cells. MinION flow cell reached a perfect F1-score of 100%, while the more cost-effective Flongle flow cell remained a viable alternative (mean F1-score: 98.2% ± 4.2). Throughput analysis indicated that a single MinION flow cell could process up to 96 samples and ⁓40 long sequencing regions, whereas a Flongle flow cell could support sequencing of 96 samples and one long region. The proposed nanopore-based SNV identification workflows may support the development of long-read, targeted gene panels, offering a promising tool for both diagnostic and discovery applications, particularly in multi-gene settings such as oncology and cardiology.