Triglyceride-glucose index threshold for cardiovascular mortality in hypertensive individuals - URRAH project.

Aims: The triglyceride-glucose (TyG) index is a surrogate marker of insulin resistance (IR). Data regarding this topic is constantly increasing, however, few and heterogeneous data are available on the relationship between this index and cardiovascular mortality risk in hypertensive populations. In this context, we aimed to explore the relationship between TyG and cardiovascular mortality in a large sample of hypertensive individuals from the URRAH cohort.

Single nuclei RNA-sequencing unveils alveolar macrophages as drivers of endothelial damage in obese HFpEF-related pulmonary hypertension.

Background: Pulmonary hypertension (PH) is a frequent complication in obese patients showing heart failure with preserved ejection fraction (HFpEF) and correlates with poor prognosis. PH associated with cardiometabolic HFpEF (PH-cHFpEF) is characterized by inflammation and metabolic dysregulation. Alterations in the immune landscape, particularly activation of alveolar macrophages (AMs), may propagate the inflammatory response and lead to endothelial damage and vascular remodeling in the lung.

Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cardiovascular risk (CV) factor. Interleukin-1β (IL-1β), a cytokine involved in the pathogenesis of obesity-associated inflammation and type 2 diabetes (T2D), promotes hepatic steatosis. The Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOS) trial showed that the inhibition of the IL-1β pathway was associated with a reduction of CV events in high-risk patients.

The HS-donor Erucin modulates SIRT1 and rescues obesity-induced vascular dysfunction in human vessels.

Evidence highlights the potential role of hydrogen sulfide (H₂S)-donors in preventing vascular dysfunction by modulating pathways associated with oxidative stress. We investigate the H₂S-donor Erucin for its potential to reduce oxidative stress and endothelial dysfunction in obesity. Patients undergoing laparoscopic surgery were categorized by body mass index in controls and patients with obesity.

Refining the link between obesity and heart failure: insights from GLP-1 receptor agonist trials and studies adopting direct adiposity measures.

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.

Chromatin Rewiring by SETD2 Drives Lipotoxic Injury in Cardiometabolic HFpEF.

Background: Cardiometabolic heart failure with preserved ejection fraction (cHFpEF) is a highly prevalent and deadly condition. Histone 3 trimethylation at lysine 36 (H3k36me3)-a chromatin signature induced by the histone methyltransferase SETD2 (SET domain containing 2)-correlates with changes in gene expression in human failing hearts; however, its role remains poorly understood. This study investigates the role of SETD2 in cHFpEF.

Circulating mitochondrial DNA signature in cardiometabolic patients.

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.

Targeting SETD7 Rescues Diabetes-Induced Impairment of Angiogenic Response by Transcriptional Repression of Semaphorin-3G.

Unlabelled: Revascularization strategies failed to improve outcome in patients with diabetes with peripheral artery disease (PAD). Histone modifications are key modulators of gene expression and could play a role in angiogenic response. This study investigates the role of chromatin remodelling in modulating angiogenesis in diabetes.

Predictive value of TG/HDL-C and GFR-adjusted uric acid levels on cardiovascular mortality: the URRAH study.

Background: Insulin resistance (IR) and serum uric acid (SUA) are closely interconnected: SUA contributes to adversely affects the insulin signaling pathway and contributes to IR, while IR is a known predictor for the development of hyperuricemia. The triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio has been proposed as an easily obtainable marker for IR. This research aimed to investigate the interaction between IR and glomerular filtration rate (GFR)-adjusted uricemia (SUA/GFR ratio) in determining CV risk in a large population cohort study.

Associations of iron deficiency with cardiac function, congestion, exercise capacity and prognosis in heart failure.

Aims: Uncertainty exists about defining true iron deficiency (ID) in heart failure (HF) patients. We assessed the relationship of different ID definitions with cardiac structure and function, congestion, exercise capacity, and prognosis in HF outpatients.

Methods And Results: Iron deficiency was defined according to guidelines (G-ID: ferritin <100 ng/ml or ferritin 100-299 ng/ml with transferrin saturation [TSAT] <20%).

Liver DE(HP)toxification: luteolin as "phthalates-cleaner" to protect from environmental pollution.

Environmental pollution is a major health problem that affects the health of individuals worldwide and is cumulative with other environmental stressors, contributing to the increasing prevalence of cancer, cardiometabolic, neurological and autoimmune diseases (Favé et al, 2018). Although being extensively studied, therapeutic strategies still rely primarily on exposure prevention, often with no option available to allow pollutant detoxification. In this issue of , Wang et al (Wang et al, 2024) investigated potential pharmacological strategies to allow the direct removal of phthalates, major environmental pollutants, from the liver.

Serum Uric Acid, Hypertriglyceridemia, and Carotid Plaques: A Sub-Analysis of the URic Acid Right for Heart Health (URRAH) Study.

High levels of serum uric acid (SUA) and triglycerides (TG) might promote high-cardiovascular-risk phenotypes, including subclinical atherosclerosis. An interaction between plaques xanthine oxidase (XO) expression, SUA, and HDL-C has been recently postulated. Subjects from the URic acid Right for heArt Health (URRAH) study with carotid ultrasound and without previous cardiovascular diseases (CVD) (n = 6209), followed over 20 years, were included in the analysis.

In-depth Microbiological Characterization of Urine From Subjects With Type 2 Diabetes.

Context: Lower urinary tract symptoms (LUTS) are common in type 2 diabetes (T2D), affecting quality of life and potentially leading to medication discontinuation. Among various factors contributing to LUTS, recent observations suggest a critical role of the urinary microbiota. Research on urinary dysbiosis in T2D remains underexplored.

Novel Techniques, Biomarkers and Molecular Targets to Address Cardiometabolic Diseases.

Cardiometabolic diseases (CMDs) are interrelated and multifactorial conditions, including arterial hypertension, type 2 diabetes, heart failure, coronary artery disease, and stroke. Due to the burden of cardiovascular morbidity and mortality associated with CMDs' increasing prevalence, there is a critical need for novel diagnostic and therapeutic strategies in their management. In clinical practice, innovative methods such as epicardial adipose tissue evaluation, ventricular-arterial coupling, and exercise tolerance studies could help to elucidate the multifaceted mechanisms associated with CMDs.

Serum Uric Acid/Serum Creatinine Ratio and Cardiovascular Mortality in Diabetic Individuals-The Uric Acid Right for Heart Health (URRAH) Project.

Several studies have detected a direct association between serum uric acid (SUA) and cardiovascular (CV) risk. In consideration that SUA largely depends on kidney function, some studies explored the role of the serum creatinine (sCr)-normalized SUA (SUA/sCr) ratio in different settings. Previously, the URRAH (URic acid Right for heArt Health) Study has identified a cut-off value of this index to predict CV mortality at 5.

Mechanisms of Vascular Inflammation and Potential Therapeutic Targets: A Position Paper From the ESH Working Group on Small Arteries.

Inflammatory responses in small vessels play an important role in the development of cardiovascular diseases, including hypertension, stroke, and small vessel disease. This involves various complex molecular processes including oxidative stress, inflammasome activation, immune-mediated responses, and protein misfolding, which together contribute to microvascular damage. In addition, epigenetic factors, including DNA methylation, histone modifications, and microRNAs influence vascular inflammation and injury.

Prognostic Value and Relative Cutoffs of Triglycerides Predicting Cardiovascular Outcome in a Large Regional-Based Italian Database.

Background: Despite longstanding epidemiologic data on the association between increased serum triglycerides and cardiovascular events, the exact level at which risk begins to rise is unclear. The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension has conceived a protocol aimed at searching for the prognostic cutoff value of triglycerides in predicting cardiovascular events in a large regional-based Italian cohort.

Methods And Results: Among 14 189 subjects aged 18 to 95 years followed-up for 11.

Early time-restricted carbohydrate consumption vs conventional dieting in type 2 diabetes: a randomised controlled trial.

Aims/hypothesis: Early time-restricted carbohydrate consumption (eTRC) is a novel dietary strategy that involves restricting carbohydrate-rich food intake to the morning and early afternoon to align with circadian variations in glucose tolerance. We examined the efficacy, feasibility and safety of eTRC in individuals with type 2 diabetes under free-living conditions.

Methods: In this randomised, parallel-arm, open label, controlled trial, participants with type 2 diabetes and overweight/obesity (age 67.

Treatment with recombinant Sirt1 rewires the cardiac lipidome and rescues diabetes-related metabolic cardiomyopathy.

Background: Metabolic cardiomyopathy (MCM), characterized by intramyocardial lipid accumulation, drives the progression to heart failure with preserved ejection fraction (HFpEF). Although evidence suggests that the mammalian silent information regulator 1 (Sirt1) orchestrates myocardial lipid metabolism, it is unknown whether its exogenous administration could avoid MCM onset. We investigated whether chronic treatment with recombinant Sirt1 (rSirt1) could halt MCM progression.

The Results of the URRAH (Uric Acid Right for Heart Health) Project: A Focus on Hyperuricemia in Relation to Cardiovascular and Kidney Disease and its Role in Metabolic Dysregulation.

The relationship between Serum Uric Acid (UA) and Cardiovascular (CV) diseases has already been extensively evaluated, and it was found to be an independent predictor of all-cause and cardiovascular mortality but also acute coronary syndrome, stroke and heart failure. Similarly, also many papers have been published on the association between UA and kidney function, while less is known on the role of UA in metabolic derangement and, particularly, in metabolic syndrome. Despite the substantial number of publications on the topic, there are still some elements of doubt: (1) the better cut-off to be used to refine CV risk (also called CV cut-off); (2) the needing for a correction of UA values for kidney function; and (3) the better definition of its role in metabolic syndrome: is UA simply a marker, a bystander or a key pathological element of metabolic dysregulation?.