Search Results (1,432)

Background/Objectives: Axial spondyloarthritis (axSpA) is a chronic immune-mediated inflammatory disorder affecting the spine and sacroiliac joints, with variable clinical expression. This study assessed serum levels of inflammatory (TNF-α, IL-17A) and metabolic (leptin, adiponectin) biomarkers and their associations with disease activity, inflammation, structural damage, and comorbidities. Methods: This prospective cross-sectional study assessed 89 axSpA patients using clinical, laboratory, and radiological evaluations. Disease activity was measured using ASDAS-CRP and BASDAI scores. Radiographic damage was quantified using the Modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Serum concentrations of TNF-α, IL-17A, leptin, and adiponectin were quantified by enzyme-linked immunosorbent assay (ELISA). Clinical and imaging correlations were analyzed. Results: Serum leptin levels correlated significantly with higher disease activity scores, inflammatory markers (CRP, ESR), radiographic progression (syndesmophyte formation, mSASSS), and arterial hypertension. Adiponectin levels were inversely associated with disease activity, structural damage, and arterial hypertension, suggesting anti-inflammatory, bone- and cardio-protective properties. TNF-α levels showed an association with inflammatory markers and were higher in patients with peripheral enthesitis. IL-17A levels were weakly correlated with disease activity and structural severity and were significantly lower in patients with a history of anterior uveitis. Conclusions: Leptin and adiponectin may serve as complementary biomarkers in axSpA, reflecting both inflammatory burden and structural damage. While TNF-α and IL-17A remain key therapeutic targets, their correlation with structural changes appears limited. Biomarker profiling could support personalized disease monitoring. Longitudinal studies are needed to validate prognostic implications. Full article

Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article

Cardiovascular–Kidney–Metabolic (CKM) syndrome symbolizes a single pathophysiologic entity including obesity, type 2 diabetes, chronic kidney disease, and cardiovascular disease. These conditions altogether accelerate adverse outcomes when they coexist. Recent evidence has shown that the function of glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium–glucose cotransporter-2 inhibitors (SGLT2i) alleviate stress on multiple organs. SGLT2i has been demonstrated to benefit heart failure, hemodynamic regulation, and renal protection while GLP-1RA on the other hand has been shown to demonstrate a strong impact on glycemic management, weight loss, and atherosclerotic cardiovascular disease. This review will aim to understand and evaluate the mechanistic rationalization, clinical evidence, and the potential therapeutic treatment of SGLT2 inhibitors and GLP-1 receptor agonists to treat individuals who have CKM syndrome. This analysis also assesses whether combination therapy can be a synergistic approach that may benefit patients but is still underutilized because of the lack of clear guidelines, the associated costs, and disparities in accessibility. Therefore, in this review, we will be discussing the combination therapy’s additive and synergistic effects, current recommendations and clinical evidence, and mechanistic insights of these GLT2 inhibitors and GLP-1 receptor agonists in CKM syndrome patients. Overall, early and combination usage of GLP-1RA and SGLT2i may be essential to demonstrating a significant shift in modern cardiometabolic therapy toward patient-centered care. Full article

Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and accuracy of six biochemical and/or anthropometric indices related to lipid metabolism and adiposity for the early detection of MetS in a sample of Spanish adolescents. Methods: A cross-sectional study carried out according to the STROBE guidelines. A sample of 981 adolescents aged 11–16 years old were randomly recruited from schools in Southeastern Spain. The presence or absence of MetS was determined according to the International Diabetes Federation criteria. The following biochemical and/or anthropometric indices were evaluated: triglyceride glucose index, visceral adiposity index, logarithm children’s lipid accumulation product, triglyceride glucose-body mass index, triglyceride glucose-waist circumference, and triglyceride glucose-waist-to-hip ratio. Results: The triglyceride glucose-waist-to-hip ratio and triglyceride glucose-body mass index parameters were the strongest indicators associated with MetS in boys and girls, respectively, after adjusting for several factors. Moreover, all evaluated indices showed optimal AUC values, with the visceral adiposity index and triglyceride glucose-waist circumference index exhibiting the highest discriminative capacity in both genders. Conclusions: The evaluated biochemical and anthropometric indices—particularly visceral adiposity index and triglyceride-glucose-waist circumference—show promise as accessible biomarkers for identifying adolescents at metabolic risk. These indices may serve as practical tools in preventive health strategies aimed at improving metabolic health by screening adolescents at risk of MetS, thereby helping to reduce the future burden of non-communicable diseases. Full article

Cardiovascular diseases (CVDs) are the leading global cause of death, with long-term hospitalization becoming increasingly frequent in advanced or chronic cases. In this context, the interplay between systemic factors such as lipid metabolism, circulating metabolites, gut microbiota, and oral health is gaining attention for its potential role in influencing inflammation, cardiometabolic risk, and long-term outcomes. Despite their apparent independence, these domains are increasingly recognized as interconnected and influential in cardiovascular pathophysiology. Methods: This narrative review was conducted by analyzing studies published between 2015 and 2024 from databases including PubMed, Scopus, and Web of Science. Keywords such as “lipid profile,” “metabolomics,” “gut microbiota,” “oral health,” and “cardiovascular disease” were used. Original research, meta-analyses, and reviews relevant to hospitalized cardiac patients were included. A critical integrative approach was applied to highlight cross-domain connections. Results and Discussion: Evidence reveals significant interrelations between altered lipid profiles, gut dysbiosis (including increased TMAO levels), metabolic imbalances, and oral inflammation. Each component contributes to a systemic pro-inflammatory state that worsens cardiovascular prognosis, particularly in long-term hospitalized patients. Despite isolated research in each domain, there is a paucity of studies integrating all four. The need for interdisciplinary diagnostic models and preventive strategies is emphasized, especially in populations with frailty or immobilization. Conclusions: Monitoring lipid metabolism, metabolomic shifts, gut microbial balance, and oral status should be considered part of comprehensive cardiovascular care. Gut microbiota exerts a dual role in cardiac health: when balanced, it supports anti-inflammatory and metabolic homeostasis; when dysbiotic, it contributes to systemic inflammation and worsened cardiac outcomes. Future research should aim to develop integrative screening tools and personalized interventions that address the multifactorial burden of disease. A systemic approach may improve both short- and long-term outcomes in this complex and vulnerable patient population. Full article

Background/Objectives: Neuromedin U (NMU) is a highly conserved gene encoding a neuropeptide involved in the regulation of feeding behavior and energy homeostasis. We aimed to analyze the association between NMU genetic and epigenetic variations and cardio-metabolic parameters in an Italian population to identify the role of these variants in cardio-metabolic risk. Methods: A total of 4028 subjects were randomly selected from the Moli-sani study cohort. NMU haplotypes were estimated using seven SNPs located in the gene body and in the promoter region; DNA methylation levels in the promoter region, previously associated with lipid-related variables in the same population, were also used. Results: Among the haplotypes inferred, the haplotype carrying the highest number of minor variants (frequency 16.6%), when compared with the most frequent haplotype, was positively associated with insulin levels, HOMA-IR, and diastolic blood pressure, and negatively with HDL-cholesterol. The multivariable analysis that considered methylation levels along with their interactions with SNPs showed that increased methylation levels in two close CpG sites were associated with higher levels of lipid-related variables. Conclusions: This study supports a role for NMU as a regulator of human metabolism. This finding suggests that NMU could be a potential target for preventive interventions against coronary and cerebrovascular diseases, and that NMU genetic and epigenetic variability may serve as a biomarker for cardio-metabolic risk. Full article

Background: Menopause increases the risk of cardiovascular diseases (CVD) accompanied by a decline in muscle function. Myokines, released by skeletal muscle, could play a significant role in cardiovascular health. Objectives and Methods: This study aimed to investigate the changes induced by a 16-week resistance training (RT) program and/or the docosahexaenoic acid (DHA)-rich n-3 PUFA supplementation on myokine and cytokine circulating levels and to study their associations with parameters of body composition, muscle function, and glucose and lipid serum markers in postmenopausal women with overweight/obesity. Results: At baseline, interleukin-6 (IL-6) levels were positively correlated with body fat and with tumor necrosis factor-alpha (TNF-α) levels and negatively associated with meterorin-like (METRNL) levels. Moreover, METRNL was inversely associated with insulin levels and with HOMA-IR. After the intervention, muscle quality improved with either treatment but more notably in response to RT. N-3 supplementation caused significant improvements in cardiometabolic health markers. TNF-α decreased in all experimental groups. Myostatin levels decreased in the RT and in the n-3 groups, and IL-6 increased in the n-3+RT group. Lastly, no interactions between treatments were observed. Conclusions: In postmenopausal women with overweight or obesity, RT could help improve skeletal muscle function, while DHA-rich n-3 supplementation might decrease CVD risk and might potentially improve muscle function. The modulation of myokine levels could be underlying some of the effects of DHA or RT; however, further research is necessary. Full article

Childhood obesity increases chronic disease risk, but no comprehensive synthesis has evaluated the impact of school-based combined nutrition education and physical activity interventions on cardiometabolic biomarkers in children aged 3 to 12 years. This systematic review was conducted in accordance with PRISMA guidelines and registered in PROSPERO (CRD420251085194). Five databases were systematically searched through June 2025. Twelve randomized controlled trials involving 18,231 children were included and assessed using the PEDro scale. Ten trials demonstrated significant improvements in at least one cardiometabolic biomarker. Blood pressure (8 studies) outcomes showed systolic reductions of 1.41–6.0 mmHg in six studies. Glucose metabolism (5 studies) improved in two studies with reductions of 0.20–0.22 mmol/L. Lipid profiles (7 studies) improved in three studies, including total cholesterol (−0.32 mmol/L). Insulin levels (5 studies) decreased significantly in two investigations. Anthropometric improvements included BMI and body fat. Physical activity increased by >45 min/week and dietary habits improved significantly. Programs with daily implementation (90-min sessions 4x/week), longer duration (≥12 months), family involvement (parent education), and curriculum integration (classroom lessons) showed superior effectiveness. Interventions targeting children with overweight/obesity demonstrated higher changes compared to the general population. However, methodological limitations included a lack of assessor blinding, absence of subject/therapist blinding, and inadequate retention rates. School-based interventions combining nutrition and physical activity can produce significant improvements in cardiometabolic biomarkers, supporting comprehensive, sustained multicomponent programs for early chronic disease prevention. Full article

Introduction: Breakfast has emerged as a critical factor in preventing cardiovascular diseases, driven not only by its nutritional content but also by its alignment with circadian rhythms. However, gaps remain in the literature regarding its clinical impact and thematic evolution. Objective: To characterize the global scientific output on the relationship between breakfast quality and cardiovascular health through a systematic bibliometric analysis. Methodology: The PRISMA 2020 protocol was applied to select 1436 original articles indexed in Scopus and Web of Science (1957–2025). Bibliometric tools, including R (v4.4.2) and VOSviewer (v1.6.19) were used to map productivity, impact, collaboration networks, and emerging thematic areas. Results: Scientific output has grown exponentially since 2000. The most influential journals are the American Journal of Clinical Nutrition, Nutrients, and Diabetes Care. The United States, United Kingdom, and Japan lead in publication volume and citations, with increasing participation from Latin American countries. Thematic trends have shifted from traditional clinical markers to innovative approaches such as chrononutrition, digital health, and personalized nutrition. However, methodological gaps persist, including a predominance of observational studies and an underrepresentation of vulnerable populations. Conclusions: Breakfast is a dietary practice with profound implications for cardiometabolic health. This study provides a comprehensive overview of scientific literature, highlighting both advancements and challenges. Strengthening international collaboration networks, standardizing definitions of a healthy breakfast, and promoting evidence-based interventions in school, clinical, and community settings are recommended. Full article

High-intensity interval training (HIIT) has emerged as a promising non-pharmacological intervention for improving cardiometabolic health. In populations with diabetes, cardiovascular disease, obesity, or metabolic dysfunction, redox imbalance—characterized by elevated oxidative stress and impaired antioxidant defense—is a key contributor to disease progression. This narrative review synthesizes current evidence on the effects of HIIT on oxidative stress and antioxidant capacity across diverse cardiometabolic disease cohorts. While findings are heterogeneous, the majority of studies demonstrate that HIIT intervention can reduce levels of oxidative stress markers and enhance antioxidant enzyme expression. These redox adaptations may underpin improvements in vascular endothelial function, inflammation, and metabolic regulation. Importantly, variations in intensity, duration, and health status influence these responses, highlighting the need for individualized exercise prescriptions. Safety considerations are emphasized, including the necessity for medical clearance, gradual progression, and individualized training prescriptions in higher-risk individuals. In conclusion, HIIT shows potential as a targeted strategy to restore redox homeostasis and improve cardiometabolic outcomes, although further research is needed to clarify optimal protocols and the underlying mechanisms. Full article

Metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis are cardiometabolic twin disorders with shared underlying pathophysiological mechanisms such as insulin resistance and chronic inflammation. This review explores the salient role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in linking hepatic dysfunction to cardiovascular disease. Findings in mice with genetic modulation of Ceacam1 gene established a critical role for CEACAM1 protein in regulating insulin and lipid metabolism and endothelial integrity and modulating immune response. Loss of CEACAM1 in hepatocytes impairs insulin clearance, causing chronic hyperinsulinemia, a process that ultimately leads to insulin resistance and hepatic and extra-hepatic fat accumulation, which in turn causes inflammatory infiltration. This prompts a paradigm shift that positions impaired hepatic CEACAM1 function as a mechanistic underpinning of the link between insulin resistance, MASH, and atherosclerosis. Full article

Inflammatory biomarkers, including high-sensitivity C-reactive protein (hsCRP), serum amyloid A (SAA), and interleukin-6 (IL-6), have been associated with an increased risk of future cardiovascular events. While they provide valuable prognostic information, these associations do not necessarily imply a direct causal role. The combined prognostic utility of these markers, however, remains insufficiently studied. We analysed 3300 well-characterised participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, all of whom underwent coronary angiography. Participants were stratified based on their serum concentrations of hsCRP, SAA, and IL-6. Associations between biomarker combinations and mortality were assessed using multivariate Cox regression and ROC analysis. Individuals with elevated hsCRP and SAA or IL-6 showed higher prevalence rates of coronary artery disease, heart failure, and adverse metabolic traits. These “both high” groups had lower estimated glomerular filtration rate, higher NT-proBNP, and increased HbA1c. Combined elevations of hsCRP and SAA were significantly associated with higher all-cause and cardiovascular mortality in partially adjusted models. However, these associations weakened after adjusting for IL-6. IL-6 alone demonstrated the highest predictive power (AUC: 0.638) and improved risk discrimination when included in multi-marker models. The co-elevation of hsCRP, SAA, and IL-6 identifies a high-risk phenotype characterised by greater cardiometabolic burden and increased mortality. IL-6 may reflect upstream inflammatory activity and could serve as a therapeutic target. Multi-marker inflammatory profiling holds promise for refining cardiovascular risk prediction and advancing personalised prevention strategies. Full article

Background and Aims: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have shown promise in metabolic dysfunction-associated steatotic liver disease (MASLD). This large real-world study aimed to evaluate the effects of SGLT2 inhibitors on MASLD patients’ clinical outcomes and liver-related complications over extended follow-up. Patients and Method: Data were sourced from TriNetX, a global health research platform with de-identified electronic medical records spanning 135 million patients across 112 healthcare organizations worldwide. We included MASLD adults diagnosed according to ICD9/10 criteria. Following propensity score matching based on 34 variables (demographics, comorbidities, laboratory tests and medication history), SGLT2 inhibitor-treated (n = 19,922) patients were compared with non-SGLT2 inhibitor (n = 19,922) cases. Exclusion criteria included baseline improved alanine aminotransferase (ALT) and alkaline phosphatase (ALP) levels > 4 upper normal limit (UNL), baseline advanced liver disease, liver transplant and cancer, past anticoagulation and non-MASLD etiologies. Assessed outcomes included survival, biochemical, hematologic, AFP, metabolic and cardiovascular parameters, progression to advanced liver disease (ALD), synthetic function, and metabolic markers over 1, 5, and 10 years. Results: Following matching, both cohorts were well-balanced across baseline characteristics. After one year, the SGLT2 inhibitor group demonstrated significantly reduced BMI (33.2 ± 6.2 vs. 34.1 ± 6.5 kg/m², p < 0.001), improved ALT (40.3 ± 31.5 vs. 48.3 ± 41.2 U/L, p < 0.001), and better glycemic control (HbA1c 7.35 ± 1.51% vs. 7.93 ± 1.72%, p < 0.001). The SGLT2 inhibitor group showed higher 10-year survival rates (95.00% vs. 88.69%, p < 0.001), fewer cardiovascular events (10.19% vs. 11.80%, p < 0.001), and markedly reduced progression to advanced liver disease (6.90% vs. 14.15%, p < 0.001). These benefits were consistent across clinical, laboratory, and medication-defined ALD categories. Notably, rates of hepatic decompensation events were significantly lower with SGLT2 inhibitor therapy. Conclusions: In this large real-world cohort, SGLT2 inhibitor use in MASLD patients was associated with significantly improved long-term survival, cardiovascular, and liver-related outcomes over 10 years of follow-up. These benefits likely result from combined metabolic improvements, anti-inflammatory effects, and direct hepatoprotective mechanisms. SGLT2 inhibitors represent a promising therapeutic strategy for improving outcomes in MASLD. Full article

Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m²). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO_{2 peak}) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO₂ peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article

In healthy humans, insulin at physiological concentrations exerts acute vasodilatory actions on both resistance and terminal arterioles, leading, respectively, to increased total blood flow and the microvascular network volume being perfused. The process of increasing capillary network volume is frequently referred to as “capillary recruitment”. Together these two vascular actions of insulin enhance the delivery of oxygen, nutrients, and insulin itself to tissues. Both processes are diminished by insulin resistance. Here we examined interactions between insulin’s acute (within 2 h) actions on blood pressure (both central and peripheral) and on capillary recruitment in healthy controls and in four distinct groups of people with heightened cardio-metabolic disease (CMD) risk: individuals with obesity, metabolic syndrome, and type 1 or type 2 diabetes. Insulin increased microvascular blood volume (MBV) more effectively in controls than in each of the four CMD risk groups (p < 0.001). Conversely, insulin lowered both central and peripheral systolic pressure (p < 0.05 or less) in each of the CMD risk groups but not in the controls. The insulin-induced blood pressure decrements were greater in the metabolic syndrome, type 2 diabetes, and obesity groups (p < 0.05 or less) than in the controls. The greater blood pressure declines likely reflect decreased sympathetic baroreceptor reflex tone. These effects on blood pressure combined with the diminished dilation of terminal arterioles due to microvascular insulin resistance in the CMD risk subjects led to decreased distal microvascular perfusion as evidenced by changes in MBV. These findings highlight the complex interplay between insulin’s actions on resistance and terminal arterioles in individuals with a high CMD risk, underscoring the importance of addressing microvascular dysfunction in these conditions. Full article