Search Results (1,884)

In the original randomised Dietary Intervention to Stop Coronary Atherosclerosis (DISCO-CT) trial, a 12-month Dietary Approaches to Stop Hypertension (DASH) project led by dietitians improved cardiovascular and metabolic risk factors and reduced platelet chemokine levels in patients with coronary artery disease (CAD). It is unclear whether these benefits are sustained. Objective: To determine whether the metabolic, inflammatory, and clinical benefits achieved during the DISCO-CT trial are sustained six years after the structured intervention ended. Methods: Ninety-seven adults with non-obstructive CAD confirmed in coronary computed tomography angiography were randomly assigned to receive optimal medical therapy (control group, n = 41) or the same therapy combined with intensive DASH counselling (DASH group, n = 43). After 301 ± 22 weeks, 84 individuals (87%) who had given consent underwent reassessment of body composition, meal frequency assessment, and biochemical testing (lipids, hs-CRP, CXCL4, RANTES and homocysteine). Major adverse cardiovascular events (MACE) were assessed. Results: During the intervention, the DASH group lost an average of 3.6 ± 4.2 kg and reduced their total body fat by an average of 4.2 ± 4.8 kg, compared to an average loss of 1.1 ± 2.9 kg and a reduction in total body fat of 0.3 ± 4.1 kg in the control group (both p < 0.01). Six years later, most of the lost body weight and fat tissue had been regained, and there was a sharp increase in visceral fat area in both groups (p < 0.0001). CXCL4 decreased by 4.3 ± 3.0 ng/mL during the intervention and remained lower than baseline values; in contrast, in the control group, it initially increased and then decreased (p < 0.001 between groups). LDL cholesterol and hs-CRP levels returned to baseline in both groups but remained below baseline in the DASH group. There was one case of MACE in the DASH group, compared with four cases (including one fatal myocardial infarction) in the control group (p = 0.575). Overall adherence to the DASH project increased by 26 points during counselling and then decreased by only four points, remaining higher than in the control group. Conclusions: A one-year DASH project supported by a physician and dietitian resulted in long-term suppression of the proatherogenic chemokine CXCL4 and fewer MACE over six years, despite a decline in adherence and loss of most anthropometric and lipid benefits. It appears that sustained systemic reinforcement of behaviours is necessary to maintain the benefits of lifestyle intervention in CAD. 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

Background: Aortic stenosis (AS) has long been considered a degenerative disease and is typically diagnosed in older men at an advanced stage. However, accumulating evidence has highlighted the similarities between AS and atherosclerosis, particularly regarding shared risk factors and overlapping pathophysiological mechanisms. This connection has led to a paradigm shift, suggesting that AS may be preventable in its early stages. Methods: This narrative review synthesizes the existing literature exploring the parallels between AS and atherosclerosis, focusing on common risk factors, pathogenic pathways, and evolving therapeutic strategies. Clinical trials and translational studies were examined to assess the effectiveness of atherosclerosis-based treatments for AS. Results: Multiple studies have confirmed the shared inflammatory, lipid-mediated, and calcific mechanisms of AS and atherosclerosis. Despite these similarities, therapeutic strategies effective in atherosclerosis, such as statin therapy, have not consistently shown benefits in AS. New medical approaches aim to delay aortic valve replacement and reduce the associated morbidity. The partially overlapping pathogenesis continues to guide future research. Conclusions: While AS and atherosclerosis share several pathogenic features, their clinical courses and treatment responses diverge. Understanding the limits and potential of their overlap may inform future preventive and therapeutic strategies. Earlier detection and targeted intervention in AS remain key goals, drawing on insights from cardiovascular disease management. Full article

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

Obesity is a growing global health concern with widespread impacts on physical, psychological, and social well-being. Clinically, it is a major driver of type 2 diabetes (T2D), cardiovascular disease (CVD), non-alcoholic fatty liver disease (NAFLD), and cancer, reducing life expectancy by 5–20 years and imposing a staggering economic burden of USD 2 trillion annually (2.8% of global GDP). Despite its significant health and socioeconomic impact, earlier obesity medications, such as fenfluramine, sibutramine, and orlistat, fell short of expectations due to limited effectiveness, serious side effects including valvular heart disease and gastrointestinal issues, and high rates of treatment discontinuation. The advent of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., semaglutide, tirzepatide) has revolutionized obesity management. These agents demonstrate unprecedented efficacy, achieving 15–25% mean weight loss in clinical trials, alongside reducing major adverse cardiovascular events by 20% and T2D incidence by 72%. Emerging therapies, including oral GLP-1 agonists and triple-receptor agonists (e.g., retatrutide), promise enhanced tolerability and muscle preservation, potentially bridging the efficacy gap with bariatric surgery. However, challenges persist. High costs, supply shortages, and unequal access pose significant barriers to the widespread implementation of obesity treatment, particularly in low-resource settings. Gastrointestinal side effects and long-term safety concerns require close monitoring, while weight regain after medication discontinuation emphasizes the need for ongoing adherence and lifestyle support. This review highlights the transformative potential of incretin-based therapies while advocating for policy reforms to address cost barriers, equitable access, and preventive strategies. Future research must prioritize long-term cardiovascular outcome trials and mitigate emerging risks, such as sarcopenia and joint degeneration. A multidisciplinary approach combining pharmacotherapy, behavioral interventions, and systemic policy changes is critical to curbing the obesity epidemic and its downstream consequences. Full article

Animal venoms are complex biochemical secretions rich in highly potent and selective bioactive molecules, including peptides, enzymes, and small organic compounds. Once associated primarily with toxicity, these venoms are now recognized as a promising source of therapeutic agents for a wide range of medical conditions. This review provides a comprehensive analysis of the pharmacological potential of venom-derived compounds, highlighting their mechanisms of action, such as ion channel modulation, receptor targeting, and enzyme inhibition. Successful venom-derived drugs like captopril and ziconotide exemplify the translational potential of this biological arsenal. We discuss therapeutic applications in cardiovascular diseases, chronic pain, cancer, thrombosis, and infectious diseases, as well as emerging peptide candidates in clinical development. Technological advancements in omics, structural biology, and synthetic peptide engineering have significantly enhanced the discovery and optimization of venom-based therapeutics. Despite challenges related to stability, immunogenicity, and ecological sustainability, the integration of AI-driven drug discovery and personalized medicine is expected to accelerate progress in this field. By synthesizing current findings and future directions, this review underscores the transformative potential of animal venoms in modern pharmacotherapy and drug development. We also discuss current therapeutic limitations and how venom-derived compounds may address unmet needs in specific disorders. 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: Although semaglutide (Ozempic^®) is being prescribed off-label to individuals with obesity, some concerns have arisen regarding its use, particularly regarding the risk of thyroid and pancreatic disorders. Therefore, it is crucial to screen patients’ medical and family disease histories, as well as certain clinical parameters, before initiating this treatment for obesity or weight management. However, there is limited research investigating whether pretreatment assessment is adopted in clinical practice. Method: This is a single-center retrospective study involving adults who were prescribed semaglutide for obesity or weight management. Demographic data, comorbid conditions, semaglutide-related lab work, and disease history assessments, including pancreatitis, thyroid abnormalities, oculopathy, neuropathy, and any family history of thyroid cancer, were evaluated and documented prior to treatment initiation. Results: In total, 715 patients were included in the study, with an average age of 40.2 ± 12.0 years, and 49.5% of participants were male. The average weight and BMI prior to using semaglutide were 99.8 ± 18.1 kg and 36.3 ± 8.3 kg/m², respectively, with predominantly overweight and obese individuals (collectively 91.3%). Approximately 69% of patients had 3–5 complications, with a high prevalence of cardiovascular and metabolic diseases before using semaglutide. Although HbA1c, serum creatinine, TSH, T3, T4, triglycerides, HDL, LDL, total cholesterol, and total bilirubin were monitored prior to semaglutide use, none of the patients’ pancreatic lipase, amylase, or calcitonin levels were measured. Although it is important to investigate all personal and family disease histories, including thyroid abnormalities, thyroid cancer, pancreatitis, retinopathy, eye problems, and neuropathy prior to semaglutide initiation, checks were only conducted in 1.8% of patients, despite 98.6% having at least one of the diseases assessed pretreatment. Conclusions: The current pretreatment assessment approach for patients prescribed semaglutide for weight reduction is underdeveloped, particularly with regard to assessing the influence of disease history on semaglutide use. This predisposes patients to a risk of severe clinical outcomes, including thyroid cancer, pancreatitis, and retinopathy. Full article

A considerable amount of scientific evidence demonstrates that the regime of magnitude, direction, and/or frequency of wall shear stress (WSS) modulates endothelial cell function and structure, influencing vascular biology in health and disease. Advances in computational fluid dynamics (CFD) and fluid–structure interaction (FSI) simulations in cardiovascular medicine have enabled accurate WSS quantification, correlating flow behavior and its interaction with the vessel wall with disease progression. To effectively analyze and interpret the results of numerical simulations, various descriptors of blood flow were defined. Such indicators allow researchers to quantify and characterize key aspects of blood flow, facilitating the study of healthy and pathological conditions, medical device design, and treatment planning. However, a very fast-growing collection of hemodynamic metrics were defined and used: whether called indicators, parameters, metrics, or indexes, they will be here referred to as hemodynamic descriptors. This narrative review was aimed at synthesizing scientific literature about the descriptors used to analyze blood flow in computational cardiovascular studies, highlighting their significance, applications, and advancements. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Hyperlipidemia (HLP) is a disorder of human lipid metabolism or transport, primarily characterized by abnormally elevated levels of total cholesterol (TC), triglycerides (TGs), and low-density lipoprotein cholesterol (LDL-C) in the blood. It is a key factor contributing to the development of non-alcoholic fatty liver disease, obesity, diabetes, atherosclerosis, and cardiovascular and cerebrovascular diseases. Statistics show that the prevalence of dyslipidemia among Chinese adults is as high as 35.6%, and it has shown a trend of younger onset in recent years, posing a serious threat to public health. Therefore, the prevention and treatment of dyslipidemia carry significant social significance. The pathogenesis of hyperlipidemia is complex and diverse, and currently used medications are often accompanied by side effects during treatment, making the research and development of new therapeutic approaches a current focus. Numerous studies have shown that flavonoids, which are abundant in most medicinal plants, fruits, and vegetables, exert effects on regulating lipid homeostasis and treating hyperlipidemia through a multi-target mechanism. These compounds have demonstrated significant effects in inhibiting lipid synthesis, blocking lipid absorption, promoting cholesterol uptake, enhancing reverse cholesterol transport, and suppressing oxidative stress, inflammation, and intestinal microbiota disorders. This article reviews the latest progress in the mechanisms of flavonoids in the treatment of hyperlipidemia, providing a theoretical basis for future research on drugs for hyperlipidemia. Full article

Continuous blood pressure (BP) monitoring provides valuable insight into the body’s dynamic cardiovascular regulation across various physiological states such as physical activity, emotional stress, postural changes, and sleep. Continuous BP monitoring captures different variations in systolic and diastolic pressures, reflecting autonomic nervous system activity, vascular compliance, and circadian rhythms. This enables early identification of abnormal BP trends and allows for timely diagnosis and interventions to reduce the risk of cardiovascular diseases (CVDs) such as hypertension, stroke, heart failure, and chronic kidney disease as well as chronic stress or anxiety disorders. To facilitate continuous BP monitoring, we propose an AI-powered estimation framework. The proposed framework first uses an expert-driven feature engineering approach that systematically extracts physiological features from photoplethysmogram (PPG)-based arterial pulse waveforms (APWs). Extracted features include pulse rate, ascending/descending times, pulse width, slopes, intensity variations, and waveform areas. These features are fused with demographic data (age, gender, height, weight, BMI) to enhance model robustness and accuracy across diverse populations. The framework utilizes a Tab-Transformer to learn rich feature embeddings, which are then processed through an ensemble machine learning framework consisting of CatBoost, XGBoost, and LightGBM. Evaluated on a dataset of 1000 subjects, the model achieves Mean Absolute Errors (MAE) of 3.87 mmHg (SBP) and 2.50 mmHg (DBP), meeting British Hypertension Society (BHS) Grade A and Association for the Advancement of Medical Instrumentation (AAMI) standards. The proposed architecture advances non-invasive, AI-driven solutions for dynamic cardiovascular health monitoring. Full article

Background/Objectives: Peripheral artery disease (PAD) impacts more than 200 million individuals globally and leads to mortality and morbidity secondary to progressive limb dysfunction and amputation. However, clinical management of PAD remains suboptimal, in part because of the lack of standardized biomarkers to predict patient outcomes. Growth differentiation factor 15 (GDF15) is a stress-responsive cytokine that has been studied extensively in cardiovascular disease, but its investigation in PAD remains limited. This study aimed to use explainable statistical and machine learning methods to assess the prognostic value of GDF15 for limb outcomes in patients with PAD. Methods: This prognostic investigation was carried out using a prospectively enrolled cohort comprising 454 patients diagnosed with PAD. At baseline, plasma GDF15 levels were measured using a validated multiplex immunoassay. Participants were monitored over a two-year period to assess the occurrence of major adverse limb events (MALE), a composite outcome encompassing major lower extremity amputation, need for open/endovascular revascularization, or acute limb ischemia. An Extreme Gradient Boosting (XGBoost) model was trained to predict 2-year MALE using 10-fold cross-validation, incorporating GDF15 levels along with baseline variables. Model performance was primarily evaluated using the area under the receiver operating characteristic curve (AUROC). Secondary model evaluation metrics were accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). Prediction histogram plots were generated to assess the ability of the model to discriminate between patients who develop vs. do not develop 2-year MALE. For model interpretability, SHapley Additive exPlanations (SHAP) analysis was performed to evaluate the relative contribution of each predictor to model outputs. Results: The mean age of the cohort was 71 (SD 10) years, with 31% (n = 139) being female. Over the two-year follow-up period, 157 patients (34.6%) experienced MALE. The XGBoost model incorporating plasma GDF15 levels and demographic/clinical features achieved excellent performance for predicting 2-year MALE in PAD patients: AUROC 0.84, accuracy 83.5%, sensitivity 83.6%, specificity 83.7%, PPV 87.3%, and NPV 86.2%. The prediction probability histogram for the XGBoost model demonstrated clear separation for patients who developed vs. did not develop 2-year MALE, indicating strong discrimination ability. SHAP analysis showed that GDF15 was the strongest predictive feature for 2-year MALE, followed by age, smoking status, and other cardiovascular comorbidities, highlighting its clinical relevance. Conclusions: Using explainable statistical and machine learning methods, we demonstrated that plasma GDF15 levels have important prognostic value for 2-year MALE in patients with PAD. By integrating clinical variables with GDF15 levels, our machine learning model can support early identification of PAD patients at elevated risk for adverse limb events, facilitating timely referral to vascular specialists and aiding in decisions regarding the aggressiveness of medical/surgical treatment. This precision medicine approach based on a biomarker-guided prognostication algorithm offers a promising strategy for improving limb outcomes in individuals with PAD. Full article

Oxidative stress directly or indirectly contributes to the development and progression of various diseases; therefore, regulating oxidative stress is a promising strategy for preventing or treating these conditions. The unique substances in soybeans, soy isoflavones, notably genistein, which have a strong antioxidant capacity, are considered to regulate various signaling pathways, alleviate oxidative stress, and improve gut microbiota imbalance as well as mitochondrial dysfunction. In this literature review, we summarize the latest research on genistein, providing evidence of its development and application as a potential drug for preventing and treating five selected diseases (Parkinson’s disease, Alzheimer’s disease, diabetes mellitus, cardiovascular disease, and cancers). The literature was searched using keywords that include tripartite combinations of genistein and oxidative stress, along with each of the five selected diseases, from PubMed, Science Direct, and Google Scholar between 2014 and 2024. According to current in vitro, in vivo, and clinical trials, we comprehensively discuss the therapeutic dose used to target various disease entities to achieve optimal efficacy and meet safety requirements. Moreover, considering the poor water solubility and limited bioavailability of genistein, strategies for improving its therapeutic efficacy, such as combining it with exercise, existing medications, and advanced technologies, as well as applying nanotechnology, were assessed. Therefore, this review aims to provide robust evidence for the development and application of genistein as a potential therapeutic agent or functional food for preventing and treating these diseases. Full article

Large language models (LLMs) are increasingly being applied to clinical tasks, but it remains unclear whether medical-specific models consistently outperform smaller, generalpurpose ones. This study investigates that assumption in the context of cardiovascular disease (CVD) risk assessment. We fine-tuned eight LLMs—both general-purpose and medical-specific—using textualized data from the Behavioral Risk Factor Surveillance System (BRFSS) to classify individuals as “High Risk” or “Low Risk”. To provide actionable insights, we integrated a Retrieval-Augmented Generation (RAG) framework for personalized recommendation generation and deployed the system within an interactive chatbot interface. Notably, Gemma2, a compact 2B-parameter general-purpose model, achieved a high recall (0.907) and F1-score (0.770), performing on par with larger or medical-specialized models such as Med42 and BioBERT. These findings challenge the common assumption that larger or specialized models always yield superior results, and highlight the potential of lightweight, efficiently fine-tuned LLMs for clinical decision support—especially in resource-constrained settings. Overall, our results demonstrate that general-purpose models, when fine-tuned appropriately, can offer interpretable, high-performing, and accessible solutions for CVD risk assessment and personalized healthcare delivery. Full article