Search Results (9,363)

The increasing prevalence of chronic metabolic diseases poses a significant challenge in the modern world, impacting healthcare systems and individual life expectancy. The World Health Organization (WHO) recommends that older adults (65+ years) engage in 150–300 min of moderate-intensity or 75–150 min of vigorous-intensity physical activity, alongside muscle-strengthening and balance-training exercises at least twice a week. However, nearly one-third of the adult population (31%) is physically inactive, which increases the risk of developing obesity, type 2 diabetes, cardiovascular diseases, hypertension, and psychological issues. Physical activity in the form of aerobic exercise, resistance training, or a combination of both is effective in preventing and managing these metabolic diseases. In this review, we explored the effects of exercise training, especially on respiratory and pulmonary factors, including oxygen consumption, pulmonary ventilation, and blood gas analyses among adults. During exercise, oxygen consumption can increase up to 15-fold (from a resting rate of ~250 mL/min) to meet heightened metabolic demands, enhancing tidal volume and pulmonary efficiency. During exercise, the increased energy demand of skeletal muscle leads to increases in tidal volume and pulmonary function, while blood gases play a key role in maintaining the pH of the blood. In this review, we explored the influence of age, body composition (BMI and obesity), lifestyle factors (smoking and alcohol use), and comorbidities (diabetes, hypertension, neurodegenerative disorders) in the modulation of these physiological responses. We underscored exercise as a potent non-pharmacological intervention for improving cardiopulmonary health and mitigating the progression of metabolic diseases in aging populations. Full article

Atherosclerosis is a progressive, multifactorial disease driven by the interplay of lipid dysregulation, chronic inflammation, oxidative stress, and maladaptive vascular remodeling. Despite advances in systemic lipid-lowering and anti-inflammatory therapies, residual cardiovascular risk persists, highlighting the need for more precise interventions. Targeted drug delivery represents a transformative strategy, offering the potential to modulate key pathogenic processes within atherosclerotic plaques while minimizing systemic exposure and off-target effects. Recent innovations span a diverse array of platforms, including nanoparticles, liposomes, exosomes, polymeric carriers, and metal–organic frameworks (MOFs), engineered to engage distinct pathological features such as inflamed endothelium, dysfunctional macrophages, oxidative microenvironments, and aberrant lipid metabolism. Ligand-based, biomimetic, and stimuli-responsive delivery systems further enhance spatial and temporal precision. In parallel, advances in in-silico modeling and imaging-guided approaches are accelerating the rational design of multifunctional nanotherapeutics with theranostic capabilities. Beyond targeting lipids and inflammation, emerging strategies seek to modulate immune checkpoints, restore endothelial homeostasis, and reprogram plaque-resident macrophages. This review provides an integrated overview of the mechanistic underpinnings of atherogenesis and highlights state-of-the-art targeted delivery systems under preclinical and clinical investigation. By synthesizing recent advances, we aim to elucidate how precision-guided drug delivery is reshaping the therapeutic landscape of atherosclerosis and to chart future directions toward clinical translation and personalized vascular medicine. Full article

The pathophysiological mechanism linking oxidative stress and cardiovascular disease (CVD) is not completely elucidated, especially in young individuals. This study aimed to examine redox status in an adolescent Montenegrin population in relation to cardiovascular risk score (CVRS). A cohort of 182 adolescents (76% girls) aged between 16 and 19 was examined. Total antioxidant status (TAS), superoxide dismutase (SOD), advanced oxidation protein products (AOPPs), malondialdehyde (MDA), and total oxidant status (TOS) were determined. Pro-oxy score, anti-oxy score, and oxy score were calculated as comprehensive parameters of overall redox homeostasis status. CVRS was calculated by summarizing several risk factors (i.e., sex, age, obesity, hypertension, dyslipidemia, impaired fasting glucose, and smoking). A significant positive correlation between CVRS and TOS (rho = 0.246, p = 0.001) and AOPP (rho = 0.231, p = 0.002) and MDA (rho = 0.339, p < 0.001), respectively, and a negative correlation with the TAS/TOS ratio (rho= −0.208, p = 0.005) was observed. An increase in pro-oxy scores as well as oxy scores with CVRS risk increase were observed. Anti-oxy scores did not differ between CVRS subgroups. There is a significant relationship between cardiovascular risk score and oxidative stress in the adolescent Montenegrin population. These findings support the possibility for improvement of age-specific CVD risk algorithms by adding redox homeostasis parameters in addition to conventional ones. Full article

As people with cystic fibrosis (PwCF) live longer, kidney disease is emerging as a significant comorbidity that is increasingly linked to cardiovascular complications and progression to end-stage kidney disease. In our recent review, we proposed the unifying term CF-related kidney disease (CFKD) to encompass the spectrum of kidney dysfunction observed in this population. Early detection of kidney injury is critical for improving long-term outcomes, yet remains challenging due to the limited sensitivity of conventional laboratory tests, particularly in individuals with altered muscle mass and unique CF pathophysiology. Emerging approaches, including novel blood and urinary biomarkers, urinary extracellular vesicles, and genetic risk profiling, offer promising avenues for identifying subclinical kidney damage. When integrated with machine learning algorithms, these tools may enable the development of personalized risk stratification models and targeted therapeutic strategies. This precision medicine approach has the potential to transform kidney disease management in PwCF, shifting care from reactive treatment of late-stage disease to proactive monitoring and early intervention. Full article

Background/Objectives: Periodontitis is a chronic infectious inflammatory disorder that affects the supporting structures of the teeth. The gingival epithelium plays a crucial role as a physical and immunological barrier, producing pro-inflammatory cytokines in response to microbial pathogens. Modulation of gingival epithelial function has been proposed as a therapeutic strategy to prevent the progression of periodontal disease. Houttuynia cordata, a perennial herb traditionally used in Asian medicine, is recognized for its anti-inflammatory properties, with documented benefits in the cardiovascular, respiratory, and gastrointestinal systems. However, its potential therapeutic role in oral pathologies, such as periodontitis, remains underexplored. This study aimed to investigate the anti-inflammatory effects of H. cordata extract on interleukin (IL)-1β-stimulated primary gingival keratinocytes (PGKs) subjected to IL-1β-induced inflammatory stress, simulating the conditions encountered during orthodontic treatment. Methods: Inflammation was induced in PGKs using IL-1β, and the impact of H. cordata extract pretreatment was assessed using quantitative real-time reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, and immunoblotting. Results: H. cordata extract significantly downregulated the mRNA and protein expression levels of tumor necrosis factor-alpha, IL-8, and intercellular adhesion molecule-1 in IL-1β-stimulated PGKs without inducing cytotoxicity. Conclusions: These findings suggest that H. cordata holds promise as a preventive agent against periodontitis by attenuating inflammatory responses in gingival epithelial tissues. We believe that our findings will inform the development of prophylactic interventions to reduce periodontitis risk in patients undergoing orthodontic therapy. Full article

Background/Objectives: Iron deficiency without anemia (IDWA) is common among female patients with chronic kidney disease (CKD), yet the clinical implications of iron therapy in this population remain uncertain. While iron supplementation is frequently used in anemic CKD patients, evidence regarding its outcomes in non-anemic, iron-deficient individuals is limited and conflicting. Methods: This retrospective cohort study utilized the multi-institutional TriNetX database to examine the 5-year outcomes of iron therapy in adult women with stage 3 CKD, normal hemoglobin (≥12 g/dL), normal mean corpuscular volume (MCV), and low serum ferritin (<100 ng/mL). Primary outcomes included all-cause mortality, major adverse cardiovascular events (MACE), acute kidney injury (AKI), pneumonia, progression to advanced CKD (estimated glomerular filtration rate ≤30 mL/min/1.73 m²), and gastrointestinal (GI) bleeding. Results: We identified 53,769 eligible non-anemic patients with stage 3 CKD, low serum ferritin levels, and normal MCV. Propensity score matching (1:1) was conducted on demographic variables to compare iron-treated (n = 6638) and untreated (n = 6638) cohorts. Over the 5-year follow-up, iron therapy in non-anemic females with stage 3 CKD, low ferritin levels, and iron supplementation was significantly associated with increased risks of MACE, AKI, pneumonia, CKD progression, and GI bleeding (log-rank p < 0.0001). No significant difference in all-cause mortality was observed. Data on transferrin saturation and the dosage of iron supplementation were unavailable. Conclusions: In non-anemic women with stage 3 CKD and low ferritin levels, iron supplementation was linked to increased MACE, renal, and pneumonia risks without evident survival benefits. These findings suggest that iron therapy in this group of patients may not confer cardiovascular benefit and may pose risks. Full article

Obstructive sleep apnea (OSA) syndrome is a severe, debilitating, and pervasive sleep disorder. OSA mainly affects people with obesity, type 2 diabetes mellitus (T2DM), hypertension, and dyslipidemia and is strongly associated with cardiovascular complications. Based on the bidirectional relationship between T2DM and OSA, the latter represents a risk factor for the former, and, vice versa, people with T2DM have a high risk of OSA. Mechanical and hormonal factors, inflammatory mediators, and a dysregulated autonomic nervous system contribute to the mechanisms underlying the disease. Treatment of OSA is necessary even if the available remedies are not always effective. In addition to traditional treatments, including lifestyle adaptations and bariatric surgery, CPAP equipment, i.e., a breathing device ensuring continuous positive pressure to keep the airways open during sleep, represents the most common treatment tool. More recently, pharmacological research has paved the way to newer seemingly effective therapeutic strategies involving, in particular, two hypoglycemic agent classes, i.e., sodium–glucose co-transporter 2 inhibitors (SGLT2-is) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP1-ras). This narrative review provides an update on all of the above. Full article

Background: Arteriovenous fistulas (AVFs) may contribute to cardiac remodeling and consequently to an increased risk of heart failure and cardiovascular mortality in patients with end-stage kidney disease (ESKD). We aimed to assess cardiac changes following AVF creation and identify potential parameters associated with cardiac remodeling. Methods: In our prospective, single-center study, ESKD patients without significant pre-existing cardiac disease underwent 2D and 3D echocardiographic evaluation before and after AVF creation, along with AVF flow measurement. Cardiac remodeling was assessed using 3D indexed left and right ventricular end-diastolic volumes (LVEDVi, RVEDVi), while systolic function was assessed using longitudinal strain and 3D ejection fraction. Results: We included 20 patients (18 men; median age 73.5 years [IQR: 67–77]) with a mean AVF flow of 1140 ± 345 mL/min. At a median of 8.2 months (IQR: 7.3–9.3) following AVF creation, significant biventricular dilatation was observed: LVEDVi increased from 89 ± 14 to 97 ± 21 mL/m² (p < 0.05) and RVEDVi from 80 ± 15 to 91 ± 18 mL/m² (p < 0.05), while the systolic function of both ventricles did not change significantly. The right ventricle showed the most pronounced remodeling and it was independently associated with volume overload (p = 0.003) and elevated left ventricular filling pressure (p = 0.030), but not with AVF flow. Conclusions: Moderate AVF flow was associated with cardiac remodeling, primarily affecting the right ventricle. Fluid overload and left ventricular filling pressure were key factors associated with right ventricular remodeling, underscoring the need for careful fluid management and vascular access planning in ESKD patients. Full article

Calcific aortic stenosis (CAS) is a newly emerging pandemic in elderly individuals due to the aging of the population in the world. Surgical Aortic Valve Replacement (SAVR) and Transcatheter Aortic Valve Replacement (TAVR) are the cornerstone of the management of severe aortic stenosis accompanied by one or more symptoms. Moreover, an appropriate interventional treatment of CAS, in elderly patients, is a very complex decision for heart teams, to avoid bad outcomes such as operative mortality, cardiovascular and all-cause death, hospitalization for heart failure, worsening of quality of life. In fact, CAS in the elderly is not only a focal valve disease, but a very complex clinical picture with different risk factors and etiologies, differing underlying pathophysiology, large phenotypic heterogeneity in a context of subjective biological, phenotypic and functional aging until frailty and disability. In this review, we analyzed separately and in a more integrated manner, the natural and prognostic histories of the progression of aortic stenosis, the phenotypes of myocardial damage and heart failure, within the metrics and aging trajectory. The aim is to suggest, during the clinical timing of valve disease, the best interval time for an appropriate and effective interventional treatment in each older patient, beyond subjective symptoms by integration of clinical, geriatric, chemical, and advanced imaging biomarkers. 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

Cigarette smoking is acknowledged as the most preventable risk factor for thrombogenesis-associated cardiovascular disease. Mice prenatally exposed to the thirdhand smoke (THS) form of tobacco exhibited a higher tendency to develop occlusive thrombosis, along with enhancement of several platelet functional responses. Our objective was to investigate whether prenatal (in utero) THS exposure impacts the platelet transcriptome, resulting in enhanced platelet functional responses, thereby underlying THS-associated thrombogenicity. Blood samples obtained from twenty male mice prenatally exposed to THS, along with an equal number of age-matched male mice exposed to clean air (CA) as a control, were divided into pools of five animals and used to prepare leukocyte and red blood cell-depleted platelets. RNA sequencing for mRNA and microRNA (miRNA) was utilized to analyze and compare the platelet expression profiles of the two exposure groups. RNA seq analyses revealed distinct changes in both gene expression and miRNA profiles, with 448 coding genes and 18 miRNAs significantly altered between the two groups. miRNA–mRNA interaction analysis highlighted 14 differentially expressed miRNAs that potentially target 120 of the differentially expressed genes in our data set. Interestingly, altered genes in miRNA–mRNA pairs were functionally enriched into pathways associated with platelet physiology, including platelet activation, signaling and aggregation, and cellular response to chemical stimuli. Our findings establish—for the first time—that prenatal exposure to THS modifies the platelet transcriptome, thereby rendering platelets hypersensitive to stimuli and more prone to thrombogenicity. Additionally, we illuminate the coordinated function of platelet miRNA and mRNA targets in mediating this response. Full article

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

Sodium–glucose co-transporter-2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1 RAs) are now established as cornerstone therapies for patients with type 2 diabetes mellitus (T2DM), given their cardiovascular and renal protective properties. However, their use in patients with peripheral artery disease (PAD) remains controversial due to concerns raised in early trials about potential increases in lower limb complications, particularly amputations. This narrative review examines current evidence on the association between SGLT2is and GLP-1 RAs in PAD-related outcomes, including limb events, amputation risk, and cardiovascular and renal endpoints. Drawing from randomized controlled trials, real-world cohort studies, and systematic reviews, we provide an integrated perspective on the safety and utility of SGLT2is and GLP-1 RAs in individuals with PAD, highlight patient selection considerations, and identify areas for future investigation. Full article

The frequency of specific variants associated with the risk of developing cardiovascular diseases has been extensively studied through genome-wide association studies (GWASs). Differences between populations may be caused by the interaction of several factors, such as environmental and genetic backgrounds. Here, we studied 19 SNPs involved in atherosclerosis (AT) and venous thromboembolism (VTE) risk in the Azorean and mainland Portuguese populations and compared their frequencies with other European, Asian, and African populations. Results revealed that, although there was no difference between Azorean and mainland populations, eight SNPs in ADAMTS7, PCSK9, APOE, and LDLR genes showed significant statistical differences (χ², p < 0.05) when compared with the European population. The multilocus genetic profile (MGP) analysis demonstrated that 7.4% of mainlanders and 11.2% of Azoreans have a high-risk of developing atherosclerosis. The opposite tendency was observed for venous thromboembolism risk, where the mainland population presented a higher risk (6.5%) than the Azorean population (4.1%). Significant differences in VTE-MGP distribution were found among the Azorean geographic groups (p < 0.05), with the Eastern group showing the highest VTE risk. Conversely, for the risk AT-MGP, the Central group shows the highest risk (12.9%). Taken together, the data suggest a risk of developing a cardiovascular disease consistent with the European population. However, the Azorean-specific genetic background and socio-cultural habits (dietary and sedentary) may explain the differences observed, validating the need to assess the allelic and genotypic frequencies between different populations, especially in small geographical locations, such as the Azores archipelago. In conclusion, these findings can improve the prevention, diagnosis, and treatment of high-risk individuals, and contribute to reducing the lifelong burden of cardiovascular diseases in the Azorean population. Full article

Monitoring cardiovascular health enables continuous and real-time risk assessment. This study utilized the Framingham Heart Study dataset to develop and evaluate machine-learning models for predicting mortality risk based on key cardiovascular parameters. Some machine-learning algorithms were applied to multiple machine-learning models. Among these, XGBoost achieved the highest predictive performance, each with an area under the curve (AUC) value of 0.83. Feature importance analysis revealed that coronary artery disease, glucose levels, and diastolic blood pressure (DIABP) were the most significant risk factors associated with mortality. The primary contribution of this research lies in its implications for public health and preventive medicine. By identifying key risk factors, it becomes possible to calculate individual and population-level risk scores and to design targeted early intervention strategies aimed at reducing cardiovascular-related mortality. Full article