Search Results (3,807)

Driven by rapid socioeconomic progress and changing lifestyles, the global burden of cardiovascular diseases (CVDs) continues to escalate, with surging morbidity and mortality rates imposing a severe threat to public health. Clinical treatments are focused on the alleviation of treatments, highlighting the need for a deeper understanding of CVDs pathogenesis and the development of targeted therapies. Recent studies have identified imbalances in intracellular Ca²⁺ homeostasis as a key pathological mechanism in the progression of CVDs. Notably, sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 2 (SERCA2), a membrane protein encoded by the ATP2A2 gene and ranging from 97 to 115 kDa in molecular weight, plays a pivotal role in regulating intracellular Ca²⁺ levels. Extensive evidence links abnormal SERCA2 function to various CVDs, including heart failure, cardiac hypertrophy, atherosclerosis, and diabetic cardiomyopathy. This review systematically explores the regulatory mechanisms of SERCA2 expression and its functional regulation—including transcriptional regulation, post-translational modifications, and protein–protein interactions—and further investigates its pathological roles in cardiovascular diseases as well as its potential as a therapeutic target. By synthesizing current knowledge, this article aims to provide new insights for future basic research and establish a theoretical foundation for clinical applications. Full article

Background: Type 2 diabetes (T2D) increases cardiovascular disease (CVD) risk and predisposes individuals to heart failure with preserved ejection fraction. Metabolic dysfunction-associated steatotic liver disease (MASLD), prevalent in T2D, may worsen cardiac remodelling and haemodynamics. This secondary analysis of the DIASTOLIC trial examined the relationship of liver fat to cardiac remodelling in T2D at baseline and after a 12-week intervention or standard care. Methods: Adults with obesity and T2D and matched controls underwent hepatic MRI, cardiac MRI, echocardiography, and adipokine profiling as part of the DIASTOLIC study (NCT02590822). Participants with T2D were randomised to supervised exercise, a low-calorie meal-replacement plan (MRP), or routine care for 12 weeks. A baseline case–control and then pre- and post-analyses in those with T2D were performed. Associations between changes in liver fat and cardiovascular measures were assessed using correlation and adjusted generalised linear models. Results: At baseline, 81 T2D and 35 healthy controls were compared, and 76 subjects with T2D completed the trial. Participants with T2D had ~4× higher hepatic fat and adverse haemodynamics. The MRP arm achieved the greatest reductions in BMI, blood pressure, dysglycaemia, insulin resistance, and hepatic fat (−8.9%), with favourable adipokine changes. Overall, hepatic fat loss was associated with reductions in cardiac index and stroke volume and with additional reductions in end-diastolic volume in the MRP arm, independent of BMI. Conclusions: In T2D, hepatic fat is strongly linked to pathological haemodynamic profiles. Intensive caloric restriction achieves substantial hepatic fat loss and normalisation of hyperdynamic cardiovascular physiology independent of weight loss, identifying hepatic steatosis as a potential therapeutic target for early cardiovascular risk reduction. Full article

Background/Objectives: The Metabolic Score for Insulin Resistance (METS-IR), a non-insulin-based index of insulin resistance (IR), and subclinical myocardial injury (SCMI), identified by electrocardiogram (ECG), are each associated with cardiovascular disease (CVD). However, their joint impact on mortality remains unclear. We examined the association of the METS-IR with SCMI and evaluated the individual and combined associations of SCMI and IR with cardiovascular mortality. Methods: We analyzed adults without baseline CVD from the Third National Health and Nutrition Examination Survey (1988–1994) with mortality follow-up through 31 December 2019. The METS-IR was calculated from fasting glucose, triglycerides, high-density lipoprotein cholesterol, and body mass index and categorized as low (<75th percentile) or high (≥75th percentile). SCMI was defined as a cardiac infarction injury score ≥ 10 on ECG. Multivariable logistic regression assessed associations between the METS-IR and SCMI, and Cox regression estimated cardiovascular mortality risk across SCMI-IR combinations. Results: Among 6079 participants, 14.1% had SCMI. Higher METS-IR values were associated with greater SCMI odds (OR (95% CI): 1.58 (1.31–1.90)). Over a median of 18.8 years, 563 (9.1%) cardiovascular deaths occurred. Both SCMI and high IR were individually associated with increased cardiovascular mortality ((HR (95% CI): 1.41 (1.19–1.69) and 1.32 (1.09–1.59), respectively). Participants with both SCMI and high IR had the highest risk (HR 1.92; 95% CI 1.49–2.50) compared with those with neither condition. Conclusions: In adults without prior CVD, the METS-IR was positively associated with SCMI. The coexistence of SCMI and high IR identified a subgroup at nearly twofold higher risk of cardiovascular mortality, supporting the combined use of ECG-based injury markers and metabolic indices for cardiovascular risk stratification. Full article

Cardiovascular diseases (CVDs) and Alzheimer’s disease (AD) are among the most prevalent chronic conditions, contributing significantly to global morbidity and healthcare burdens. These diseases are increasingly recognized as interconnected through shared mechanisms such as vascular dysfunction, oxidative stress, hypertension, and systemic inflammation, collectively referred to as the CVD-AD axis. Although therapeutic strategies exist for each condition, integrated approaches targeting these common pathways remain limited. This review highlights marine-derived bioactive peptides (BAPs) as multifunctional, sustainable agents for the simultaneous prevention of CVD and AD. It summarizes recent advances in their production, purification, and characterization, with emphasis on enzymatic hydrolysis and separation techniques. Marine BAPs exhibit diverse bioactivities, antioxidant, anti-inflammatory, lipid-lowering, antihypertensive, and neuroprotective, addressing key pathological mechanisms of the CVD-AD axis. Their small size, stability, and favorable safety profile support absorption and initial bioavailability, while sustainable sourcing from underutilized marine biomass enables eco-friendly production. Despite their potential, barriers to scalable production, product standardization, and regulatory approval remain; however, incremental advances are being made toward overcoming these issues. Together with these advances, marine BAPs remain promising candidates for functional foods and nutraceuticals, providing integrated preventive strategies for age-related diseases and supporting long-term cardiovascular and cognitive health. Full article

Background/Objectives: It is well documented that people with human immunodeficiency virus (HIV) have nearly twice the risk of incident acute myocardial infarction compared to the general population. The elevated risk stems from a multi-layered interplay of factors such as persistent immune activation inherent to HIV infection and higher prevalence of traditional risk factors associated with nutritional needs. A large proportion of people living with HIV (PWH) reside in Sub-Saharan African countries such as Tanzania; however, there is a dearth of data on nutrition, particularly fruit and vegetable (F&V) intake, a key factor in the prevention of cardiovascular disease (CVD). This study aimed to contribute to the growing literature on CVD prevention for PWH globally. Methods: We conducted secondary analyses of original data collected from a study using the World Health Organization (WHO) STEPS survey among PWH and the general population in Mwanza City between December 2018 and May 2019. Approval for the parent study was obtained from Bugando Medical Center. Multinomial logistic regression analysis examined F&V intake and associated factors between PWH and people living without HIV (PWoH) using sex, employment, and BMI. Results: A total of 537 participants (277 PWoH and 260 PWH) were included in the analysis. PWH were more likely to consume fruits ≥ 4 days per week than PWoH (38% vs. 25%, p = 0.002), whereas vegetable intake did not differ significantly between groups. Fruit intake was higher in males (OR = 5.63; 95% CI: 2.48–12.79) and employed individuals (OR = 3.85; 95% CI: 1.82–8.14). Conclusions: PWH were more likely to consume more fruits than PWoH in this study, a phenomenon that is more novel than previous research. These findings are encouraging to support nutrition-based interventions for PWH who are at a higher risk of CVD. Full article

Background: Globally, an estimated 1.4 billion people had hypertension in 2014, yet only just over 20% had controlled blood pressure, and about 580 million remained undiagnosed. Evidence indicates that salt substitutes facilitate meaningful blood-pressure reductions, yet their implementation remains restricted by social and healthcare constraints. The comparative effectiveness of alternative sodium-reduction interventions for elevated blood pressure remains unclear, limiting their introduction across diverse clinical and public health contexts. This study is registered with PROSPERO (CRD420251130153). Methods: We systematically searched PubMed, MEDLINE, and supplementary sources for randomised controlled trials (RCTs) published between 2000 and 2025. All behavioural sodium-reduction interventions among populations with elevated blood pressure, including hypertension, were included. The mean difference in systolic blood pressure (SBP) was the primary outcome, as evidence indicates that intensive control of SBP to levels below 120–130 mmHg is significantly associated with a reduced risk of major cardiovascular disease (CVD) and all-cause mortality. Network and subgroup pairwise meta-analyses were performed, with sensitivity analyses conducted to assess robustness of the findings and subgroup analyses used to explore clinical and public health factors influencing intervention effectiveness (clinical factors: blood pressure stage, trial duration, and medication status; public health factors: setting, implementation period, and country income level). Results: Of 10,404 records identified, 42 studies (46 trials, n = 46,771) were included. While the use of salt substitutes was ranked the most effective intervention in the network meta-analysis, with reductions of −6.78 mmHg (95% CI, −8.42, −5.14) compared to no intervention and −5.35 mmHg (95% CI, −7.89, −2.81) compared to conventional health education, self-monitoring devices and low-sodium diets, when combined with health education, demonstrated similar magnitudes of SBP reductions. Digital health education showed a larger point estimate for SBP reduction by −3.59 mmHg (95% CI −7.40 to 0.22) than conventional education (−1.43 mmHg; 95% CI −3.49 to 0.63), but both confidence intervals crossed zero, indicating no statistically significant difference. Subgroup analyses indicated that, except for trial duration, intervention setting, and country income level in specific intervention comparisons, clinical and public health factors did not generally account for differences in SBP reduction. No evidence of publication bias was observed, except between salt substitutes and no intervention and low-sodium diets and no intervention. Conclusions: Network meta-analysis ranked the use of salt substitutes as the most effective intervention, yet self-regulated interventions, such as low-sodium diets and self-monitoring devices, when combined with education-based sodium-reduction approaches, showed comparable point estimates for SBP reductions. Digital health education showed promise as a supportive adjunct to self-regulated interventions, although its effects were variable and require further quantification. These findings underscore the need for alternative sodium-reduction interventions supported by digital or conventional health education to improve blood pressure control. Health education on sodium reduction, including clinical counselling, should be viewed primarily as a complementary component that enhances other interventions. Full article

Background/Objectives: Every country and territory worldwide is affected by varying degrees of under- and overconsumption of food. A substantial share of the economic burden of unsustainable malnutrition arises from diet-related health impacts, although existing research has largely focused on environmental consequences. Methods: This study addresses this gap by combining cost-of-illness (COI) and True Cost Accounting (TCA) approaches, as well as Global Burden of Disease (GBD) data, to estimate external diet-induced health costs. A comprehensive database covering 204 countries and territories is established, quantifying health costs by disease category and dietary risk factor. Results: The results indicate that USD 1719.94 billion in annual global health costs are attributable to poor diets. This corresponds to an average burden of USD 211.08 per capita per year. Cardiovascular diseases (CVDs) constitute the largest share of costs, followed by diabetes mellitus (DM). In absolute and per capita terms, the United States contributes disproportionately. Regionally, North America bears 44.36% of the global monetary burden, while Oceania accounts for only 1.22%. The highest per-capita costs occur in North America, Europe, and Oceania. The most influential dietary risk factors are the overconsumption of processed and red meat, and the underconsumption of whole grains. A strong positive correlation is observed between diet-related health costs and national prosperity levels. Conclusions: This framework represents a novel approach to standardized and holistic valuation, providing a robust basis for deriving policy-relevant insights to inform sustainable nutrition strategies and advance the United Nations (UN) Sustainable Development Goals (SDGs), especially the second SDG, zero hunger. Full article

The gut microbiota is one of the key elements responsible for maintaining the body’s homeostasis. Its diverse composition affects, among others, the digestive and immune systems and also the circulatory system. Imbalances within the microbial community, referred to as dysbiosis, may lead to increased intestinal barrier permeability, chronic inflammation, and abnormal immune responses, which can be associated with the development of numerous diseases. Gut dysbiosis results in disturbances in the production of short-chain fatty acids, which exert anti-inflammatory effects, regulate blood pressure, and inhibit cardiac fibrosis. At the same time, it promotes the increased synthesis of trimethylamine N-oxide, a metabolite linked to inflammation, endothelial dysfunction, a higher risk of thrombosis, and the occurrence of arrhythmias. Additionally, small intestinal bacterial overgrowth (SIBO) may increase inflammation and contribute to metabolic and cardiovascular diseases (CVDs). The gut microbiota also influences the immune system through the production of neurotransmitters and modulation of T-cell activity, which may play a role in the development of autoimmune diseases. Reduced microbial diversity and an increased abundance of pathogenic bacteria are observed in individuals with hypertension and CVD, underscoring the importance of the microbiota as both a preventive and therapeutic factor. These findings highlight the crucial role of the gut microbiota in maintaining cardiovascular health and emphasize the need for further research into its modulation in the treatment of chronic diseases. Full article

Cardiovascular disease (CVD) continues to be the primary cause of morbidity and mortality worldwide, underscoring the urgent need for novel therapeutic alternatives. In recent years, marine ecosystems have garnered increasing attention as a promising source of bioactive compounds with unique structural and pharmacological properties. Marine-derived toxins and venoms, including tetrodotoxin, ω-conotoxins, anthopleurins, palytoxin, brevetoxin, aplysiatoxin, and asterosaponins, exert cardioprotective effects through diverse mechanisms such as modulation of ion channels, inhibition of sympathetic overactivity, antioxidative actions, and enhancement of myocardial contractility. These properties make them potential candidates for addressing various CVD manifestations, including arrhythmia, hypertension, ischemia–reperfusion injury, and heart failure. However, despite their therapeutic promise, the clinical application of these marine compounds remains limited due to poor tissue selectivity, narrow therapeutic indices, proinflammatory activity, and limited metabolic stability. Structural modifications, advanced drug delivery platforms, and in vivo validation studies are crucial for overcoming these challenges. This review highlights the pharmacological actions, molecular targets, and cardiovascular relevance of selected marine toxins and venoms while also addressing key translational barriers. Advances in biotechnology and peptide engineering are enabling the safer and more targeted use of these compounds. Collectively, marine-derived toxins and venoms represent a largely untapped but highly promising frontier in cardiovascular drug discovery. Strategic research focused on elucidating mechanisms, optimizing delivery, and translating clinical applications will be critical to unlocking their full therapeutic potential. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide. CVDs are associated with multiple factors, including oxidative stress, mediated endothelial dysfunction, vascular inflammation, and atherothrombosis. Although traditional antioxidant supplementation (such as vitamins C, E, and β-carotene) has shown promising results in rigorous animal model studies, it has consistently failed to demonstrate clinical benefit in most human trials. Consequently, there is a substantial unmet need for novel paradigms involving mechanistically and biologically relevant pharmaceutical-grade antioxidant therapies (“next-generation antioxidants”). Rapid advancements in redox biology, nanotechnology, genetic modulation of redox processes, and metabolic regulation have enabled the development of new antioxidant therapeutics, including mitochondrial-targeted agents, NADPH oxidase (NOX) inhibitors, selenoprotein and Nrf2 activators, engineered nanoparticles, catalytic antioxidants, and RNA-based and gene-editing strategies. These interventions have the potential to modulate specific oxidative pathways that contribute to CVD pathogenesis. This review provides a comprehensive assessment of current oxidative stress–modulating modalities and their potential to inform personalized cardiovascular prevention and treatment strategies. Full article

Cardiovascular disease (CVD) is increasingly recognized as a significant comorbidity in people living with HIV (PWH), contributing to increased morbidity and mortality. Epidemiological studies indicate that PWH have a 1.2–2-fold higher risk of myocardial infarction (MI) and other CVD events compared to HIV-negative individuals. While the mechanisms underlying HIV-associated CVD are not fully understood, they are likely to include a combination of cardiovascular-related adverse effects of HIV medications, vascular dysfunction caused by HIV-induced monocyte activation, and cytokine secretion, in addition to existing comorbidities and lifestyle choices. This comprehensive review examines the complex relationship between HIV infection and CVD, highlighting key pathophysiological mechanisms such as chronic immune activation, inflammation, endothelial dysfunction, and the role of antiretroviral therapy (ART) in promoting cardiovascular risk. Alongside conventional risk factors such as smoking, hypertension, and dyslipidemia, HIV-specific elements, especially metabolic abnormalities associated with ART, significantly contribute to the development of CVD. Prevention strategies are crucial, focusing on the early identification and management of cardiovascular risk factors as well as optimizing ART regimens to minimize adverse metabolic effects. Clinical guidelines now recommend routine cardiovascular risk assessment in PWH, emphasizing aggressive management tailored to their unique health profiles. However, challenges exist in fully understanding the cardiovascular outcomes in this population. Future research directions include exploring the role of inflammation-modulating therapies and refining sustainable prevention strategies to mitigate the growing burden of CVD in PWH. Full article

The natural polypeptide drug hirudin, a direct thrombin inhibitor, exhibits potent anticoagulant, anti-myocardial fibrotic, and anti-inflammatory effects in the treatment of cardiovascular diseases (CVD), but its clinical application remains limited by its low bioavailability, insufficient targeting capability, and bleeding risk. In recent years, the development of nanotechnology has enabled peptide drug delivery systems to demonstrate substantial promise in medical practice. Significant progress has been made in overcoming limitations and enhancing therapeutic efficacy against CVD through the use of Hirudin-based drug delivery systems by addressing drug stability in vivo, improving targeting ability, and ultimately achieving responsive release. This paper systematically reviews the mechanisms of action, clinical applications, and novel delivery strategies of the peptide drug hirudin in the treatment of CVD, with a particular focus on recent advances in hirudin-based drug delivery systems, and it also looks forward to future research directions for hirudin delivery systems, including the development of scalable intelligent carriers, the construction of real-time feedback systems, and the establishment of standardized in vitro and in vivo evaluation systems, aiming to present novel strategies for safe and efficient treatment of CVD. Full article

This study aimed to identify metabolomic biomarkers for diabetes progression and validate their response to lifestyle intervention. A two-phase design was employed: first, untargeted metabolomics distinguished normoglycemic, prediabetic (PDM), and diabetic (DM) individuals, identifying 1,5-anhydroglucitol (1,5-AG) as the most significant biomarker for differentiating PDM from DM (apparent AUC = 0.97, 95% CI: 0.95–1.00; corrected AUC = 0.94, 95% CI: 0.83–1.00; q < 0.001). Second, in a 3-month randomized controlled trial involving 300 adults with PDM, the combined diet and exercise intervention significantly improved fasting blood glucose and glycated hemoglobin levels, while concurrently elevating serum 1,5-AG levels compared with the control group, though it did not yield significant improvements in other cardiovascular disease-related risk factors including body mass index, waist circumference, systolic blood pressure, and diastolic blood pressure. The intervention also showed a trend toward reduced diabetes incidence. Integrated analysis establishes 1,5-AG as a sensitive biomarker of dysglycemia that is responsive to lifestyle modification, supporting its potential as a mechanistic tool for monitoring intervention efficacy in diabetes prevention. Full article

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide and constitute a substantial economic burden. Despite population aging, recent years have witnessed an increasing prevalence of conditions such as heart failure (HF), including among young adults. In this context, coronary artery disease (CAD) has also become an increasingly discussed issue. It has long been recognized that control of risk factors is crucial for prevention. Researchers stress the need to monitor these factors from the earliest stages of life, and detailed analyses indicate an influence of the prenatal period on the development of chronic diseases, including cardiovascular disorders. Transgenerational and intergenerational epigenetic mechanisms are also taken into account. This review aims to systematically evaluate the existing literature and summarize the mechanisms that may link these factors. We consider epigenetic, metabolic, immunological, and inflammatory influences. We describe examples of environmental exposures, such as air pollution, maternal diet, toxins, and infections, and analyze data derived from clinical studies. We discuss gaps in the literature and identify limitations, outlining directions for future research and emphasizing the need for CVD prevention initiated at the earliest stages of life. Full article