Search Results (512)

Background: Patients with catastrophic health conditions have continuously faced substantial out-of-pocket (OOP) costs for non-covered services despite universal health coverage in South Korea. In 2013, the National Health Insurance Service (NHIS) expanded coverage for four major catastrophic conditions—cancers, cardiovascular diseases, cerebrovascular diseases, and rare illnesses—aiming to strengthen financial protection for patients with catastrophic conditions. However, concerns remain that providers may respond by inducing more use of non-covered services, potentially offsetting reductions in patients’ financial burden. Methods: We evaluated the impact of the 2013 catastrophic coverage expansion on patients’ OOP spending for non-covered services using a quasi-experimental difference-in-differences design. Using nationally representative longitudinal healthcare expenditure data, the Korean Health Panel Survey (KHPS), from 2011 to 2016, we compared patients with the four targeted conditions to a control group with clinically comparable conditions. A two-part model was applied to separately estimate changes in the probability of incurring any non-covered OOP spending and changes in spending levels conditional on positive expenditures. We further examined whether effects differed by supplemental private health insurance (PHI) status. Results: We found that 7.3-, 5.2-, and 7.7-percentage-point decreases in annual probability of incurring any non-covered OOP spending for total, inpatient, and outpatient services, respectively, after policy implementation. Among patients with positive spending, OOP spending for total and inpatient non-covered services decreased by approximately 164 USD and 254 USD per year, while outpatient spending showed no statistically significant change. No statistically significant differential effects were also observed by PHI status. Conclusion: The catastrophic coverage expansion reduced patients’ exposure to and burden of non-covered OOP spending, indicating improved financial protection without evidence of compensatory increases in non-covered service use. These findings suggest that targeted benefit expansions for high-cost conditions can enhance financial equity within universal health systems. Full article

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. This increases the demand for real-world evidence to complement findings from randomized controlled trials. The German IQVIA Disease Analyzer (DA) database, which is populated with anonymized electronic medical records from general practitioners and specialists, has become an increasingly valuable source for cardiovascular research. Over the past two decades, and especially between 2020 and 2025, numerous epidemiological studies have used this database to explore associations between cardiovascular risk factors, comorbidities, therapeutic patterns, and cardiovascular outcomes in large, broadly representative outpatient populations. This review synthesizes evidence from 13 selected DA-based studies examining atrial fibrillation, heart failure, cardiometabolic disease, lipid management, non-alcoholic fatty liver disease (NAFLD)–related cardiovascular risks, cerebrovascular complications, COVID-19-associated vascular events, and modifiable behavioral and anthropometric factors. These studies were selected based on predefined criteria including cardiovascular relevance, methodological rigor, large sample size, and representativeness of key disease domains across the 2000–2025 period. Eligible studies were identified through targeted searches of peer-reviewed literature using the German IQVIA Disease Analyzer database and were selected to reflect major cardiovascular disease domains, risk factors, and therapeutic areas. Across disease domains, the reviewed studies consistently demonstrate the DA database’s capacity to identify reproducible associations between cardiometabolic risk factors, comorbidities, and cardiovascular outcomes in routine outpatient care. While causal inference is not possible, the database enables the identification of clinically meaningful associations that inform hypothesis generation, help quantify disease burden, and highlight gaps in prevention or treatment. The database’s strengths include large sample sizes (often exceeding 100,000 patients), long follow-up periods, and high external validity, while limitations relate to coding accuracy, residual confounding, and the absence of detailed clinical measures. Collectively, the evidence underscores the importance of the DA database as a crucial platform for real-world cardiovascular research. Full article

Carotid atherosclerosis remains one of the primary etiological factors underlying ischemic stroke, contributing to adult neurological disability and mortality. In recent years, non-coding RNAs (ncRNAs) have emerged as key regulators of gene expression, actively modulating molecular pathways involved in atherogenesis. This systematic review, the first to be exclusively focused on carotid atherosclerosis, aimed at synthesizing current findings on the differential expression of ncRNAs throughout the natural history of the disease, thus providing the first comprehensive attempt to delineate a stage-specific ncRNA expression profile in carotid disease. A comprehensive literature search was conducted in PubMed and Scopus databases in January 2025, following PRISMA guidelines. Original studies involving human subjects with carotid atherosclerosis, evaluating the expression of intracellular or circulating ncRNAs, were included and then categorized according to their association with cardiovascular risk factors, carotid intima-media thickness (cIMT), presence of atherosclerotic plaques, plaque vulnerability, clinical symptoms, and ischemic stroke. Out of 148 articles initially identified, 49 met the inclusion criteria and were analyzed in depth. Among the different classes of ncRNAs, microRNAs (miRNAs) were the most frequently reported as dysregulated, followed by circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs). Notably, the majority of identified ncRNAs were implicated in key pathogenic mechanisms such as inflammatory signaling, vascular smooth muscle cell (VSMC) phenotypic modulation, and ABCA1-mediated cholesterol efflux. Collectively, the evidence underscores the association and possible involvement of ncRNAs in the initiation and progression of carotid atherosclerosis and its cerebrovascular complications. Their relative stability in biological fluids and cell-specific expression profiles highlight their strong potential as minimally invasive biomarkers and—possibly—novel therapeutic targets. Full article

Background/Objectives: Cardiovascular (CV) and cerebrovascular diseases, primarily attributed to atherosclerosis, stand as leading global causes of morbidity and mortality. This study aims to evaluate the impact of preclinical atherosclerosis parameters, including intima-media thickness (IMT) and arterial stiffness, in a seven-year follow-up of 100 patients with CV risk factors but no known history of CV or cerebrovascular diseases. Methods: Between April 2014 and December 2015, 100 patients presenting with suspected ischemic heart disease were enrolled. The study integrates the color Doppler examination of the supra-aortic trunks with the evaluation of preclinical parameters of atherosclerosis, such as intima-media thickness (IMT), βeta index, and pulse wave velocity (PWV), as well as echocardiographic evaluations, including global longitudinal strain (GLS). CV risk factors, metabolic syndrome, and insulin resistance were assessed and measured for each patient using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Two- and seven-year follow-ups assessed various CV events. Results: The study population comprised 67% males and 33% females. Metabolic syndrome, impaired fasting glycemia and hypertension were prevalent. The mean value of IMT was 1.21 ± 0.26 mm, and PWV was 8.47 ± 2.14 m/s. The 7-year follow-up identified IMT, PWV, and HOMA-IR as strong positive predictors of cardiovascular events, with PWV emerging as a particularly sensitive indicator of early events. Conclusions: Insulin resistance and cardiovascular risk factors may contribute to early alterations in myocardial and vascular function, even in the absence of overt disease. PWV, as a recognized surrogate marker of arterial stiffness, may serve as a sensitive tool for the early prediction of cardiovascular events. A comprehensive screening, including the assessment of markers indicating subclinical vascular alterations, along with the implementation of preventive interventions, is crucial for populations at risk. Full article

Endothelial cells (ECs) regulate vascular homeostasis, and their dysfunction is a key driver of many cardiovascular and cerebrovascular diseases. Human-induced pluripotent stem cell-derived endothelial cells (hiPSC-ECs) provide access to patient-specific vascular cells that can be directed toward arterial, venous, or organotypic phenotypes, enabling personalized in vitro modeling of endothelial pathology. In this review, we discuss how patient-specific iPSC-ECs are used as predictive and personalized two- and three-dimensional models to dissect disease mechanisms and prioritize targeted therapies. We highlight some limitations of this methodology and outline future directions for integrating iPSC-EC-based assays into individualized treatment algorithms. Full article

Objective: This systematic review and meta-analysis aims to investigate the association between hearing loss (HL) and incident cardiovascular disease (CVD), a composite of stroke and myocardial infarction (MI), and to explore the specificity of the underlying pathophysiology and the consistency of this association across key demographics and HL types. Methods: Adhering to PRISMA and MOOSE guidelines, we searched PubMed and Web of Science for studies published in English over the past 16 years. The analysis encompassed the spectrum of HL types. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for CVD (a composite of stroke and MI) and for each outcome separately. Extensive subgroup and sensitivity analyses were performed to assess robustness amid heterogeneity. Results: The analysis included 15 studies (12 cohort, 3 cross-sectional/case–control). HL was significantly associated with a high incidence of CVD (pooled OR = 1.31, 95% CI 1.05–1.65). A significant association was found for stroke (OR = 1.41, 95% CI 1.07–1.85) but not for MI (OR = 1.15, 95% CI 0.88–1.50). A consistent pattern of elevated risk was observed across all subgroups, and the primary findings remained robust in sensitivity analyses. Conclusion: Our meta-analysis indicates that HL, across its various types, is significantly associated with incident stroke, but not MI. This differential risk profile is compatible with a pathophysiology that may involve the cerebrovascular system more prominently than systemic coronary arteries. The findings highlight the potential of HL as a cost-effective indicator meriting further investigation for targeted cerebrovascular risk assessment in prevention strategies. Full article

Nitric oxide (NO), a fundamental gaseous signaling molecule, is indispensable for cardiovascular homeostasis. This review synthesizes the expansive field of NO biology within the unifying framework of Nitric Oxide Equilibrium (NOE), i.e., the critical balance between its synthesis, bioavailability, and degradation. In a physiological state, NOE maintains vascular health by regulating blood pressure, preventing thrombosis, suppressing inflammation, and optimizing both cardiac and mitochondrial function. Here, we analyze how NOE disruption, primarily through oxidative stress and enzymatic dysfunction, underlies the pathogenesis of major cardiovascular diseases, including atherosclerosis, heart failure, ischemia–reperfusion injury, and cerebrovascular diseases like stroke. A critical evaluation of therapeutic strategies designed to restore NOE is presented, encompassing classic NO donors and phosphodiesterase-5 inhibitors, alongside next-generation soluble guanylate cyclase modulators and precision nanomedicine approaches. By identifying key knowledge gaps and methodological hurdles, this review charts a course for future research focused on biomarker-guided interventions and personalized medicine. Ultimately, we frame the restoration of NOE as a paramount therapeutic goal, crucial to translating decades of molecular research into effective clinical practice. Full article

Background: Coronary artery bypass grafting (CABG) is a well-established revascularization strategy for patients with multivessel coronary artery disease. The effectiveness of CABG is significantly influenced by antiplatelet therapy aimed at maintaining graft patency and reducing thrombotic complications. However, substantial inter-individual variability exists in platelet function responses to standard therapies such as aspirin and clopidogrel, leading to antiplatelet resistance. This variability has been linked to increased risks of myocardial infarction, stroke, and early graft failure. Platelet function testing (PFT) offers a potential strategy to identify resistance and guide more personalized antiplatelet therapy. This study aims to evaluate the association between perioperative platelet function test results and clinical outcomes following CABG. By assessing platelet responsiveness at multiple timepoints and correlating findings with postoperative events, the study seeks to determine whether PFT can stratify risk and improve patient management. Methods: This is a prospective, single-centre, observational cohort study conducted at a tertiary NHS cardiac surgery centre. Patients having elective or urgent isolated CABG will be enrolled and undergo perioperative PFT using the TEG6s system. Clinical outcomes will be monitored for 12 months postoperatively, with primary endpoints assessing the correlation between platelet function results and major adverse cardiovascular and cerebrovascular events (MACCE). Secondary endpoints will include the prevalence of antiplatelet resistance, demographic predictors, and the feasibility of integrating PFT into clinical workflows. Results: This study will report the prevalence of aspirin and clopidogrel resistance in CABG patients based on TEG6s PFT, as well as the correlation between platelet function results and MACCE, postoperative bleeding, and the need for surgical re-exploration. Additionally, it will examine the associations between demographic and clinical factors—such as diabetes status, renal function, BMI, and surgical technique—and variability in platelet responsiveness. The feasibility of incorporating PFT into perioperative workflows will also be evaluated, assessing whether results could support personalized antiplatelet management in future clinical trials. Conclusions: Findings from this study will provide real-world evidence regarding platelet function variability in CABG patients and suggest that PFT may identify those at increased risk of thrombotic complications. This exploratory analysis supports the need for larger interventional trials aimed at optimizing individualized postoperative antiplatelet therapy to improve surgical outcomes. Full article

Background and Objectives: The obesity paradox in maintenance hemodialysis (MHD) patients (better survival of obese as compared to non-obese patients in MHD) remains controversial, with many published papers supporting the idea that higher BMI is protective. Data from Eastern Europe, in particular from the elderly population on hemodialysis, are limited. The aim of this study was to describe the distribution of body weight status and cardiometabolic comorbidities and to evaluate the association of BMI categories with all-cause mortality in a multi-center Romanian hemodialysis cohort. Materials and Methods: We conducted a retrospective cohort study of 679 patients with end-stage kidney disease (ESKD) undergoing maintenance haemodialysis in eight Romanian centers. All patients received thrice-weekly treatments (≥4 h/session) using high-flux dialysers. Baseline demographic, clinical, laboratory, and echocardiographic data were extracted from dialysis records. Survival across BMI groups was assessed using Kaplan–Meier curves and the log-rank test. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality, with normal weight as the reference category. Multivariable models incorporated progressive adjustment for age, sex, dialysis vintage, diabetes, major cardiovascular comorbidities, and ESKD-related factors, including anemia parameters and CKD–mineral and bone disorder (CKD-MBD) markers. Results: A total of 679 haemodialysis patients were included (mean age 57.2 ± 12.9 years; 59.1% male); 52.7% were normal weight, 28.9% overweight, and 18.4% obese. During follow-up, 360 patients (53.0%) died, with similar crude mortality across BMI groups (normal weight 51.7%, overweight 55.1%, obese 53.6%; p > 0.05). In univariate Cox analyses, older age, obesity, hypoalbuminaemia, elevated CRP, hyperphosphataemia, peripheral and cerebrovascular disease, diabetes, low dialysis adequacy (eKt/V < 1.2), and lower ultrafiltration were associated with higher mortality, whereas preserved LVEF (≥50%) was protective. In multivariable analyses, independent predictors of mortality included older age (HR 1.042 per year, p < 0.001), obesity (HR 1.411, p = 0.045), elevated CRP (HR 1.781, p < 0.001), diabetes (HR 1.775, p < 0.001), inadequate dialysis dose (eKt/V < 1.2; HR 1.343, p = 0.029), and preserved LVEF remained protective (HR 0.665, p = 0.013). The Kaplan–Meier analysis showed significantly lower survival with increasing BMI: median survival was 7.56 years in normal-weight patients, 4.56 years in overweight patients, and 3.92 years in obese individuals (log-rank p < 0.05). Conclusions: In this Romanian cohort of multicenter hemodialysis patients, obesity as measured by BMI was associated with an increased incidence of all-cause mortality, while overweight did not confer a clear survival advantage over normal weight. These findings call into question the classic hemodialysis obesity paradox and support a more cautious interpretation of the increased BMI. Full article

Background/Objectives: Patients with combined cardiovascular and cerebrovascular disease face poorer prognoses. Early, accurate assessment of the risk of cerebral ischaemic events (including transient ischaemic attacks (TIAs) and ischaemic strokes (ISs)) in patients with coronary artery disease (CAD) is therefore vital for clinical guidance. This study aims to develop a comprehensive risk assessment model for early warning in this population. Methods: In this study, we conducted a retrospective multicentre recruitment of CAD patients undergoing concurrent coronary CTA and cervical CTA (n = 326), with follow-up to observe the occurrence of cerebral ischaemic events. We performed an analysis of high-risk plaque (HRP) characteristics and subcomponent plaque in coronary and cervical arteries, measured the pericoronary fat attenuation index (FAI) and cervical perivascular fat density (PFD), and extracted corresponding radiomic features. Five models were constructed to identify the CAD patients who developed IS/TIA, respectively: Model 1—clinical characteristics; Model 2—coronary CTA parameters + Radscore_coronary; Model 3—cervical CTA parameters + Radscore_cervical; Model 4—Model 1 + Model 2; Model 5—Model 1 + Model 2 + Model 3. Results: In the cerebral ischaemia group, the prevalence of coronary and/or cervical HRP was higher than in the non-ischaemia group (28.0% vs. 26.1%, 57.0% vs. 44.0%, p = 0.02). Multivariate logistic regression confirmed that RCA FAI and PFD remained significant independent risk factors for IS/TIA (all p < 0.05). The model prediction results showed that progressively incorporating coronary and cerebral vascular risk factors into the clinical features gradually improved model performance (Model 4 vs. Model 5, AUC: 0.711 [0.645–0.777] vs. 0.821 [0.769–0.873]). Model 5 achieved a sensitivity of 0.788 [0.485–0.909] and specificity of 0.827 [0.385–0.923], demonstrating the best overall clinical benefit. Conclusions: RCA FAI and PFD are independent predictors of cerebral ischaemic events. By integrating clinical characteristics, coronary CTA and cervical CTA parameters, combined with Radscore_coronary and Radscore_cervical, the risk stratification capability for IS/TIA in CAD patients can be significantly enhanced. Full article

Black rice has gained increasing attention due to its abundant phenolic compounds and gut microbiota modulation potential, but its health benefits are highly dependent on processing methods. In the present study, the effects of extrusion, traditional cooking, and their combinations with solid-state fermentation (SSF) on phenolic bioaccessibility and the gut microbiota modulation potential of black rice were compared. Results indicated that extrusion combined with SSF (E-SSF) was the most prominent in improving the bioaccessibility of phenolics, flavonoids, and antioxidant activities of black rice during in vitro gastrointestinal digestion. In addition, black rice after SSF induced significantly lower gas production and higher pH during in vitro fecal fermentation. Particularly, black rice after E-SSF showed great advantages in the yield of propionic acid, butyric acid, and total short-chain fatty acids. Consequently, black rice after SSF increased alpha diversity and Bacteroidetes abundance but decreased Firmicute abundance of gut microbiota, while black rice after E-SSF induced the highest alpha diversity and Bacteroide abundance. These results suggested that SSF was beneficial to improve the gut microbiota modulation potential of black rice, and E-SSF was the most preferred. In conclusion, E-SSF was the most suitable to improve the phenolic bioaccessibility and gut microbiota modulation potential of black rice. Full article

Diabetes mellitus (DM) is a complex, heterogeneous, hyperglycemic chronic metabolic disorder. Type 2 diabetes mellitus (T2DM) is characterized by progressive loss of insulin secretion from pancreatic islet β-cells due to IR (insulin resistance), which is a feature of metabolic syndrome (MetS). Chronic hyperglycemia in patients with T2DM in synergy with other metabolic abnormalities causes complications such as diabetic ketoacidosis, osmotic diuresis and hyperglycemic diabetic coma, as well as chronic microvascular and macrovascular complications such as atherosclerotic cardiovascular disease (ASCVD), peripheral artery disease (PAD) and cerebrovascular events, which implicate the formation of reactive species and the promotion of inflammatory pathways. In these events, natural or synthetic antioxidants and minerals seem to have ameliorative effects and may serve as beneficial co-treatment options. In view of these terms, the aim of this study is to investigate the underlying mechanisms of T2DM, its clinical presentation, and its complications. Additionally, the association of the pathogenesis of T2DM and the occurrence of its complications with obesity, chronic inflammation, oxidative stress (OS), insulin resistance (IR), hepatic steatosis, and dyslipidemia is examined, whilst molecular pathways, such as NF-κB and JAK/STAT, are also summarized, under the scope of the effects of several antioxidant compounds and minerals on their progression. The interrelation of T2DM with these conditions, as well as the effects of antioxidant supplementation, seems to be bidirectional, and it is recommended that obese patients be screened for T2DM and adopt lifestyle changes, including exercise, diet modification, and weight loss, in addition to potentially taking multifunctional supplements that offer antioxidant and anti-inflammatory potential. However, many aspects of the protective mechanisms of such antioxidants remain to be elucidated, with more drawbacks in their pharmacokinetic behavior, such as their poor absorption and solubility, waiting to be resolved. Full article

Background: Inflammatory bowel disease (IBD) is associated with systemic inflammation and potential cardiovascular complications. This meta-analysis evaluates long-term cardiovascular risks in IBD. Methods: Electronic databases were searched for studies examining cardiovascular, cerebrovascular, and thromboembolic risks in IBD. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were pooled using a random-effects model. Results: Fifty-three studies comprising 1,406,773 patients were analyzed. IBD was linked to increased risk of ischemic heart disease (aHR 1.25; p = 0.001) myocardial infarction (aHR 1.25; p = 0.01), acute coronary syndrome (aHR 1.43; p < 0.00001), heart failure (aHR 1.24; p < 0.00001), atrial fibrillation (aHR 1.20; p < 0.00001), and stroke (aHR 1.13; p < 0.00001). Elevated risks were also observed for peripheral arterial disease (aHR 1.41; p < 0.00001), diabetes mellitus (aHR 1.40; p < 0.00001), venous thromboembolism (aHR 1.98; p < 0.00001), deep vein thrombosis (aHR 2.85; p = 0.0004), and pulmonary embolism (aHR 1.98; p = 0.03). Importantly, IBD was associated with increased cardiovascular (aHR 1.14; p = 0.03) and all-cause mortality (aHR 1.53; p < 0.00001). Conclusions: IBD patients face higher risk for adverse cardiovascular outcomes, thromboembolic disease, and mortality, necessitating early cardiovascular risk assessment and targeted interventions in this population. Full article

Background/Objectives: Cardiovascular disease (CVD) and cerebrovascular disease (CeVD) remain leading causes of death in the United States, with Mississippi consistently reporting some of the nation’s highest mortality rates. Despite earlier national declines, recent evidence suggests stagnation or increases, particularly in high-burden regions. This study examined short-term trends in CVD and CeVD mortality in Mississippi between 2018 and 2022, stratified by age, sex, and race. Methods: Mortality data for adults aged ≥45 years were obtained from the Mississippi Statistically Automated Health Resource System (MSTAHRS). Age-adjusted mortality rates were calculated per 100,000 population and standardized to the 2000 U.S. population. Joinpoint regression was used to estimate annual percent change (APC) and average annual percent change (AAPC) with 95% confidence intervals (CIs). Analyses were stratified by sex, and within each racial group (White, Black, Other), mortality trends were further examined across age categories (45–54, 55–64, 65–74, 75–84, ≥85 years). Results: Cardiovascular mortality increased significantly among White women in midlife (ages 45–74), while “Other race” men in early midlife and “Other race” women in the oldest age group showed steep increases. Although Black adults did not experience significant changes over time, their mortality rates remained consistently higher than those of White adults. Conclusions: Progress in reducing cardiovascular and cerebrovascular mortality in Mississippi has reversed in several subgroups, particularly midlife White women and smaller racial populations. These findings mirror national stagnation and pandemic-related disruptions, highlighting the urgent need for equity-focused prevention, improved healthcare access, and targeted interventions addressing structural determinants of health. Full article

Atherosclerosis is a leading contributor to cerebrovascular and cardiovascular diseases, which can be driven by multiple pathological processes, including chronic inflammation, lipid dysregulation, and vascular remodeling. Currently, lifestyle intervention and pharmacological intervention, like statins, are recommended in clinical treatments. However, the mortality and morbidity rates caused by atherosclerosis remain high. Kruppel-like transcription factors (KLFs) are zinc-finger-containing transcription factors that are involved in various physiological and pathological processes. By modulating endothelial cell homeostasis, smooth muscle cell phenotypic switching, and inflammatory responses, members of the KLF family—particularly KLF2, KLF4, KLF5, KLF6, and KLF14—emerge as pivotal regulators in the initiation and progression of atherosclerotic lesions. In this review, we constructed a comprehensive network of KLFs in the pathogenesis of atherosclerosis. Based on the molecular mechanism, this review for the first time highlighted newly identified substances that exploit KLF-modulated pathways to attenuate atherosclerosis, and discussed emerging gene therapy and nanotechnology approaches, addressing both the therapeutic promise and challenges associated with targeted KLF modulation. This first offered new avenues for translational and precision medicine in atherosclerotic cardiovascular disease from the perspective of KLF. Full article