Search Results (401)

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, arising from complex interactions among metabolic, genetic, and environmental factors. Nicotinamide N-methyltransferase (NNMT) has recently emerged as a key metabolic regulator in CVD pathogenesis. By consuming nicotinamide and methyl groups, NNMT perturbs epigenetic, metabolic, and redox pathways that are critical for cardiovascular health. NNMT-mediated NAD⁺ depletion impairs mitochondrial function, sirtuin (SIRT) activity, redox balance, and energy metabolism, thereby creating a pro-atherogenic environment. NNMT and its product 1-methylnicotinamide (1-MNA) show a complex duality: they modulate SIRT activity—particularly SIRT1 and SIRT3—to influence gluconeogenesis, cholesterol synthesis, lipogenesis, and mitochondrial antioxidant defenses. NNMT upregulation also elevates homocysteine levels, activating pro-inflammatory and pro-oxidative cascades (e.g., TLR4–NF-κB and STAT3–IL-1β). Growing evidence links NNMT to major CVD risk factors, including hyperlipidemia, hypertension, diabetes mellitus, and obesity. Thus, NNMT has a multifaceted role in cardiovascular health: while its enzymatic activity is often pathogenic (via NAD⁺/SAM consumption and homocysteine production), its metabolite 1-MNA can exert protective effects (via NRF2 activation and anti-thrombotic mechanisms). This duality highlights the need to delineate the molecular processes that balance these opposing actions. Experimental studies using small-molecule NNMT inhibitors and RNA interference have shown promising cardiometabolic benefits in preclinical models, including improved insulin sensitivity, reduced atherosclerosis, and attenuated cardiac dysfunction. However, no clinical trials have yet targeted NNMT specifically in CVD. Future research should clarify the tissue-specific functions of NNMT and translate these insights into novel therapeutic strategies. Full article

In individuals with non-adipogenic traits and enhanced ketogenic capacity, plasma triglyceride (TG) levels are typically low, while low-density lipoprotein cholesterol (LDL-C) levels often exceed the normal range, complicating cardiovascular risk assessment. We analyzed lipid profiles to better characterize cardiovascular risk in this population. Drug-naïve patients newly diagnosed with prediabetes or type 2 diabetes (T2D) were divided into two groups based on serum β-hydroxybutyrate levels: enhanced versus non-enhanced ketogenesis. Among those with enhanced ketogenesis, 27 individuals with high LDL-C (≥100 mg/dL) and low TG (<150 mg/dL) were selected. For comparison, 27 individuals with high TG (>150 mg/dL) from the non-enhanced group were included. The enhanced ketogenesis group demonstrated more favorable lipid characteristics, including a significantly larger average LDL particle size (26.8 ± 0.3 nm vs. 25.9 ± 0.6 nm, p < 0.001), a lower proportion of small dense LDL particles, and reduced oxidized LDL to LDL-C ratio. Importantly, enhanced ketogenesis remained an independent predictor of larger LDL particle size after adjusting for potential confounders including TG. Despite the potential of selection bias intentionally induced by the predefined inclusion criteria, our findings suggest that patients with T2D or prediabetes who exhibit enhanced ketogenesis, even in the presence of elevated LDL-C levels, may have a more favorable atherogenic profile and are not necessarily at increased cardiovascular risk. Full article

Background and Objectives: Dyslipidemia, a modifiable cardiovascular risk factor, is associated with chronic low-grade inflammation. While leukocyte-derived indices have been investigated in this context, eosinophil-related inflammatory markers remain underexplored. This study examined patterns of eosinophil-to-lymphocyte ratio (ELR) and eosinophil-adjusted systemic inflammation response index (EA-SIRI) across dyslipidemia phenotypes. Materials and Methods: In this retrospective study, adult subjects were classified into six dyslipidemia phenotypes. Leukocyte-derived indices were evaluated across groups, and analyses included comparisons of medians, prevalence rates, tertile distributions, odds ratios, and risk estimates. Results: Both ELR and EA-SIRI were significantly higher in individuals with atherogenic dyslipidemia (ELR: 0.18; EA-SIRI: 1.53) and combined dyslipidemia (ELR: 0.17; EA-SIRI: 1.49) compared to the normolipidemic group (ELR: 0.11; EA-SIRI: 0.92). Notably, these patterns were more pronounced in males aged <40 years and younger females (<40), suggesting sex- and age-related variations in eosinophil-related inflammatory responses to dyslipidemia. Moreover, the highest tertiles of both ELR and EA-SIRI exhibited higher triglycerides and lower HDL-C compared to the lowest tertiles (p < 0.001). The odds of atherogenic dyslipidemia were more than doubled in individuals with elevated ELR (OR = 2.02; p < 0.001) and EA-SIRI (OR = 2.19; p < 0.001). ROC curve analysis indicated modest discriminative power for identifying atherogenic dyslipidemia, with ELR and EA-SIRI yielding AUC of 0.60 (p < 0.001) and 0.62 (p < 0.001), respectively. Conclusions: Our findings suggest eosinophil-related inflammation contributes to immunometabolic dysregulation underlying dyslipidemia. ELR and EA-SIRI may offer insights into inflammation-driven lipid disturbances and help detect subclinical inflammatory activity associated with atherogenic lipid profiles. Full article

Background: Futile reperfusion (FR), which is defined as successful revascularization without a favorable functional outcome, is a major limitation of endovascular treatment (EVT) for acute ischemic stroke. Although clinical and imaging predictors of FR have been studied, the role of systemic metabolic markers, such as the atherogenic index of plasma (AIP), remains unclear. No prior studies have examined the use of AIP in patients with large artery atherosclerosis (LAA)-related stroke. Methods: We analyzed data from four university-affiliated, prospectively maintained registries in the Republic of Korea (2015–2024). We included patients with anterior-circulation LVO who underwent EVT and achieved successful reperfusion. AIP was calculated as log(triglyceride/HDL-C) in mmol/L. The primary outcome was FR, defined as modified Rankin Scale (mRS) 3–6 at 3 months. The secondary outcome was early neurological deterioration (END). Multivariable logistic regression and ROC analysis were used. Results: Among the 406 LAA patients, 227 (55.9%) experienced FR, while 82 (20.2%) had END. Higher AIP quartiles were significantly associated with an increased risk of both FR and END (p for trend < 0.01). The highest AIP quartile (Q4 ≥ 0.26) had adjusted odds ratios of 4.34 (95% CI: 2.18–8.65) for FR and 9.62 (95% CI: 3.66–25.26) for END. The AUCs were 0.775 for FR and 0.726 for END. Conclusions: In a multicenter cohort of EVT-treated LAA stroke with successful reperfusion, elevated AIP independently predicted FR and END. AIP is a simple, widely available biomarker that may support pre-procedural risk stratification and inform post-reperfusion management after EVT. Full article

Plasma triglyceride levels are a strong cardiovascular risk marker. However, triglyceride–lowering therapies have not demonstrated a reduction in cardiovascular events, suggesting that triglycerides may serve as surrogate markers for other atherogenic mechanisms. The aim is to investigate the role of triglycerides in derangements of the global lipoprotein profile, as assessed by ¹H–NMR spectroscopy. Serum lipoprotein profiles were analyzed in patients with metabolic alterations attending the Lipid Unit of a University hospital (n = 822). Lipoprotein particle number, size, and composition were evaluated and visualized through a graphic representation of a lipoprotein network analysis referred to lipid silhouette in patients sorted by triglyceride quartiles. Profound alterations in lipoprotein quantity and composition were associated with incremental triglyceride concentrations independently on the presence of diabetes or obesity, including a significantly increased number of VLDL and smaller LDL particles, and higher remnant cholesterol, representing up to 30% of all cholesterol in quartile 4. It was also a significant triglyceride enrichment of LDL and HDL particles. Triglycerides are not merely components of atherogenic dyslipidemia; they are a key driver of the overall changes and are strongly associated with a proatherogenic plasma lipoprotein profile. Visualization of these alterations provides supplementary insights to support cardiovascular prevention strategies. Full article

Background/Objectives: In the last decade, several studies revealed individual response variability to different antiplatelet agents, and patients who have no response to these drugs are considered poor responders. Some studies explored platelet function during antiplatelet treatment to identify those patients with “high on-treatment platelet reactivity” (HPR), which exposes them to increased risk of major adverse cardiovascular events (MACE). Methods: We conducted a study with patients with ST-elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) with ticagrelor and aspirin, including long-term follow-up after 5 years. We used thromboelastography, the total thrombus formation analysis system, and vasodilator-stimulated phosphoprotein phosphorylation assay (VASP) to analyze HPR with different methods; selected laboratory parameters were measured during hospitalization to check significant correlations. Results: We identified STEMI patients treated with DAPT with HPR as a risk group for MACE in a 5-year follow-up. Additionally, we have shown that HPR is associated with atherosclerosis by analyzing lipid profile parameters. Conclusions: High on-treatment platelet reactivity (HPR) increases the risk of major adverse cardiovascular events in the long term, especially with elevated C-reactive protein or an atherogenic lipid profile. Standardizing HPR assessment is crucial for optimizing individualized antiplatelet therapy and improving patient outcomes post-STEMI. Full article

Background: The increasing prevalence of overweight and obesity worldwide is one of the most serious public health challenges, reaching epidemic proportions. Excessive body weight is often accompanied by metabolic disorders such as insulin resistance, atherogenic dyslipidaemia and hypertension—collectively known as metabolic syndrome. This cross-sectional study aimed to identify predictors of metabolic syndrome in women using logistic regression analysis based on selected sociodemographic, anthropometric, and lifestyle variables. Methods: The study included 250 women aged 23–85 recruited in the Podkarpackie region of Poland. Data on sociodemographic characteristics and smoking status were collected via a questionnaire. Physical activity and sedentary behaviours were assessed using the Global Physical Activity Questionnaire. Body composition was measured using bioelectrical impedance analysis. Fasting capillary blood samples and blood pressure measurements were obtained by qualified medical staff in accordance with standard procedures. Results: Obesity was strongly associated with metabolic syndrome components, particularly abnormal blood pressure (66.3%) and fasting glucose (64%), both of which were statistically significant (p < 0.01). Age was a significant predictor of metabolic syndrome (OR = 1.06; p < 0.01) and its components, including hypertension, dysglycaemia and dyslipidaemia. Waist-to-hip ratio was strongly linked to metabolic syndrome (OR = 356.97; p < 0.01) and obesity (OR = 5.89 × 10³⁰; p < 0.001); however, these exceptionally high values should be interpreted with caution, as they may reflect statistical artifacts due to model instability or sample characteristics, rather than a meaningful or generalizable association. Higher body fat mass was associated with an increased risk of obesity, hypertension and dysglycaemia (OR = 1.42, 1.06 and 1.06 respectively; p < 0.01). Conclusions: These results emphasise the significant role of obesity as a risk factor for metabolic syndrome in women, highlighting the need for personalised preventive strategies that consider lifestyle and sociodemographic factors, such as targeted health education, promotion of physical activity, and dietary counselling adapted to the needs of women at risk. Full article

Cardiovascular diseases remain the leading cause of mortality worldwide, with multiple risk factors contributing to their development. Among these, obesity and hyperhomocysteinemia have been recognized as significant contributors to endothelial dysfunction, a key early event in the pathogenesis of atherosclerosis. Our study aimed to evaluate the relationship between total homocysteine (tHcy) levels and traditional cardiovascular risk factors in overweight and obese adolescents. We enrolled 42 obese, 14 overweight, and 25 non-obese children. No significant differences in tHcy levels were observed between overweight, obese, and non-obese adolescents. Homocysteine positively correlated with age (r = 0.433, p < 0.011) and creatinine concentrations (r = 0.363, p = 0.001) in the overall group of overweight, obese, and non-obese children, as well as in the combined group of overweight and obese children (for age: r = 0.275, p = 0.025; for creatinine: r = 0.278, p = 0.025). We did not find any association between homocysteine and atherogenic lipid profile, insulin-resistance status, blood pressure, and inflammatory parameters in overweight and obese patients. Age emerged as the strongest independent predictor of homocysteine levels. The observed association with creatine suggests a potential renal contribution to homocysteine metabolism. Full article

Background: Obesity-associated liver dysfunction is a key feature of metabolic syndrome. Marine by-products, such as fish oils, offer promising dietary interventions. In this study, we aimed to assess the anti-obesity and hepatoprotective effects of herring–saury by-product-derived fermented fish oil—Gwamegi oil (GmO)—and the same oil fermented with Lactobacillus brevis KCCM13538P (GmOLb) in a high-fat-diet (HFD)-induced obese mouse model. Methods: GmO was extracted and fermented. Anti-obesity and hepatoprotective effects were assessed using in vitro and in vivo studies. For the in vivo study, female C57BL/6J mice were fed an HFD supplemented with lard (control), GmO, or GmOLb for 60 days. Metabolic and liver function parameters were assessed. Results: In 3T3-L1 adipocytes, GmOLb significantly reduced lipid accumulation and intracellular triglyceride (TG) levels compared with GmO. In HFD-fed mice, GmOLb significantly reduced body weight gain, ovarian fat mass, serum TG, low-density lipoprotein cholesterol, leptin concentration, atherogenic indices, and cardiac risk factor ratio. Furthermore, it reduced liver damage indicators, including alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels. Conclusions: Fermenting herring–saury oil with L. brevis KCCM13538P enhanced its anti-obesity and hepatoprotective effects in HFD-fed mice. GmOLb shows strong potential as a functional dietary lipid for preventing and managing metabolic disorders. Full article

Background: Asymptomatic left ventricular diastolic dysfunction (LVDD) occurs in type 2 diabetes mellitus (T2DM) patients, particularly among the elderly. Aim: This study aimed to identify diastolic function changes over a 52-week follow-up and the predictive factors for LVDD in T2DM patients without atherosclerotic manifestations. Methods: Diastolic function, metabolic profile, atherogenic indexes, and subclinical inflammatory markers were assessed at baseline and after one year in 138 T2DM outpatients. All variables were compared in patients with and without LVDD across three age groups. Results: The patients were 57.86 ± 8.82 years old, 49.3% male, with a mean 5-year diabetes duration and a median HbA_1c of 7.8%. At baseline, 71 patients had grade 1 LVDD, 12 had grade 2 and 3 LVDD, and 15 had indeterminate LVDD. In the elderly group, 29 patients had LVDD. The logistic regression analysis identified age over 65 as an independent risk factor for LVDD (Exp B = 9.85, 95% CI: 1.29–75.36, p = 0.027). LVDD patients had a longer diabetes duration and a higher prevalence of diabetic neuropathy. Elderly patients had the lowest E/A, e’, lateral s’, atherogenic and Castelli risk indexes, and significantly higher E/e’, EDT, LAVI and TNF-alpha values (p < 0.05). After 52 weeks, diastolic function worsened in 27 patients, who had no significant differences compared to those with stable or improved diastolic function. Conclusions: LVDD was common in our T2DM patients without known cardiovascular disease, and age increases the LVDD risk. Echocardiographic assessment is necessary, especially in elderly T2DM patients with co-morbidities, to identify patients at risk of progression to heart failure early. Full article

Elevated levels of atherogenic lipoproteins are known to be associated with an increased risk of incident and recurrent cardiovascular events. Knowing that the immediate post-acute coronary syndrome (ACS) period is associated with the maximum risk of recurrent events, the gradual escalation of therapy allows the patient to remain above the targets during the most vulnerable period. In addition, the percentage of lipid-lowering levels for each class of drugs is predictable and has a ceiling. Hence, it is prudent to immediately start with a combination of lipid-lowering drugs following ACS according to the baseline lipid levels. Multiple studies with injectable lipid-lowering agents (PCSK9 inhibitors) such as EVOPACS, PACMAN MI, and HUYGENS MI have shown the feasibility of achieving LDL-C goals by day 28 and beneficial plaque modification in non-infarct-related coronary arteries. Recently, a study from India demonstrated that an upfront triple combination of oral lipid-lowering agents was able to achieve LDL-C goals in a majority of patients in the early post-ACS period. This notion is also supported by a few recent lipid-lowering guidelines advocating for an upfront dual combination of a high-intensity statin and ezetimibe following ACS. Henceforth, the goal should not only be the achievement of lipid targets but also their early achievement. However, the impact of this strategy on long-term cardiovascular outcomes is yet to be ascertained. Full article

Familial dysbetalipoproteinemia (FD) is a prevalent and highly atherogenic hyperlipoproteinemia associated with the ε2/ε2 APOE genotype or rare APOE variants. The contributions of additional genetic and clinical factors to the FD phenotype remain unclear. We investigated these factors in both autosomal recessive and autosomal dominant forms of FD. Targeted (n = 4666) and exome (n = 194) sequencing were used to identify the ε2/ε2 APOE genotype or rare FD-causative APOE variants. Twenty-four lipid-related genes and forty variants included in a polygenic risk score for hypertriglyceridemia (HTG) were analyzed. FD was defined by the presence of FD variants and triglycerides (TG) ≥ 1.5 mmol/L (main study group). The comparison group consisted of patients with FD variants but TG < 1.5 mmol/L. Univariable and multivariable regression analyses were performed. A total of 71 unrelated subjects were identified (45.1% male, median age 50 years). FD was diagnosed in 52 patients, while 19 had FD variants only. Age (p = 0.019), elevated polygenic risk for HTG (p = 0.001), and the presence of metabolic syndrome components (p = 0.014) were independently associated with the FD phenotype. TG levels were significantly associated with polygenic burden (0.05 mmol/L per percentile), the presence of additional rare lipid-related variants (7.0 mmol/L), and glucose metabolism disorders (3.62 mmol/L), together explaining 30% of TG variance in cross-validated model. These results highlight the interplay of genetic and metabolic factors in FD development and support the integration of HTG genetic risk scores and metabolic control into personalized FD management. Full article

A high intake of saturated fats and cholesterol from processed meats is associated with increased cardiovascular disease risk. This study aimed to develop a nutritionally enhanced Bologna-type sausage by partially replacing the beef content with a structured emulsion gel (EG) formulated from pine nut oil, inulin, carrageenan, and whey protein concentrate. The objective was to improve its lipid quality and functional performance while maintaining product integrity and consumer acceptability. Three sausage formulations were prepared: a control and two variants with 7% and 10% EG, which substituted for the beef content. The emulsion gel was characterized regarding its physical and thermal stability. Sausages were evaluated for their proximate composition, fatty acid profile, cholesterol content, pH, cooking yield, water-holding capacity, emulsion stability, instrumental texture, microstructure (via SEM), oxidative stability (TBARSs), and sensory attributes. Data were analyzed using a one-way and two-way ANOVA with Duncan’s test (p < 0.05). The EG’s inclusion significantly reduced the total and saturated fat and cholesterol, while increasing protein and unsaturated fatty acids. The 10% EG sample achieved a PUFA/SFA ratio of 1.00 and an over 80% reduction in atherogenic and thrombogenic indices. Functional improvements were observed in emulsion stability, cooking yield, and water retention. Textural and visual characteristics remained within acceptable sensory thresholds. SEM images showed more homogenous matrix structures in the EG samples. TBARS values increased slightly over 18 days of refrigeration but remained below rancidity thresholds. This period was considered a pilot-scale evaluation of oxidative trends. Sensory testing confirmed that product acceptability was not negatively affected. The partial substitution of beef content with pine nut oil-based emulsion gel offers a clean-label strategy to enhance the nutritional quality of Bologna-type sausages while preserving functional and sensory performance. This approach may support the development of health-conscious processed meat products aligned with consumer and regulatory demands. Full article

Background/Objectives: Cardiovascular diseases remain the leading cause of global mortality, with the gut microbiome emerging as a critical factor. This study aimed to characterize gut microbiome composition and metabolic pathways in individuals with low cardiovascular risk (LCR) compared to healthy controls to reveal insights into early disease shifts. Methods: We performed shotgun metagenomic sequencing on fecal samples from 25 LCR individuals and 25 matched healthy controls. Participants underwent a comprehensive cardiovascular evaluation. Taxonomic classification used MetaPhlAn 4, and functional profiling employed HUMAnN 3. Results: Despite similar alpha diversity, significant differences in bacterial community structure were observed between groups (PERMANOVA, p < 0.05). The LCR group showed enrichment of Faecalibacterium prausnitzii (p = 0.035), negatively correlating with atherogenic markers, including ApoB (r = −0.3, p = 0.025). Conversely, Fusicatenibacter saccharivorans positively correlated with ApoB (r = 0.4, p = 0.006). Metabolic pathway analysis revealed upregulation of nucleotide biosynthesis, glycolysis, and sugar degradation pathways in the LCR group, suggesting altered metabolic activity. Conclusions: We identified distinct gut microbiome signatures in LCR individuals that may represent early alterations associated with cardiovascular disease development. The opposing correlations between F. prausnitzii and F. saccharivorans with lipid parameters highlight their potential roles in cardiometabolic health. These findings suggest gut microbiome signatures may serve as indicators of early metabolic dysregulation preceding clinically significant cardiovascular disease. Full article

Background: The atherogenic index of plasma (AIP), a prognostic indicator for cardiovascular disease, has not been fully explored in relation to clinical outcomes in patients receiving peritoneal dialysis. This study aims to elucidate the relationship between baseline AIP levels and all-cause mortality, cardiovascular mortality, and the peritonitis risk in this population. Methods: This retrospective cohort study included incident peritoneal dialysis patients in our center from 1 January 2006 through 31 December 2021. The end of the follow-up time was 31 December 2023. The participants were stratified by baseline AIP levels. Kaplan–Meier curves, Cox regression analyses, and subgroup analyses were used to evaluate associations with clinical outcomes. Results: The average age of the 2460 participants in this study was 45.9 years, and 1456 (59.2%) of them were men. Diabetic nephropathy (19.5%) was the second most common kidney disease, after primary glomerulonephritis (60.8%). The higher AIP tertile group was significantly associated with increased risks of all-cause mortality, cardiovascular mortality, and peritonitis compared to the lowest AIP group, as evidenced by the Kaplan–Meier curves and the multivariate analyses. Continuous AIP levels also showed a positive correlation with the all-cause mortality and peritonitis risk, even after controlling for covariates. Conclusions: Our study highlights AIP as a predictive marker for adverse outcomes in PD patients, emphasizing its potential utility in risk stratification and clinical management. Full article