Cholesterol Fractions Research Articles

Trend of the lipid profile in a cohort with severe hypercholesterolemia in Osona county (Barcelona, Spain), between 2009 and 2021

BackgroundVarious studies confirm that the prevalence of dyslipidemia and other cardiovascular factors is high.ObjectiveTo evaluate the trend of the lipid profile (LP) in a cohort with severe hypercholesterolemia and its relationship with lipid-lowering treatment during the period 2009–2021.MethodsCross-sectional study carried out in the Osona county (Barcelona). Outpatients from the first period (2009–2011) who were aged between 25 and 65 years and had severe hypercholesterolemia were selected (n = 2,608). In a second period (2019–2021), these patients (n = 1,855) were followed up to evaluate the trend of LP and its relationship with lipid-lowering treatment. The Student’s T-test (paired data) was used to identify differences between observations from the two periods.ResultsLipid-lowering treatment was prescribed to 61.9% of patients.The group of patients of the cohort improved the data of the mean results of the LP.Approximately 75% of cases were unable to establish their cholesterol and atherogenic fraction values.The prescription of lipid-lowering treatment in the cardiovascular disease group (CVD) was 80.9% vs 61.9% of the total cohort.ConclusionThree out of four cases failed to reduce the levels of LDL-C and non-HDL-C, recommended by the guidelines of scientific societies.Primary Care is the ideal framework to implement improvement strategies to control severe hypercholesterolemia, and it is therefore essential to strengthen it.

Unraveling Cholesterol-Dependent Interactions of Alkylphospholipids with Supported Lipid Bilayers.

Alkylphospholipids are single-chain lipid amphiphiles that possess clinically relevant biological activities driven by membrane-destabilizing interactions. Subtle variations in alkylphospholipid structure can lead to significant differences in their biological effects, yet corresponding membrane interactions remain underexplored. Herein, we employed the quartz crystal microbalance-dissipation (QCM-D) technique to characterize the real-time membrane interactions of three alkylphospholipids-edelfosine, miltefosine, and perifosine-on supported lipid bilayers with varying cholesterol fractions. Our findings reveal that the tested alkylphospholipids had distinct membrane-interaction profiles: (1) edelfosine exhibited irreversible binding and caused weak membrane disruption; (2) miltefosine caused major disruption by affecting membrane packing; and (3) perifosine exhibited reversible binding while triggering structural rearrangements and modest disruption. Overall, alkylphospholipid micelles showed greater activity than monomers, and higher membrane cholesterol fractions resulted in more extensive disruption, highlighting the interplay between membrane stiffness and responsiveness. These results provide biophysical evidence that different alkylphospholipids have distinct membrane-interaction behaviors that align well with reported biological activities. Our supported lipid bilayer approach offers a valuable platform for designing and assessing alkylphospholipids with tailored membrane-interaction profiles.

Exposure to a choline-deficient diet during pregnancy and lactation alters the liver transcriptome profile in offspring of dams with fatty liver.

The developmental origin of health and disease hypothesis shows that early adverse exposures can have lifelong health effects. Thus, the aim of this study was to analyze the impact of choline intake during pregnancy and/or lactation on gene expression profiles in the liver of 24-day-old male rat offspring from dams with non-alcoholic fatty liver disease (NAFLD). Phenotypic characteristic, histological examination and global transcriptome pattern of liver tissue specimens obtained from offspring of dams suffering from fatty liver, provided with proper choline intake during pregnancy and lactation (NN), fed a choline-deficient diet during both periods (DD), deprived of choline only during pregnancy (DN), or only during lactation (ND), was performed. The global gene expression profile was analyzed by using microarray approach (Affymetrix® Rat Gene 2.1 ST Array Strip). The relative expression of selected genes was validated by real-time polymerase chain reaction (qPCR). The histological examination of rat liver sections indicated alternations typical for fatty liver in all analyzed groups with increased progression among groups deprived of choline. Choline deficiency in the maternal diet was associated with changes in body mass and composition but not with biochemical marker levels, except for the high density lipoprotein fraction of cholesterol (HDL). Enhanced expression of genes involved in oxidative stress, cell proliferation, activation of catabolic processes related to hepatocyte dysfunction and cell membrane composition were simultaneously observed in all choline-deficient groups. An adequate amount of choline in the diet of a mother with fatty liver during pregnancy and/or lactation can regulate gene expression in the offspring's liver and contribute to a milder stage of the disease in the progeny. Moreover, proper choline supply during the postpartum period is as crucial as during the prenatal period.

Very broad distribution of β sheet registries of the HIV gp41 fusion peptide supports mutational robustness for fusion and infection

HIV, like other membrane-enveloped viruses, has protein spikes that include a fusion peptide (Fp) segment that binds the host cell membrane and plays a critical role in fusion (joining) viral and cell membranes. The HIV Fp is the ~23 N-terminal residues of the gp41 spike protein. Fp adopts intermolecular antiparallel β sheet structure when lipid fraction cholesterol ≈0.3, which is comparable to host cells. Rotational-echo double-resonance NMR was applied to probe the registries (alignments) of adjacent Fp molecules in membrane-bound sheets. The data were fitted to determine quantitative populations, f(t)'s, of individual antiparallel registries indexed by t, the number of residues in the registry. Both wild-type (WT) and fusion-defective V2E Fp sheets have broad but very different registry distributions, each with at least eight populated registries with f(t) > 0.02, and [Formula: see text] and ⟨t⟩V2E = 18.5. The broad WT distribution likely improves mutational robustness for HIV, as Fp is a neutralization epitope of the immune system, and Fp mutations are required for immune evasion during chronic HIV infection. V2E fusion is reduced because longer Fp sheets increase separation between initially apposed membranes. The f(t)WT were well-fitted to free energies that were sums of contributions from sheet length, aligned leucines, and sidechain membrane insertion. The f(t)V2E's were similarly well-fitted except there wasn't the insertion contribution. Relative to V2E, WT fusion is enhanced by deeper membrane insertion of Fp with accompanying greater dislocation of neighboring lipids. This study provides a rare quantitative determination of broad molecular structural distributions by experiment.

Racial and regional disparities in the risk of noncommunicable disease between sub-Saharan black and European white patients.

Greater vulnerability of Black vs. White individuals to cardiovascular disease (CVD) and chronic kidney disease (CKD) is well charted in the United States, but studies involving sub-Saharan blacks are scarce. Baseline data (2021-2024) were collected in 168 sub-Saharan Blacks and 93 European Whites in an ongoing clinical trial (NCT04299529), using standardized patient selection criteria. Data included clinical and biochemical risk factors, ECG and echocardiographic traits, Framingham CVD risk, CKD grades (KDIGO 2024), self-assessed symptoms (WHO questionnaire), and urinary proteomic profiles predictive of left ventricular dysfunction (LVD) and CKD, HF1, and CKD273, respectively. Racial comparisons rested on unadjusted and multivariable-adjusted analyses. Despite being younger (60.4 vs. 68.3 years), blacks had a worse risk profile, as evidenced by higher diabetes prevalence, higher BMI, faster heart rate, unfavourable serum cholesterol fractions, lower estimated glomerular filtration rate, microalbuminuria, and sedentary lifestyle. This resulted in blacks having higher 10-year CVD risk, higher heart age (index of vascular ageing with chronological age as reference), and a worse CKD grades. In both races, CKD273 increased with CKD grade, but CKD273 and HF1 were not different by race. These observations were robust in subgroup and adjusted analyses. This study did not differentiate host (genetic, molecular, and pathogenic) from environmental drivers of disease. Nonetheless, the findings call for a multipronged and comprehensive implementation of innovative health policies in sub-Saharan countries. Education, research, empowerment of stakeholders, and international learned societies connecting experts from a wide array of disciplines should vigorously sustain this effort.

Analysis of the Prevalence of Cardiovascular Risk Factors in Patients with Chronic Hepatitis C

Cardiovascular diseases are the most common and important cause of morbidity, hospitalisation, and mortality in Poland and worldwide. Hence, in recent years there has been a strong emphasis on preventive cardiology, aimed at early identification and prevention of cardiovascular risk factors and lifestyle changes. The main classical risk factors include lipid disorders, hypertension, diabetes, obesity, and smoking. A new non-classical risk factor is HCV infection. The study group consisted of 320 patients with a mean age of 43 years, diagnosed with chronic hepatitis C. In the study group, ischaemic heart disease was diagnosed in 4 patients, representing 1.25%. Six people had a history of ischaemic stroke, representing 1.87% of the study group. Among the subjects, the most common cardiovascular risk factor was hyperlipidaemia (28%); there was no correlation with the severity of liver fibrosis for total cholesterol, LDL fraction, or TG, but more advanced liver fibrosis was observed in patients with low HDL fraction cholesterol values. Hypertension was present in 25% of patients and occurred in patients with more advanced liver fibrosis and steatosis. Diabetes was found in 11,56% of patients, also the mean fasting glucose level was elevated and was associated with more advanced liver fibrosis. The majority of patients were overweight and 32% were diagnosed as obese. The mean CRP value was 1.73 which may indicate moderate -cardiovascular risk. The results obtained may contribute to the awareness of physicians and the attempt to create recommendations for comprehensive - interdisciplinary care of patients chronically infected with HCV, concerning the need for systematic periodic examinations to assess individual cardiovascular risk factors, with the aim of prevention and early prevention of cardiovascular events.

Non-lipid metabolomic biomarkers are associated with adverse cardiac remodelling and cardiovascular outcomes

Abstract Background Metabolomics is the detailed profiling of circulating metabolites including carbohydrates, lipids, amino and fatty acids, and ketones, all of which are substrates used in energy metabolism by cardiomyocytes. Purpose The role of cholesterol fractions with cardiovascular risk is well-established. This novel study examines the association between non-lipid circulating metabolites and markers of cardiac remodelling as assessed by cardiovascular magnetic resonance (CMR) imaging. Metabolites associated with adverse remodelling were taken forward to examine their impact on incident cardiovascular disease (CVD); ischaemic heart disease (IHD) and heart failure (HF). Methods This study used data from the UK Biobank. After exclusions (prevalent IHD, HF; outliers), there were a maximum of 34,727 individuals for CMR analyses and 262,536 individuals for incident CVD analysis. For CMR analyses, outcome variables were LV end-diastolic volume (EDV), LV mass, LV mass:volume ratio (MVR), LV global longitudinal strain (GLS) and native T1. Separate regression models were built for each of the 40 scaled metabolite biomarkers. Each model incorporated one metabolite at a time with additional covariates: age, sex, ethnicity, systolic blood pressure, cholesterol medication use, type 2 diabetes, dietary intake, smoking status, fasting time, and time between recruitment and CMR examination. A Bonferroni-corrected significance threshold of 2.4x10-4 was used. To account for correlation between metabolites, Lasso regression with 10 fold cross-validation to identify the most important predictors was performed for LV MVR, LV GLS and native T1 whereby all metabolites and above covariates were included in the model. Metabolite predictors of adverse remodelling were included in an adjusted logistic regression model with incident CVD as an outcome. Results Metabolites demonstrating significant (p < 2.4x10-4) associations with CMR parameters are presented in Fig 1. For higher LV MVR and more positive LV GLS, the metabolites with the largest effect were monounsaturated fatty acids and glycoprotein acetyls. Higher omega-6:omega-3 ratio was associated with higher T1 values. The Lasso model identified 8 important predictors for adverse cardiac remodelling. Of these, two were routine biomarkers (creatinine, glucose). Of the remainder, monounsaturated fatty acids, glycoprotein acetyls and apolipoprotein B:apolipoprotein A1 ratio were significantly associated with increased risk of incident CVD (Fig 2). Current evidence regarding monounsaturated fatty acids in CVD is mixed. Glycoprotein acetyls are implicated in vascular inflammation. Apolipoproteins are thought to be a potential therapeutic target for CVD risk reduction. Conclusion This study demonstrates a role of non-lipid metabolites on subclinical CVD as assessed by adverse remodelling with CMR as well as associations with incident CVD. We highlight potential novel biomarkers for identification of CVD.Metabolite association with LV MVR/GLSMetabolite association with incident CVD

Lipid and brain volumetric measures in multiple sclerosis patients: findings from a large observational study

ObjectivesThis study aimed to investigate relationships between cholesterol profile, brain volumetric MRI, and clinical measures in a large observational cohort of multiple sclerosis (MS) patients.Materials and methodsWe included 1.505 patients with 4.966 time points including complete lipid, clinical, and imaging data. The time among lipid, brain MRI and clinical measures was under 90 days. Cross-sectional statistical analysis at baseline was performed using an adjusted linear regression and analysis of longitudinal lipid and MRI measures data was performed using adjusted linear mixed models.ResultsWe found associations between higher high-density lipoprotein cholesterol (HDL-C) and lower brain parenchymal fraction (BPF) at cross-sectional analysis at baseline (B = −0.43, CI 95%: −0.73, −0.12, p = 0.005), as well as in longitudinal analysis over follow-up (B = −0.32 ± 0.072, χ2 = 36.6; p = < 0.001). Higher HDL-C was also associated with higher T2-lesion volume in longitudinal analysis (B = 0.11 ± 0.023; χ2 = 23.04; p = < 0.001). We observed a weak negative association between low-density lipoprotein cholesterol (LDL-C) levels and BPF at baseline (B = −0.26, CI 95%: −0.4, −0.11, p = < 0.001) as well as in longitudinal analysis (B = −0.06 ± 0.03, χ2 = 4.46; p = 0.03). T2-LV did not show an association with LDL-C. We did not find any association between lipid measures and disability. The effect of lipid levels on MRI measures and disability was minimal (Cohen f2 < 0.02).ConclusionsOur results contradict the previously described exclusively positive effect of HDL-C on brain atrophy in patients with MS. Higher LDL-C was weakly associated with higher brain atrophy but not with higher lesion burden.

The Impact of Atorvastatin Treatment on the Distribution of Low-Density Lipoprotein Subfractions and the Level of Vitamin D in Patients After Acute Myocardial Infarction: Preliminary Findings

Clinical trial results indicate that statin therapy aimed at normalising the lipid profile can prevent and reduce the risk of cardiovascular events. Both LDL and HDL consist of several subfractions, with only the smallest and densest subfractions being the most atherogenic. We examine the effect of Atorvastatin treatment not only on basic lipid profile parameters but also atherogenic lipoprotein subfractions and 25(OH)D levels in patients after the first acute myocardial infarction. The study population had not previously received lipid-lowering medications. Serum 25(OH)D concentration was determined by direct competitive immunochemiluminescent assays. Lipoprotein subfractions, including VLDL, IDL-C, IDL-B, and IDL-A, as well as LDL1, LDL2 (large LDL), and LDL3-7 (sdLDL), were measured in serum (Lipoprint® system). Almost all patients had 25(OH)D deficiency. Atorvastatin primarily reduced strongly atherogenic sdLDL and decreased the less atherogenic large LDL subfractions. A statistically significant reduction in VLDL cholesterol and IDL fractions was also observed. Analysing LDL subfractions provides a more detailed insight into lipid metabolism and enables the identification of patients with a more atherogenic phenotype. LDL subfractions may thus become not only more accurate prognostic biomarkers but also targets for lipid-lowering therapy. Vitamin D deficiency is associated with atherogenic dyslipidaemia, particularly high levels of sdLDL.

Role of gene polymorphism in the development of disorders of the lipid profile in individuals exposed to chemicals

Introduction. The prevalence of arterial hypertension and dyslipidemia in the Russian population exceeds 50%. By a number of working industrial factors have been proved to play the negative role in their development. The results of earlier studies indicate to the epigenetic role of toxic substances in relation to various genes. The aim of the study was to establish associations of polymorphic variants of cardiovascular risk genes with disorders of lipid metabolism in workers performing liquidation works in the accumulated environmental risks zone. Materials and methods. Ninety two and 82 employees from Federal Environmental Operator (FEO) and EMERCOM, respectively were studied. Parameters of lipid metabolism and polymorphic variants of APOE Cys130Arg (rs429358) and PPARG Pro12Ala (rs1801282) genes were investigated. Results. In FEO workers, each variant allele of the APOE Cys130Arg gene is associated with impaired LDL-C concentration in an additive manner (OR = 2.69; 95% CI = 1.03–7.08, p=0.04). Carrying either the T/C or C/C variant allele of this polymorphic variant or the C/G or G/G polymorphic variant Pro12Ala of the PPARG gene increases the odds of developing abnormalities in total cholesterol levels by more than 3.5-times. The risk influence of the mutant genotype G/G and allele G on the increase of Apo B concentration was also established. In EMERCOM workers, the presence of both alleles of this polymorphic variant increased the probability of a decrease in HDL-H levels by 5 times. Limitations. Male persons are employees of the FEO and the Ministry of Emergency Situations. Age accounts of 30–50 years. Conclusions. An increased risk of deviations of total cholesterol concentration, proatherogenic cholesterol, and lipoprotein fractions associated with the PPARG Pro12Ala and APOE Cys130Arg genes polymorphisms was found in FEO workers, whereas only the reduced high-density lipoprotein cholesterol risk in carriers of the PPARG Pro12Ala gene mutant allele was found in EMERCOM workers.

No causal relationship serum lipids on age-related hearing loss based on Mendelian randomized evidence

ObjectivesPresbycusis, or age-related hearing loss (ARHL) has been a common disability disease among the elderly population. It is particularly essential to identify the underlying role of related risk factors for ARHL diagnosis and treatment. Observational studies have shown that cardiovascular disease may be a factor in ARHL. Serum lipids are a key risk factor for cardiovascular disease. Therefore, it may be a potentially influencing factor for elderly deafness. We conduct the study to analyze the causal relationship between serum lipids and European elderly deafness. DesignUsing genetic variation data related to serum lipids (total cholesterol levels [TCL], total triglycerides levels [TGL], and lipoprotein fractions, including apolipoprotein A1 levels [APOA1L], apolipoprotein B levels [APOBL], high-density lipoprotein cholesterol levels [HDL], and low-density lipoprotein cholesterol levels [LDL]) as instrumental variables, the outcome events were summarized from the genome-wide association study data of elderly deafness, and Mendelian randomization (MR) analysis was used in our analysis. The relationship between serum lipids levels and ARHL was analyzed using five methods, including inverse variance weighted, weighted mode, MR-Egger, weighted median, and simple mode. The study aims to use bidirectional MR analysis. ResultsAmong all 5 methods, no significant causal effects were found between serum lipids (TCL OR = 0.936, p = .488; TGL OR = 0.955, p = 0.657; APOA1L OR = 0.864, p = .061; APOBL OR = 0.979, p = .786; HDL OR = 0.998, p = .979; LDL OR = 1.089, p = .281) and presbycusis. ConclusionThe findings of MR causal inference analysis did not support the causal relationship between presbycusis and serum lipids, including cholesterol, triglycerides, and lipoprotein fractions (APOA1L, APOBL, HDL and LDL).

Lipid redistribution due to a cell-cell fusion pore

We consider the redistribution of lipids comprising the plasma membranes during cell-cell fusion, particularly due to the presence of a fusion pore. Assuming the membranes are of constant thickness, we find that the mole fraction of cholesterol increases in the directly apposed exoplasmic leaflets, and is decreased in the cytoplasmic leaflets. The redistribution of the phospholipids is obtained as well.

Effect of Substitution of Beef and Broiler Meat with Tuna Meat on Chemical and Sensory Quality of Meatballs.

Tuna meat is rich in protein and polyunsaturated fatty acids (PUFA), but low in cholesterol and fat, which makes it an excellent candidate for replacing beef and broiler chicken to produce higher quality meatballs. The aim of this study is to determine how substituting beef and broiler meat with tuna meat affects the chemical and sensory characteristics of meatballs. In this study, 1000 g of meatballs were prepared from 60 % of beef or broiler chicken. Each meat was replaced with tuna meat at mass fractions of 0, 20 and 40 %. The meat was finely ground and mixed with mass fractions (in %) of: tapioca flour 20, garlic 1.2, salt 2, ground pepper 0.5, egg white 0.3 and ice cubes 16. The tested variables included the chemical quality (moisture, protein, fat, ash, cholesterol and fatty acids) and sensory quality (colour, aroma, elasticity, texture and taste) of the meatballs. The data obtained were statistically analysed using a completely randomised factorial design analysis of variance. The results show that increasing the mass fraction of tuna as a substitute for beef and broiler meat significantly increased (p<0.01) the moisture, protein and PUFA mass fractions and colour, but decreased (p<0.01) the cholesterol and fat mass fraction of the meatballs. A significant interaction (p<0.01) was observed between the tuna mass fraction and the type of meat, which affected the mass fractions of moisture, protein, cholesterol and fat as well as colour of the meatballs. In particular, increasing the tuna mass fraction to 40 % significantly increased (p<0.01) the moisture mass fraction of the beef meatballs, as well as the protein mass fraction and colour of the beef and chicken meatballs. However, the moisture mass fraction of chicken meatballs and the fat and cholesterol mass fraction of beef and chicken meatballs decreased significantly (p<0.01). In conclusion, replacing 40 % of beef and chicken meatballs with tuna can improve protein content and colour, and reduce fat and cholesterol content. These results suggest that tuna can be used as a substitute for beef and chicken to produce higher quality meatballs that are rich in protein but low in cholesterol and fat. This approach can also be applied to other processed meat products such as sausages and nuggets to improve their nutritional quality.

The consumption of ultra-processed foods was associated with adiposity, but not with metabolic indicators in a prospective cohort study of Chilean preschool children

BackgroundIncreasing consumption of ultra-processed foods (UPF) has been identified as a risk factor for obesity and various diseases, primarily in adults. Nonetheless, research in children is limited, especially regarding longitudinal studies with metabolic outcomes. We aimed to evaluate the longitudinal association between consumption of UPF, adiposity, and metabolic indicators in Chilean preschool children.MethodsWe conducted a prospective analysis of 962 children enrolled in the Food and Environment Chilean Cohort (FECHIC). Dietary data were collected in 2016 at age 4 years with 24-h recalls. All reported foods and beverages were classified according to the NOVA food classification, and the usual consumption of UPF in calories and grams was estimated using the Multiple Source Method. Adiposity (z-score of body mass index [BMI z-score], waist circumference [WC], and fat mass [in kg and percentage]) and metabolic indicators (fasting glucose, insulin, HOMA-IR, triglycerides, total cholesterol, and cholesterol fractions) were measured in 2018, at the age of 6 years. Linear regression models ((0) crude, (1) adjusted for covariables, and (2) adjusted for covariables plus total caloric intake) were used to evaluate the association between UPF and outcomes. All models included inverse probability weights to account for the loss to the follow-up.ResultsAt 4 years, usual consumption of UPF represented 48% of the total calories and 39% of the total food and beverages grams. In models adjusted for covariables plus caloric intake, we found a positive association between UPF and BMI z-score (for 100 kcal and 100 g, respectively: b = 0.24 [95%CI 0.16–0.33]; b = 0.21 [95%CI 0.10–0.31]), WC in cm (b = 0.89 [95%CI 0.41–1.37]; b = 0.86 [95%CI 0.32–1.40]), log-fat mass in kg b = 0.06 [95%CI 0.03–0.09]; b = 0.04 [95%CI 0.01–0.07]), and log-percentage fat mass (b = 0.03 [95%CI 0.01–0.04]; b = 0.02 [95%CI 0.003–0.04]), but no association with metabolic indicators.ConclusionsIn this sample of Chilean preschoolers, we observed that higher consumption of UPF was associated with adiposity indicators 2 years later, but not with metabolic outcomes. Longer follow-up might help clarify the natural history of UPF consumption and metabolic risks in children.

Potential impact of sodium glucose co-transporter (SGLT2) inhibitors on cholesterol fractions in stage 3 chronic kidney disease

IntroductionData on sodium glucose co-transporter 2 inhibitors impact on lipids in patients with diabetes are available and only a handful of studies have explored this effect in individuals with both diabetes and renal impairment; lipid parameters were not the primary focus of those earlier studies. However, there is a significant research gap specifically addressing the influence of SGLT2 inhibitors on cholesterol fractions in patients exclusively with chronic kidney disease. This aim constitutes the central objective in this particular study.MethodsIn this 3-month randomized controlled study, 30 patients with stage 3 chronic kidney disease and dyslipidemia were randomly assigned to receive either dapagliflozin 10 mg or placebo. Lipid profiles, renal function, and urinary albumin levels were assessed at baseline and after 3 months.ResultsCompared to baseline, patients receiving dapagliflozin for 3 months showed significant improvements in serum creatinine (p < .001) and eGFR (p = .001). Total cholesterol and LDL-C levels decreased significantly (p = .010 and .006, respectively). While albumin-creatinine ratio also decreased, this change was not statistically significant. Additionally, HDL-C and TG not significantly increased. The control group without intervention experienced deterioration in serum creatinine and eGFR (p = .008, and .011, respectively), but no statistically significant lipid changes were observed. Furthermore, post-intervention total cholesterol moderately correlated with BMI (p = .032, R = .554), yet no predictors significantly influenced lipid levels in the multiple linear regression analysis.ConclusionsDapagliflozin has a favorable effect on cholesterol fractions in stage 3 CKD patients without diabetes mellitus and this effect was different from that observed in patients with diabetes alone.

Influence of maternal α-lipoic acid supplementation in Sprague Dawley rats on maternal and fetal metabolic health in pregnancies complicated by obesity

The objective of this study was to investigate the influence of α-lipoic acid (LA; R enantiomer) supplementation on maternal and fetal metabolic health in pregnancies complicated by maternal obesity. Forty female Sprague-Dawley rats were randomized to one of 4 treatment groups (n=10/group) throughout prepregnancy (3 weeks) and gestation (20 days): (1) a low calorie control (CON); (2) a high calorie obesity-inducing diet (HC); (3) the HC diet with 0.25% LA (HC+LA) or; (4) the HC diet pair-fed to match the caloric intake of the HC+LA group (HC+PF). On gestation day 20, pregnant rats were placed under anesthesia for collection of maternal/fetal blood and tissues. Compared with the HC group, LA-supplemented mothers demonstrated lower maternal prepregnancy and gestational weight gain (GWG), improved glycemic control (lower homeostatic model assessment for insulin resistance), and higher cholesterol concentrations in serum [high-density lipoprotein cholesterol (HDL-C) and low-and very-low density lipoprotein cholesterol (LDL/VLDL) fractions] and liver. Male and female fetuses from LA-supplemented mothers exhibited lower body weight, improved insulin sensitivity, and evidence of altered lipid metabolism including lower serum HDL-C, lower serum triglyceride (TG), and increased hepatic TG accumulation. Although maternal LA supplementation showed some benefit for both mothers and fetuses with respect to obesity and glycemic control, concern about the potential longer-term implications of liver cholesterol (mothers) and TG accumulation (fetuses) needs further investigation.

Short-term impact of vitamin K2 supplementation on biochemical parameters and lipoprotein fractions.

This study explored the short-term effects of vitamin K2 (VK2) supplementation on biochemical parameters (vitamin D, vitamin E, vitamin A, alkaline phosphatase, calcium, phosphorus (P), magnesium, metallothionein, triglycerides, cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and lipoprotein fractions (albumin, HDL, very low-density lipoprotein (VLDL), LDL, and chylomicrons). A short-term experiment (24h, six probands) was performed to track changes in VK2 levels after a single-dose intake (360µg/day). Liquid chromatography-tandem mass spectrometry was used to monitor vitamin K levels (menaquinone-4 (MK-4), menaquinone-7 (MK-7), and vitamin K1 [VK1]) with a limit of detection of 1.9pg/mL for VK1 and 3.8pg/mL for the two forms of VK2. Results showed that MK-7 levels significantly increased within 2-6h post-administration and then gradually declined. MK-4 levels were initially low, showing a slight increase, whereas VK1 levels rose initially and then decreased. Biochemical analyses indicated no significant changes in sodium, chloride, potassium, calcium, magnesium, albumin, or total protein levels. A transient increase in P was observed, peaking at 12h before returning to baseline. Agarose gel electrophoresis of lipoprotein fractions revealed distinct chylomicron bands and variations in VLDL and HDL mobility, influenced by dietary lipids and VK2 supplementation. These findings suggest effective absorption and metabolism of MK-7 with potential implications for bone metabolism and cardiovascular health.

Analysis of long non-coding RNA RMRP in the diagnosis and prognosis of coronary artery disease

BackgroundLong non-coding RNAs (lncRNAs) are abundant and closely related to the occurrence and development of human diseases. LncRNAs are known to play a key role in many cardiovascular diseases. The purpose of this study was to investigate the effect of the RNA component of mitochondrial RNA-processing endoribonuclease (RMRP) on the degree of coronary artery lesions and prognosis in patients with coronary artery disease (CAD).MethodsPatients who underwent coronary angiography (CAG) and dynamical-single photon emission computed tomography (D-SPECT) were selected as study subjects, and the results of CAG were reviewed, and the patients were grouped according to SYNTAX score. Evaluate the factors affecting SYNTAX scores. The follow-up analysis was conducted, and the endpoint events were major adverse cardiovascular events (MACEs). Kaplan–Meier method was used to estimate the survival rate, and multivariate Cox regression was used to analyze the relationship between RMRP and MACEs.ResultsThe expression level of serum RMRP in patients with CAD was significantly higher than that in healthy people. Multivariate Logistic regression analysis showed that age, low-density lipoprotein cholesterol (LDL-C), RMRP and rest left ventricular ejection fraction (LVEF) were independent factors that affected SYNTAX scores. There were 19 cases of MACEs in the high RMRP group and 9 cases in the low RMRP group, and there was a significant difference in the MACE free survival curve between the two groups. Multivariate Cox regression analysis showed that age, SYNTAX score, rest LVEF and RMRP were risk factors for MACEs.ConclusionsSerum RMRP is a key factor affecting the degree of coronary artery disease and prognosis in CAD patients.

The serum metabolomic profiles of atrial fibrillation patients treated with direct oral anticoagulants or vitamin K antagonists

AimsLong-term oral anticoagulation is the primary therapy for preventing ischemic stroke in patients with atrial fibrillation (AF). Different types of oral anticoagulant drugs can have specific effects on the metabolism of patients. Here we characterize, for the first time, the serum metabolomic and lipoproteomic profiles of AF patients treated with anticoagulants: vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs). Materials and methodsSerum samples of 167 AF patients (median age 78 years, 62 % males, 70 % on DOACs treatment) were analyzed via high resolution 1H nuclear magnetic resonance (NMR) spectroscopy. Data on 25 metabolites and 112 lipoprotein-related fractions were quantified and analyzed with multivariate and univariate statistical approaches. Key findingsOur data provide evidence that patients treated with VKAs and DOACs present significant differences in their profiles: lower levels of alanine and lactate (odds ratio: 1.72 and 1.84), free cholesterol VLDL-4 subfraction (OR: 1.75), triglycerides LDL-1 subfraction (OR: 1.80) and 4 IDL cholesterol fractions (ORs ∼ 1.80), as well as higher levels of HDL cholesterol (OR: 0.48), apolipoprotein A1 (OR: 0.42) and 7 HDL cholesterol fractions/subfractions (ORs: 0.40–0.51) are characteristic of serum profile of patients on DOACs' therapy. SignificanceOur results support the usefulness of NMR-based metabolomics for the description of the effects of oral anticoagulants on AF patient circulating metabolites and lipoproteins. The higher serum levels of HDL cholesterol observed in patients on DOACs could contribute to explaining their reduced cardiovascular risk, suggesting the need of further studies in this direction to fully understand possible clinical implications.

Comparison of the Clinical Utility of Two Insulin Resistance Indices: IRI-HOMA and IRI-Belfiore in Diagnosing Insulin Resistance and Metabolic Complications in Children Based on the Results Obtained for the Polish Population.

Background: Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In our study, we compare the effectiveness of IRI-HOMA and IRI-Belfiore (OGTT-based) in detecting IR and its metabolic complications in children. Methods: The analysis included 553 children who were hospitalized at the Department of Endocrinology and Metabolic Diseases of the Polish Mother's Memorial Hospital Research Institute (PMMH-RI) in Lodz, Poland, between 2002 and 2018 due to various reasons-of these, 67.5% were girls. All underwent OGTT for glucose and insulin assessment. IR diagnosis relied on IRI-HOMA and IRI-Belfiore. IR based on IRI-HOMA was evaluated using three criteria: (A) >2.5; (B) >2.67 in boys and >2.22 in girls before puberty and >5.22 and >3.82 during puberty, respectively; (C) >95th percentile according to charts for IRI-HOMA in children. Results: Prepubertal children exhibited significantly lower IRI-HOMA and IRI-Belfiore than their pubertal counterparts (p < 0.00005). IRI-HOMA and IRI-Belfiore values positively correlated with age and BMI SDS value (p < 0.000001 for all calculations). As many as 26% to 46.9% of children with normal IRI-HOMA showed elevated IRI-Belfiore, with notably higher levels of triglycerides, a lower HDL cholesterol fraction, and a lower HDL/total cholesterol ratio in this subgroup. Conclusions: A notable proportion of children exhibited elevated IRI-Belfiore levels despite having normal IRI-HOMA values. This suggests the possibility of peripheral IR preceding hepatic IR in children-omitting an OGTT may therefore lead to overlooking cases of IR. Children diagnosed with IR via OGTT displayed significantly poorer lipid profiles compared to those without IR (characterized by normal values in both IRI-HOMA and IRI-Belfiore). This underscores the ability of OGTT-derived IR indices to identify individuals at risk of developing complications associated with obesity and IR before the onset of metabolic syndrome (MS) symptoms. If IR is already detected in children based on fasting glucose and insulin levels (IRI-HOMA), further evaluation may not be warranted, as OGTT results often simply confirm the diagnosis.