Elevated Cholesterol Research Articles

Associations of blood selenium with dyslipidemia in children and adolescents: a cross-sectional analysis.

This study aims to examine the association between blood selenium levels and dyslipidemia in children and adolescents. Data from the National Health and Nutrition Examination Survey (NHANES) 2011-2020 were analyzed, including 8191 participants aged 6-19 years. Dyslipidemia was defined by elevated total cholesterol (TC ≥ 200 mg/dL), lowered high-density lipoprotein cholesterol (HDL-C < 40 mg/dL), or elevated non-HDL-C (≥ 145 mg/dL). Associations between blood selenium levels and dyslipidemia were examined using multivariate logistic regression, linear regression, and restricted cubic spline (RCS) analysis. The study population had a mean age of 12.33 years, with 51.21 % boys. After adjusting for multiple confounding factors, including dietary selenium intakes and supplementation, higher blood selenium levels were associated with increased odds of dyslipidemia and its components. In the highest quartile of blood selenium (>193.99 μg/L), adjusted odds ratios (ORs) were 1.60 (95 % confidence interval [CI]: 1.23-2.08) for dyslipidemia, 1.70 (95 % CI: 1.19-2.43) for elevated TC, 1.38 (95 % CI: 0.97-1.96) for lowered HDL-C, and 1.73 (95 % CI: 1.20-2.48) for elevated non-HDL-C. A significant nonlinear association was observed, with dyslipidemia prevalence increasing notably above a threshold of 184.28 μg/L (P-nonlinearity=0.02), following a J-shaped curve. Subgroup analysis revealed significant interaction by race (P-interaction=0.02), with non-Hispanic White individuals showing a stronger association (OR=1.83, 95 % CI: 1.19-2.80) compared to other racial groups (OR=1.40, 95 % CI: 1.05-1.88). Elevated blood selenium levels are associated with higher prevalence of dyslipidemia in children and adolescents, particularly among non-Hispanic White individuals. The association is nonlinear, with a notable increase in the prevalence of dyslipidemia observed above a blood selenium level of 184.28 μg/L. These findings suggest a need for further research to understand selenium's role in lipid profiles and its implications for public health.

P-588. Improved Lipid Profile in Virologically Suppressed People with HIV-1 Switching to Tenofovir DF-Containing, Ainuovirine-Based Compared to Tenofovir Alafenamide-Containing, Boosted Elvitegravir-Based Antiretroviral Regimen: the Secondary Analyses of 48-Week Results of the SPRINT Trial, a Randomized, Active-Controlled Phase 3 Study

Abstract Background ACC008 is a tenofovir DF (TDF) containing, ainuovirine (ANV), a new-generation NNRTI, based fixed-dose combination (FDC). This FDC has shown noninferior virological efficacy but improved lipid profile compared to tenofovir alafenamide (TAF) containing, boosted elvitegravir (EVG/c) regimen among virologically suppressed people with HIV-1 (PWHs) switching from NNRTI-based regimen. We herein reported the secondary analyses of 48-week lipids profile as prespecified.Figure 1.Lipid metabolism adverse events at week 48.ACC008, ainuovirine/ lamivudine/ tenofovir disoproxil; E/C/F/TAF, elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; TC, total cholesterol; TG, triglyceride. Methods Virologically suppressed PWHs were randomized to ACC008 (n=381) or comparator arm (n=381) for 48 weeks. Changes from baseline (CFBs) in serum lipids were primary safety outcome of interest, including LDL-C, non-HDL-C, total cholesterol (TC), triglycerides (TG), and HDL-C. Other secondary safety outcomes of interest included lipid metabolism adverse events (AEs), and atherosclerotic cardiovascular disease (ASCVD) risk stratification as per the primary prevention target for Chinese low-risk adults.Figure 2.The proportions of PWHs with optimal/acceptable serum lipids and with decreased HDL-C at week 48.ACC008, ainuovirine/ lamivudine/ tenofovir disoproxil; E/C/F/TAF, elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; PWHs, peoples with HIV; TC, total cholesterol; TG, triglyceride. For indicators of serum lipids, optimal/acceptable level is defined as LDL-C＜2.6 mmol/L, non-HDL-C ＜3.4 mmol/L, TC ＜5.2 mmol/L, or TG＜1.7 mmol/L, and decreased HDL-C as ＜1.0 mmol/L. Results Primary safety outcomes of interest were reported elsewhere. PWHs on ACC008 experienced significantly less frequent lipid metabolism AEs compared to those on comparator (elevated LDL-C, 6.0% vs. 21.3%, estimated treatment difference [95%CI], 0.152 [0.105, 0.200], p&amp;lt; 0.001; elevated cholesterol, 5.0% vs. 31.8%, 0.268 [0.216, 0.319], p&amp;lt; 0.001; elevated TG, 11.8% vs. 34.1%, 0.223 [0.165, 0.280], p&amp;lt; 0.001), but a marginally more frequent decreased HDL-C AE (9.4% vs. 5.5%, 0.039 [0.002, 0.078], p=0.040). The two arms showed a comparable ASCVD risk stratification at the baseline. However, ACC008 arm had a significantly greater proportion of PWHs with optimal/acceptable LDL-C (&amp;lt; 2.6 mmol/L, 49.2% vs. 27.4%, 0.213 [0.144, 0.278], p&amp;lt; 0.01), non-HDL-C (&amp;lt; 3.4 mmol/L, 70.5%, 35.4%, 0.344 [0.275, 0.408], p&amp;lt; 0.001), TC (&amp;lt; 5.2 mmol/L, 90.6% vs. 59.8%, 0.307 [0.249, 0.363], p&amp;lt; 0.001), and TG (&amp;lt; 1.7 mmol/L, 84.0% vs. 53.0%, 0.310 [0.246, 0.370], p&amp;lt; 0.001), but also those with decreased HDL-C (&amp;lt; 1.0 mmol/L, 28.6% vs. 17.3%, 0.113 [0.053, 0.172], p&amp;lt; 0.001) compared to comparator arm at week 48. Conclusion TDF-containing, ANV-based ARV regimen improved lipid metabolism in virologically suppressed adult PWHs with noncompromised virologically efficacy compared to TAF-containing, EVG/c-based regimen. Disclosures Hong Qin, MD, PhD, Jiangsu Aidea Pharmaceutical Co., Ltd: Honoraria

Impact of dietary Spirulina on performance, antioxidant status, carcass traits and pathological alteration in broilers exposed to ochratoxin A stress

IntroductionThis study examined the influence of Spirulina platensis, ochratoxin A (OTA), and their combination on growth, antioxidant status, liver and kidney functions, immunity, and carcass traits of broiler chickens.Methods160 unsexed 1-day broiler chicks were divided into four treatment groups, each consisting of 4 replications of 10 chicks. The duration of this study was six weeks, during which the experimental groups were organized as follows: G1 consumed a basal diet (control), G2 consumed a basal diet treated with OTA at a level of 1 mg/kg of diet, G3 consumed a basal diet treated with Spirulina platensis at a level of 1 g/kg of diet, G4 consumed a basal diet treated with OTA at a level of 1 mg/kg of diet and Spirulina platensis at a level of 1 g/kg diet.Results and discussionThe results illustrated that OTA-contaminated feed resulted in a significant elevation in total cholesterol, triglyceride, low- and very low density lipoprotein, and malondialdehyde, along with a significant reduction in antioxidant status and immunological response. On the other hand, Spirulina supplementation significantly enhanced performance performance (body weight, body weight gain and feed conversion ratio). Lipid profile was significantly decreased by Spirulina supplementation. Antioxidant activity (superoxide dismutase, catalase, total antioxidant capacity, and glutathione peroxidase) of broilers exposed to OTA was significantly increased by Spirulina supplementation. Finally, supplementing Spirulina platensis in broiler chickens fed on OTA contaminated diet attenuated the harmful effects of OTA, while improving the growth performance, antioxidant activity, lipid profile, and immune response of broiler chickens.

A mutation in LXRα uncovers a role for cholesterol sensing in limiting metabolic dysfunction-associated steatohepatitis

Liver x receptor alpha (LXRα) functions as an intracellular cholesterol sensor that regulates lipid metabolism at the transcriptional level in response to the direct binding of cholesterol derivatives. We have generated mice with a mutation in LXRα that reduces activity in response to endogenous cholesterol derived LXR ligands while still allowing transcriptional activation by synthetic agonists. The mutant LXRα functions as a dominant negative that shuts down cholesterol sensing. When fed a high fat, high cholesterol diet LXRα mutant mice rapidly develop pathologies associated with Metabolic Dysfunction-Associated Steatohepatitis (MASH) including ballooning hepatocytes, liver inflammation, and fibrosis. Strikingly LXRα mutant mice have decreased liver triglycerides but increased liver cholesterol. Therefore, elevated cholesterol in the liver may play a critical role in the development of MASH. Reengaging LXR signaling by treatment with synthetic agonist reverses MASH in LXRα mutant mice suggesting that LXRα normally functions to impede the development of liver disease.

The Impact of Glomerular Disease on Dyslipidemia in Pediatric Patients Treated with Dialysis

Background/Objectives: Children on dialysis have a 10-fold increase in cardiovascular disease (CVD)-related mortality when compared to the general population. The development of CVD in dialysis patients is attributed to Chronic Kidney Disease–Mineral Bone Disorder (CKD-MBD) and dyslipidemia. While the prevalence of dyslipidemia in adult dialysis patients has been described, there are limited data on prevalence, severity, and risk factors for pediatric dyslipidemia. Methods: Data from 1730 pediatric patients ≤ 21 years receiving maintenance hemodialysis or peritoneal dialysis with at least one lipid panel measurement were obtained from USRDS between 2001 and 2016. Disease etiology was classified as being glomerular (n = 1029) or non-glomerular (n = 701). Comparisons were made across etiologies using both linear and logistic regression models to determine the relationship between disease etiology and lipid levels. Results: The cohort had a mean age of 15.2 years and were 54.5% female. Adjusting for age, sex, race/ethnicity, modality, time with End Stage Kidney Disease (ESKD), and body mass index (BMI) and using non-glomerular etiology as the reference, glomerular disease [mean (95% CI)] was associated with +19% (+14.7%, +23.8%) higher total cholesterol level (183 mg/dL vs. 162 mg/dL), +21% (+14.8%, +26.6%) higher low density lipoprotein cholesterol level (108 mg/dL vs. 87 mg/dL), and +22.3% (+15.5%, +29.5%) higher triglyceride level (169 mg/dL vs. 147 mg/dL). Glomerular disease [OR (95% CI)] was associated with 3.0-fold [2.4, 3.9] higher odds of having an abnormal total cholesterol level, 3.8-fold [2.8, 5.0] higher odds of having an abnormal LDL-C level, and 1.9-fold [1.5, 2.4] higher odds of having an abnormal triglyceride level when compared to non-glomerular disease. Conclusions: Pediatric dialysis patients have a high prevalence of dyslipidemia, particularly from elevated triglyceride levels. Specifically, patients with glomerular disease have an even higher risk of dyslipidemia from elevated non-HDL cholesterol and triglyceride levels than patients with non-glomerular disease. The long-term impact of this unfavorable lipid profile requires further investigation.

Concentrations of Serum Per- and Polyfluoroalkyl Substances and Lipid Health in Adolescents: A Cross-Sectional Study from the Korean National Environmental Health Survey 2018–2020

Emerging evidence indicates that environmental exposure to per- and polyfluoroalkyl substances (PFASs) may influence lipid metabolism, though studies on adolescents remain scarce. This study aimed to investigate the association between PFAS mixture exposure and lipid profiles in Korean adolescents. Using data from the Korean National Environmental Health Survey (2018–2020), we analyzed 824 adolescents aged 12–17 years. Serum concentrations of PFAS, including perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorodecanoic acid (PFDeA), and lipid profiles were assessed. In multivariate regression models, PFDeA and PFNA were positively associated with elevated total cholesterol and low-density lipoprotein cholesterol levels, and PFDeA was associated with hypercholesterolemia risk in boys. In girls, PFDeA was associated with higher high-density lipoprotein cholesterol and lower triglycerides, though no significant association with hypercholesterolemia risk was observed. Bayesian kernel machine regression demonstrated positive associations between PFAS mixture exposure and hypercholesterolemia risk in boys but not in girls. The quantile g-computation model also demonstrated an odds ratio (OR) of 1.47 (95% CI: 0.99–2.19, p = 0.057) for PFAS mixture exposure in boys, suggesting borderline statistical significance. These findings suggest that PFAS exposure may disrupt lipid metabolism, elevating hypercholesterolemia risk in adolescents, particularly boys.

Timosaponin B II as a novel KEAP1-NRF2 inhibitor to alleviate alcoholic liver disease:Receptor structure-based virtual screening and biological evaluation.

Oxidative stress induced by excess ethanol is an important factor in the progression of alcoholic liver disease (ALD). In recent years, inhibiting Kelch-like ECH-associated protein 1 (KEAP1) to activate the antioxidant regulator Nuclear factor erythroid 2-related factor 2 (NRF2) has been considered an effective strategy for treating oxidative stress-related diseases, but its application in ALD remains insufficiently explored. This study aims to discover high-affinity inhibitors targeting the KEAP1 receptor. We conducted virtual screening of a compound library based on a structure-based pharmacophore model, ultimately identifying the candidate compound Timosaponin B II (TBII). Subsequently, we established ALD models in AML-12 cells and C57BL/6 mice, and evaluated the therapeutic effects and mechanisms of TBII on ALD using methods including Immunofluorescence, Western blotting, RT-qPCR, Biochemical assays, and histological staining. Results indicate that TBII significantly improved ethanol-induced liver injury, inhibited the elevation of serum Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Total Cholesterol (T-CHO), and Triglycerides (TG) levels, and reduced lipid droplet accumulation in liver tissues. Furthermore, TBII treatment enhanced the antioxidant capacity of AML-12 cells and mouse liver, increasing Glutathione (GSH) and Superoxide Dismutase (SOD) levels while reducing Malondialdehyde (MDA) and Reactive Oxygen Species (ROS) levels. Mechanistic studies indicated that TBII inhibited the ethanol-induced increase in KEAP1 and reversed the ethanol-induced changes in NRF2 and its downstream targets. In conclusion, this study suggests that TBII may become a potential therapeutic agent for ALD by modulating the KEAP1-NRF2 pathway to alleviate oxidative stress and lipid metabolism abnormalities.

Perturbations in plasma amino acid and lipoprotein subfraction profiles in anorexia nervosa before and after refeeding: A metabolomic cross-sectional and longitudinal analysis.

Anorexia nervosa (AN) is a life-threatening eating disorder, which is increasingly being considered a metabo-psychiatric condition. We aimed to assess how the lipoprotein subfraction and plasma metabolome are altered in acutely underweight patients with AN (AcAN), if they change with short-term weight-restoration, and whether these changes point towards altered cardiometabolic risk. Using nuclear magnetic resonance spectroscopy, we measured and compared the plasma concentrations of 132 metabolites, aminoacids and lipoprotein subfractions in young female patients with AcAN before (n=72) versus after (n=46) a short-term inpatient refeeding program resulting in weight-restoration (longitudinal analysis), as well as versus female healthy control (HC) participants of similar age (n=74) (cross-sectional analysis). Patients with AcAN showed elevated plasma cholesterol levels due to higher concentrations of small and dense Low Density Lipoprotein (LDL-6) and of large and less dense High Density Lipoprotein (HDL-1) subfractions compared to HC. Additionally, they had lower plasma concentrations of branched chain amino acids and glucose and higher concentrations of the gluconeogenic amino acids glutamine, alanine and methionine. Refeeding elevated the plasma cholesterol levels further, but with a different pattern compared to AcAN, by increasing the concentrations of the larger and less dense LDL (LDL-1, LDL-2, LDL-3) particles and of smaller and more dense HDL (HDL-2, HDL-3) subfractions. However, refeeding only partially restored the amino acid concentrations. Lipoprotein profiles in AcAN point towards a potentially elevated risk for atherosclerosis; an altered lipoprotein profile was also detected after refeeding. Metabolite profiles in AcAN indicate an advanced catabolic state with only partial restoration after refeeding.

Taurine alleviates dysfunction of cholesterol metabolism under hyperuricemia by inhibiting A2AR-SREBP-2/CREB/HMGCR axis.

Dysfunctional cholesterol metabolism is highly prevalent in patients with hyperuricemia. Both uric acid and cholesterol are independent risk factors for atherosclerosis, contributing to an increased incidence of cardiovascular disease in hyperuricemia. Investigating the pathological mechanisms underlying cholesterol metabolism dysfunction in hyperuricemia is essential. This study identified adenosine and inosine, two major purine metabolites, as key regulators of cholesterol biosynthesis. These metabolites up-regulate 3-hydroxy-3-methylglutaryl-CoA (HMGCR). Further mechanistic studies revealed that adenosine/inosine up-regulated the expression of HMGCR by activating adenosine A2A receptor (A2AR) via the sterol-regulatory element binding protein 2 (SREBP-2)/CREB axis in hyperuricemia. Additionally, we found that taurine deficiency contributes to cholesterol metabolism dysfunction in hyperuricemia. Taurine administration in hyperuricemia mice significantly reduced cholesterol elevation by inhibiting A2AR. This study provides a promising strategy for treating comorbid hypercholesterolemia and hyperuricemia.

Pine (Pinus koraiensis) Nut Oil Ameliorates Cholesterol Homeostasis and Inflammation via Modulating the miR-34a/122 Pathways in the Liver of Rats Fed a High-Cholesterol Diet.

Pine (Pinus koraiensis) nut oil (PNO) has been reported to have various beneficial effects on hepatic triglyceride accumulation and atherosclerosis in animal models. MicroRNAs (miRs) are involved in various diseases by modulating physiological processes. However, the mechanism underlying PNO's effects on the regulation of miRs involved in hepatic cholesterol homeostasis and inflammation remains unclear. This study investigated the effects of PNO on the regulation of the miR-34a/122 pathways involved in cholesterol homeostasis and inflammation in the liver using a high-cholesterol diet (HCD) rat model. Six-week-old male Sprague-Dawley rats were randomly divided into three groups (n = 8/group) and provided with (1) a cholesterol-free diet, (2) an HCD containing 1% cholesterol and 0.5% cholic acid, or (3) an HCD containing 5% PNO for 4 weeks. Lipid analysis of serum and liver, histological evaluation, and analysis of gene and protein expression were performed. PNO supplementation in HCD improved hepatic lipid profiles and elevated serum high-density lipoprotein cholesterol compared to the HCD group. PNO significantly upregulated hepatic gene expression levels of liver X receptor α and ATP-binding cassette transporter A1/G1, which are involved in cholesterol efflux (P < 0.05). Gene expressions of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1β, monocyte chemoattractant protein-1, and inducible nitric oxide synthase were downregulated by PNO (P < 0.05). PNO also suppressed TNF-α and IL-6 protein levels by 22.3% and 17.3%, respectively (P < 0.05). PNO reduced hepatic nuclear factor-kappa B activity by 16.4% and decreased nitric oxide production in the liver and serum (P < 0.05). Furthermore, hepatic miR-34a and miR-122 expressions decreased by 16.4% and 15.7% by PNO, respectively (P < 0.05). These results suggest that PNO may affect cholesterol homeostasis and inflammation, which are partially associated with the miR-34a/122 pathways in the liver under an HCD.

Cellular Cholesterol Loss Impairs Synaptic Vesicle Mobility via the CAMK2/Synapsin-1 Signaling Pathway.

Neuronal cholesterol deficiency may contribute to the synaptopathy observed in Alzheimer's disease (AD). However, the underlying mechanisms remain poorly understood. Intact synaptic vesicle (SV) mobility is crucial for normal synaptic function, whereas disrupted SV mobility can trigger the synaptopathy associated with AD. In this study, we investigated whether cellular cholesterol deficiency affects SV mobility, with the aim of identifying the mechanism that links cellular cholesterol loss to synaptopathy in AD. Lentiviruses carrying 3β-hydroxysteroid-Δ24 reductase-complementary DNA (DHCR24-cDNA), DHCR24-short hairpin RNA (DHCR24- shRNA) or empty lentiviral vectors were transfected into SHSY-5Y cells in order to construct DHCR24 knock-down and knock-in models, along with corresponding controls. Filipin III cholesterol staining was employed to visualize membrane and intracellular cholesterol in the different cell models, and fluorescence intensity was assessed using confocal microscopy. Additionally, we performed immunoblotting to quantify the expression of DHCR24, total calmodulin-dependent protein kinase 2 (CAMK-2), p-CAMK2 (T286), caveolin-1, total synapsin-1, phosphorylated synapsin-1 (p-synapsin-1; S605), and synaptophysin in each experimental group. In DHCR24-silenced cells, the loss of cellular cholesterol caused by knock-down of DCHR24 resulted in a significant decrease in the levels of phosphorylated CAMK2 (p-CAMK2) and phosphorylated synapsin-1 (p-synapsin-1) compared to control cells. The reduction in p-CAMK2 and p-synapsin-1 could disrupt SV mobility, thereby reducing replenishment of the readily releasable pool (RRP) from the reserve pool (RP). Furthermore, cells with DHCR24 knock-down showed downregulation of caveolin-1, a crucial lipid raft marker, compared to control cells. Conversely, elevated cellular cholesterol levels caused by knock-in of DHCR24 reversed the effects of cholesterol deficiency, suggesting that CAMK2-mediated synapsin-1 phosphorylation may be regulated in a lipid raft-associated manner. Additionally, we found that cellular cholesterol loss could significantly downregulate the expression of synaptophysin protein, which is vital for SV biogenesis and synaptic plasticity. These results suggest that depletion of cellular cholesterol following knock-down of DHCR24 can decrease synaptophysin protein expression and impair SV mobility by regulating the CAMK2-meditated synapsin-1 phosphorylation pathway, potentially via a lipid raft-associated mechanism. Our study indicates a critical role for cellular cholesterol deficiency in AD-related synaptopathy, thus highlighting the potential for targeting cellular cholesterol metabolism in therapeutic strategies.

Fabrication of oat β-glucan-starch composite systems by sequential extraction as batters for deep-fried mushrooms to prevent oil penetration.

Deep-fat frying (DF) of mushrooms is favored by consumers due to its appealing sensory characteristics. However, their high oil absorption can lead to obesity and elevated cholesterol levels. Therefore, developing healthy food coatings as oil barriers and water-holding layers is essential. In this study, oat starch (OS), oat β-glucan (OBG), and OS-OBG composite systems were prepared and evaluated for their effects on the processing characteristics and oil-repellent capacity of DF mushrooms. Results from 13C solid-state NMR and microstructures demonstrated that incorporating OBG into OS restricted the expansion of OS and reduced moisture migration, thereby forming continuous layers with enhanced cohesive strength. Confocal laser scanning microscopy (CLSM) and gas chromatography-mass spectrometry (GC-MS) further confirmed that OS-OBG decreased oil uptake, improved the nutritional quality and desirable aroma typically associated with fried mushrooms. This study offers scientific and economic guidance for the large-scale production of low-fat fried foods using oat starch-β-glucan system as coatings.

Correlation of dyslipidemia characterized by abnormal cholesterol in first trimester with early pregnancy loss: a retrospective study.

Dyslipidemia has been linked to adverse pregnancy outcomes in observational studies. This study aimed to explore how variations in lipid levels during the first trimester might influence early pregnancy loss (EPL). Blood samples from pregnant women were analyzed to examine the relationship between EPL and lipid metabolism using logistic regression and restricted cubic splines (RCS). Sensitivity analysis was conducted to verify the robustness of the results. Elevated low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels at most times of 4-9weeks of gestation were associated with a higher risk of EPL, regardless of whether the control group was successful pregnancy or live birth. Specifically, taking the successful pregnancy group as a control example, increased EPL risks were observed in the highest quartile of plasma TC at 4weeks (OR = 2.18, 95%: 1.14-4.21) and 7weeks (OR = 4.30, 95%: 1.87-9.93) of pregnancy. Significant EPL risks were also noted in the third (Q3) and fourth (Q4) quartiles of LDL-C at 4weeks (Q3, OR = 2.98, 95%: 1.47-6.08; Q4, OR = 2.66, 95%: 1.27-5.55) and 7weeks (Q3, OR = 3.12, 95%: 1.44-6.73; Q4, OR = 5.17, 95%: 2.14-12.49). High TC levels (> 3.25-3.78mmol/L) and high LDL-C levels (> 1.92-2.04mmol/L) were linked to an increased risk of EPL compared to lower levels of TC (≤ 2.91-3.05mmol/L) and LDL-C (≤ 1.64-1.75mmol/L).RCS analysis further confirmed this finding that plasma TC and LDL-C levels at 4 and 7weeks of gestation may have a linear relationship with the risk of EPL. By the way, triglyceride levels at 6 and 8weeks of gestation were associated with a higher risk of EPL, whereas high-density lipoprotein cholesterol (HDL-C) levels at 5 and 9weeks of gestation have a completely opposite relationship with EPL risk. Elevated cholesterol levels during the first trimester are associated with an increased risk of early pregnancy loss, emphasizing the need for lipid monitoring during pregnancy and even before pregnancy.

Ages at coronary heart disease and death in familial hypercholesterolaemia: a Danish nationwide study spanning 44 years.

Familial hypercholesterolaemia leads to lifelong elevated low-density lipoprotein cholesterol with increased risk of coronary heart disease and pre-mature death. It is unknown whether the prognosis for individuals with familial hypercholesterolaemia has improved over the past four decades as registration of this condition has been limited worldwide. However, in Danish nationwide registries, modified ICD coding has allowed such registration since 1978. This study tested the hypothesis that age at death and coronary heart disease has improved from 1978 to 2021 in individuals with vs. those without familial hypercholesterolaemia. From nationwide registries, all Danish residents were included in a retrospective cohort study. Inclusion and follow-up were from 1978 to 2021. Individuals diagnosed with familial hypercholesterolaemia were identified, and trends over time were examined for age at death and age at coronary heart disease. During follow-up for those with (n = 10 199) and without (n = 9 174 926) familial hypercholesterolaemia, 27% and 27% died and 34% and 9% experienced coronary heart disease. Age at death was 22 years younger in 1978 (P < .001) but similar in 2021 (P = .16) in individuals with vs. without familial hypercholesterolaemia. Although the corresponding age at coronary heart disease was 20 years younger in 1978 (P < .001), it was still 7 years younger in 2021 (P < .001) in individuals with vs. without familial hypercholesterolaemia. These results were similar in women and men and in a 1:100 matched analysis by sex, ethnicity, and time of birth. Nationwide from 1978 to 2021 in Denmark, normalization of age at death but not age at coronary heart disease was observed for individuals diagnosed with familial hypercholesterolaemia.

Association of Insomnia, Lipid Profile, and Lipid-Lowering Medications: A Narrative Review.

Sleep is a fundamental phenomenon that helps maintain normal physiological processes. Conversely, sleep disorders, usually presented as insomnia, are a common public health problem that can lead to multiple pathophysiological changes in humans, including lipid metabolic abnormality. Interestingly, several previous studies have examined the potential relation of insomnia to metabolic syndrome and hyperlipidemia and found that insomnia was associated with elevated plasma cholesterol and triglyceride concentrations. This review summarizes evidence regarding the linkage between insomnia and lipid abnormalities. Moreover, the underlying physiologic mechanisms linking insomnia to lipid abnormalities are systemically discussed. Finally, issues with lipid-lowering drugs and the risk of insomnia are also presented. This knowledge can improve our understanding of the pathophysiological features of insomnia, which may help to prevent and treat insomnia-induced dyslipidemia clinically.

Risk factor clusters for non-communicable diseases in adolescents in Eastern Cape, South Africa

Background: The increasing prevalence of non-communicable diseases (NCDs) among adolescents in South Africa is a growing public health concern.Aim: To examine the clustering of NCD risk factors, with a focus on gender, socio-economic status (SES) and perceived stress among adolescents.Setting: The study involved adolescents from eight schools in Buffalo City Metropolitan Municipality and Amatole district, Eastern Cape.Methods: A stratified random sample of 266 adolescents (aged 12 years–18 years) was assessed for anthropometric, physiological, and perceived stress measures. Data included body mass index (BMI), blood pressure (BP), cholesterol, glucose levels, and perceived stress (via the Perceived Stress Scale). Analysis involved descriptive statistics, Chi-square tests, t-tests, and k-means clustering.Results: Females (n = 155) showed a higher prevalence of NCD risk factors, with 80.2% classified as overweight or obese compared to 19.8% of males, and 77.2% had elevated cholesterol versus 22.8% of males. Perceived stress was higher in affluent schools (59.8%) despite fewer metabolic risks. K-means analysis identified four health profiles with significant SES and health differences (p 0.001). Cluster 1 (high SES) showed elevated BP, BMI, and stress, while Clusters 2–4 (low SES) varied in risks, with Cluster 4 showing the highest BP and metabolic risks despite low stress.Conclusion: These results highlight unique health profiles and risk factors across socio- economic contexts, with female adolescents from lower socio-economic backgrounds facing greater metabolic risks.Contribution: This Study provides original insights into the interplay between gender, SES and perceived stress in shaping NCD risk among South African adolescents.

Impact of Early Childhood Malnutrition on Cardiometabolic Risk Factors in Young Adults from Marginalized Areas of Chiapas, Mexico.

The presence of malnutrition in early life is a determining factor in the onset of metabolic alterations and chronic diseases in adults. Therefore, the objective of this study was to determine the impact of malnutrition in early childhood with the presence of cardiometabolic risk factors in adulthood in marginalized populations from Chiapas, Mexico. The present investigation was based on a prospective cohort study that began in 2002, with young adults aged 18 to 25 years belonging to De Los Bosques region in Chiapas, Mexico. Sociodemographic, anthropometric, clinical and biochemical data were obtained in adulthood. Binary logistic regression models with 95% confidence intervals were fitted to assess the association between nutritional status in childhood (≤5 years of age) and cardiometabolic risk in adulthood. Individuals with overweight/obesity in childhood were more likely to have overweight/obesity (OR = 2.65, 95% CI: 1.09-6.45), high waist circumference (3.78, 95% CI: 1.55-9.24), high waist to height ratio (OR = 5.38, CI 95%: 1.60-18.10), elevated total cholesterol (OR = 3.95, 95% CI: 1.36-11.43) and metabolic syndrome (OR = 4.71, 95% CI: 1.49-14.90) in adulthood. In conclusion, malnutrition presented in early childhood increased the probability of developing cardiometabolic alterations in young adults from southern Mexico.

The pleiotropic effects of PCSK9 in cardiovascular diseases beyond cholesterol metabolism.

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally, with elevated low-density lipoprotein cholesterol (LDL-C) levels being a major risk factor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in regulating LDL-C levels by promoting the degradation of hepatic low-density lipoprotein receptors (LDLR) responsible for clearing LDL-C from the circulation. PCSK9 inhibitors are novel lipid-modifying agents that have demonstrated remarkable efficacy in reducing plasma LDL-C levels and decreasing the incidence of CVD. However, the broader clinical impacts of PCSK9 functions beyond cholesterol metabolism, including both desired and undesired effects from therapeutic PCSK9 inhibition, underscore the urgent necessity to elucidate the underlying mechanisms. Recent studies have shown that local PCSK9 in the vascular system can interact with other receptors such as CD36, LRP-1, and ABCA1. This provides new evidence supporting the potential contribution of PCSK9 to CVD through LDLR-independent signaling pathways. Therefore, this review aimed to outline the diverse effects of PCSK9 on CVD and discuss the underlying mechanisms in non-cholesterol-related processes, which will provide a rational basis for its long-term pharmacological inhibition in the clinic.

Phenotypes, Genotypes, Treatment, and Outcomes of 14 Children with Sitosterolemia at Vietnam National Children's Hospital.

Background: Sitosterolemia is a rare autosomal recessive disorder characterized by diverse clinical manifestations ranging from asymptomatic cases to the development of xanthomas, hypercholesterolemia, premature atherosclerosis, or even sudden death during childhood. It results from homozygous or compound heterozygous pathogenic variants in the ABCG5 or ABCG8 genes. Prompt detection and intervention are essential to managing this condition and preventing severe outcomes. Methods: This study aims to retrospectively analyze the phenotype, genotype, treatment, and outcomes of 14 children-seven boys and seven girls-all of Vietnamese origin, diagnosed with sitosterolemia at the Vietnam National Children's Hospital between March 2015 and July 2024. Results: The median ages at disease onset and diagnosis were 5.7 years (range: 1.5-17.9) and 7.2 years (range: 1.7-17.9), respectively. Xanthomas were observed in 85.7% of patients (12/14), arthralgia in 14.3% (2/14), and anemia in 7.1% (1/14), with no cases of thrombocytopenia. At diagnosis, all patients exhibited elevated total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), with considerably higher levels in patients with xanthomas compared to those without. Mutations in the ABCG5 gene were identified in 71.4% (10/14) of the patients, while 28.6% (4/14) had mutations in the ABCG8 gene. Fourteen variants were detected, nine in ABCG5 and five in ABCG8, with five variants reported for the first time in sitosterolemia patients. Initial management for all patients involved dietary modifications. After three months, 10 patients with persistently elevated TC and LDL-C received ezetimibe or cholestyramine treatment. Among the eight patients who continued treatment for over three months, the median TC and LDL-C concentrations decreased by 54.9% and 67.3%, respectively. Conclusions: Among Vietnamese patients with sitosterolemia, variants in the ABCG5 gene were more prevalent than those in the ABCG8 gene. Patients showed a positive response to ezetimibe or cholestyramine treatment. Genetic testing is essential for establishing a diagnosis of sitosterolemia and guiding accurate management strategies.

The relevance of remnant cholesterol as a guide for lipid management in Indian subjects undergoing coronary revascularization.

The atherogenic potential of remnant cholesterol, which refers to the cholesterol content of triglyceride-rich, non-low-density lipoprotein (LDL) particles in circulation, has gained increasing attention recently. Unfortunately, very limited information is available regarding remnant cholesterol levels in Indian subjects. This was a retrospective study conducted at a premier, tertiary care center in North India. A total of 3064 consecutive subjects [mean age 61.3±10.3 years, 2550 (83.2%) men] with newly diagnosed coronary artery disease (CAD) undergoing coronary revascularization were included. Enzymatic assays were used for measuring various lipid parameters. Remnant cholesterol was calculated by subtracting LDL cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol. A value>30mg/dL was considered elevated. The mean LDL-C was 79.1±33.1mg/dL with 46.4% of all subjects having LDL-C <70mg/dL and only 16.9% having LDL-C <50mg/dL. The median remnant cholesterol level was 17.0mg/dL (interquartile range 12.0-24.0mg/dL) with only 11.9% of subjects having values>30mg/dL. Only 4.5% of the patients with LDL-C <70mg/dL and 2.9% of those with LDL-C <50mg/dL had elevated remnant cholesterol. These proportions were significantly greater in patients with serum triglycerides >200mg/dL. Our study shows that in a North-Indian population with CAD, elevated remnant cholesterol was present in only a small proportion. The prevalence of elevated remnant cholesterol decreased further as the LDL-C control improved. These findings suggest that elevated remnant cholesterol may not be a clinically relevant therapeutic target in most patients with LDL-C below the currently recommended goals.