LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry.

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

Normal caloric intake with high-fat diet induces metabolic dysfunction-associated steatotic liver disease and dyslipidemia without obesity in rats.

Excessive caloric intake and obesity due to high-fat (HFD) and high-disaccharide (HDD) diets have been recognized as major contributing factors to dyslipidemia and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the effect of HFD and HDD without excessive caloric intake is obscure. The aim of the study was to evaluate the effect of physiological caloric intake delivered through HFD and HDD on liver and lipid profiles. The study was performed on 6-week-old male and female (50/50%) Sprague Dawley rats, receiving either a standard (controls, n = 16), HFD (n = 14) or HDD (n = 14) chow. All groups received the same, standard daily calorie rations, titrated weekly to the age of growing rats, for 12 weeks. A panel of metabolic in vivo measurement were performed, followed by histological, biochemical and molecular biology assays on tissues harvested from sacrificed rats. There was no significant difference between the groups in body weight. In contrast to controls, HFD and HDD groups showed metabolic dysfunction-associated steatohepatitis (MASH) characterized by liver steatosis, inflammation, ballooning of hepatocytes and fibrosis. These changes were more pronounced in the HFD than in the HDD group. The HFD group showed significantly higher serum LDL than controls or HDD rats. Furthermore, the HFD group had higher liver protein levels of low-density lipoprotein receptor (LDLR) but lower plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) than the controls or HDD group. There were no differences between sexes in evaluated parameters. The excessive caloric intake and obesity are not prerequisites for the development of MASH and dyslipidemia in rats. The liver changes induced by the HFD and HDD diets exhibit differences in severity, as well as in the expression patterns of LDLR and PCSK9. Notably, these effects are independent of the sex of the rats.

Regulatory role of Heparan sulfate in leptin signaling.

Leptin, a hormone mainly secreted by adipocytes, has attracted significant attention since its discovery in 1994. Initially known for its role in appetite suppression and energy regulation, leptin is now recognized for its influence on various physiological processes, including immune response, bone formation, and reproduction. It exerts its effects by binding to receptors and initiating an intracellular signaling cascade. Heparan sulfate (HS) is known to regulate the intracellular signaling of various ligands. HS is present as the glycan portion of HSPGs on cell surfaces and in intercellular spaces, with diverse structures due to extensive sulfation and epimerization. Although HS chains on HSPGs are involved in many physiological processes, the detailed effects of HS chains on leptin signaling are not well understood. This study examined the role of HS chains on HSPGs in leptin signaling using Neuro2A cells expressing the full-length leptin receptor (LepR). We showed that cell surface HS was essential for efficient leptin signaling. Enzymatic degradation of HS significantly reduced leptin-induced phosphorylation of downstream molecules, such as signal transducer and activator of transcription 3 and p44/p42 Mitogen-activated protein kinase. In addition, HS regulated LepR expression and internalization, as treatment with HS-degrading enzymes decreased cell surface LepR. HS was also found to exhibit a weak interaction with LepR. Enzymatic removal of HS enhanced the interaction between LepR and low-density lipoprotein receptor-related protein 1, suggesting that HS negatively regulates this interaction. In conclusion, HS plays a significant role in modulating LepR availability on the cell surface, thereby influencing leptin signaling. These findings provide new insights into the complex regulation of leptin signaling and highlight potential therapeutic targets for metabolic disorders and obesity.

Comparison of Multiple Equations for Low-Density Lipoprotein Cholesterol Calculation Against the Direct Homogeneous Method.

Objective: Several equations have been proposed as alternatives for the reference method of measuring low-density lipoprotein cholesterol (LDL-C). This study aimed to evaluate these alternatives in comparison to the homogeneous method and validate their clinical utility. Methods: Data on the lipid profiles of 1,006 Sudanese individuals were analyzed. The paired t-test was used to compare the results of direct and calculated LDL-C. Bland-Altman plots were used to demonstrate the differences between the measured and calculated LDL-C against the mean values. Linear regression was conducted, using the correlation coefficient (r) to quantify the relationship between methods. The bias between measured and calculated LDL-C was compared to the National Cholesterol Education Program Laboratory Standardization Panel criteria (i.e., accuracy within ±4% of expected values). Results: The Martin and Anandaraja equations showed no significant difference compared to directly measured LDL-C (p>0.05). The DeLong equation indicated an insignificant difference only with a 99% confidence interval (p>0.01). The Martin, DeLong, and Teerakanchana equations exhibited the smallest limits of agreement, with data points concentrated closely around the mean difference line. Linear regression analysis revealed strong positive correlations (r>0.8) for most equations, except for the Ahmadi equation. The DeLong, Rao, and Martin equations demonstrated superior performance for LDL cutoff points (bias within ± 4%). The DeLong formula also showed superior performance at different lipid levels, closely followed by the Martin equation (bias within ±4%). Conclusion: The DeLong and Martin equations outperformed others, such as the widely used Friedewald equation, in calculating LDL-C. Further validation studies are needed.

Effect of Siegesbeckia glabrescens Extract on Foam Cell Formation in THP-1 Macrophages.

The accumulation of cholesterol-bearing macrophage foam cells in the initial stages of atherosclerosis serves as a characteristic feature of atherosclerotic lesions. The inhibitory effect of Siegesbeckia glabrescens, a species of flowering plant in the Asteraceae family, on foam cell formation in THP-1 macrophages has not yet been elucidated. In this study, we explored the effect of S. glabrescens ethanol extract (SGEE) and hot water extract (SGWE) on foam cell formation via co-treatment with oxidized low density lipoprotein (ox-LDL) and lipopolysaccharide (LPS), mimicking the occurrence of atherosclerosis in vitro, and studied the regulation of its underlying mechanisms. THP-1 cells differentiated by PMA (1 µM) for 48 h were subsequently treated with/without SGWE and SGEE for 48 h. THP-1 macrophages were treated with ox-LDL (20 µg/mL) and LPS (500 ng/mL) for 24 h. Treatment with ox-LDL and LPS for 24 h enhanced the lipid accumulation in foam cells compared to in untreated cells, as determined by oil red O staining. In contrast, SGWE and SGEE treatment inhibited lipid accumulation in foam cells. Both extracts significantly upregulated ABCA1, LXRα, and PPARγ expression in ox-LDL- and LPS-treated cells (P<0.05). Moreover, both SGWE and SGEE decreased LOX-1, CD36, and SR-A1 expression. The co-treatment of ox-LDL and LPS increased NF-κB, COX-2, and pro-inflammatory activation and expression compared with untreated cells. However, this increase suppressed NF-κB, COX-2, and pro-inflammatory expression by SGWE and SGEE. The results indicated that both extracts can partially inhibit foam cell formation and contribute to protective effects by suppressing cholesterol accumulation during the onset of atherosclerosis.

Vascular-endothelial adaptations following low and high volumes of high-intensity interval training in patients after myocardial infarction.

BACKGROUND: Determinants of coronary artery disease, such as endothelial dysfunction and oxidative stress, could be attenuated by high-intensity aerobic interval exercise training (HIIT). However, the volume of this type of training is not well established. OBJECTIVE: To assess the impact of two volumes of HIIT, low (LV-HIIT, <10 min at high intensity) and high (HV-HIIT, >10 min at high intensity), on vascular-endothelial function in individuals after an acute myocardial infarction (AMI). MATERIALS AND METHODS: Clinical trial in 80 AMI patients (58.4 ± 8.3 years, 82.5% men) with three study groups: LV-HIIT (n = 28) and HV-HIIT (n = 28) with two sessions per week for 16 weeks and control group (CG, n = 24) with unsupervised physical activity recommendations. Endothelial function (brachial flow-mediated dilation, FMD), atherosclerosis (carotid intima-media thickness ultrasound, cIMT), and levels of oxidized low-density lipoprotein (ox-LDL) as a marker of oxidative stress were determined before and after the intervention period. RESULTS: After the intervention, in the exercise groups, there was an increase in FMD (LV-HIIT, ↑58.8%; HV-HIIT, ↑94.1%; p < 0.001) concurrently with a decrease in cIMT (LV-HIIT, ↓3.0%; HV-HIIT, ↓3.2%; p = 0.019) and LDLox (LV-HIIT, ↓5.2%; HV-HIIT, ↓8.9%; p < 0.001), with no significant changes in the CG. Furthermore, a significant inverse correlation was observed between ox-LDL and endothelial function related to the volume of HIIT training performed (LV-HIIT: r = -0.376, p = 0.031; HV-HIIT: r = -0.490, p < 0.004), with no significance in the CG (r = 0.021, p = 0.924). CONCLUSION: In post-AMI patients, HIIT may lead to a volume-dependent enhancement in endothelial function, attributed to a decrease in oxidative stress, with added beneficial effects in reducing vascular wall thickness. An LV-HIIT program, with less than 10 min at high intensity per session, has proven enough efficiency to initiate favorable vascular-endothelial adaptations, potentially reducing cardiovascular risk among patients with coronary artery disease. TRIAL REGISTRATION: INTERFARCT, ClinicalTrials.gov: NCT02876952.

Comparison between statistical and machine learning methods to detect the hematological indices with the greatest influence on elevated serum levels of low-density lipoprotein cholesterol.

INTRODUCTION: Elevated levels of low-density lipoprotein-cholesterol (LDL-C) is a significant risk factor for the development of cardiovascular diseases (CVD)s. Furthermore, studies have revealed an association between indices of the complete blood count (CBC) and dyslipidemia. We aimed to investigate the relationship between CBC parameters and serum levels of LDL. METHOD: In a prospective study involving 9704 participants aged 35-65 years, comprehensive screening was conducted to estimate LDL-C levels and CBC indicators. The association between these biomarkers and high LDL-C (LDL-C≥130 mg/dL (3.25 mmol/L)) was investigated using various analytical methods, including Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) methodologies. RESULT: The present study found that age, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), lymphocyte (LYM), PLT-LYM ratio (PLR), PLT-High-Density Lipoprotein (HDL) ratio (PHR), HGB-LYM ratio (HLR), red blood cell count (RBC), Neutrophil-HDL ratio (NHR), and PLT-RBC ratio (PRR) were all statistically significant between the two groups (p<0.05). Another important finding was that red cell distribution width (RDW) was a significant predictor for higher LDL levels in women. Furthermore, in men, RDW-PLT ratio (RPR) and PHR were the most important indicators for assessing the elevated LDL levels. CONCLUSION: The study found that sex increases LDL-C odds in females by 52.9 %, while age and HCT increase it by 4.1 % and 5.5 %, respectively. RPR and PHR were the most influential variables for both genders. Elevated RPR and PHR were negatively correlated with increased LDL levels in men, and RDW levels was a statistically significant factor for women. Moreover, RDW was a significant factor in women for high levels of HDL-C. The study revealed that females have higher LDL-C levels (16 % compared to 14 % of males), with significant differences across variables like age, HGB, HCT, PLT, RLR, PHR, RBC, LYM, NHR, RPR, and key factors like RDW and SII.

Maternal Lipids in Pregnancy and Later Life Dyslipidemia: The POUCHmoms Longitudinal Cohort Study.

OBJECTIVE: Maternal lipid levels increase in normal pregnancies. Here, we examine whether pregnancies with the highest total cholesterol, low-density lipoprotein (LDL) or triglyceride levels or the lowest high-density lipoprotein (HDL) levels predict future dyslipidemia post-pregnancy. DESIGN: Longitudinal cohort study. SETTING: Five communities in Michigan, USA. SAMPLE: Pregnant women (n = 649) with blood lipid levels measured at mid-pregnancy in the Pregnancy Outcomes and Community Health (POUCH) Study and at the POUCHmoms Study follow-up, 7-15 years later. METHODS: Maternal mid-pregnancy lipid levels were defined as 'high' (upper quartile of triglycerides ≥ 216 mg/dL, LDL ≥ 145 mg/dL and total cholesterol ≥ 256 mg/dL) or 'low' (lower quartile, HDL < 58 mg/dL) using whole sample lipid distributions. At follow-up, dyslipidemia was classified by the clinical cutoffs of triglycerides and total cholesterol ≥ 200 mg/dL, LDL ≥ 130 mg/dL and HDL < 50 mg/dL. Weighted regression models estimated the risk of dyslipidemia at follow-up in relation to pregnancy lipid levels, adjusted for baseline confounders. MAIN OUTCOME MEASURE: Dyslipidemia later in life. RESULTS: Mid-pregnancy triglycerides, LDL, and total cholesterol levels at the upper quartile were associated with at least threefold increase in the risk of abnormal triglycerides, LDL and total cholesterol levels later in life. Women with low mid-pregnancy HDL levels had just over a twofold increased risk of abnormally low HDL levels at follow-up. These associations persisted following adjustment for covariates, i.e. demographics, lifestyle, and years of follow-up. CONCLUSIONS: Higher mid-pregnancy LDL, total cholesterol and triglycerides and lower levels of HDL may signal future dyslipidemia risk and the need for closer lipid monitoring to ensure timely interventions that can attenuate cardiovascular disease risk.

Long-term effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia: an observational case series.

BACKGROUND: We assessed long-term real-world effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia (HoFH). METHODS: Retrospective case series of six patients with HoFH treated with lomitapide in an Italian clinic. Changes in low-density lipoprotein cholesterol (LDL-C) during lomitapide treatment were assessed. The effect on LDL-C of PCSK9 inhibitors, apheresis and lomitapide was evaluated. Additionally, high-density lipoprotein cholesterol (HDL-C), gastrointestinal tolerability, hepatic steatosis/elasticity, transaminases, and cardiovascular events and symptoms were assessed. RESULTS: Median age at HoFH clinical and molecular diagnoses was 25 (range 2-49) and 40 (29-71) years, respectively. Five (83.3%) had prior cardiovascular events. One patient received apheresis, which was subsequently discontinued. All patients received PCSK9 inhibitors but discontinued due to minimal effectiveness. Median (range) age at lomitapide initiation was 44 (28-73) years, with a median 47 (18-85) months' treatment (mean dose 17.5 [5-40] mg/day). Mean (SD) baseline LDL-C was 263.2 (148.1) mg/dL, which decreased by 80% at nadir (52.8 [19.2] mg/dL) and 69% at last follow-up (81.3 [30.5] mg/dL). Four patients (66.7%) achieved LDL-C < 70 mg/dL sometime during follow-up, all of whom also achieved LDL-C < 55 mg/dL. Adverse events (AEs) were generally mild to moderate, hepatic steatosis was either absent or mild/moderate and hepatic elasticity remained normal in all but two patients (> 70 years old). All patients with reported cardiovascular symptoms had improvements in symptoms, and all patients reported stabilization or regression of intima-media thickness and atheromatous plaques. CONCLUSIONS: These long-term, real-world data demonstrate that lomitapide substantially reduced LDL-C for up to seven years. Most patients achieved LDL-C goal at some point, consistent with published Phase III trial and real-world evidence data. No patient discontinued lomitapide treatment. Further long-term follow-up in a larger patient population will be important to determine cardiovascular and other outcomes.

A Study of Non-alcoholic Fatty Liver Disease in Patients With Hypothyroidism: A Cross-Sectional Study in a Tertiary Care Hospital.

Background Hypothyroidism occurs when the thyroid gland is underactive and fails to produce sufficient thyroid hormones. It can affect multiple organs including the heart, brain, liver, kidneys, and reproductive system, leading to symptoms such as fatigue, cognitive impairment, elevated cholesterol, fluid retention, fatty liver, and menstrual irregularities. Given the higher prevalence of fatty liver disease in patients with hypothyroidism, it is important to evaluate the need for routine screening for fatty liver in these patients. Materials and methods This observational, cross-sectional study was conducted at Dr. D. Y. Patil Medical Hospital, Pune, Maharashtra, India, from October 2022 to June 2024. The study included 60 patients aged over 12 years who were known or recently diagnosed with hypothyroidism. Patients with type 2 diabetes mellitus, pregnant women, or those with chronic liver disease were excluded. Data collected included physical examination findings and laboratory test results. Fatty liver was diagnosed using magnetic resonance elastography. Statistical analysis was performed using IBM SPSS statistics for Windows, version 20 (IBM Corp., Armonk, New York). The statistical significance of parametric data was evaluated using the Chi-square test. A p-value less than 0.05 and a confidence interval of 95% were considered statistically significant. Result The study population had an average age of about 45 years, with most participants aged between 40 and 49 years. The majority of the participants were female, making up over 83% of the group, while males constituted about 17%. The most commonly reported symptom was weight gain, followed by constipation and fatigue. For individuals with fatty liver, the average thyroid-stimulating hormone (TSH) level was notably higher compared to those without fatty liver. Additionally, low-density lipoprotein (LDL) levels were higher in individuals with non-alcoholic fatty liver disease (NAFLD) compared to those without. Both TSH and LDL levels showed a statistically significant association with the occurrence of NAFLD. Conclusion Hypothyroidism was more prevalent in females and in the age group 40-49 years. There was a statistical significance between TSH and the occurrence of NAFLD. In this study, statistical significance was also found between LDL and the occurrence of NAFLD.

Lipoprotein Receptor-Related Protein 4 Antibody Positivity in the Youngest Patient in the Caucasus Region: A Case Report.

Juvenile myasthenia gravis is a rare disorder where antibodies targeting the acetylcholine receptor or, less frequently, muscle-specific kinase can be detected in the serum while about half of the patients can be seronegative. A pediatric patient with ocular myasthenia is presented whose serum was negative for acetylcholine receptor and muscle-specific kinase antibodies but tested positive for low-density lipoprotein receptor-related protein 4 antibodies. A favourable clinical response was observed to medical treatment with pyridostigmine and prednisolone, as expected in isolated ocular juvenile myasthenia gravis. This case exemplifies the very rare association of juvenile myasthenia gravis with low-density lipoprotein receptor-related protein 4 positivity, reported in only a few cases so far. The specificity of the antibody and the efficiency of medical treatment emphasize the importance of clinical suspicion and appropriate serological testing in juvenile myasthenia gravis in the absence of acetylcholine receptor and muscle-specific kinase antibodies.

The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors combined with statins in patients with hypercholesterolemia: a network meta-analysis.

Background: In recent years, the position of PCSK9 inhibitors as adjuvant therapy to statins in guidelines has further improved. However, there remained a dearth of direct comparative studies among different PCSK9 inhibitors. Therefore, this study aimed to conduct a network meta-analysis to evaluate the efficacy and safety of different PCSK9 inhibitors combined with statins. Methods: A comprehensive literature search was conducted from the study's inception to 12 November 2023, encompassing multiple online databases including PubMed, Embase, Cochrane Central, Web of Science, and ClinicalTrials.gov to obtain relevant randomized controlled trials. Frequentist network meta-analysis was employed to compare the efficacy and safety of different PCSK9 inhibitors. The efficacy endpoints were low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and lipoprotein (a) (Lp(a)). The safety endpoints were any adverse events (AE), severe adverse events (SAE), AE leading to treatment discontinuation, and injection-site reaction. Results: Compared with placebo and ezetimibe, all PCSK9 inhibitors demonstrated significant reductions in LDL-C levels. Notably, evolocumab exhibited the most pronounced effect with a treatment difference of -63.67% (-68.47% to -58.87%) compared with placebo. Regarding dosage selection for evolocumab, the regimen of 140 mg Q2W (-69.13%, -74.55% to -63.72%) was superior to 420 mg QM (-61.51%, -65.97% to -57.05%). Based on rankings and P-scores analysis, tafolecimab 150 mg Q2W demonstrated superior efficacy in reducing ApoB levels (-61.70%, -84.38% to -39.02%) and Lp(a) levels (-43%, 30%, -68%, 81% to -17%, 79%). Furthermore, the safety profile of PCSK9 inhibitors was favorable with no increase in the incidence of AE, SAE, or AE leading to treatment discontinuation; however, alirocumab, inclisiran, and tafolecimab may potentially entail a potential risk associated with injection-site reactions. Conclusion: Compared with placebo and ezetimibe, PCSK9 inhibitors can significantly reduce LDL-C, ApoB, and Lp(a) when combined with statins to treat hypercholesterolemia. Furthermore, PCSK9 inhibitors and ezetimibe exhibit similar safety profiles. Systematic Review Registration: [PROSPERO], identifier [CRD42023490506].

The non-HDL-C to APOB ratio as a predictor of inaccurate LDL-C measurement in patients with chronic intrahepatic cholestasis and jaundice: a retrospective study.

Background: Cholestasis is characterized by the accumulation of bile in the liver or biliary system due to obstruction or impaired flow, necessitating lipid profiling to assess lipid metabolism abnormalities. Intrahepatic cholestasis, being the most significant type of cholestasis, further complicates the assessment of lipid abnormalities. However, the accuracy of low-density lipoprotein cholesterol (LDL-C) measurement in intrahepatic cholestasis patients remains uncertain. Objective: This study aimed to evaluate the consistency of the homogeneous assay and the Friedewald formula in detecting LDL-C levels and identify factors influencing LDL-C test results in intrahepatic patients with cholestasis. Methods: Retrospective analysis of laboratory data was conducted on intrahepatic cholestatic patients. Correlations between LDL-C values obtained using the homogeneous method (LDL-C(D)) and the Friedewald formula (LDL-C(F)), as well as associations between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (ApoA1), LDL-C(D) and LDL-C(F), and apolipoprotein B (ApoB), were analyzed. Logistic regression analyses were employed to identify diagnostic indicators for inaccurate LDL-C measurements in intrahepatic cholestatic patients. Results: Compared to patients with intrahepatic cholestasis without jaundice, the correlation between LDL-C(F) and LDL-C(D) was weaker in those with jaundice. Additionally, HDL-C exhibited a strong correlation with ApoA1 in both jaundice and non-jaundice cholestasis cases. Elevated non-HDL-C to APOB ratio (NH-C/B Ratio) levels (>4.5) were identified as a reliable predictor of inaccurate LDL-C measurements in patients with chronic intrahepatic cholestasis accompanied by jaundice. Conclusions: LDL-C measurement reliability is moderately weaker in patients with intrahepatic cholestasis accompanied by jaundice. Elevated levels of the NH-C/B ratio serve as a significant predictor of inaccurate LDL-C measurements in this chronic patient population, highlighting its clinical relevance for diagnostic assessments.

Low-Density Lipoprotein Cholesterol Gymnastics: Exploring the Advantages and Limitations of the Friedewald, Martin-Hopkins, and Sampson Equations for Personalized Lipid Management.

BACKGROUND: The most commonly used method for low-density lipoprotein cholesterol (LDL-C) estimation is the Friedewald equation, which has notable limitations. However, more accurate methods have been proposed. This study investigates the advantages and limitations of these methods and identifies the contexts in which each equation is the most or least applicable. METHODS: A cohort of 222 individuals underwent a standard lipid profile assessment, including directly measuring their LDL-C (dLDL-C). LDL-C was also estimated using the Friedewald, Martin-Hopkins, and Sampson equations. The differences (%Delta) between the estimated and measured LDL-C were analyzed in relation to dLDL-C, high-density lipoprotein cholesterol (HDL-C), and triglyceride levels. RESULTS: The %Delta was significantly lower (p < 0.0001) for the Martin-Hopkins (-8.8 ± 9.8) and Sampson (-9.5 ± 9.2) equations compared to Friedewald (-12.2 ± 9.2). All equations increasingly underestimated LDL-C as the dLDL-C levels decreased. The %Delta of the Martin-Hopkins equation showed significant positive correlations with dLDL-C (≤130 mg/dL) and triglycerides and a significant negative correlation with HDL-C. In a subgroup of 30 individuals with extreme %Delta values, patterns of gross underestimation were observed, particularly when low LDL-C, low triglycerides, and high HDL-C coincided. CONCLUSIONS: The Martin-Hopkins equation is a superior method for LDL-C estimation and a valuable tool in precision medicine. However, clinicians and laboratory professionals must be aware of its limitations and recognize patterns that could lead to significant LDL-C underestimation. We propose an algorithm for clinical laboratories to provide personalized LDL-C assessments.

Evaluation of Mechanical Properties of Composite Material with a Thermoplastic Matrix Reinforced with Cellulose Acetate Microfibers.

Low-density polyethylene (LDPE) has been widely used in various applications due to its flexibility, lightness, and low production cost. However, its massive use in disposable products has raised environmental concerns, prompting the search for more sustainable alternatives. This study aims to investigate the mechanical properties achievable in a composite material utilizing low-density polyethylene (LDPE), potato starch (PS), and cellulose microfibrils (MFCA) at loadings of 0.05%, 0.15%, and 0.30%. Initially, the cellulose acetate microfibrils (MFCA) were produced via an electrospinning process. Subsequently, a dispersive mixture of the aforementioned materials was created through the extrusion and pelletizing process to form pellets. These pellets were then molded by injection molding to produce test specimens in accordance with ASTM D 638, the standard for tensile strength testing. The evaluation of the properties was conducted through mechanical tensile tests (ASTM D638), hardness tests (ASTM D 2240), melt flow index (ASTM D1238), and scanning electron microscopy (SEM). This study determined the influence of cellulose acetate microfibril loadings below 0.3% as reinforcement within a thermoplastic LDPE matrix. It was demonstrated that these microfibrils, due to their length-to-diameter ratio, contribute to an enhancement in the mechanical properties.

Coronary artery disease risk prediction by combined stratification of low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol levels across different glucose statuses.

AIM: To investigate the association between low-density lipoprotein-cholesterol (LDL-C) levels and coronary artery disease (CAD) incidence based on combining high-density lipoprotein-cholesterol (HDL-C) levels and glucose status. MATERIALS AND METHODS: In this retrospective cohort study, we used data from a nationwide claims database (1,524,289 individuals without a history of CAD or familial hypercholesterolaemia; 2008-2019). Cox proportional hazards modelling identified the risk of incident CAD by a novel combination of four HDL-C levels, seven LDL-C levels and glucose status. RESULTS: During the follow-up period (mean: 5.5 years), 8301 (0.99/1000 person-years) events occurred. The risk of CAD increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of the glucose status. Using the most favourable levels of HDL-C and LDL-C (i.e. 60-99 mg/dL and <80 mg/dL, respectively) as references, the hazard ratios (95% confidence interval) for the group with HDL-C levels <40 mg/dL and LDL-C levels <80 mg/dL were 2.74 (1.47-5.11), 2.52 (1.30-4.91) and 2.85 (1.68-4.84) for normoglycaemia, borderline glycaemia and diabetes, respectively. Comparison of the most favourable levels of HDL-C and LDL-C with their least favourable levels (i.e. <40 mg/dL and 180-199 mg/dL, respectively) revealed that the risk of new-onset CAD exhibited a 19-, nine- and seven-fold increase in individuals with normoglycaemia, borderline glycaemia and diabetes, respectively. CONCLUSIONS: To prevent CAD, LDL-C levels should be strictly controlled in patients with low HDL-C levels regardless of glucose tolerance. Individualized treatment, which involves setting target LDL-C levels based on glucose tolerance and HDL-C values, is required.

Dynamic trends of ischemic heart disease mortality attributable to high low-density lipoprotein cholesterol: a joinpoint analysis and age-period-cohort analysis with predictions.

AIMS: The purpose of this study was to analyze the dynamic trends of ischemic heart disease (IHD) mortality attributable to high low-density lipoprotein cholesterol (LDL-C). METHODS: Data on IHD mortality attributable to high LDL-C from 1990 to 2021 were extracted from the global disease burden database. Joinpoint software was used to estimate the average annual percentage change (AAPC) in the age-standardized mortality rate (ASMR). An age‒period‒cohort model was used to analyze the impacts of age, period, and cohort on these changes. The Bayesian framework was used to predict IHD mortality attributable to high LDL-C from 2022 to 2040. RESULTS: The overall ASMR of IHD attributable to high LDL-C decreased from 50. 479 per 100,000 people in 1990 to 32.286 per 100,000 people in 2021, and ASMR of IHD attributable to high LDL-C was higher in males than in females. The longitudinal age curves of the overall IHD mortality attributable to high LDL-C showed a monotonic upward trend, especially after 65 years of age. The period and cohort effect relative risk (RR) values of overall IHD mortality attributable to high LDL-C showed a downward trend. The overall ASMR of IHD attributable to high LDL-C is predicted to show a downward trend, and male IHD mortality attributable to high LDL-C is expected to be higher than that of females. CONCLUSION: This study revealed a sustained decrease in IHD mortality attributable to high LDL-C over three decades, with a continued decline expected. Despite this, gender disparities persist, with males experiencing higher mortality rates and elderly individuals remaining a vulnerable group.

Impact of body mass index on repeat coronary revascularization rates in patients with LDL-C below 55 mg/dL and LDL-C below 70 mg/dL: a 42-month cohort study in Korea.

Background: Previous studies revealed a linear relationship between body mass index (BMI) and repeat coronary revascularization rate in patients who underwent percutaneous coronary intervention (PCI). However, this relationship has not been demonstrated in Korean patients who meet old and new target low-density lipoprotein cholesterol (LDL-C) levels of Korean dyslipidemia guidelines. Therefore, we conducted this study to find out the effect of BMI on repeat coronary revascularization rate in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL. Methods: This cohort study was followed for 42 months in Daegu Catholic Medical Center, Korea. We included 429 patients with LDL-C <70 mg/dL 1 year after PCI. We compared repeat revascularization rates using Kaplan-Meier survival curves between the normal weight group (18.5 kg/m2 ≤ BMI < 23 kg/m2) and the pre-obesity and obesity group (23 kg/m2 ≤ BMI) in patients with LDL-C <55 mg/dL and patients with LDL-C <70 mg/dL. Results: During a follow-up period, there was no significant difference in repeat coronary revascularization-free survival between a group with LDL-C <55 mg/dL and a group with LDL-C <70 mg/dL (79.6% vs. 76.2%, P=0.32). In normal weight patients, LDL-C <55 mg/dL group showed higher repeat coronary revascularization-free survival than LDL-C <70 mg/dL group (89.3% vs. 77.1%, P=0.05). There was no significant difference in repeat revascularization-free survival between the normal weight group and the pre-obesity and obesity group in patients with LDL-C <70 mg/dL (77.1% vs. 75.7%, P=0.67). However, the normal weight group showed significantly higher repeat revascularization-free survival compared to the pre-obesity and obesity group in patients with LDL-C <55 mg/dL (89.3% vs. 74.3%, P=0.03). Normal body weight and LDL-C <55 mg/dL [hazard ratio (HR): 0.421, 95% confidence interval (CI): 0.193-0.916, P=0.02] was the only independent predictor for repeat revascularization. Conclusions: In Korean PCI patients with normal body weight whose LDL-C level is less than 70 mg/dL, but more than 55 mg/dL, should be treated with more intensive therapy to lower LDL-C to less than 55 mg/dL. For obese patients who have succeeded in reducing LDL-C below 55 mg/dL, it seems that weight loss should be attempted to a normal body weight level.

The therapeutic effect of liver transplantation in 14 children with homozygous familial hypercholesterolemia: a prospective cohort: Liver transplant for familial hypercholesterolemia.

OBJECTIVES: Homozygous familial hypercholesterolemia (HoFH) is characterized by elevated low-density lipoprotein cholesterol (LDL-C) and early-onset cardiovascular disease. To assess the therapeutic effects of liver transplantation (LT) on HoFH patients, we observed and analyzed the outcomes of HoFH children after LT. STUDY DESIGN: This prospective cohort study included all LT candidates under 18 years old diagnosed with HoFH at Ren Ji Hospital between November 2017 and July 2021. The patients were followed until October 2023. They were treated according to the standard protocol at our center. We collected data on changes in lipid profiles, clinical manifestations, and cardiovascular complications at different time points, and recorded postoperative recipient and graft survival. RESULTS: Fourteen HoFH patients with a median age of 7 (2-12) years were included. Preoperatively, xanthomas and arcus corneas occurred in 14 and 3 patients, respectively, with 10 patients showing mild cardiovascular disease. All patients underwent LT. Recipient and graft survival rates were 100 % over a median follow-up duration of 35 (27-71) months. Median LDL-C levels dropped from 11.83 (7.99-26.14) mmol/L preoperatively to 2.3 (1.49-3.39) mmol/L postoperative at the last measurement. Thirteen patients discontinued lipid-lowering treatment after LT, while only one patient resumed statins 6 months post-operation. Xanthomas and arcus corneas significantly improved. Cardiovascular complications regressed in five patients, with no progression observed in the others. CONCLUSIONS: LT is a safe and effective treatment for severe HoFH patients beyond lipid-lowering control. Early LT improves prognosis and quality of life while minimizing the risk of cardiovascular complications.

Truncated mini LRP1 transports cargo from luminal to basolateral side across the blood brain barrier.

BACKGROUND: The most crucial area to focus on when thinking of novel pathways for drug delivery into the CNS is the blood brain barrier (BBB). A number of nanoparticulate formulations have been shown in earlier research to target receptors at the BBB and transport therapeutics into the CNS. However, no mechanism for CNS entrance and movement throughout the CNS parenchyma has been proposed yet. Here, the truncated mini low-density lipoprotein receptor-related protein 1 mLRP1_DIV* was presented as blood to brain transport carrier, exemplified by antibodies and immunoliposomes using a systematic approach to screen the receptor and its ligands' route across endothelial cells in vitro. METHODS: The use of mLRP1_DIV* as liposomal carrier into the CNS was validated based on internalization and transport assays across an in vitro model of the BBB using hcMEC/D3 and bEnd.3 cells. Trafficking routes of mLRP1_DIV* and corresponding cargo across endothelial cells were analyzed using immunofluorescence. Modulation of γ-secretase activity by immunoliposomes loaded with the γ-secretase modulator BB25 was investigated in co-cultures of bEnd.3 mLRP1_DIV* cells and CHO cells overexpressing human amyloid precursor protein (APP) and presenilin 1 (PSEN1). RESULTS: We showed that while expressed in vitro, mLRP1_DIV* transports both, antibodies and functionalized immunoliposomes from luminal to basolateral side across an in vitro model of the BBB, followed by their mLRP1_DIV* dependent release of the cargo. Importantly, functionalized liposomes loaded with the γ-secretase modulator BB25 were demonstrated to effectively reduce toxic Aß42 peptide levels after mLRP1_DIV* mediated transport across a co-cultured endothelial monolayer. CONCLUSION: Together, the data strongly suggest mLRP1_DIV* as a promising tool for drug delivery into the CNS, as it allows a straight transport of cargo from luminal to abluminal side across an endothelial monolayer and it's release into brain parenchyma in vitro, where it exhibits its intended therapeutic effect.