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Abstract Background Infection with the hepatitis C virus (HCV) is a worldwide health problem. HCV infection is linked to a variety of metabolic abnormalities as it interferes with lipid metabolism, causing steatosis and a wide range of adipocytokine alterations, as well as impairing glucose metabolism, resulting in a rising prevalence of insulin resistance (IR) and type 2 diabetes. Over the last few years, numerous oral anti-HCV medicines (direct-acting antivirals; DAAs) have been introduced. With DAA therapy, HCV can now be eradicated from the infected host within 12 weeks. There is a need for more research because there is minimal information on the effects of DAA therapy on metabolic profiles, lipid profiles, and adiponectin levels. Thus, the purpose of this study was to see how direct-acting antivirals (DAAs) affected metabolic profiles and serum adiponectin levels in 2 different categories of Egyptian patients with chronic hepatitis C infection. This study included 100 patients with chronic HCV who were separated into two groups. Group I consisted of 50 patients who were treated for 12 weeks with sofosbuvir, daclatasvir, and ribavirin). Group II consisted of 50 patients who were treated for 12 weeks with ombitasvir, paritaprevir, and ritonavir/ribavirin. This regimen was chosen because these patients had an eGFR of 30 ml/min. Fasting lipid profiles (total cholesterol, triglyceride, HDL, and LDL), metabolic profiles (fasting blood sugar, fasting insulin, HOMA-IR, and HbA1C), and serum adiponectin levels were measured before and after the end of treatment. Results Statistical analysis of the data showed a significant difference in the lipid profile in group I before and after treatment, as we found a significant reduction in serum triglycerides after treatment (113.2 ± 22.9 mg/dL vs 105.6 ± 23.2 mg/dL, P < 0.001) and a significant elevation of serum total cholesterol, LDL, and HDL after treatment (TC: 153.2 ± 20.1 mg/dL vs 174.1 ± 19 mg/dL, P < 0.001; LDL: 74.7 ± 9.9 mg/dL vs 93.3 ± 12 mg/dL, P < 0.001; HDL: 54.6 ± 10.1 mg/dL vs 57.2 ± 10.3 mg/dL, P 0.010). But in group II, there was no significant difference in the lipid profile before and after treatment. We also found a significant reduction in fasting insulin, HOMA-IR, and HBA1C after treatment in group I (fasting insulin: 11.4 ± 3.3 (µU/L)/ml vs 9.7 ± 2.2 (µU/L)/ml, P < 0.001; HOMA-IR: 2.7 ± 0.9 vs 2.2 ± 0.6, P < 0.001; HBA1C: 5.6 ± 0.4 vs 5.4 ± 0.3, P 0.003). But in group II, there was no significant difference in fasting insulin, HOMA-IR, and HBA1C before and after treatment. Also, we found that there were no significant changes in the serum adiponectin level in either group before or after treatment. Conclusion HCV clearance with DAAs had an impact on the lipid and metabolic profiles of the patients at the end of treatment. This could depend on the type of DAAs used in the treatment, the stage of the liver disease, and the associated conditions of patients. However, serum adiponectin levels are unaffected.

We tested the association of polygenic risk scores (PRS) for low-density lipoprotein cholesterol (LDL-C) and coronary artery disease (CAD) with LDL-C and risk of ischemic heart disease (IHD) in the Danish general population. We included a total of 21,485 individuals from the Copenhagen General Population Study and Copenhagen City Heart Study. For everyone, LDL-PRS and CAD-PRS were calculated, each based on >400,000 variants. We also genotyped four rare variants in LDLR or APOB known to cause familial hypercholesterolemia (FH). Heterozygous carriers of FH-causing variants in APOB or LDLR had a mean LDL-C of 5.40 and 6.09 mmol/L, respectively, and an odds ratio for IHD of 2.27 (95 % CI 1.43–3.51) when compared to non-carriers. The LDL-PRS explained 13.8 % of the total variation in LDL-C in the cohort. Individuals in the lowest and highest 1 % of LDL-PRS had a mean LDL-C of 2.49 and 4.75 mmol/L, respectively. Compared to those in the middle 20–80 %, those in the lowest and highest 1 % of LDL-PRS had odds ratios for IHD of 0.58 (95 % CI, 0.38–0.88) and 1.83 (95 % CI, 1.33–2.53). The corresponding odds ratios for CAD-PRS were 0.61 (95 % CI, 0.41–0.92) and 2.06 (95 % CI, 1.49–2.85). The top 1 % of LDL-PRS and CAD-PRS conferred effects on LDL-C and risk of IHD comparable to those seen for carriers of rare FH-causing variants in APOB or LDLR. These results highlight the potential value of implementing such PRS clinically. [Display omitted] • The top 1 % of an LDL-PRS conferred 1.18 mmol/L higher LDL-C and 1.8-fold higher IHD risk compared to percentiles 20-80 %. • Individuals with a PRS for CAD in the top 1 % had a 2.1-fold higher risk of IHD as compared to the population average. • Carriers of FH-causing variants in APOB or LDLR had 2.24 mmol/L higher LDL-C and 2.3-fold higher risk of IHD than non-carriers. • These results demonstrate the potential clinical value of an LDL-PRS or CAD-PRS. [ABSTRACT FROM AUTHOR]

A growing life expectancy may result in a chronic medical condition and multimorbidity because the aging process leads to a decrease in cognitive and physiological function. These risks may affect the quality of life of geriatrics. The present study aims to determine the correlation between cognitive status (in terms of SIRT1, a nicotinamide adenine dinucleotide (NAD+)-dependent class III deacetylase) and metabolic function (in terms of the lipid profile, kidney function, and blood glucose) in geriatric patients. The differences in the parameters of metabolic function in the participants’ cognitive status were determined by using the Indonesian version of the Montreal Cognitive Assessments (MoCA-Ina). The elderly participants (n = 120) were recruited at three sites in Indonesia from March to October 2022. Our study demonstrated a negative correlation between the cognitive status of geriatric patients and their metabolic function, represented by the MoCA-Ina score with a linear regression equation of y = 0.27 − 2.4 ×10−3x. Higher levels of LDL-C, cystatin C, and HbA1c were found in the Severe-Moderate Cognitive Impairment group. Determining the SIRT1 levels may be beneficial in predicting both the cognitive and metabolic status of geriatrics because this protein is among numerous metabolic sensors in the hypothalamus.

Familial hypercholesterolemia (FH) is the most common monogenic disorder in humans. It affects millions of people globally, increasing the risk of developing cardiovascular disease (CVD) at a younger age due to elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth. While effective traditional and novel treatments are available, the most significant challenge with FH is the lack of timely diagnosis. As a result, many patients remain undertreated leading to an increased risk of CVD. To mitigate risk, initiating early and aggressive LDL-C-lowering therapies is recommended. Moreover, given its autosomal dominant inheritance patterns, it is also recommended to perform cascade lipid and/or genetic testing of all first-degree relatives. This review highlights the importance of early FH diagnosis and available treatment options. Greater awareness and improved screening efforts can help diagnose and treat more individuals, ultimately reducing the CVD risk associated with FH.

Background: Dyslipidemia is an abnormal lipid metabolism characterized by an increase in total cholesterol, LDL (Low-Density Lipoprotein), triglycerides (TG), and a decrease in HDL (High-Density Lipoprotein). Increased levels of total cholesterol, TG, LDL, and decreased HDL levels can increase the risk of cardiovascular disease. According to TCM, dyslipidemia is categorized into “Tan Zheng” (phlegm syndrome), “Shi Zuo” (damp retention), “Xuan Yun” (vertigo), and “Fei Pang” (obesity). Purpose: The purpose of this review is to analyze the literature study on TCM within the treatment of dyslipidemia with different acupuncture methods and points. The primary data search was conducted using online e-resources (Google Scholar, Proquest, and Pubmed). Review: The results of the study should include at least one of the outcomes indicators for total cholesterol, TG, LDL, and HDL. The result there were 20 journals consisting of studies that used several acupuncture methods, manual acupuncture (AM), electroacupuncture (EA), moxa (MOK), auricular acupuncture (AA), Cupping (CUP), and found additional interventions such as nutritional interventions, and exercise; body points often used are Zusanli (ST 36), Fenglong (ST 40), Quchi (LI 11), Daheng (SP15), Zhongwan (CV 12), Qihai (CV 6), Guanyuan (CV 4), Sanyinjiao (SP 6), Shenque (CV 8), Tianshu (ST 25), and therefore for AA are Spleen (CO 13), Stomach (CO 4), Shenmen (TF 4), and hunger point. Twenty journals showed a decrease in total cholesterol, TG, LDL levels, and an increase in HDL levels. Conclusion: In conclusion, all types of acupuncture methods can reduce total cholesterol, TG and LDL levels, and increase HDL levels.

Abstract Background Current TB diagnostic methods available have been developed for adults and development efforts have neglected the differences in disease and sampling that occur between adults and children. Diagnostic challenges are even greater in HIV co-infected children and infants. Methods and results We established a sandwich ELISA assay to detect Mycobacterium tuberculosis modified lipoprotein (TLP) ex vivo in plasma. The study population contains plasma samples from 21 patients with active TB and 24 control samples with no TB, collected in the International Maternal Pediatric Adolescent AIDS Clinical Trails (IMPAACT) P1041 study. Retrospective analysis was performed and the results demonstrate that the median plasma levels of TLP in control subjects are 2.7 fold higher than the median plasma values in active TB subjects (p

Purpose: To evaluate corneal densitometry (CD) of patients with arcus senilis (AS) and its association with the serum lipid markers. Methods: This is a cross-sectional, case-control study. The AS diagnosis was made clinically. Forty-five eyes of 45 patients with AS and 38 eyes of 38 age-matched control subjects with no noticeable AS were enrolled in the study. All participants underwent detailed ophthalmologic examination along with corneal Scheimpflug imaging with CD measurement. The evaluated serum lipid markers of the participants included total cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). The Spearman correlation analysis was used to correlate the serum lipid values and the CD. P < 0.05 was defined as statistically significant. Results: The male to female ratio was 26/19 and 14/24 in the study and control groups, respectively (P = 0.057). The mean age was 59.56 ± 8.7 and 56.47 ± 8.6 years in the study and control groups, respectively (P = 0.117). The mean total CD values in the zones extending from 2 to 12 mm were higher in the study group than in the control group (P < 0.001). The serum HDL level was found to be significantly decreased in the study group compared to the control group (P = 0.048 and Z = −1.976). There was a significant positive correlation between the serum triglyceride level and the CD value of the outermost zone (10–12 mm) (r = 0.334 and P = 0.025). Conclusion: The CD of patients with AS was found to increase not only in the peripheral zone but also in the cornea's paracentral zone compared to the healthy controls. The serum triglyceride level should give an insight into the intensity of arcus senilis. The serum HDL levels were decreased in patients with AS.

Egg-yolk low-density lipoprotein (LDL) has a natural liposome structure. Using ultrasound-assisted pH-shifting (pH 12), a naturally safe and stable aqueous solution of vitamin D3 (VD3) was constructed employing LDL as the carrier. Images from electron microscopy showed that pH-shifting remodeled LDL molecules, resulting in a dramatic reduction in particle size (∼50%) and an increase in specific surface area, which reduced the turbidity (27.7%) and provided new interfaces for VD3 loading. Fluorescence analyses showed that the binding of VD3 to LDL under pH-shifting was strong, involved quenching, and the binding constant was 6.19 × 104 M−1. Thermogravimetric analysis and Fourier transform-infrared spectroscopy showed that pH-shifting hydrolyzed the esters in LDL to fatty acid salts, and the maximum weight loss of LDL occurred from 381.9 °C to 457.0 °C. Ultrasonic treatment enhanced the binding of LDL and VD3 (binding constant increased to 2.56 × 107 M−1), reduced the particle size, and increased the ζ-potential of the complex between LDL and VD3, thereby resulting in the improvement of solution stability and storage stability of VD3. Ultrasound-assisted pH-shifting could remodel LDL to construct a stable aqueous solution of VD3, which showed the potential of LDL as a carrier for lipid-soluble components.

BackgroundMost clinical practice guidelines support the use of statins in patients with type 2 diabetes mellitus to lower the risk of cardiovascular disease. However, nothing is known about the prescribing patterns of statins at Jugol General Hospital in eastern Ethiopia.ObjectiveThis study aimed to assess the prescribing patterns of statins and associated factors among type 2 diabetes mellitus patients attended at Jugol General Hospital in eastern EthiopiaMethodsA retrospective cross-sectional study was conducted among 423 patients with type 2 diabetes mellitus who received follow-up care from 1 June 2017 to 1 June 2022. The study participants were enrolled consecutively using a convenience sampling technique. The data were extracted from patients’ medical records using a data abstraction checklist. The extracted data were entered into EpiData, version 3.1, and exported to Statistical Package for the Social Sciences (SPSS), version 22, for analysis. Associations were considered to be statistically significant at a p-value < 0.05 and presented as adjusted odds ratios and 95% confidence intervals.ResultThe medical records of 423 patients were reviewed. The review revealed that medical records were complete for 410 of these patients, and these records were included in the analysis. The majority of the study participants were female (72.2%) and between the age of 40 and 65 years (61.2%). All of the study participants were eligible for statin prescription; however, statins were prescribed for only 257 (62.7%) study participants. Of the statins prescribed, moderate-dose-intensity statins were prescribed for 40 (15.6%) participants who were at high risk of cardiovascular disease. Atorvastatin was the most commonly (93.3%) prescribed statin. The presence of hypertension, coronary artery disease, and cerebrovascular events was significantly associated with statin prescribing.ConclusionThe magnitude of prescribing statins for patients with type 2 diabetes mellitus was low in comparison with the clinical practice guidelines recommendation. This finding is alarming and is a call for action to improve the execution of clinical practice guidelines for the benefit of this high-risk population.

Several studies have shown a high prevalence of dyslipidemia in children. Since childhood lipid concentrations continue into adulthood, recognition of lipid abnormalities in the early period is crucial to prevent the development of future coronary heart disease (CHD). Low density lipoprotein cholesterol (LDL-C) is one of the most used parameters in the initiation and follow-up of treatment in patients with dyslipidemia. It is a well known fact that LDL-C lowering therapy reduces the risk of future CHD. Therefore, accurate determination of the LDL-C levels is so important for the management of lipid abnormalities. This study aimed to validate different LDL-C estimating equations in the Turkish population, composed of children and adolescents. A total of 3,908 children below 18 years old at Sivas Cumhuriyet University Hospital (Sivas, Turkey) were included in this study. LDL-C was directly measured by direct homogeneous assays, i.e., Roche, Beckman, Siemens and estimated by Friedewald’s, Martin/Hopkins’, extended Martin-Hopkins’ and Sampson’s formulas. The concordances between the estimations obtained by the formulas and the direct measurements were evaluated both overall and separately for the LDL-C, triglycerides (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) sublevels. Linear regression analysis was performed and residual error plots were generated between each estimation and direct measurement method. Coefficient of determination (R2) and mean absolute deviations were also evaluated. The overall concordance of Friedewald, Sampson, Martin-Hopkins and the extended Martin-Hopkins formula were 64.6%, 69.9%, 69.4%, and 84.3% for the Roche direct assay, 69.8%, 71.6%, 73.6% and 80.4% for the Siemens direct assay, 66.5%, 68.8%, 68.9% and 82.1% for the Beckman direct assay, respectively. The extended Martin-Hopkins formula had the highest concordance coefficient in both overall and all sublevels of LDL-C, non-HDL-C, and TG. When estimating the LDL-C categories, the highest underestimation degrees were obtained with the Friedewald formula. Our analysis, conducted in a large pediatric population, showed that the extended Martin-Hopkins equation gives more reliable results in estimation of LDL-C compared to other equations.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a single-turnover protease which regulates serum low-density lipoprotein (LDL) levels and, consequently, cardiovascular disease. Although PCSK9 proteolysis is required for its full hypercholesterolemic effect, the evaluation of its proteolytic function is challenging: PCSK9 is only known to cleave itself, undergoes only a single turnover, and after proteolysis, retains its substrate in its active site as an auto-inhibitor. The methods presented here describe an assay which overcomes these challenges. The assay focuses on intermolecular proteolysis in a cell-based context and links successful cleavage to the secreted luciferase activity, which can be easily read out in the conditioned medium. Via sequential steps of mutagenesis, transient transfection, and a luciferase readout, the assay can probe PCSK9 proteolysis under conditions of either genetic or molecular perturbation in a high-throughput manner. This system is well suited for both the biochemical evaluation of clinically discovered missense single-nucleotide polymorphisms (SNPs), as well as for the screening of small-molecule inhibitors of PCSK9 proteolysis.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) down-regulates the low-density lipoprotein (LDL) receptor, elevating LDL cholesterol and accelerating atherosclerotic heart disease, making it a promising cardiovascular drug target. To achieve its maximal effect on the LDL receptor, PCSK9 requires autoproteolysis. After cleavage, PCSK9 retains its prodomain in the active site as a self-inhibitor. Unlike other proprotein convertases, however, this retention is permanent, inhibiting any further protease activity for the remainder of its life cycle. Such inhibition has proven a major challenge toward a complete biochemical characterization of PCSK9's proteolytic function, which could inform therapeutic approaches against its hypercholesterolemic effects. To address this challenge, we employed a cell-based, high-throughput method using a luciferase readout to evaluate the single-turnover PCSK9 proteolytic event. We combined this method with saturation mutagenesis libraries to interrogate the sequence specificities of PCSK9 cleavage and proteolysis-independent secretion. Our results highlight several key differences in sequence identity between these two steps, complement known structural data, and suggest that PCSK9 self-proteolysis is the rate-limiting step of secretion. Additionally, we found that for missense SNPs within PCSK9, alterations in both proteolysis and secretion are common. Last, we show that some SNPs allosterically modulate PCSK9's substrate sequence specificity. Our findings indicate that PCSK9 proteolysis acts as a commonly perturbed but critical switch in controlling lipid homeostasis and provide a new hope for the development of small-molecule PCSK9 inhibitors.

BACKGROUND Limited joint mobility (LJM) is the most common joint-related complications in patients with diabetes mellitus (DM) and indicates the presence of microvascular complications. This study aimed to assess the frequency of LJM among adolescents with type 1 DM (T1DM), its risk factors, and the other microangiopathies. METHODS In this cross-sectional study, 75 patients (adolescents between 10 and 17 years old) with T1DM were assessed for hand joint mobility using a prayer sign test. It was carried out from January 15 to June 1, 2022 in Baghdad city, Iraq. The patients' height, body mass index, blood pressure, glycated hemoglobin, and low-density lipoprotein (LDL) were recorded. Only 44 subjects were screened for diabetic nephropathy and 64 for diabetic retinopathy based on the eligibility criteria by the American Diabetes Association guidelines. RESULTS Mean age was 13.60 (1.85) years, with a mean diabetes duration of 5.61 (2.87) years. LJM was found in 18 patients (24%). It was associated with a longer duration of diabetes (p<0.001), high LDL level (p = 0.012), diabetic nephropathy (p = 0.04), and diabetic retinopathy (p<0.001). CONCLUSIONS The proportion of LJM was high among adolescents with T1DM, especially in those with a long duration of DM. It was associated with high LDL levels and diabetic microangiopathies (nephropathy and retinopathy). [ABSTRACT FROM AUTHOR]

Introduction: We searched for risk factors of cardiovascular assessment among children on dialysis. Methods: This is a cross‐sectional study of cardiovascular assessment of all patients on dialysis at Ege University Children's Hospital. Pediatric patients between the ages of 6 and 21 who were on HD and peritoneal dialysis treatment were included in the study. Cardiovascular evaluation included left ventricular mass index (LVMI), pulse wave velocity (PWV), and carotid intima‐media thickness (cIMT) measurements. Results: Nineteen patients were included in this study. The LDL had a correlation with the cIMT z‐score, but not to PWVz‐score. Binary Logistic regression analysis found that only LDL was significantly associated to increased cIMT. Conclusion: This study reports an association between high LDL and high BP increased cIMT on dialyzed children. Strategies to reduce LDL and BP in dialysis patients may prevent vasculopathy and long‐term cardiovascular complications. [ABSTRACT FROM AUTHOR]

Introduction: Repeated hepatic arterial delivery of therapeutic agents to the liver by percutaneously implanted port-catheter systems has been widely used to treat unresectable liver cancer. This approach is applied to assess the therapeutic efficacy of repeated low-density lipoprotein-docosahexaenoic acid (LDL-DHA) nanoparticle treatments in a rat model of hepatocellular carcinoma. Methods: N1S1 hepatoma bearing rats underwent placement of a percutaneously implanted hepatic artery port-catheter system and were allocated to untreated, control LDL-triolein (LDL-TO) or LDL-DHA nanoparticle infusions groups. Treatments were performed every three days over a nine day study period. MRI was performed at baseline and throughout the study. At the end of the study tissue samples were collected for analyses. Results and Discussion: Implantation of the port catheters was successful in all rats. MRI showed that repeated infusions of LDL-DHA nanoparticles significantly impaired the growth of the rat hepatomas eventually leading to tumor regression. The tumors in the LDL-TO treated group showed delayed growth, while the untreated tumors grew steadily throughout the study. Histopathology and MRI support these findings demonstrating extensive tumor necrosis in LDL-DHA treated groups while the control groups displayed minor necrosis. Molecular and biochemical analyses also revealed that LDL-DHA treated tumors had increased levels of nuclear factor-kappa B and lipid peroxidation and depletion of glutathione peroxidase 4 relative to the control groups. Evidence of both ferroptosis and apoptosis tumor cell death was observed following LDL-DHA treatments. In conclusion repeated transarterial infusions of LDL-DHA nanoparticles provides sustained repression of tumor growth in a rat hepatoma model. [ABSTRACT FROM AUTHOR]

Homozygous familial hypercholesterolemia (HoFH) is a rare, genetic condition characterized by markedly elevated plasma low-density lipoprotein cholesterol (LDL-C) concentrations from birth and increased risk of premature atherosclerotic cardiovascular disease. Evinacumab is an inhibitor of angiopoietin-like 3 protein that offers a new approach for correcting high LDL-C in HoFH. Evinacumab was administered intravenously (15 mg/kg Q4W) for 24 months in 7 patients with genetically confirmed HoFH, receiving background lipoprotein apheresis (LA) and/or lipid-lowering treatment (LLT). Assessment of efficacy and safety were carried out before and after 24 months of evinacumab treatment. The LDL-C lowering effect of evinacumab without LA were also investigated in the 7 HoFH patients after a subsequent compassionate extension period. Twenty-four months of treatment with evinacumab against background LA and LLT resulted in a significant reduction in LDL-C (−46.8%; p < 0.001). LDL-C reduction with evinacumab was maintained during the compassionate extensions period in the absence of treatment with LA (−43.4%; mean follow-up of 208 ± 90 days). Evinacumab was well-tolerated, with no major adverse event reported or significant changes in liver and muscle enzyme concentrations. Our findings suggest that evinacumab is a safe and effective treatment for patients with HoFH receiving best standard of care in a routine setting. [ABSTRACT FROM AUTHOR]

Background: Blood lipid profiles are known as one of the most important factors in health disorders such as obesity and diabetes, which mostly end in cardiovascular diseases (CVDs) such as coronary heart disease (CHD). Purslane, as an edible herbal plant has shown to have beneficial components for dyslipidemia treatment. This study aimed to evaluate the effects of purslane supplementation on blood lipid profiles in the adult population. Methods: The terms Portulaca, Portulaca, Portulaca oleracea, and Purslane together with lipid profile ingredients including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were searched in the following databases until 30 October 2020: PubMed, MEDLINE, Scopus, EMBASE, Science Direct, and SID. A meta-analysis was conducted with eight randomized controlled trials (RCTs) on 444 patients using the STATA software version 14. Results: Eight eligible studies on 444 patients were identified for the present study. The purslane supplementation caused significant reduction in TG (-18.55 mg/dL, 95% CI [-31.712, -5.388]), TC (-8.43 mg/dL; 95% CI [-14.99, -1.87]), and LDL-C (-6.45 mg/dL, 95% CI [-11.13, -1.77]); however, no significant effect was observed on HDL-C (1.28 mg/dL, 95% CI [-0.56, 2.93], P=0.170). Conclusion: Our results suggested that purslane supplementation could reduce TG, TC, and LDL-C. However, no significant effect was observed on HDL-C. [ABSTRACT FROM AUTHOR]

Polyphenol-rich foods protect the cellular systems of the human body from oxidative damage, thereby reducing the risk of chronic diseases such as cardiovascular disease (CVD). We investigated the effect of phenolic-rich apple/berry juice (chokeberry, blueberry, and cranberry) on lipidemic profiles in overweight/obese women. The 6 week single-arm pre–post intervention study involved 20 women (mean age 52.95 ± 5.8 years, body mass index ≥25 kg/m2, and ≥1 CVD risk factors) consuming 300 mL/day of the apple/berry juice. Lipid profile, low-density lipoprotein (LDL) subfractions assessed using Lipoprint® electrophoresis, and other parameters related to cardiovascular risk (C-reactive protein, glucose, blood pressure) were analyzed before and again after the intervention in the monitored group of women. High-density lipoprotein cholesterol (HDL-C) increased from 1.30 ± 0.29 to 1.55 ± 0.32, magnesium from 0.85 ± 0.03 to 0.90 ± 0.05, and total antioxidant status from 1.68 ± 0.08 to 1.81 ± 0.10. The LDL/HDL ratio significantly decreased from 3.40 ± 0.99 to 2.66 ± 0.63 mmol/L, and the glucose from 5.50 ± 0.72 to 5.24 ± 0.74 mmol/L. However, the hs-CRP did not change significantly. Women with atherogenic subfractions LDL3-7 at baseline (n = 6) showed a significant reduction from 0.45 ± 0.19 to 0.09 ± 0.07 mmol/L. Overweight/obese women may benefit from apple/berry juice as part of a healthy lifestyle to improve their lipid profile, and thus, contribute to cardiovascular health. [ABSTRACT FROM AUTHOR]

Thorough understanding of metabolic changes, including lipidome alteration, associated with the development of COVID-19 appears to be crucial, as new types of coronaviruses are still reported. In this study, we analyzed the differences in the plasma phospholipid profiles of the deceased COVID-19 patients, those who recovered and healthy people. Due to identified abnormalities in plasma phospholipid profiles, deceased patients were further divided into two subgroups (D1 and D2). Increased levels of phosphatidylethanolamines (PE), phosphatidylcholines (PC) and phosphatidylserines (PS) were found in the plasma of recovered patients and the majority of deceased patients (first subgroup D1) compared to the control group. However, abundances of all relevant PE, PC and PS species decreased dramatically in the plasma of the second subgroup (D2) of five deceased patients. These patients also had significantly decreased plasma COX-2 activity when compared to the control, in contrast to unchanged and increased COX-2 activity in the plasma of the other deceased patients and recovered patients, respectively. Moreover, these five deceased patients were characterized by abnormally low CRP levels and tremendous increase in LDH levels, which may be the result of other pathophysiological disorders, including disorders of the immune system, liver damage and haemolytic anemia. In addition, an observed trend to decrease the autoantibodies against oxidative modifications of low-density lipoprotein (oLAb) titer in all, especially in deceased patients, indicate systemic oxidative stress and altered immune system that may have prognostic value in COVID-19. [ABSTRACT FROM AUTHOR]

BACKGROUND: The pathogenesis of liver function abnormalities and cardiac dysfunction in hyperthyroid patients after I131 treatment is still unclear. The aim of this study was to determine the effects of radioiodine I131 on liver function parameters, lactate dehydrogenase(LDH) and low-density lipoproteins(LDL) before and after I131 therapy in hyperthyroidism patients. METHOD: Total 52 patients of hyperthyroidism recommended for I131 were involved in this study with age ranging from 12 - 65 years (mean age=38.6 - 14.8 & BMI=11.5 - 3.7). The significance of the differences between the results of 1st, 2nd and 3rd time serum analysis was assessed by unpaired student s t-test. Associations between the parameters were assessed by Spearman correlation analysis. RESULTS: Significant variations were observed for thyroid profile FT3 (p=0.04), FT4 (p=0.01), TSH (p=0.005) during the follow-up treatment. Before taking I131 (serum analyzed at 1st time), negative correlation of FT3 with AST (r= -0.458, p=0.032) and LDL (r= -0.454, p=0.039) were observed. During 2nd time (after stopping carbimazole) no correlation were assessed. Two months after administration of I131 drops, significant negative association of FT3 (r= -0.62, p=0.04) and FT4 (r= -0.61, p=0.02) with ALB were observed. FT3 (r= -0.82, p=0.00) & FT4 (r= -0.71, p=0.00) also showed negative correlation with LDL after I131 therapy. Whereas TSH showed significant positive association with ALB (r=0.61, p=0.01) and LDL (r=0.70, p=0.00) respectively. CONCLUSION: Our findings suggest that the association of TFTs with biochemical parameters in patients with goiter recommended for iodine therapy is an important diagnostic and therapeutic tool. The increase in transaminases and LDL level after administration of I131 therapy may adversely affect heart and liver function. [ABSTRACT FROM AUTHOR]

The transport of low-density lipoprotein (LDL) through the endothelium is a key step in the development of atherosclerosis, but it is notorious that phenotypic differences exist between endothelial cells originating from different vascular beds. Endothelial cells forming the blood–brain barrier restrict paracellular and transcellular passage of plasma proteins. Here, we systematically compared brain versus aortic endothelial cells towards their interaction with LDL and the role of proteins known to regulate the uptake of LDL by endothelial cells. Both brain endothelial cells and aortic endothelial cells bind and internalize LDL. However, whereas aortic endothelial cells degrade very small amounts of LDL and transcytose the majority, brain endothelial cells degrade but do not transport LDL. Using RNA interference (siRNA), we found that the LDLR–clathrin pathway leads to LDL degradation in either endothelial cell type. Both loss- and gain-of-function experiments showed that ALK1, which promotes transcellular LDL transport in aortic endothelial cells, also limits LDL degradation in brain endothelial cells. SR-BI and caveolin-1, which promote LDL uptake and transport into aortic endothelial cells, limit neither binding nor association of LDL to brain endothelial cells. Together, these results indicate distinct LDL trafficking by brain microvascular endothelial cells and aortic endothelial cells. [ABSTRACT FROM AUTHOR]

Background: It is indicated that Low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (LDL-C/HDL-C ratio) has greater predictive value for thickened carotid intima-media thickness (CIMT) comparing with classic lipid parameters. However, there have been few reports about their association in general Chinese population. Method: We included a total of 1220 CIMT participants and 2440 matched controls, who had ultrasonography of carotid artery during 2009 and 2016. Univariate and multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for thickened CIMT risk associated with LDL-C/HDL-C ratio. Result: In the univariate logistic regression model, there was significant association between LDL-C/HDL-C ratio and thickened CIMT (Q4 vs. Q1, OR = 1.94, 95% CI: 1.60–2.36; p trend < 0.05). After adjusting for potential covariates, LDL-C/HDL-C ratio remained significantly associated with thickened CIMT (Q4 vs. Q1, OR = 1.81, 95% CI: 1.41–2.34, p trend < 0.001; ≥3.05 v.s. <3.05, OR = 1.66, 95% CI: 1.37–2.02). In subgroup analyses, the association between LDL-C/HDL-C ratio and thickened CIMT remained significant in the subgroups stratified by sex, impaired fasting glucose (IFG), hypertension, and fatty liver disease but only remained significant in the subgroups of ≥45 years (OR = 2.01, 95% CI: 1.46–2.76; P trend < 0.05), BMI ≥24 (kg/m2) (OR = 2.22; 95% CI = 1.63-3.03; Ptrend < 0.05) and BMI ≥25 (kg/m2) (OR = 2.50, 95% CI: 1.76–3.54; P trend < 0.05), dyslipidemia (OR = 3.28, 95% CI: 1.83–5,85; P trend < 0.001), and without periodontitis (OR = 2.08, 95% CI: 1.54–2.81 ; Ptrend < 0.05) comparing Q4 to Q1. Similar results were observed in the subgroup analyses for LDL-C/HDL-C ratio ≥3.05 v.s. <3.05 except for the age stratification. Conclusion: High LDL-C/HDL-C ratio could significantly increase the risk of thickened CIMT independent of gender, IFG, hypertension, and fatty liver disease in general Chinese population. [ABSTRACT FROM AUTHOR]

Background: People with HIV (PWH) are at increased risk of atherosclerotic cardiovascular disease (ASCVD). Lowering low-density lipoprotein cholesterol (LDL-C) is central of cardiovascular disease prevention. The aim of this study was to assess the prevalence, treatment, and control of high LDL-C levels as assessed on the basis of the ASCVD risk profiles indicated by European Society of Cardiology (ESC) guidelines of a cohort of PWH in order to evaluate the state of LDL-C management in current clinical practice., Methods: We retrospectively assessed the prevalence, treatment, and control of high LDL-C levels in a cohort of PWH aged ≥40 years who accessed our HIV outpatient clinic between 1 March 2022 and 31 March 2023. Their 10-year ASCVD risk was calculated on the basis of their age and co-morbidities as recommended by guidelines. High LDL-C levels were defined as those above the "step two" target of their specific ASCVD risk category., Results: Among the 1404 assessed PWH, who were prevalently male (74.5 %) and Caucasian (85.6 %), and had a median age of 56 years (interquartile range [IQR] 49-61), 295 (21 %) were at very high risk (VHR), 634 (45.2 %) at high-risk (HR), and 348 (24.8 %) not at HR. The overall median LDL-C level was 116 mg/dL (IQR 96-141). Five hundred and sixteen (37 %) were undergoing lipid lowering treatment (LLT), and 650 (46.3 %) failed to achieve any step of their target LDL-C levels., Conclusions: Despite the high prevalence of PWH at VHR/HR for ASCVD, LDL-C levels were poorly controlled and LLT was greatly under used., Competing Interests: Declaration of competing interest AG has received consultancy fees and speakers' honoraria from ViiV, Gilead, Janssen, MSD and Mylan, outside the present work. CG has received personal fees from MSD, ViiV, Gilead, and Janssen Cilag, outside the present work. SA has received support for research activities from Pfizer, ViiV, Gilead and Merck Sharp & Dome, outside the present work. APM has received personal fees for participating in committees of studies supported by Bayer, Novartis, Sanofi, and Astra Zeneca, outside the present work. GC, BC, LO, SC, SL, AP, SP, MLC, MB, GC, and ALR have nothing to declare., (Copyright © 2024. Published by Elsevier B.V.)

Lipids are implicated in the development of coronary atherosclerosis. Achieving a significant reduction in lipid levels remains a crucial aspect of secondary prevention following an acute coronary syndrome event. Novel lipid-lowering therapies now provide clinicians with a variety of therapeutic strategies to choose from and tailor to individual patient needs. This review focuses on evidence supporting the importance of early and intensive lipid-lowering therapy use in patients presenting with acute coronary syndrome, specifically addressing data relating to atorvastatin and ezetimibe use in this high-risk cohort of patients., Competing Interests: Disclosures: DC: has received research funding, fees for lectures, consulting fees and honoraria from Daiichi Sankyo, Novartis and Amgen and has been a member of each institution’s UK and European advisory boards; has had expenses paid by Daiichi Sankyo to attend the American College of Cardiology meeting in New Orleans in 2023; is on the UK national council of the Primary Care Cardiovascular Society; and is on the European Cardiology Review editorial board; this did not affect peer review. All other authors have no conflicts of interest to declare., (Copyright © The Author(s), 2024. Published by Radcliffe Group Ltd.)

While apolipoprotein E (APOE) is the strongest genetic modifier for late-onset Alzheimer's disease (LOAD), the molecular mechanisms underlying isoform-dependent risk and the relevance of ApoE-associated lipids remain elusive. Here, we report that impaired low-density lipoprotein (LDL) receptor (LDLR) binding of lipidated ApoE2 (lipApoE2) avoids LDLR recycling defects observed with lipApoE3/E4 and decreases the uptake of cholesteryl esters (CEs), which are lipids linked to neurodegeneration. In human neurons, the addition of ApoE carrying polyunsaturated fatty acids (PUFAs)-CE revealed an allelic series (ApoE4 > ApoE3 > ApoE2) associated with lipofuscinosis, an age-related lysosomal pathology resulting from lipid peroxidation. Lipofuscin increased lysosomal accumulation of tau fibrils and was elevated in the APOE4 mouse brain with exacerbation by tau pathology. Intrahippocampal injection of PUFA-CE-lipApoE4 was sufficient to induce lipofuscinosis in wild-type mice. Finally, the protective Christchurch mutation also reduced LDLR binding and phenocopied ApoE2. Collectively, our data strongly suggest decreased lipApoE-LDLR interactions minimize LOAD risk by reducing the deleterious effects of endolysosomal targeting of ApoE and associated pathogenic lipids., Competing Interests: Declaration of interests All authors, except N.N., A.L., and D.M.H., are full-time employees and/or shareholders of Denali Therapeutics. J.L.G., D.B., G.A.F., Y.-T.H., M. Steffek, and S.J.H. are currently full-time employees and shareholders of NICO Therapeutics. D.M.H. is on the scientific advisory board of Denali Therapeutics, Genentech, Cajal Neuroscience, C2N Diagnostics, and Cell. D.M.H. consults for Asteroid., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Abstract Background Atherosclerosis is a chronic lipid-driven inflammatory disease with infiltration of low-density lipoprotein and is considered as the pivotal step in plaque formation. The aim of the review is to get into the fine details of pathophysiologic mechanisms responsible for atherosclerosis with atherosclerotic lesion classification. It also provides a summary of current biomarkers other than the traditional risk factors so that new treatment modalities can emerge and reduce the morbidity and mortality associated with atherosclerosis. Main body In the classification of atherosclerosis made by American Heart Association (AHA), AHA Type I lesion is the earliest vascular change described microscopically. AHA Type II lesion is primarily composed of abundant macrophages. AHA Type III lesion is the earliest of progressive lesions, while AHA Type IV lesion consists of an acellular necrotic core. Various biomarkers are implicated in different stages of the pathophysiological mechanism of plaque formation and evolution. C Reactive Protein plays a direct role in promoting the inflammatory component of atherosclerosis. Fibrinogen was demonstrated to be elevated among patients with acute thrombosis. Higher leukocyte count is associated with a greater cardiovascular risk. Cytokines have been implicated in atheroma formation and complications. High rates of protease activated receptor expression are also induced by interleukin-6 secretion in atherosclerotic lesions and areas of vascular tissue injury. Cluster of differentiation 40 receptor and its ligand have been also detected in atherosclerotic plaques. Osteopontin, acidic phosphoprotein, and osteoprotegerin have emerged as novel markers of atherosclerotic plaque composition. There are also overproductions of matrix metalloproteinases in the rupture-prone regions and promote lipid-necrotic core formation in the atherosclerotic plaque. Myeloperoxidase has been proposed as a marker of plaque instability. Oxidized low-density lipoprotein receptor 1 provides a route of entry for oxidized low-density lipoprotein into the endothelium. A human atherosclerotic lesion also expresses lipoprotein-associated phospholipase A2. Short conclusion Atherosclerotic plaques are the battlefield between an unbalanced immune response and lipid accumulation in the intima of arteries. Most of the biomarkers associated with atherosclerosis are indicators of inflammatory response and will also be used for medical purposes.

Background: Coronary Heart Disease (CHD) is widely prevalent across the globe and significantly high level of Cholesterol in circulation is a single major risk factor associated with coronary heart disease. It is well established that cardiovascular disease is associated with hypertension and elevated blood levels of low-density lipoprotein (LDL), total cholesterol, and triglycerides. In disparity, a low level of high-density lipoprotein (HDL) is a risk factor for mortality from cardiovascular disease. Aim: The present study was conducted with the aim to assess the lipid profile in patients of Acute Coronary Syndrome (ACS) undergoing coronary angiography (CAG) in rural coastal population. Patients and Methods: The present study was done on 62 patients with Acute Coronary Syndrome (ACS) undergoing coronary angiography (CAG) Serum levels of total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides were examined in biochemical laboratory of the hospital. Coronary angiography was performed for the presence of lesions. Results: 43.5% of the patients (n=27) were elderly (age>60 years). Approximately 82% of the patients (n=51) aged more than 50 years. Males outnumbered females with a ratio of 2.4:1. 71% of the patients were males. Mean cholesterol levels were 177.86 mg/dl. Approx 3/4th of the patients (n=41) had cholesterol level

Abstract Background To determine the effect of genetic polymorphism of drug transporters on the efficacy of treatment with Rosuvastatin, Atorvastatin and Simvastatin in patients with hyperlipidemia. Methods The study consists of 180 patients, aged 40–75 years, with hyperlipidemia. All patients were divided into two equal groups: patients with different SLCO1B1 (521CC, 521CT and 521TT) and MDR1 (3435CC, 3435TC and 3435TT) genotypes. Each group was divided into rosuvastatin-treated, atorvastatin-treated and simvastatin-treated subgroups. The lipid-lowering effect of statins was assessed by tracing changes in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. Results The use of statins over a 4-month period led to substantial reductions in TC and LDL-C levels. The hypolipidemic effect of studied agents was seen in both groups. However, it was less pronounced in patients with 521CC genotype. No statistically significantly differences were found between carriers of 3435TT, 3435CT and 3435CC genotypes. Conclusions The lipid-lowering efficacy of rosuvastatin was higher compared to other two statins. Patients with SLCO1B1 521CC genotype are more likely to encounter a decrease in the hypolipidemic effect of statins. Such a risk should be considered when treating this category of patients. MDR1 polymorphism had no significant effect on statin efficacy.

Abstract Background Osteonecrosis of the femoral head (ONFH) is a common but intractable disease that appears to involve lipid metabolic disorders. Although numerous studies have demonstrated that high blood levels of low-density lipoprotein (LDL) are closely associated with ONFH, there is limited evidence to explain the pathological role of LDL. Pathological and in vitro studies were performed to investigate the role of disordered metabolism of LDL and oxidized LDL (ox-LDL) in the femoral head in the pathology of ONFH. Methods Nineteen femoral head specimens from patients with ONFH were obtained for immunohistochemistry analysis. Murine long-bone osteocyte Y4 cells were used to study the effects of LDL/ox-LDL on cell viability, apoptosis, and metabolism process of LDL/ox-LDL in osteocytes in normoxic and hypoxic environments. Results In the pathological specimens, marked accumulation of LDL/ox-LDL was observed in osteocytes/lacunae of necrotic regions compared with healthy regions. In vitro studies showed that ox-LDL, rather than LDL, reduced the viability and enhanced apoptosis of osteocytes. Pathological sections indicated that the accumulation of ox-LDL was significantly associated with impaired blood supply. Exposure to a hypoxic environment appeared to be a key factor leading to LDL/ox-LDL accumulation by enhancing internalisation and oxidation of LDL in osteocytes. Conclusions The accumulation of LDL/ox-LDL in the necrotic region may contribute to the pathology of ONFH. These findings could provide new insights into the prevention and treatment of ONFH.

Introduction The phase IIIb open-label ODYSSEY APPRISE study prospectively assessed the safety and efficacy of alirocumab (a proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitor) in a real-life setting in high cardiovascular risk patients with heterozygous familial hypercholesterolemia or low-density lipoprotein cholesterol (LDL-C) not at goal despite maximally tolerated dose statins ± other lipid-lowering therapies (NCT02476006). This post-hoc analysis assessed patient adherence to statins and alirocumab, plus alirocumab efficacy and safety, according to concomitant statin intensity and prior ezetimibe usage. Material and methods Patients received alirocumab 75 or 150 mg (dose adjustment based on physician’s judgment) every 2 weeks (for ≥3 to ≤30 months). Results Of 994 enrolled and treated patients, 58.4% received concomitant high-intensity statins, 18.2% moderate/low-intensity statins, and 23.4% no statin; 55.9% received prior ezetimibe. Mean alirocumab adherence (percent adherence defined as injections received ÷ theoretical injections x 100) was 96.6% over 72.4 weeks’ mean treatment duration. Mean LDL-C reduction from baseline at Week 12 was similar between statin intensity subgroups (53.6–55.7%). More patients achieved LDL-C

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are important therapeutic options for reducing cardiovascular disease risk; however, questions remain regarding potential differences in the neuropsychiatric impact of long‐term PCSK9 inhibition between men and women. Methods and Results Using PCSK9 gene single‐nucleotide polymorphisms from European ancestry–based genome‐wide association studies of low‐density lipoprotein cholesterol (N=1 320 016), circulating PCSK9 protein levels (N=10 186), tissue‐specific PCSK9 gene expression, sex‐specific genome‐wide association studies of anxiety, depression, cognition, insomnia, and dementia (ranging from 54 321 to 194 174), we used drug‐target inverse variance–weighted Mendelian randomization (MR) and complementary MR methods (MR Egger, weighted median, and weighted mode) to investigate potential neuropsychiatric consequences of genetically proxied PCSK9 inhibition in men and women. We failed to find evidence surpassing correction for multiple comparisons of relationships between genetically proxied PCSK9 inhibition and the risk for the 12 neuropsychiatric end points in either men or women. Drug‐target analyses were generally well‐powered to detect effect estimates at several hypothesized thresholds for both combined‐sex and sex‐specific end points, especially analyses using PCSK9 instruments derived from protein and expression quantitative trait loci. Further, MR estimates across complementary MR methods and additional models using genetic instruments derived from circulating PCSK9 protein levels and tissue‐specific PCSK9 expression were in alignment, strengthening causal inference. Conclusions Genetically proxied PCSK9 inhibition showed a neutral neuropsychiatric side effect profile with no major sex‐specific differences. Given statistical power considerations, replication with larger samples, as well as data from other ancestral populations, are necessary. These findings may have important clinical implications for lipid‐lowering drug‐prescribing practices and side effect monitoring of approved and future PCSK9 therapies.

BackgroundRecent studies have demonstrated a causal role for elevated triglycerides (TG) in incident cardiovascular (CV) events in patients with established coronary heart disease (CHD) and those with CV risk factors alone, particularly diabetes.ObjectiveUsing a large cohort of U.S. veterans with statin-controlled LDL-C levels (40–100 mg/dL), we explored residual CV risk among patients with elevated baseline TG levels (150–499 mg/dL) vs. those with normal TG levels (

Methylglyoxal (MG) is a precursor for advanced glycation end-products (AGEs), which have a significant role in diabetes. The present study is designed to probe the immunological response of native and glycated low-density lipoprotein (LDL) in experimental animals. The second part of this study is to probe glycoxidative lesion detection in low-density lipoproteins (LDL) in diabetes subjects with varying disease duration. The neo-epitopes attributed to glycation-induced glycoxidative lesion of LDL in DM patients’ plasma were, analyzed by binding of native and MG-modified LDL immunized animal sera antibodies using an immunochemical assay. The plasma purified human LDL glycation with MG, which instigated modification in LDL. Further, the NewZealand-White rabbits were infused with unmodified natural LDL (N-LDL) and MG-glycatedLDL to probe its immunogenicity. The glycoxidative lesion detection in LDL of DM with disease duration (D.D.) of 5–15 years and D.D. > 15 years was found to be significantly higher as compared to normal healthy subjects (NHS) LDL. The findings support the notion that prolonged duration of diabetes can cause structural alteration in LDL protein molecules, rendering them highly immunogenic in nature. The presence of LDL lesions specific to MG-associated glycoxidation would further help in assessing the progression of diabetes mellitus.

The unregulated uptake of modified low-density lipoproteins (LDL) by macrophages leads to foam cell formation, promoting atherosclerotic plaque progression. The cholesterol efflux capacity of macrophages by the ATP-Binding Cassette transporters depends on the ATP mitochondrial production. Therefore, the mitochondrial function maintenance is crucial in limiting foam cell formation. Thus, we aimed to investigate the mechanisms involved in the mitochondrial dysfunction that may occur in cholesterol-laden macrophages. We incubated THP-1 macrophages with acetylated LDL (acLDL) to obtain cholesterol-laden cells or with mildly oxidized LDL (oxLDL) to generate cholesterol- and oxidized lipids-laden cells. Cellular cholesterol content was measured in each condition. Mitochondrial function was evaluated by measurement of several markers of energetic metabolism, oxidative phosphorylation, oxidative stress, mitochondrial biogenesis and dynamics. OxLDL-exposed macrophages exhibited a significantly reduced mitochondrial respiration and complexes I and III activities, associated to an oxidative stress state and a reduced mitochondrial DNA copy number. Meanwhile, acLDL-exposed macrophages featured an efficient oxidative phosphorylation despite the decreased activities of aconitase, isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. Our study revealed that mitochondrial function was differently impacted according to the nature of modified LDL. Exposure to cholesterol and oxidized lipids carried by oxLDL leads to a mitochondrial dysfunction in macrophages, affecting the mitochondrial respiratory chain functional capacity, whereas the cellular cholesterol enrichment induced by acLDL exposure results in a tricarboxylic acid cycle shunt while maintaining mitochondrial energetic production, reflecting a metabolic adaptation to cholesterol intake. These new mechanistic insights are of direct relevance to the understanding of the mitochondrial dysfunction in foam cells. • AcLDL exposure induces a decrease of aconitase, IDH and α-KGDH activities in macrophages. • Mitochondrial energetic production is maintained in acLDL-exposed macrophages. • Mildly OxLDL exposure induces respiratory chain dysfunction in macrophages. [ABSTRACT FROM AUTHOR]

Background: Mechanisms by which chronic kidney disease (CKD) influences fibrin clot properties in atrial fibrillation (AF) remain ill-defined. We aimed to investigate the effects of AF and CKD on fibrin clot properties and lipoproteins, and determine the relationship between these factors. Methods: Prospective cross-sectional study of patients recruited from cardiology services in Liverpool between September 2019 and October 2021. Primary groups consisted of anticoagulated AF patients with and without CKD in a 1:1 ratio. Control group comprised anticoagulated patients without AF or CKD. Fibrin clot properties were analysed using turbidity and permeation assays. Detailed lipoprotein characteristics, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL and oxidised LDL, were measured. Results: Fifty-six anticoagulated patients were enrolled (median age 72.5; 34% female); 46 with AF (23 with CKD and 23 without CKD) and 10 controls. AF was associated with changes in three indices of fibrin clot properties using PTT (Tlag 314 vs. 358 s, p = 0.047; Abspeak 0.153 vs. 0.111 units, p = 0.031; Tlysis50% 884 vs. 280 s, p = 0.047) and thrombin reagents (Tlag 170 vs. 132 s, p = 0.031; Tmax 590 vs. 462 s, p = 0.047; Tpeak50% 406 vs. 220 s, p = 0.005) while the concomitant presence of CKD led to changes in fibrin clot properties using kaolin (Tlag 1072 vs. 1640 s, p = 0.003; Tmax 1458 vs. 1962 s, p = 0.005; Tpeak50% 1294 vs. 2046, p = 0.008) and PPP reagents (Tlag 566 vs. 748 s, p = 0.044). Neither of these conditions were associated with changes in fibrin clot permeability. Deteriorating eGFR was significantly correlated to the speed of clot formation, and CKD was independently associated with unfavourable clot properties (Tlag −778, p = 0.002; Tmax −867, p = 0.004; Tpeak50% −853, p = 0.004 with kaolin reagent). AF alone was not associated with changes in lipoprotein distribution while AF patients with CKD had lower total cholesterol, LDL-C and small dense LDL due to the presence of other risk factors. No significant relationship was observed between fibrin clot properties and lipoprotein distribution. Conclusions: There are important changes that occur in fibrin clot properties with AF and CKD that may account for the increased risk of thromboembolic complications. However, these changes in fibrin clot properties were not attributable to alterations in lipoprotein distribution. [ABSTRACT FROM AUTHOR]

Introduction: Effective hypercholesterolemia management is essential in primary prevention of cardiovascular events. The objective of PROCYON was to assess the perception on hypercholesterolemia management in primary prevention and to identify reasons for insufficient target attainment in clinical practice in Germany.Methods: PROCYON was a two-part online survey including a patient questionnaire on treatment status and disease knowledge and a physician questionnaire on guideline awareness and patient management. A conjoint analysis on the relative importance of cardiovascular risk factors was incorporated.Results: Of 3798 primary prevention patients included, 1632 (43.0%) received lipid-lowering medication. Of these, 790 (48.4%) reported improved low-density lipoprotein cholesterol (LDL-C) levels, 670 (41.1%) reported no improvement, and 172 (10.5%) had no information. Of the treated patients with (N' = 790) and without (N' = 670) improvement, 52.4% vs. 47.9% were on their initial drug and dose, 8.9% vs. 9.0% received multiple drug therapy, 34.7% vs. 38.8% reported a dose change, and 16.0% vs. 19.4% had discontinued at least one drug (multiple answers). In total, 109 physicians participated. In the conjoint analysis, LDL-C level was attributed the highest relative importance (32.0%), followed by diabetes (24.5%) and systolic blood pressure (15.8%). Lipid-lowering therapy is initiated at an LDL-C level > 150 mg/dl by 63 physicians (57.8%). One third (n = 35; 32.1%) stated that ≥ 60% of their primary prevention patients do not receive lipid-lowering medication.Conclusion: PROCYON suggests a need for consequent LDL-C target-based treatment implementation. [ABSTRACT FROM AUTHOR]

An elevated cholesterol concentration has been suspected to increase the susceptibility for SARS-COV-2 infection. Cholesterol plays a central role in the mechanisms of the SARS-COV-2 infection. In contrast, higher HDL-cholesterol levels seem to be protective. During COVID-19 disease, LDL-cholesterol and HDL-cholesterol appear to be decreased. On the other hand, triglycerides (also in different lipoprotein fractions) were elevated. Lipoprotein(a) may increase during this disease and is most probably responsible for thromboembolic events. This lipoprotein can induce a progression of atherosclerotic lesion formation. The same is suspected for the SARS-COV-2 infection itself. COVID-19 patients are at increased risk of incident cardiovascular diseases, including cerebrovascular disorders, dysrhythmias, ischemic and non-ischemic heart disease, pericarditis, myocarditis, heart failure, and thromboembolic disorders. An ongoing lipid-lowering therapy, including lipoprotein apheresis, is recommended to be continued during the COVID-19 disease, though the impact of lipid-lowering drugs or the extracorporeal therapy on prognosis should be studied in further investigations. [ABSTRACT FROM AUTHOR]

Background and aims: Acute myocardial infarction (MI) is one of the most prevalent heart diseases across the world, including in Iran. The purpose of the present study was to investigate the relationship between acute MI and serum low-density lipoprotein (LDL) levels in patients with acute MI. Methods: In this descriptive-inferential study, 1274 MI patients hospitalized in Shahrekord Hajar Hospital were selected using the census method. The required information was drawn from the patient’s medical records according to inclusion criteria. Statistical analyses were performed using analysis of variance (ANOVA) and chi-square test to examine the relationship between the LDL level and awareness in patients. Results: In this study, the average age of patients with acute heart attack was 13.79±63.18 years. Of the 1274 studied patients, 78% (999 people) were men and the rest were women. In both male and female genders, most patients had LDL levels between 70 and 129 mg/dL. Regarding statin use, 757, 287, and 162 people had a history of statin use, hypertension (HTN), and cardiovascular disease, respectively. In addition, 150 and 152 people had diabetes and a history of smoking, respectively. In this study, a significant relationship was found between the history of statin use (P<0.0001) and the frequency of MI (P=0.049) in LDL groups. Conclusion: The results of this research revealed a significant relationship between LDL groups and the number of times acute heart attack occurs as a long-term complication in people who have had one. [ABSTRACT FROM AUTHOR]

Background and Aims: (Poly)phenols might contribute to prevent cardiovascular disease, but limited prospective studies exist among adolescents. This study aimed to evaluate within-subject longitudinal changes in (poly)phenols intakes and food group contributors while also exploring the association with metabolic syndrome risk (MetS) during 10 years of follow up in European adolescents becoming young adults.Methods and Results: In 164 participants (58% girls, 13-18 y at baseline) from Ghent, Zaragoza and Lille, longitudinal data (2006-2016) on (poly)phenol intake was retrieved via 2 or 3 24 h recalls. Linear and logistic longitudinal regression tested the association of (poly)phenols intake (total and classes) with Mets risk or its components (waist-height-ratio, HDL cholesterol, LDL cholesterol, triglycerides, blood pressure and insulin resistance index), adjusted for age, sex, country and other nutrient intakes. The total (poly)phenols intake was 421 ± 107 mg/day (192 mg/1000 kcal/day) at baseline, while 610 ± 101 mg/day (311 mg/1000 kcal/day) at follow-up. The three major food sources for (poly)phenols were 'chocolate', 'fruit and vegetable juices', 'cakes and biscuits' during adolescence and 'coffee', 'tea' and 'chocolate' during adulthood. Phenolic acid intake was associated with less LDL increase over time, while stilbene intake with a steeper increase in triglycerides over time.Conclusions: Differences in major (poly)phenols contributors over time were partially explained by age-specific dietary changes like increased coffee and tea during adulthood. Some significant (poly)phenols-MetS associations might argue for nutrition-based disease prevention during adolescence, especially since adolescents had low (poly)phenols intake. [ABSTRACT FROM AUTHOR]

Small dense low-density cholesterol (sdLDL) has been the focus of studies due to its potential as an independent risk factor for atherosclerotic cardiovascular diseases. We aimed to investigate the utilization of sdLDL testing by LDL particle size analysis and the prevalence of an sdLDL predominant phenotype in Korean adult patients by visiting local clinics and hospitals. Among 9222 Korean adults (4577 men and 4645 women) with a median age of 62.8 years (interquartile range, IQR 54.5 to 71.8 years) undergoing lipid profile testing using LDL particle size analysis, the prevalence of hypercholesterolemia (total cholesterol ≥ 240 mg/dL), hypo HDL cholesterolemia (<40 mg/dL), and hyper LDL cholesterolemia (≥160 mg/dL) was 7.8%, 12.9%, and 0.5%, respectively. The overall prevalence of the sdLDL predominant non-A phenotype of LDL was 46.8% of study subjects. Approximately 32.8% of the study subjects possessed lipid test results that did not exhibit increased risk except for sdLDL (only the sdLDL predominant non-A phenotype as a risk factor). In Korea, sdLDL testing was utilized in patients whose LDL cholesterol level was not increased. Future studies to clarify the clinical significance of this test in the Korean population are needed. [ABSTRACT FROM AUTHOR]

Background: The effect of cannabis on cholesterol and lipid balance has been reported for decades. However, there are conflicting reports on the reduction of low-density lipoprotein (LDL-C) and total cholesterol. The purpose of this study was to determine the immediate changes of Cannabis spp. consumption by pyrolytic route in heavy users. Methods: A cross-sectional study on 20 Peruvian heavy cannabis users (mean age: 31 ± 9.5 years). The inclusion criteria were males with an average weight of 50–70 kg, normal BMI, and having used cannabis, without association with other drugs, for at least one year with a high frequency per week (use: 4–7 days/week). High-density lipoprotein (HDL-C), LDL-C, and total cholesterol were evaluated 30 and 120 min after the administration of Cannabis spp. (~0.2 g by inhalation). Results: Of the total 12 (60%), 10 (50%), and 11 (55%) had desirable total cholesterol, fairly good HDL-C (40–60 mg/dL) and fairly good LDL-C (100–129 mg/dL) values, respectively. The mean basal concentration of total cholesterol, HDL-cholesterol, and LDL-cholesterol was 193.37 ± 20.18 mg/dL, 60.05 ± 6.36 mg/dL, and 129.65 ± 14.50 mg/dL, respectively. HDL-cholesterol showed progressive increases in participants with desirable HDL-C > 60 mg/dL at 30 min (10 vs. 14 participants, p < 0.001) and at 120 min (10 vs. 16 participants, p < 0.001), while LDL-C peaked in participants with concentrations < 100 mg/dL at 30 min (desirable cholesterol: 0 vs. 2, p = 0.001). HDL-C concentration showed differences after cannabis consumption, showing increases at 30 (63.25 ± 7.68 mg/dL) and 120 min (69.15 ± 18.67 mg/dL) and total cholesterol concentration changed to 180.95 ± 19.3 mg/dL (95%CI 172.5 to 189.4) at 120 min (p = 0.007). Conclusions: HDL-C cholesterol increased 30 and 120 min after Cannabis spp. ingestion, while LDL-C and total cholesterol showed partial reductions in heavy-users from Cusco, Peru. [ABSTRACT FROM AUTHOR]

Lowering of low‐density lipoprotein (LDL) levels in blood of patients with hyperlipidaemia can effectively prevent the progression of atherosclerosis and coronary heart disease. The present study demonstrated a facile synthesis strategy to prepare biomembrane‐mimetic LDL adsorbent (PVA@COOH‐PE) via directional immobilization of phospholipid onto macro‐porous cross‐linked poly(vinyl alcohol) spheres. The binding between the prepared adsorbent and LDL particles simulates the cytosolic lipid droplets to form a lipid‐packing structure. The adsorbent possesses satisfactory removal efficiency for LDL and total cholesterol (TCH) in hyperlipemia serum, while remains high‐density lipoprotein (HDL) concentration within the normal range. The adsorption capacities for LDL and TCH are about 1.13 and 1.74 mg/ml respectively, which are nearly three and four times higher than that of HDL (0.42 mg/ml). The adsorbent also possesses satisfactory anticoagulant properties, causes negligible effect on blood cells and produces low hemolysis ratios. The excellent blood compatibility plus LDL removal efficiency of PVA@COOH‐PE indicates its good application prospect as hemoperfusion adsorbent in the treatment of hyperlipidaemia. [ABSTRACT FROM AUTHOR]

Background: Liver fibrosis is thought to have a close relationship with lipid profile. The possible association between lipids and liver fibrosis of different etiologies has been widely explored. However, the association between lipids and liver fibrosis in patients infected with Schistosoma japonicum remains unclear. In the present study we undertook a preliminary exploration of the association between lipid profile and liver fibrosis, and developed a new predictive index for liver fibrosis in S. japonicum-infected patients. Methods: A total of 1503 patients diagnosed with S. japonicum at Xiangyue Hospital, China were enrolled in this retrospective study. The patients were divided into two groups, i.e., those with and those without liver fibrosis, by two experienced schistosomiasis specialists, according to the results of liver ultrasound examination. Demographic, clinical, and laboratory data were collected. Multivariable logistic models were used to estimate the independent associations between lipid profile and liver fibrosis. Receiver operating characteristic (ROC) curves were used to assess the discriminative ability of the new index in predicting liver fibrosis in patients with schistosomiasis. Results: Logistic regression analysis showed that high-density lipoprotein (HDL) [adjusted odds ratio (aOR), 95% confidence interval (CI) 7.334, 5.051–10.649; P < 0.001], low-density lipoprotein (LDL) (aOR, 95% CI 0.434, 0.370–0.509; P < 0.001), hemoglobin (HB) (aOR, 95% CI 0.979, 0.971–0.987; P < 0.001) and platelets (PLT) (aOR, 95% CI 0.996, 0.994–0.999; P < 0.001) were independently associated with liver fibrosis in patients with schistosomiasis. ROC analysis indicated that the combination of HDL, LDL and HB levels [(HDL × 100)/(LDL × HB)] had a higher area under the ROC curve (AUC = 0.773), and thus may better predict liver fibrosis than the aspartate transaminase-to-platelet ratio index (AUC = 0.608) and fibrosis index based on four factors (AUC = 0.624). Conclusions: To the best of our knowledge, this is the first study to report that HDL, LDL, HB and PLT levels are independently associated with liver fibrosis in patients with schistosomiasis. (HDL × 100)/(LDL × HB) outperformed the aspartate transaminase-to-platelet ratio index and fibrosis index based on four factors in terms of ROC, and thus could be a new predictive index for liver fibrosis. These findings may help clinicians to more easily and effectively diagnose liver fibrosis in patients with schistosomiasis. [ABSTRACT FROM AUTHOR]