Apolipoprotein-L1 G1 variant contributes to hydrocephalus but not to atherosclerosis in apolipoprotein-E knock-out mice.

Introduction: In USA, six million individuals with Sub-Saharan ancestry carry two high-risk variants, which increase the risk for kidney diseases. Whether APOL1 high-risk variants are independent risk factors for cardiovascular diseases is unclear and requires further investigation.

Methods: We characterized a mouse model to investigate the role of APOL1 in dyslipidemia and cardiovascular diseases.

Structure of apolipoprotein B100 bound to the low-density lipoprotein receptor.

Apolipoprotein B100 (apoB100) is a structural component of low-density lipoprotein (LDL) and a ligand for the LDL receptor (LDLR). Mutations in apoB100 or in LDLR cause familial hypercholesterolaemia, an autosomal dominant disease that is characterized by a marked increase in LDL cholesterol (LDL-C) and a higher risk of cardiovascular disease. The structure of apoB100 on LDL and its interaction with LDLR are poorly understood.

HDL-free cholesterol influx into macrophages and transfer to LDL correlate with HDL-free cholesterol content.

High-density lipoprotein (HDL)-free cholesterol (FC) transfers to other lipoproteins and cells, the former by a spontaneous mechanism and the latter by both spontaneous and receptor-mediated mechanisms. Macrophages are an important cell type in all stages of atherosclerotic cardiovascular disease (ASCVD), and the magnitude of FC efflux from macrophages to HDL, a metric of HDL function, inversely associated with several metrics of ASCVD. Very high plasma HDL concentrations are associated with increased all-cause and ASCVD mortality, suggesting that the reverse process, FC influx from HDL into macrophages, is atherogenic.

An equation for estimating low-density lipoprotein-triglyceride content and its use for cardiovascular disease risk stratification.

Background: The triglyceride (TG) content of low-density lipoprotein (LDL-TG) has been shown to be more predictive of atherosclerotic cardiovascular disease (ASCVD) events than the cholesterol content of LDL (LDL-C). The goal of our study was to develop an equation for estimating LDL-TG (LDL-TG) based on the standard lipid panel and to compare it to estimated LDL-C as an ASCVD risk biomarker.

Methods: Using least-square regression analysis, the following LDL-TG equation was developed: .

Untargeted lipidomics reveals novel HDL metabotypes and lipid-clinical correlates.

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured.

Nuclear-Magnetic-Resonance-Spectroscopy-Derived Serum Biomarkers of Metabolic Vulnerability Are Associated with Disability and Neurodegeneration in Multiple Sclerosis.

Purpose: Metabolic vulnerabilities can exacerbate inflammatory injury and inhibit repair in multiple sclerosis (MS). The purpose was to evaluate whether blood biomarkers of inflammatory and metabolic vulnerability are associated with MS disability and neurodegeneration.

Methods: Proton nuclear magnetic resonance spectra were obtained from serum samples from 153 healthy controls, 187 relapsing-remitting, and 91 progressive MS patients.

Dyslipidemias in multiple sclerosis.

Purpose: To investigate the frequency of dyslipidemia phenotypes in multiple sclerosis and to assess the associations with lipoprotein particle size distributions.

Methods: This cross-sectional study included 203 healthy controls (HC), 221 relapsing-remitting MS (RRMS), and 126 progressive MS (PMS). A lipid profile with total cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, and apolipoprotein B levels were measured.

Role of apolipoprotein B in the clinical management of cardiovascular risk in adults: An Expert Clinical Consensus from the National Lipid Association.

This National Lipid Association (NLA) Expert Clinical Consensus provides an overview of the physiologic and clinical considerations regarding the role of apolipoprotein B (apoB) measurement to guide clinical care based on the available scientific evidence and expert opinion. ApoB represents the total concentration of atherogenic lipoprotein particles in the circulation and more accurately reflects the atherogenic burden of lipoproteins when compared to low-density lipoprotein cholesterol (LDL-C). ApoB is a validated clinical measurement that augments the information found in a standard lipoprotein lipid panel; therefore, there is clinical value in using apoB in conjunction with a standard lipoprotein lipid profile when assessing risk and managing lipid-lowering therapy (LLT).

High-Density Lipoprotein-Specific Phospholipid Efflux in Familial Hypercholesterolemia.

Objective: Familial hypercholesterolemia (FH) is characterized by elevated levels of low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD). Although the role of LDL-C in FH has been studied, the contribution of high-density lipoproteins (HDL) to CVD in FH remains unknown. This study aimed at highlighting the role of HDL in FH.

The clinical impact of estimating low-density lipoprotein cholesterol (LDL-C) using different equations in the general population.

Background: Low-density lipoprotein cholesterol (LDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD). Friedewald, Sampson, and Martin-Hopkins equations are used to calculate LDL-C. This study compares the impact of switching between these equations in a large geographically defined population.

The triglyceride-glucose index is superior to homeostasis model assessment of insulin resistance in predicting metabolic syndrome in an adult population in the United States.

Background: Metabolic syndrome (MetS) is a cluster of cardio-metabolic features portending an increased risk for both type 2 diabetes mellitus (T2DM) and premature atherosclerotic cardiovascular disease (ASCVD). Homeostasis model assessment of insulin resistance (HOMA-IR) is a widely used surrogate measure of insulin resistance. The triglyceride-glucose (TyG) index is another validated measure of insulin resistance that predicts both diabetes and cardiovascular disease in low and medium-income countries, but only diabetes in high income countries.

Cellular senescence induced by cholesterol accumulation is mediated by lysosomal ABCA1 in APOE4 and AD.

Background: Cellular senescence is a hallmark of aging and has been implicated in Alzheimer's disease (AD) pathogenesis. Cholesterol accumulation drives cellular senescence; however, the underlying mechanisms are unclear. ATP-binding cassette transporter A1 (ABCA1) plays an important role in cholesterol homeostasis.

Discordance Between Very Low-Density Lipoprotein Cholesterol and Low-Density Lipoprotein Cholesterol Increases Cardiovascular Disease Risk in a Geographically Defined Cohort.

Background: Clinical risk scores are used to identify those at high risk of atherosclerotic cardiovascular disease (ASCVD). Despite preventative efforts, residual risk remains for many individuals. Very low-density lipoprotein cholesterol (VLDL-C) and lipid discordance could be contributors to the residual risk of ASCVD.

Lipoprotein Insulin Resistance Score and Mortality Risk Stratification in Heart Failure.

Background: Higher total serum cholesterol is associated with lower mortality in heart failure. Evaluating associations between lipoprotein subfractions and mortality among people with heart failure may provide insights into this observation.

Methods: We prospectively enrolled a community cohort of people with heart failure from 2003 to 2012 and assessed vital status through 2021.

Frailty and Metabolic Vulnerability in Heart Failure: A Community Cohort Study.

Background: Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact.

Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study.

Background: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure.

A High-Throughput NMR Method for Lipoprotein-X Quantification.

Lipoprotein X (LP-X) is an abnormal cholesterol-rich lipoprotein particle that accumulates in patients with cholestatic liver disease and familial lecithin-cholesterol acyltransferase deficiency (FLD). Because there are no high-throughput diagnostic tests for its detection, a proton nuclear magnetic resonance (NMR) spectroscopy-based method was developed for use on a clinical NMR analyzer commonly used for the quantification of lipoproteins and other cardiovascular biomarkers. The LP-X assay was linear from 89 to 1615 mg/dL (cholesterol units) and had a functional sensitivity of 44 mg/dL.

Selective transcriptomic dysregulation of metabolic pathways in liver and retina by short- and long-term dietary hyperglycemia.

A high glycemic index (HGI) diet induces hyperglycemia, a risk factor for diseases affecting multiple organ systems. Here, we evaluated tissue-specific adaptations in the liver and retina after feeding HGI diet to mice for 1 or 12 month. In the liver, genes associated with inflammation and fatty acid metabolism were altered within 1 month of HGI diet, whereas 12-month HGI diet-fed group showed dysregulated expression of cytochrome P450 genes and overexpression of lipogenic factors including and .

An improved method for estimating low LDL-C based on the enhanced Sampson-NIH equation.

Background: The accurate measurement of Low-density lipoprotein cholesterol (LDL-C) is critical in the decision to utilize the new lipid-lowering therapies like PCSK9-inhibitors (PCSK9i) for high-risk cardiovascular disease patients that do not achieve sufficiently low LDL-C on statin therapy.

Objective: To improve the estimation of low LDL-C by developing a new equation that includes apolipoprotein B (apoB) as an independent variable, along with the standard lipid panel test results.

Methods: Using β-quantification (BQ) as the reference method, which was performed on a large dyslipidemic population (N = 24,406), the following enhanced Sampson-NIH equation (eS LDL-C) was developed by least-square regression analysis: [Formula: see text] RESULTS: The eS LDL-C equation was the most accurate equation for a broad range of LDL-C values based on regression related parameters and the mean absolute difference (mg/dL) from the BQ reference method (eS LDL-C: 4.

Circulating ketone bodies and mortality in heart failure: a community cohort study.

Background: The relationship between ketone bodies (KB) and mortality in patients with heart failure (HF) syndrome has not been well established.

Objectives: The aim of this study is to assess the distribution of KB in HF, identify clinical correlates, and examine the associations between plasma KB and all-cause mortality in a population-based HF cohort.

Methods: The plasma KB levels were measured by nuclear magnetic resonance spectroscopy.