Cumulative exposure to atherogenic lipoprotein particles in young adults and subsequent incident atherosclerotic cardiovascular disease.

Background And Aims: Atherogenic lipoprotein exposure during young adulthood increases the risk of atherosclerotic cardiovascular disease (ASCVD) later in life. The relationships between cumulative and usual yearly apolipoprotein B (apoB), low-density lipoprotein particle (LDL-P), and triglyceride-rich lipoprotein particle (TRL-P) exposure in early adult life and incident ASCVD was quantified.

Methods: Follow-up data of young adults aged 18 to <40 years from the longitudinal population-based Coronary Artery Risk Development in Young Adults (CARDIA) cohort were used.

Atherogenic lipoproteins associate with loss of glycemic control in youth-onset type 2 diabetes: Results from the TODAY study.

Background: Type 2 diabetes (T2D) in adolescents is associated with an unfavorable lipid profile, but lipoprotein particle subspecies and branched-chain amino acid (BCAA) data are scarce.

Objective: To evaluate lipoprotein particle distributions, lipoprotein insulin resistance index (LP-IR), and BCAA levels longitudinally and their relationships with sex, race/ethnicity, treatment, and loss of glycemic control in adolescents with youth-onset T2D.

Methods: Participants from the TODAY study (n = 348) had samples analyzed yearly for glycated hemoglobin and nuclear magnetic resonance lipoprotein and BCAA assessments.

Endogenous Ketone Bodies Are Associated with Metabolic Vulnerability and Disability in Multiple Sclerosis.

: Ketone bodies could be useful biomarkers in multiple sclerosis (MS) because the pathophysiological processes underlying MS disease progression induce metabolic stress. The purpose was to assess the relationships of ketone bodies with biomarkers of metabolic, inflammatory, and oxidative stress in MS. : Blood samples and neurological assessments were obtained from 153 healthy controls (HC), 187 relapsing-remitting (RRMS), and 91 progressive MS (PMS) patients.

Refinement of a Published Gene-Physical Activity Interaction Impacting HDL-Cholesterol: Role of Sex and Lipoprotein Subfractions.

Large-scale gene-environment interaction (GxE) discovery efforts often involve analytical compromises for the sake of data harmonization and statistical power. Refinement of exposures, covariates, outcomes, and population subsets may be helpful to establish often-elusive replication and evaluate potential clinical utility. Here, we used additional datasets, an expanded set of statistical models, and interrogation of lipoprotein metabolism via nuclear magnetic resonance (NMR)-based lipoprotein subfractions to refine a previously discovered GxE modifying the relationship between physical activity (PA) and HDL-cholesterol (HDL-C).

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.

A global perspective on the status of clinical metabolomics in laboratory medicine - a survey by the IFCC metabolomics working group.

Objectives: Metabolomics aims for comprehensive characterization and measurement of small molecule metabolites (<1700 Da) in complex biological matrices. This study sought to assess the current understanding and usage of metabolomics in laboratory medicine globally and evaluate the perception of its promise and future implementation.

Methods: A survey was conducted by the IFCC metabolomics working group that queried 400 professionals from 79 countries.

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.

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.

Novel Size-Based High-Density Lipoprotein Subspecies and Incident Vascular Events.

Background High-density lipoprotein (HDL) particle concentration likely outperforms HDL cholesterol in predicting atherosclerotic cardiovascular events. Whether size-based HDL subspecies explain the atheroprotective associations of HDL particle concentration remains unknown. Our objective was to assess whether levels of specific size-based HDL subspecies associate with atherosclerotic cardiovascular disease in a multiethnic pooled cohort and improve risk prediction beyond traditional atherosclerotic cardiovascular disease risk factors.

Plant-based diet indices and lipoprotein particle subclass profiles: A cross-sectional analysis of middle- to older-aged adults.

Background And Aims: Plant-based diets (PBDs) are associated with favourable lipid profiles and cardiometabolic outcomes. However, limited data regarding PBD indices (PDIs) and lipoprotein subclasses exist. We examined overall PDI, healthful PDI (hPDI) and unhealthful PDI (uPDI) associations with lipid and lipoprotein profiles.

Combined Association of Novel and Traditional Inflammatory Biomarkers With Carotid Artery Plaque: GlycA Versus C-Reactive Protein (ELSA-Brasil).

Elevated levels of glycoprotein acetylation (GlycA) and C-reactive protein (CRP) have been associated with carotid artery plaque (CAP). However, it is not yet established if elevations in both inflammatory biomarkers provide incremental association with CAP. This study aimed evaluate the cross-sectional association of high CRP and GlycA with CAP at baseline participants from the ELSA-Brasil adult cohort.

The Metabolic Vulnerability Index: A Novel Marker for Mortality Prediction in Heart Failure.

Background: Inflammation and protein energy malnutrition are associated with heart failure (HF) mortality. The metabolic vulnerability index (MVX) is derived from markers of inflammation and malnutrition and measured by nuclear magnetic resonance spectroscopy. MVX has not been examined in HF.

Longitudinal trajectories of branched chain amino acids through young adulthood and diabetes in later life.

BACKGROUNDElevated circulating branched chain amino acids (BCAAs), measured at a single time point in middle life, are strongly associated with an increased risk of developing type 2 diabetes mellitus (DM). However, the longitudinal patterns of change in BCAAs through young adulthood and their association with DM in later life are unknown.METHODSWe serially measured BCAAs over 28 years in the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective cohort of apparently healthy Black and White young adults at baseline.

Multimarkers of metabolic malnutrition and inflammation and their association with mortality risk in cardiac catheterisation patients: a prospective, longitudinal, observational, cohort study.

Background: Complex and incompletely understood metabolic dysfunction associated with inflammation and protein-energy wasting contribute to the increased mortality risk of older patients and those with chronic organ diseases affected by cachexia, sarcopenia, malnutrition, and frailty. However, these wasting syndromes have uncertain relevance for patients with cardiovascular disease or people at lower risk. Studies are hampered by imperfect objective clinical assessment tools for these intertwined metabolic malnutrition and inflammation syndromes.

Accuracy and Clinical Impact of Estimating Low-Density Lipoprotein-Cholesterol at High and Low Levels by Different Equations.

New more effective lipid-lowering therapies have made it important to accurately determine Low-density lipoprotein-cholesterol (LDL-C) at both high and low levels. LDL-C was measured by the β-quantification reference method (BQ) (N = 40,346) and compared to Friedewald (F-LDL-C), Martin (M-LDL-C), extended Martin (eM-LDL-C) and Sampson (S-LDL-C) equations by regression analysis, error-grid analysis, and concordance with the BQ method for classification into different LDL-C treatment intervals. For triglycerides (TG) < 175 mg/dL, the four LDL-C equations yielded similarly accurate results, but for TG between 175 and 800 mg/dL, the S-LDL-C equation when compared to the BQ method had a lower mean absolute difference (mg/dL) (MAD = 10.

A Translational Tool to Facilitate Use of Apolipoprotein B for Clinical Decision-Making.

Background: Despite recent large-scale discordance studies showing definitively that atherosclerotic cardiovascular disease (ASCVD) risk correlates better with apolipoprotein B (apoB) than with low-density lipoprotein cholesterol (LDL-C), the latter remains the recommended metric for guiding lipid-lowering treatment decisions in the United States. A major barrier to change, in this regard, is the lack of guideline-recommended apoB treatment targets. We developed a simple method to "translate" apoB values into population-equivalent LDL-C units, allowing apoB-based treatment decisions to be made using LDL-C targets.

Changes in HDL cholesterol, particles, and function associate with pediatric COVID-19 severity.

Background: Myriad roles for high-density lipoprotein (HDL) beyond atheroprotection include immunologic functions implicated in the severity of coronavirus disease-2019 (COVID-19) in adults. We explored whether there is an association between HDL and COVID-19 severity in youth.

Methods: A pediatric cohort ( = 102), who tested positive for COVID-19 across a range of disease manifestations from mild or no symptoms, to acute severe symptoms, to the multisystem inflammatory syndrome of children (MIS-C) was identified.

Lipoprotein-X and Lipoprotein-Z Induced Hyperviscosity Syndrome in the Setting of Cholestatic Liver Failure.

We describe a case referred for worsening hypercholesterolemia in the setting of atorvastatin and fenofibrate-induced liver injury. The patient reported neurological complaints attributed to hyperviscosity syndrome (induced by lipoprotein-X and lipoprotein-Z). Hepatic recovery was associated with reduction of whole blood viscosity and amelioration of neurological symptoms.

The Inflammation Biomarker GlycA Reflects Plasma N-Glycan Branching.

Background: GlycA is a nuclear magnetic resonance (NMR) signal in plasma that correlates with inflammation and cardiovascular outcomes in large data sets. The signal is thought to originate from N-acetylglucosamine (GlcNAc) residues of branched plasma N-glycans, though direct experimental evidence is limited. Trace element concentrations affect plasma glycosylation patterns and may thereby also influence GlycA.

Causal analysis identifies small HDL particles and physical activity as key determinants of longevity of older adults.

Background: The hard endpoint of death is one of the most significant outcomes in both clinical practice and research settings. Our goal was to discover direct causes of longevity from medically accessible data.

Methods: Using a framework that combines local causal discovery algorithms with discovery of maximally predictive and compact feature sets (the "Markov boundaries" of the response) and equivalence classes, we examined 186 variables and their relationships with survival over 27 years in 1507 participants, aged ≥71 years, of the longitudinal, community-based D-EPESE study.