Gut microbiome dysbiosis is not associated with portal vein thrombosis in patients with end-stage liver disease: a cross-sectional study.

Background: Portal vein thrombosis (PVT) is a common complication in patients with end-stage liver disease (ESLD). The portal vein in ESLD patients is proposedly an inflammatory vascular bed due to translocation of endotoxins and cytokines from the gut. We hypothesized that a pro-inflammatory gut microbiome and elevated trimethylamine N-oxide (TMAO), a driver of thrombosis, may contribute to PVT development.

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).

Circulating Citrate Is Reversibly Elevated in Patients with End-Stage Liver Disease: Association with All-Cause Mortality.

Circulating citrate may serve as a proxy for mitochondrial dysfunction which plays a role in the progression of end-stage liver disease (ESLD). This study aimed to determine the extent of alterations in circulating citrate in patients with ESLD, and examined its association with all-cause mortality among ESLD patients while on the waiting list for liver transplantation. Plasma citrate levels were measured using nuclear magnetic resonance spectroscopy in 129 ESLD patients (TransplantLines cohort study; NCT03272841) and compared to levels in 4837 participants of the community-dwelling PREVEND cohort.

Effects of induced subclinical hypocalcemia in early-lactation Holstein cows without milking during infusion on parathyroid hormone and serotonin concentrations.

The transition to lactation demands a substantial amount of calcium (Ca) to support colostrum and milk production. Extensive research has been focused on elucidating the interplay between the traditional Ca-parathyroid hormone-vitamin D axis and mammary-derived factors, such as serotonin (5-HT) and parathyroid-hormone-like hormone (PTHLH), in regulating Ca metabolism during the transition period. Here, we investigate the impact of induced subclinical hypocalcemia (SCH) on 5-HT and parathyroid hormone (PTH) concentrations in early-lactation dairy cows under conditions of 24-h milk stasis.

Association of circulating ketone bodies with cognitive performance and dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Introduction: Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods: Associations of plasma KB with incident dementia and cognitive performances were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000-02) and detailed cognitive testing at Exam 5 (2010-2012,  = 4392), Exam 6 (2016-2018,  = 1838), and in MESA-MIND (2019-2021,  = 2060).

Circulating Ketone Bodies, Pyruvate, and Citrate and Risk of Cognitive Decline, Structural Brain Abnormalities, and Dementia.

The relationship between key energy metabolites and brain health is not well understood. We investigated the association between circulating ketone bodies, pyruvate, and citrate with cognitive decline, structural brain characteristics, and risk of dementia. We measured ketone bodies (acetoacetate, β-hydroxybutyrate, and acetone), pyruvate, and citrate species using NMR in plasma samples from 1,850 older adults in the Cardiovascular Health Study collected in 1989-90 or 1992-93.

The effects of magnitude of calcium decline at the onset of lactation on serotonin dynamics and the serotonin-calcium axis.

The onset of lactation is characterized by marked increases in calcium (Ca) metabolism. Recently emphasis was placed on understanding the profile and dynamics of blood Ca and serotonin in the peripartal cow in response to this change using a randomized 2x2 factorial design. The aims of our study were to determine i) how a prepartum dietary cation anion difference (DCAD) diet and the magnitude of Ca decline at the onset of lactation alter circulating blood serotonin and iCa concentrations dynamics in the periparturient cow, and ii) the relationship Ca versus serotonin during the peripartal period.

Cardiometabolic risk assessment in transgender individuals - differential impact of sex hormones and sex chromosomes.

Background: While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements.

Methods: 17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12).

MASLD in persons with HIV is associated with high cardiometabolic risk as evidenced by altered advanced lipoprotein profiles and targeted metabolomics.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles.

Oral citrate supplementation mitigates age-associated pathological intervertebral disc calcification in LG/J mice.

Despite the high prevalence of age-dependent intervertebral disc calcification, there is a glaring lack of treatment options for this debilitating pathology. Here, we investigate the efficacy of long-term oral KCitrate supplementation in ameliorating disc calcification in LG/J mice, a model of spontaneous age-associated disc calcification. KCitrate successfully reduced the incidence of disc calcification in LG/J mice without deleterious effects on vertebral bone structure, plasma chemistry, and locomotion.

Impact of RA treatment strategies on lipids and vascular inflammation in rheumatoid arthritis: a secondary analysis of the TARGET randomized active comparator trial.

Background: Treatments for rheumatoid arthritis (RA) are associated with complex changes in lipids and lipoproteins that may impact cardiovascular (CV) risk. The objective of this study was to examine lipid and lipoprotein changes associated with two common RA treatment strategies, triple therapy or tumor necrosis factor inhibitor (TNFi), and association with CV risk.

Methods: In this secondary data analysis of the TARGET trial, methotrexate (MTX) inadequate responders with RA were randomized to either add sulfasalazine and hydroxychloroquine (triple therapy), or TNFi for 24-weeks.

Circulating Trimethylamine-N-Oxide Is Elevated in Liver Transplant Recipients.

Liver transplant recipients (LTRs) have lower long-term survival rates compared with the general population. This underscores the necessity for developing biomarkers to assess post-transplantation mortality. Here we compared plasma trimethylamine-N-oxide (TMAO) levels with those in the general population, investigated its determinants, and interrogated its association with all-cause mortality in stable LTRs.

Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans.

Mitochondrial-secreted growth differentiation factor-15 (GDF-15) promotes weight loss in animals. Its effects in humans remain unclear, due to limited research and potential measurement interference from the H202D-variant. Our post-hoc analysis investigates total (irrespective of genetic variants) and H-specific GDF-15 (detected only in H202D-variant absence) in humans under acute and chronic energy deprivation, examining GDF-15 interaction with leptin (energy homeostasis regulator) and GDF-15 biologic activity modulation by the H202D-variant.

High LDL Particle and APOB Concentrations in Patients With Adrenal Cortical Adenomas.

Context: Patients with nonfunctioning adenomas (NFAs), adenomas with mild autonomous cortisol secretion (MACS) and Cushing syndrome (CS) demonstrate an increased cardiovascular risk.

Objective: This work aimed to determine the extent of lipoprotein abnormalities in NFA, MACS, and CS.

Methods: We conducted a single-center, cross-sectional study of patients with NFA (n = 167), MACS (n = 213), CS (n = 142), and referent individuals (n = 202) between January 2015 and July 2022.

Lipoprotein subclasses are associated with Hepatic steatosis: insights from the prospective multicenter imaging study for the evaluation of chest pain (PROMISE) clinical trial.

Objectives: To determine the relationship between lipoprotein particle size/number with hepatic steatosis (HS), given its association with traditional lipoproteins and coronary atherosclerosis.

Methods: Individuals with available CT data and blood samples enrolled in the PROMISE trial were studied. HS was defined based on CT attenuation.

Circulating total and H-specific GDF15 levels are elevated in subjects with MASLD but not in hyperlipidemic but otherwise metabolically healthy subjects with obesity.

Background: Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD.

Methods: Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT).

Association of High-Density Lipoprotein Parameters and Risk of Heart Failure: A Multicohort Analysis.

Background: High-density lipoprotein (HDL) is commonly characterized by its cholesterol concentration (HDL-C) and inverse association with atherosclerotic cardiovascular disease.

Objectives: The authors sought to evaluate the association of HDL particle concentration (HDL-P), HDL particle size (HDL-size), HDL-C, and cholesterol content per particle (HDL-C/HDL-P) with risk of overall heart failure (HF) and subtypes.

Methods: Participants from the Atherosclerosis Risk In Communities Study, Dallas Heart Study, Multi-Ethnic Study of Atherosclerosis, and Prevention of Renal and Vascular End-stage Disease studies without HF history were included.

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.

Enhanced chronic inflammation and increased branched chain amino acids in adrenal disorders: a cross-sectional study.

Context: Patients with adrenal hormone excess demonstrate increased cardiovascular risk and mortality.

Objective: We aimed to determine the impact of adrenal disorders on the inflammation marker GlycA, total branched-chain amino acids (BCAA), ketone bodies and the gut microbiome-derived metabolites trimethylamine N-oxide (TMAO) and betaine.

Methods: We conducted a single-center cross-sectional study of patients with nonfunctioning adenomas (NFA), mild autonomous cortisol secretion (MACS), primary aldosteronism (PA), Cushing syndrome (CS), pheochromocytoma/paragangliomas (PPGL), other benign or malignant adrenal masses, and adrenocortical carcinoma (ACC) between January 2015 and July 2022 (n=802).

Fasting Plasma Ketone Bodies Are Associated with NT-proBNP: A Potential Mechanism to Provide Fuel for the Failing Heart.

Heart failure (HF) features a shift in metabolism towards enhanced utilization of ketone bodies. While elevations in plasma natriuretic peptides represent a biochemical hallmark of HF, natriuretic peptides may promote lipolysis, thereby contributing to fatty acid availability for ketogenesis. We cross-sectionally tested to what extent fasting plasma total ketone bodies (measured using nuclear magnetic resonance spectroscopy) are associated with N-terminal pro-BNP (NT-proBNP; electrochemiluminescent sandwich immunoassay) in individuals with and without HF.

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.