Empagliflozin to prevent worsening of left ventricular volumes and systolic function after myocardial infarction (EMPRESS-MI).

Aims: Patients with a reduced left ventricular ejection fraction (LVEF) following an acute myocardial infarction (MI) are considered to be at risk of progressive adverse cardiac remodelling which can lead to the development of heart failure and death. The early addition of a sodium-glucose cotransporter 2 (SGLT2) inhibitor to standard treatment may delay or prevent progressive adverse remodelling in these patients.

Methods And Results: We performed a randomized, double-blind, placebo-controlled, multicentre trial using cardiovascular magnetic resonance imaging (MRI), in patients with left ventricular systolic dysfunction following MI.

Contribution of infection to mortality in people with type 2 diabetes: a population-based cohort study using electronic records.

Background: While people with type 2 diabetes (T2D) are more susceptible to infections, studies potentially underestimate the true burden of infection-related mortality since they rely on clinical coding systems primarily structured by body system, and by only focusing on underlying cause. This study examined cause-specific mortality in people with T2D compared to the general population during 2015-2019, focusing on infections.

Methods: 509,403 people aged 41-90 years with T2D alive on 1/1/2015 in Clinical Practice Research Datalink were matched to 976,431 without diabetes on age, sex, and ethnicity.

Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials.

Background: GLP-1 receptor agonists reduce the risk of major adverse cardiovascular events (MACE) and can also have kidney benefits. However, whether GLP-1 receptor agonists improve clinically important kidney outcomes remains uncertain. We aimed to comprehensively assess the effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes by performing a meta-analysis of randomised controlled trials.

Routine measurement of cardiometabolic disease risk factors in primary care in England before, during, and after the COVID-19 pandemic: A population-based cohort study.

Background: This study estimated to what extent the number of measurements of cardiometabolic risk factors (e.g., blood pressure, cholesterol, glycated haemoglobin) were impacted by the COVID-19 pandemic and whether these have recovered to expected levels.

A Proteomics-Based Approach for Prediction of Different Cardiovascular Diseases and Dementia.

Background: Many studies have explored whether individual plasma protein biomarkers improve cardiovascular disease risk prediction. We sought to investigate the use of a plasma proteomics-based approach in predicting different cardiovascular outcomes.

Methods: Among 51 859 UK Biobank participants (mean age, 56.

Adding traditional and emerging biomarkers for risk assessment in secondary prevention: A prospective cohort study of 20,656 patients with cardiovascular disease.

Background: This study aims to explore whether conventional and emerging biomarkers could improve risk discrimination and calibration in secondary prevention of recurrent atherosclerotic cardiovascular disease (ASCVD), based on a model using predictors from SMART2.

Methods: In a cohort of 20,658 UK Biobank participants with medical history of ASCVD, we analysed any improvement in C indices and net reclassification index (NRI) for future ASCVD events, following addition of LP-a, ApoB, cystatin C, HbA1c, GGT, AST, ALT, and ALP, to a model with predictors used in SMART2 for the outcome of recurrent major cardiovascular event. We also examined any improvement in C indices and NRIs replacing creatinine based estimated glomerular filtration rate (eGFR) with cystatin C based estimates.

Associations of Serum Lipid Traits With Fracture and Osteoporosis: A Prospective Cohort Study From the UK Biobank.

Background: Previous studies reveal inconsistent associations between serum lipid traits and the risks of fractures and osteoporosis in the general population.

Methods: This prospective cohort study analysed data from 414 302 UK Biobank participants (223 060 women and 191 242 men, aged 37-73 years) with serum lipid measurements: apolipoprotein A (Apo A), apolipoprotein B (Apo B), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid trait with the risks of fractures and osteoporosis.

Bayesian Model Projecting Cardiovascular Disease Related Mortality Trends in the United States.

Background: As future cardiovascular disease mortality trends have public health implications, we aimed to project ischemic heart disease (IHD), cerebrovascular disease (CeVD), and heart failure (HF) mortality rates for adults (40-79 years).

Methods And Results: In this population-level study, we linked the yearly mortality rates (per 100 000 US residents) (2000-2019) with IHD, CeVD, or HF as the primary cause of death from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research with the midyear US population estimates (2000-2035) for adults (40-79 years). We calculated the observed age-standardized mortality rates (2000-2019) (per 100 000 residents) (aSMR) and fitted Bayesian age-period-cohort models to project aSMR for IHD, CeVD, and HF up to 2035 in the United States.

The association between county-level premature cardiovascular mortality related to cardio-kidney-metabolic disease and the social determinants of health in the US.

Cardio-kidney-metabolic (CKM) syndrome is defined by the American Heart Association as the intersection between metabolic, renal and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality and recent trends in the US is essential for developing targeted public interventions. We collected state-level and county-level CKM-associated age-adjusted premature cardiovascular mortality (aaCVM) (2010-2019) rates from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER).

Impact of baseline FIB-4 score on efpeglenatide benefits on cardiovascular outcomes in people with type 2 diabetes: a participant-level exploratory analysis of the AMPLITUDE-O trial.

Aims: To estimate the incidence of major adverse cardiovascular events (MACE), expanded MACE, and MACE or Death across Fibrosis- 4 score (FIB-4) categories in people with type 2 diabetes and to determine whether efpeglenatide's effect varies with increasing FIB-4 severity.

Materials And Methods: AMPLITUDE-O trial data were used to estimate the relationship of FIB-4 score categories to the hazard of MACE, expanded MACE, and MACE or death. Interactions on these outcomes between baseline FIB-4 score, and between FIB-4 score and efpeglenatide were also assessed.

Investigating the association of the effect of genetically proxied PCSK9i with mood disorders using cis-pQTLs: A drug-target Mendelian randomization study.

PCSK9-inhibitors (PCSK9i) are new drugs recently approved to lower LDL-cholesterol levels. However, due to the lack of long-term clinical data, the potential adverse effects of long-term use are still unknown. The PCSK9 genetic locus has been recently implicated in mood disorders and hence we wanted to assess if the effect of PCSK9i that block the PCSK9 protein can lead to an increase in the incidence of mood disorders.

In which common chronic conditions can (or cannot) obesity and lifestyle factors explain higher concentrations of C-reactive protein?

Aim: Elevated C-reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity.

Materials And Methods: This cross-sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline.

DNAm scores for serum GDF15 and NT-proBNP levels associate with a range of traits affecting the body and brain.

Background: Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification.

Results: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all P < 0.

Preclinical modeling of metabolic syndrome to study the pleiotropic effects of novel antidiabetic therapy independent of obesity.

Cardiovascular-kidney-metabolic health reflects the interactions between metabolic risk factors, chronic kidney disease, and the cardiovascular system. A growing body of literature suggests that metabolic syndrome (MetS) in individuals of normal weight is associated with a high prevalence of cardiovascular diseases and an increased mortality. The aim of this study was to establish a non-invasive preclinical model of MetS in support of future research focusing on the effects of novel antidiabetic therapies beyond glucose reduction, independent of obesity.

Reaffirmation of Mechanistic Proteomic Signatures Accompanying SGLT2 Inhibition in Patients With Heart Failure: A Validation Cohort of the EMPEROR Program.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors exert a distinctive pattern of direct biological effects on the heart and kidney under experimental conditions, but the meaningfulness of these signatures for patients with heart failure has not been fully defined.

Objectives: We performed the first mechanistic validation study of large-scale proteomics in a double-blind randomized trial of any treatment in patients with heart failure.

Methods: In a discovery cohort from the EMPEROR (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure and Reduced Ejection Fraction) program, we studied the effect of randomized treatment with placebo or empagliflozin on 1,283 circulating proteins in 1,134 patients with heart failure with a reduced or preserved ejection fraction.

Association of glycaemic control with intraocular pressure in a large general population: Results from the UK Biobank.

Aim: To evaluate the association of glycated haemoglobin (HbA1c) and serum glucose with intraocular pressure (IOP) in a large UK general population.

Materials And Methods: Participants were selected from the UK Biobank, excluding those with eye conditions that may affect IOP. IOP was measured using an ocular response analyser.

Change in physical activity and its association with decline in kidney function: A UK Biobank-based cohort study.

Background: Previous research on the association between physical activity (PA) and kidney function is inconsistent. The association between muscle mass and serum creatinine (SCr) may have implications for interpreting the effect of PA on estimated glomerular filtration rate (eGFR). Few studies have reported changes in physical activity and changes in kidney function.

Rising to the challenge of cardio-renal-metabolic disease in the 21st century: Translating evidence into best clinical practice to prevent and manage atherosclerosis.

Rising rates of obesity-associated cardiometabolic disorders allied to ageing populations are driving increases in cardiovascular morbidity and mortality. These adverse trends present challenges for healthcare systems that are struggling to prevent and manage the burgeoning cardiometabolic nexus of multiple long-term conditions. While potent new medications and non-pharmacological interventions have ushered in a promising new therapeutic era, translating clinical trial data to real-world clinical practice is often suboptimal.

Weight gain leads to greater adverse metabolic responses in South Asian compared with white European men: the GlasVEGAS study.

South Asians (SAs) develop type 2 diabetes at lower body mass index values than white Europeans (WEs). This basic human experimental study aimed to compare the metabolic consequences of weight gain in SA and WE men without overweight or obesity. Fourteen SAs and 21 WEs had assessments of body composition, metabolic responses to mixed-meal ingestion, cardiorespiratory fitness and physical activity, and a subcutaneous abdominal adipose tissue biopsy, before and after 4-6 weeks of overfeeding to induce 5-7% weight gain.

Baseline Characteristics in the Remote Diet Intervention to REduce long-COVID Symptoms Trial (ReDIRECT).

Background: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC.

Methods: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms.