Early detection of heart failure using in-patient longitudinal electronic health records.

Heart Failure (HF) is common, with worldwide prevalence of 1%-3% and a lifetime risk of 20% for individuals 40 years or older. Despite its considerable health economic burden, techniques for early detection of HF in the general population are sparse. In this work we tested the hypothesis that a simple Transformer neural network, trained on comprehensive collection of secondary care data across the general population, can be used to prospectively (three-year predictive window) identify patients at an increased risk of first hospitalisation due to HF (HHF).

Association between body mass index and clinical outcomes in patients with acute myocardial infarction and reduced systolic function: Analysis of PARADISE-MI trial data.

Aims: The relationship between body mass index (BMI) and clinical outcomes in patients with cardiovascular disease, including acute heart failure (AHF) and acute myocardial infarction (AMI), remains debated. This study investigates the association between BMI and clinical outcomes within the PARADISE-MI cohort, while also evaluating the impact of angiotensin receptor-neprilysin inhibitor (ARNI) versus angiotensin-converting enzyme inhibitor (ACE-I) treatment on this relationship.

Methods And Results: The analysis included 5589 patients from the PARADISE-MI study with available baseline BMI data.

Arterial effects of anthracycline: structural and inflammatory assessments in non-human primates and lymphoma patients.

Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models, and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were (1) to evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; (2) to assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.

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.

Exploring patients' views regarding the support and rehabilitation needs of people living with myocardial ischaemia and no obstructive coronary arteries: a qualitative interview study.

Objectives: This study aimed to generate new qualitative insights to understand the rehabilitation needs of people living with a confirmed or presumed diagnosis of ischaemia with no obstructive coronary arteries (INOCA), explore which aspects of current cardiovascular prevention and rehabilitation programmes could meet the needs of people with INOCA and where adjustments (if any) may be appropriate.

Design: Semistructured qualitative interview study.

Participants: Interviews were undertaken (n=17; 88% female, age range 31-69 years) with people with a confirmed or presumed diagnosis of INOCA.

Visit-to-visit changes in heart rate in heart failure: A pooled participant-level analysis of the PARADIGM-HF and PARAGON-HF trials.

Aims: Resting heart rate (HR) is a strong risk marker in patients with heart failure (HF), but the clinical implications of visit-to-visit changes in HR (ΔHR) are less well established. We aimed to explore the association between ΔHR and subsequent outcomes in a pooled dataset of two well-characterized cohorts of patients with HF across the full range of left ventricular ejection fraction (LVEF).

Methods And Results: PARADIGM-HF and PARAGON-HF were randomized trials testing sacubitril/valsartan versus enalapril or valsartan, respectively, in patients with HF and LVEF ≤40% (PARADIGM-HF) or LVEF ≥45% (PARAGON-HF).

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.

Insights into Uromodulin and Blood Pressure.

Purpose Of Review: We review the role of uromodulin, a protein exclusively expressed in the kidney, in blood pressure regulation and hypertension.

Recent Findings: The last few years have seen a shift of focus from genetic association to mendelian randomisation and uromodulin-salt interaction studies, thus confirming the causal role of uromodulin in blood pressure regulation and hypertension. This work has been complemented by phenome-wide association studies in a wider range of ethnicities.

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.

Mineralocorticoid receptor antagonists in heart failure: an individual patient level meta-analysis.

Background: Mineralocorticoid receptor antagonists (MRAs) reduce hospitalisations and death in patients with heart failure and reduced ejection fraction (HFrEF), but the benefit in patients with heart failure and mildly reduced ejection fraction (HFmrEF) or heart failure and preserved ejection fraction (HFpEF) is unclear. We evaluated the effect of MRAs in four trials that enrolled patients with heart failure across the range of ejection fraction.

Methods: This is a prespecified, individual patient level meta-analysis of the RALES (spironolactone) and EMPHASIS-HF (eplerenone) trials, which enrolled patients with HFrEF, and of the TOPCAT (spironolactone) and FINEARTS-HF (finerenone) trials, which enrolled patients with HFmrEF or HFpEF.

Sacubitril/valsartan reduces incident anaemia and iron therapy utilization in heart failure: The PARAGON-HF trial.

Aims: Renin-angiotensin system inhibitors (RASi) have been shown to lower haemoglobin levels, potentially related to reductions in erythropoietin levels and haematopoiesis. We examined whether sacubitril/valsartan might attenuate this effect of RASi alone on incident anaemia in patients with heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF).

Methods And Results: PARAGON-HF was a global, multicentre randomized clinical trial of sacubitril/valsartan versus the RASi valsartan in patients with HF and left ventricular ejection fraction ≥45%.

Acute Dosing Strategy with Vistula Tart Cherries for Recovery of Strenuous Exercise-A Feasibility Study.

Tart cherry (TC) consumption has become a popular nutritional strategy for recovery, particularly for the attenuation of markers associated with muscle damage. However, there are relatively few studies that have examined an acute dosing strategy. The aim of this pilot study was to explore the feasibility of using powdered Vistula TC for recovery following a bout of muscle-damaging exercise.

N-terminal pro-B-type natriuretic peptide levels vary by ethnicity and are associated with insulin sensitivity after gestational diabetes mellitus.

Background: Individuals of South Asian origin have a greater risk of cardiovascular disease after gestational diabetes mellitus (GDM) than European individuals. B-type natriuretic peptide (BNP) and the amino-terminal fragment of its prohormone (NT-proBNP) are commonly used for heart failure screening and diagnosis, but biologically BNP exerts several beneficial cardiovascular effects primarily by counteracting the renin-angiotensin-aldosterone-system. We asked whether ethnic differences in circulating NT-proBNP levels could be explained by the differences in cardiometabolic and inflammatory risk markers?

Methods: We examined 162 South Asian and 107 Nordic women in Norway 1-3 years after GDM with a clinical examination, fasting blood samples and an oral glucose tolerance test.

A genome-wide association meta-analysis of all-cause and vascular dementia.

Introduction: Dementia is a multifactorial disease with Alzheimer's disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD.

Methods: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD.

Low thiamine status in adults following low-carbohydrate / ketogenic diets: a cross-sectional comparative study of micronutrient intake and status.

Background: Low-carbohydrate diets (LCD) are popular for weight loss but lack evidence about micronutrient sufficiency in real-life use. This study assessed the intake and biochemical status of selected micronutrients in people voluntarily following LCDs.

Methods: A cross-sectional study was conducted (2018-20) among 98 adults recruited as self-reporting either LCD (n = 49) or diets not restricting carbohydrates (controls; n = 49).

Arterial effects of anthracycline: structural and inflammatory assessments in non-human primates and lymphoma patients using F-FDG positron emission tomography.

Background: Anthracyclines, such as doxorubicin, are important anti-cancer therapies but are associated with arterial injury. Histopathological insights have been limited to small animal models and the role of inflammation in the arterial toxic effects of anthracycline is unclear in humans. Our aims were: 1) To evaluate aortic media fibrosis and injury in non-human primates treated with anthracyclines; 2) To assess the effect of anthracycline on aortic inflammation in patients treated for lymphoma.

A predictive model for medium-term weight loss response in people with type 2 diabetes engaging in behavioural weight management interventions.

Aims: To develop and evaluate prediction models for medium-term weight loss response in behavioural weight management programmes.

Materials And Methods: We conducted three longitudinal analyses using the Action for HEalth in Diabetes (LookAHEAD) trial, Weight loss Referrals for Adults in Primary care (WRAP) trial, and routine data from the National Health Service Greater Glasgow and Clyde Weight Management Service (NHS-GGCWMS). We investigated predictors of medium-term weight loss (>5% body weight) over 3 years in NHS-GGCWMS and, separately, predictors of weight loss response in LookAHEAD over 4 years.