Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology.

Cardiac remodelling refers to changes in left ventricular structure and function over time, with a progressive deterioration that may lead to heart failure (HF) development (adverse remodelling) or vice versa a recovery (reverse remodelling) in response to HF treatment. Adverse remodelling predicts a worse outcome, whilst reverse remodelling predicts a better prognosis. The geometry, systolic and diastolic function and electric activity of the left ventricle are affected, as well as the left atrium and on the long term even right heart chambers.

Invasive coronary physiology in patients with angina and non-obstructive coronary artery disease: a consensus document from the coronary microvascular dysfunction workstream of the British Heart Foundation/National Institute for Health Research Partnership.

Nearly half of all patients with angina have non-obstructive coronary artery disease (ANOCA); this is an umbrella term comprising heterogeneous vascular disorders, each with disparate pathophysiology and prognosis. Approximately two-thirds of patients with ANOCA have coronary microvascular disease (CMD). CMD can be secondary to architectural changes within the microcirculation or secondary to vasomotor dysfunction.

Associations between dietary patterns, FTO genotype and obesity in adults from seven European countries.

Purpose: High-fat and low-fibre discretionary food intake and FTO genotype are each associated independently with higher risk of obesity. However, few studies have investigated links between obesity and dietary patterns based on discretionary food intake, and the interaction effect of FTO genotype are unknown. Thus, this study aimed to derive dietary patterns based on intake of discretionary foods, saturated fatty acids (SFA) and fibre, and examine cross-sectional associations with BMI and waist circumference (WC), and interaction effects of FTO genotype.

Mechanistic study of the effect of Endothelin SNPs in microvascular angina - Protocol of the PRIZE Endothelin Sub-Study.

Introduction: Microvascular angina is a common cause of ischemia with non-obstructive coronary arteries (INOCA) and limited therapeutic options are available to those affected. Endothelin-1 (ET-1) is a potent vasoconstrictor implicated in the pathophysiology of microvascular angina. A large randomised, double blinded, placebo controlled crossover trial, the PRecIsion medicine with ZibotEntan in microvascular angina (PRIZE) trial is currently underway, investigating an endothelin receptor antagonist - Zibotentan, as a new drug treatment for microvascular angina.

Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis.

Tirzepatide is a novel, once weekly, dual GIP/GLP-1 receptor agonist and is under development for the treatment of type 2 diabetes (T2D) and obesity. Its association with cardiovascular outcomes requires evaluation. This pre-specified cardiovascular meta-analysis included all seven randomized controlled trials with a duration of at least 26 weeks from the tirzepatide T2D clinical development program, SURPASS.

Does Excess Tissue Sodium Storage Regulate Blood Pressure?

Purpose Of Review: The regulation of blood pressure is conventionally conceptualised into the product of "circulating blood volume" and "vasoconstriction components". Over the last few years, however, demonstration of tissue sodium storage challenged this dichotomous view.

Recent Findings: We review the available evidence pertaining to this phenomenon and the early association made with blood pressure; we discuss open questions regarding its originally proposed hypertonic nature, recently challenged by the suggestion of a systemic, isotonic, water paralleled accumulation that mirrors absolute or relative extracellular volume expansion; we present the established and speculate on the putative implications of this extravascular sodium excess, in either volume-associated or -independent form, on blood pressure regulation; finally, we highlight the prevalence of high tissue sodium in cardiovascular, metabolic and inflammatory conditions other than hypertension.

Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

Aims/hypothesis: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven.

Methods: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet.

Muscle protein synthesis and muscle/metabolic responses to resistance exercise training in South Asian and White European men.

The aims of the current study, therefore, were to compare (1) free-living MPS and (2) muscle and metabolic adaptations to resistance exercise in South Asian and white European adults. Eighteen South Asian and 16 White European men were enrolled in the study. Free-living muscle protein synthesis was measured at baseline.

Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes.

Aims: Empagliflozin treatment reduced liver fat in small type 2 diabetes cohorts. This post-hoc study evaluated effects of empagliflozin on risk for non-alcoholic fatty liver disease-related steatosis and fibrosis, as well as the relationship between risk categories and cardiorenal outcomes in the randomized, placebo-controlled EMPA-REG OUTCOME trial.

Materials And Methods: EMPA-REG OUTCOME treated 7020 people with type 2 diabetes and cardiovascular disease with 10/25 mg/day empagliflozin or placebo.

Stress Cardiac Biomarkers, Cardiovascular and Renal Outcomes, and Response to Canagliflozin.

Background: Circulating biomarkers reflecting different mechanistic pathways may identify at-risk individuals with diabetes who may benefit from sodium-glucose cotransporter-2 (SGLT2) inhibitors.

Objectives: The purpose of this study was to determine if high-sensitivity cardiac troponin T (hs-cTnT), soluble suppression of tumorigenesis-2 (sST2), and insulin-like growth factor binding protein 7 (IGFBP7) levels, either alone or in combination, may modify the treatment benefits of canagliflozin.

Methods: In the CANVAS (CANagliflozin cardioVascular Assessment Study) biomarker substudy, we evaluated the prognostic significance of baseline biomarker measurements, the long-term trajectory of each, and response to canagliflozin on key cardiovascular and kidney outcomes.

Osteoporosis and Its Association With Cardiovascular Disease, Respiratory Disease, and Cancer: Findings From the UK Biobank Prospective Cohort Study.

Objective: To investigate sex-specific associations of osteoporosis with incidence of and mortality from cardiovascular disease (CVD), respiratory disease, and cancer as well as with all-cause mortality.

Methods: In total, 305,072 participants (53% [161,383] women) of UK Biobank were included in this study (2007-2010). Self-reported diagnosis of osteoporosis at baseline was the exposure of interest.

Clinical and radiological characteristics of acute pulmonary embolus in relation to 28-day and 6-month mortality.

Background: Patients with acute pulmonary embolism (PE) exhibit a wide spectrum of clinical and laboratory features when presenting to hospital and pathophysiologic mechanisms differentiating low-risk and high-risk PE are poorly understood.

Objectives: To investigate the prognostic value of clinical, laboratory and radiological information that is available within routine tests undertaken for patients with acute PE.

Methods: Electronic patient records (EPR) of patients who underwent Computed Tomography Pulmonary Angiogram (CTPA) scan for the investigation of acute PE during 6-month period (01.

Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics.

Aims: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney.

Methods And Results: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies in ∼300 000 participants of white-British ancestry from UK Biobank and participants of predominantly European ancestry from genome-wide association studies.

The power of genetic diversity in genome-wide association studies of lipids.

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels, heart disease remains the leading cause of death worldwide. Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease.

Aspirin use is associated with increased risk for incident heart failure: a patient-level pooled analysis.

Aims: Recent trials evaluating the effect of aspirin in the primary prevention of cardiovascular disease showed little or no benefit. However, the role of aspirin on the risk of incident heart failure (HF) remains elusive. This study aimed to evaluate the role of aspirin use on HF incidence in primary and secondary prevention and whether aspirin use increases the risk of incident HF in patients at risk.

Foot Ulcer and Risk of Lower Limb Amputation or Death in People With Diabetes: A National Population-Based Retrospective Cohort Study.

Objective: To describe incidence of foot ulceration and amputation-free survival associated with foot ulceration status in a national population-based cohort study of people with diabetes.

Research Design And Methods: The study population included 233,459 people with diabetes who were alive in Scotland on 1 January 2012 identified from the national population-based register (national prevalence 4.9%).