Association of bradykinin receptor 2 (BDKRB2) variants with physical performance and muscle mass: Findings from the LACE sarcopenia trial.

Introduction: Understanding genetic contributors to sarcopenia (age-related loss of muscle strength and mass) is key to finding effective therapies. Variants of the bradykinin receptor 2 (BDKRB2) have been linked to athletic and muscle performance. The rs1799722-9 and rs5810761 T alleles have been shown to be overrepresented in endurance athletes, possibly due to increased transcriptional rates of the receptor.

Allopurinol and cardiovascular outcomes in patients with ischaemic heart disease: the ALL-HEART RCT and economic evaluation.

Background: Allopurinol is a xanthine oxidase inhibitor that lowers serum uric acid and is used to prevent acute gout flares in patients with gout. Observational and small interventional studies have suggested beneficial cardiovascular effects of allopurinol.

Objective: To determine whether allopurinol improves major cardiovascular outcomes in patients with ischaemic heart disease.

Activin type I receptor polymorphisms and body composition in older individuals with sarcopenia-Analyses from the LACE randomised controlled trial.

Background: Ageing is associated with changes in body composition including an overall reduction in muscle mass and a proportionate increase in fat mass. Sarcopenia is characterised by losses in both muscle mass and strength. Body composition and muscle strength are at least in part genetically determined, consequently polymorphisms in pathways important in muscle biology (e.

ACE I/D genotype associates with strength in sarcopenic men but not with response to ACE inhibitor therapy in older adults with sarcopenia: Results from the LACE trial.

Background: Angiotensin II (AII), has been suggested to promote muscle loss. Reducing AII synthesis, by inhibiting angiotensin converting enzyme (ACE) activity has been proposed as a method to inhibit muscle loss. The LACE clinical trial was designed to determine whether ACE inhibition would reduce further muscle loss in individuals with sarcopenia but suffered from low recruitment and returned a negative result.

Impact of beta-blockers on mortality and cardiovascular disease outcomes in patients with obstructive sleep apnoea: a population-based cohort study in target trial emulation framework.

Background: There is no real-world evidence regarding the association between beta-blocker use and mortality or cardiovascular outcomes in patients with obstructive sleep apnoea (OSA). We aimed to investigate the impact of beta-blocker use on all-cause mortality and cardiovascular diseases (CVDs) in patients with OSA.

Methods: We conducted a target trial emulation study of 37,581 patients with newly diagnosed OSA from 1st January 2000 to 30th November 2021 using the IMRD-UK database (formerly known as the THIN database).

Cardiovascular outcomes in adults with hypertension with evening versus morning dosing of usual antihypertensives in the UK (TIME study): a prospective, randomised, open-label, blinded-endpoint clinical trial.

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication.

Allopurinol versus usual care in UK patients with ischaemic heart disease (ALL-HEART): a multicentre, prospective, randomised, open-label, blinded-endpoint trial.

Background: Allopurinol is a urate-lowering therapy used to treat patients with gout. Previous studies have shown that allopurinol has positive effects on several cardiovascular parameters. The ALL-HEART study aimed to determine whether allopurinol therapy improves major cardiovascular outcomes in patients with ischaemic heart disease.

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial.

Background: This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia.

Methods: Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.

A Randomized, Controlled Trial of the Effect of Allopurinol on Left Ventricular Mass Index in Hemodialysis Patients.

Introduction: Increased left ventricular mass index (LVMI) is associated with mortality in end-stage renal disease. LVMI regression may improve outcomes. Allopurinol has reduced LVMI in randomized controlled trials in chronic kidney disease, diabetes, and ischemic heart disease.

Allopurinol in Patients with Pulmonary Hypertension Associated with Chronic Lung Disease.

Background: Oxidative stress (OS) has been implicated in the development of pulmonary hypertension (PH) and ventricular hypertrophy. Xanthine oxidase is a well-recognised source of reactive oxygen species, which lead to OS. The aim of this proof of concept study was to assess whether allopurinol (xanthine oxidase inhibitor) would reduce right ventricular mass (RVM) in patients with PH-associated chronic lung disease (PH-CLD).

Renal and Cardiovascular Effects of SGLT2 Inhibition in Combination With Loop Diuretics in Patients With Type 2 Diabetes and Chronic Heart Failure: The RECEDE-CHF Trial.

Background: SGLT2 (sodium-glucose cotransporter-2) inhibitors improve heart failure-associated outcomes in patients with type 2 diabetes. In patients with heart failure, SGLT2 inhibitors will likely be coprescribed with a loop diuretic, but this combined effect is not well-defined. Our aim was to assess the diuretic and natriuretic effect of empagliflozin in combination with loop diuretics.

Vitamin K Supplementation to Improve Vascular Stiffness in CKD: The K4Kidneys Randomized Controlled Trial.

Background: Vascular calcification, a risk factor for cardiovascular disease, is common among patients with CKD and is an independent contributor to increased vascular stiffness and vascular risk in this patient group. Vitamin K is a cofactor for proteins involved in prevention of vascular calcification. Whether or not vitamin K supplementation could improve arterial stiffness in patients with CKD is unknown.

A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial.

Aim: We tested the hypothesis that dapagliflozin may regress left ventricular hypertrophy (LVH) in people with type 2 diabetes (T2D).

Methods And Results: We randomly assigned 66 people (mean age 67 ± 7 years, 38 males) with T2D, LVH, and controlled blood pressure (BP) to receive dapagliflozin 10 mg once daily or placebo for 12 months. Primary endpoint was change in absolute left ventricular mass (LVM), assessed by cardiac magnetic resonance imaging.

Effect of allopurinol on phosphocreatine recovery and muscle function in older people with impaired physical function: a randomised controlled trial.

Background: Allopurinol has vascular antioxidant effects and participates in purinergic signalling within muscle. We tested whether allopurinol could improve skeletal muscle energetics and physical function in older people with impaired physical performance.

Methods: We conducted a randomised, double blind, parallel group, placebo-controlled trial, comparing 20 weeks of allopurinol 600 mg once daily versus placebo.

Dapagliflozin Versus Placebo on Left Ventricular Remodeling in Patients With Diabetes and Heart Failure: The REFORM Trial.

Objective: To determine the effects of dapagliflozin in patients with heart failure (HF) and type 2 diabetes mellitus (T2DM) on left ventricular (LV) remodeling using cardiac MRI.

Research Design And Methods: We randomized 56 patients with T2DM and HF with LV systolic dysfunction to dapagliflozin 10 mg daily or placebo for 1 year, on top of usual therapy. The primary end point was difference in LV end-systolic volume (LVESV) using cardiac MRI.

Cardiovascular Effects of Switching From Tobacco Cigarettes to Electronic Cigarettes.

Background: E-cigarette (EC) use is increasing exponentially worldwide. The early cardiovascular effects of switching from tobacco cigarettes (TC) to EC in chronic smokers is unknown. Meta-analysis of flow-mediated dilation (FMD) studies indicate 13% lower pooled, adjusted relative risks of cardiovascular events with every 1% improvement in FMD.

Allopurinol treatment adversely impacts left ventricular mass regression in patients with well-controlled hypertension.

Objectives: Previous studies have demonstrated that high-dose allopurinol is able to regress left ventricular (LV) mass in cohorts with established cardiovascular disease. The aim of this study was to assess whether treatment with high-dose allopurinol would regress LV mass in a cohort with essential hypertension, LV hypertrophy and well-controlled blood pressure but without established cardiovascular disease.

Methods: We conducted a mechanistic proof-of-concept randomized, placebo-controlled, double-blind trial of allopurinol (600 mg/day) versus placebo on LV mass regression.

A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial.

Aim: We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.

Methods And Results: We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.

Acceptability and feasibility of magnetic femoral nerve stimulation in older, functionally impaired patients.

Objective: Magnetic femoral nerve stimulation to test muscle function has been largely unexplored in older people. We assessed acceptability, feasibility, along with reproducibility and correlation with other physical function measures.

Results: Study 1 recruited older people with sarcopenia.

Disconnection of pulmonary and systemic arterial stiffness in COPD.

Background: Both pulmonary arterial stiffening and systemic arterial stiffening have been described in COPD. The aim of the current study was to assess pulse wave velocity (PWV) within these two arterial beds to determine whether they are separate or linked processes.

Materials And Methods: In total, 58 participants with COPD and 21 healthy volunteers (HVs) underwent cardiac magnetic resonance imaging (MRI) and were tested with a panel of relevant biomarkers.

Effect of Vitamin D Supplementation on Markers of Vascular Function: A Systematic Review and Individual Participant Meta-Analysis.

Background: Low 25-hydroxyvitamin D levels are associated with an increased risk of cardiovascular events, but the effect of vitamin D supplementation on markers of vascular function associated with major adverse cardiovascular events is unclear.

Methods And Results: We conducted a systematic review and individual participant meta-analysis to examine the effect of vitamin D supplementation on flow-mediated dilatation of the brachial artery, pulse wave velocity, augmentation index, central blood pressure, microvascular function, and reactive hyperemia index. MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.