Publications by authors named "Pemberton C"

Introduction: Control of blood pressure following acute type B aortic dissection usually requires sympatholytic antihypertensive medication. Although sympathetic nerve activity is central to blood pressure control, its role in the hypertensive response to acute aortic dissection has not been assessed.

Methods: A prospective pilot study was performed over an 18-month period.

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The heart requires a substantial amount of energy to function, utilising various substrates including lipids, glucose and lactate as energy sources. In times of increased stress, lactate becomes the primary energy source of the heart, but persistently elevated lactate levels are linked to poor patient outcomes and increased mortality. Recently, carnosine dipeptidase II (CNDP2) was discovered to catalyse the formation of Lac-Phe, an exercise-induced metabolite derived from lactate, which has been shown to suppress appetite in mice and reduce adipose tissue in humans.

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Aims: Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF.

Methods And Results: ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF.

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Soluble urokinase plasminogen activator receptor (suPAR), the soluble counterpart of urokinase plasminogen activator receptor, is found in the circulation at various levels. suPAR and its parent molecule, cell surface uPAR, exhibit similar structure and extracellular functional roles facilitating fibrinolysis, cellular adhesion, and migration. Studies have assessed the correlation between suPAR in cardiovascular disease (CVD).

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Background: Clinical decision-making for risk stratification for possible myocardial infarction (MI) uses high-sensitivity cardiac troponin (hs-cTn) thresholds that range from the limit of detection to several-fold higher than the upper reference limit (URL). To establish a minimum analytical variation standard, we can quantify the effect of variation on the population clinical measures of safety (sensitivity) and effectiveness [proportion below threshold, or positive predictive value (PPV)].

Methods: From large datasets of patients investigated for possible MI with the Abbott hs-cTnI and Roche hs-cTnT assays, we synthesized datasets of 1 000 000 simulated patients.

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Aims: The performance of circulating soluble urokinase plasminogen activator receptor (suPAR) for predicting the composite endpoint of subsequent heart failure (HF) hospitalisation and/or death at 1 year was assessed in (i) patients with undifferentiated breathlessness, and generalisability was compared in (ii) disparate Western versus Asian sub-cohorts, and in (iii) the sub-cohort adjudicated with HF.

Methods And Results: Patients with acute breathlessness were recruited from the emergency departments in New Zealand (NZ, n = 612) and Singapore (n = 483). suPAR measured in the presentation samples was higher in patients incurring the endpoint (n = 281) compared with survivors (5.

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Background: Growth differentiation factor-15 (GDF-15) has been shown to be associated with adverse clinical outcomes in patients after an acute coronary syndrome when measured soon after an event. Although dynamic in the acute phase after myocardial injury, GDF-15 has been shown to remain stable during convalescence. In this study, we aimed to assess the value of GDF-15 as a long-term prognostic marker for clinical outcomes when measured in the convalescent phase following an acute coronary syndrome.

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Background: Single-sample (screening) rule-out of acute myocardial infarction (AMI) with troponin requires derivation of a single-test screening threshold. In data sets with small event numbers, the lowest one or two concentrations of myocardial infarction (MI) patients dictate the threshold. This is not optimal.

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Objectives: In dyspneic patients with atrial fibrillation (AF) or obesity, the diagnostic performance of NT-proBNP for acute heart failure is reduced. We evaluated the erythroblast derived protein erythroferrone (ERFE) as an ancillary biomarker for the diagnosis of acute decompensated heart failure (ADHF) in these comorbid subgroups in both Western and Asian populations.

Methods: The diagnostic performance of ERFE (Intrinsic Lifesciences) and NT-proBNP (Roche Cobas e411) for ADHF was assessed in 479 New Zealand (NZ) and 475 Singapore (SG) patients presenting with breathlessness.

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Introduction: Evidence exploring the relationship between COVID-19 mitigation measures and mental health has primarily been from quantitative studies in large, developed countries. A qualitative study to explore the knowledge, attitudes and behaviors of young people living in Trinidad and Tobago was conducted to engage and collaborate with youth on matters affecting them during the pandemic.

Methods: Ten virtual focus groups were conducted with 64 participants aged 18 to 24 in 2021 when partial lockdown measures were in effect for COVID-19 prevention.

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Myoregulin is a recently discovered micropeptide that controls calcium levels by inhibiting the intracellular calcium pump sarco-endoplasmic reticulum Ca-ATPase (SERCA). Keeping calcium levels balanced in the heart is essential for normal heart functioning, thus myoregulin has the potential to be a crucial regulator of cardiac muscle performance by reducing the rate of intracellular Ca uptake. We provide the first report of myoregulin mRNA expression in human heart tissue, absence of expression in human plasma, and the effects of myoregulin on cardiac hemodynamics in an ex vivo Langendorff isolated rat heart model of ischemia/reperfusion.

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Bio-inspired cilium-based mechanosensors offer a high level of responsiveness, making them suitable for a wide range of industrial, environmental, and biomedical applications. Despite great promise, the development of sensors with multifunctionality, scalability, customizability, and sensing linearity presents challenges due to the complex sensing mechanisms and fabrication methods involved. To this end, high-aspect-ratio polycaprolactone/graphene cilia structures with high conductivity, and facile fabrication are employed to address these challenges.

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Background: Regional handling and the prognostic performance of insulin-like growth factor binding protein (IGFBP)-7, in contrast or in combination with other candidate biomarkers, in chronic heart failure (CHF) remain uncertain.

Objectives: The authors investigated the regional handling of plasma IGFBP-7 and its association with long-term outcomes in CHF in comparison with selected circulating biomarkers.

Methods: Plasma concentrations of IGFBP-7, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin-T, growth differentiation factor-15, and high-sensitivity C-reactive protein were measured prospectively in a cohort with CHF (n = 863).

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Background: In suspected myocardial infarction (MI), guidelines recommend using high-sensitivity cardiac troponin (hs-cTn)-based approaches. These require fixed assay-specific thresholds and timepoints, without directly integrating clinical information. Using machine-learning techniques including hs-cTn and clinical routine variables, we aimed to build a digital tool to directly estimate the individual probability of MI, allowing for numerous hs-cTn assays.

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Background: Patients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk stratification for the outcomes.

Materials And Methods: In a prospective AMI cohort in New Zealand ( = 464), we measured plasma proteins and lipids 30 days after hospital discharge and inferred a unified partial correlation network with echocardiographic variables and established clinical biomarkers (creatinine, c-reactive protein, cardiac troponin I and natriuretic peptides).

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Background: Elevations of high-sensitivity cardiac troponin (hs-cTn) concentrations not related to type 1 myocardial infarction are common in chest pain patients presenting to emergency departments. The discrimination of these patients from those with type 1 myocardial infarction (MI) is challenging and resource-consuming. We aimed to investigate whether the hs-cTn I/T ratio might provide diagnostic and prognostic increment in this context.

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Background: Secretion of cardioprotective B-type natriuretic peptide 1-32 (BNP1-32) is increased proportionately with cardiac dysfunction, but its measurement in plasma is difficult. Therefore, less specific BNP and amino-terminal proBNP (NT-proBNP) assays that detect the precursor molecule proBNP alongside BNP or NT-proBNP metabolites were developed to reflect BNP1-32 secretion and are now mandated in the diagnosis of heart failure (HF). We compared the diagnostic performance of 2 widely used clinical assays: the Roche proBNPII assay, and Abbott BNP assay, against our recently developed in-house assays that measure either intact BNP1-32 or NT-proBNP.

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Objectives: To evaluate the diagnostic performance of N-terminal pro-B-type natriuretic peptide (NT-proBNP) thresholds for acute heart failure and to develop and validate a decision support tool that combines NT-proBNP concentrations with clinical characteristics.

Design: Individual patient level data meta-analysis and modelling study.

Setting: Fourteen studies from 13 countries, including randomised controlled trials and prospective observational studies.

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Background: Development of a competent collateral circulation in established coronary artery disease is cardio-protective. The vascular endothelial growth factor (VEGF) system plays a key role in this process. We investigated the prognostic performance of circulating VEGF-A and three genetic variants in the VEGFA gene in a clinical coronary cohort.

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Background: Obese patients have lower plasma concentrations of the cardiac natriuretic peptides (NPs) than their age- and sex-matched counterparts. This may reflect lower production and/or increased peptide clearance. It is unclear whether NP bioactivity is affected by obesity.

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To identify circulating proteins predictive of acute cardiovascular disease events in the general population, we performed a proteomic screen in plasma from asymptomatic individuals. A "Discovery cohort" of 25 individuals who subsequently incurred a cardiovascular event within 3 years (median age = 70 years, 80% male) was matched to 25 controls remaining event-free for > 5 years (median age = 72 years, 80% male). Plasma proteins were assessed by data independent acquisition mass spectrometry (DIA-MS).

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Background: Heart failure (HF) is the most common long-term complication of acute myocardial infarction (MI). Understanding plasma proteins associated with post-MI HF and their gene expression may identify new candidates for biomarker and drug target discovery.

Methods: We used aptamer-based affinity-capture plasma proteomics to measure 1305 plasma proteins at 1 month post-MI in a New Zealand cohort (CDCS [Coronary Disease Cohort Study]) including 181 patients post-MI who were subsequently hospitalized for HF in comparison with 250 patients post-MI who remained event free over a median follow-up of 4.

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