Using matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) profiling in order to predict clinical outcomes of patients with heart failure.

Background: Current risk prediction models in heart failure (HF) including clinical characteristics and biomarkers only have moderate predictive value. The aim of this study was to use matrix assisted laser desorption ionisation mass spectrometry (MALDI-MS) profiling to determine if a combination of peptides identified with MALDI-MS will better predict clinical outcomes of patients with HF.

Methods: A cohort of 100 patients with HF were recruited in the biomarker discovery phase (50 patients who died or had a HF hospital admission vs.

PAR4 (Protease-Activated Receptor 4) Antagonism With BMS-986120 Inhibits Human Ex Vivo Thrombus Formation.

Objective: BMS-986120 is a novel first-in-class oral PAR4 (protease-activated receptor 4) antagonist with potent and selective antiplatelet effects. We sought to determine for the first time, the effect of BMS-986120 on human ex vivo thrombus formation.

Approach And Results: Forty healthy volunteers completed a phase 1 parallel-group PROBE trial (Prospective Randomized Open-Label Blinded End Point).

New Evidence Supporting the Use of Mineralocorticoid Receptor Blockers in Drug-Resistant Hypertension.

Treatment resistant hypertension (TRH), defined as a blood pressure above goal despite treatment with optimally tolerated doses of 3 antihypertensive agents of different classes, ideally including a diuretic, remains a significant problem and its management an area of uncertainty for physicians. One hypothesis is that resistant hypertension is due to abnormal sodium retention, mediated by aldosterone breakthrough occurring despite blockade of the renin-angiotensin-aldosterone system with angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB). Thus, there has been renewed interest in the use of mineralocorticoid receptor blockers (MRB) to treat this condition.

Prognostic value of human mature adrenomedullin in patients with acute myocardial infarction.

Adrenomedullin (ADM) correlates with adverse cardiovascular outcomes in patients with acute myocardial infarction (AMI) and in patients with heart failure. Measurement of human mature ADM (mADM) has been difficult, and recent studies have used its surrogate - the mid-regional pro-ADM (MRproADM). Our objective was to determine whether mADM measured by a novel sandwich immunoassay, using the anti-C-terminal and an anti-mid-regional monoclonal antibody, was prognostic of 30-day, 90-day, 1-year, and 2-year major adverse cardiovascular events (MACEs) in 1111 consecutive patients who have suffered an AMI.

Plasma growth hormone is a strong predictor of risk at 1 year in acute heart failure.

Aims: We sought to compare the prognostic utility of growth hormone (GH) with NT-proBNP) and the ADHERE score in a large cohort of acute heart failure (HF) patients, subcategorized into HF with reduced EF <50% (HFrEF) and preserved EF ≥50% (HFpEF).

Methods And Results: GH and NTproBNP levels were measured in 537 patients (HFrEF n = 415; HFpEF n = 122) with acute HF recruited into this prospective cohort study. The main outcome measure was death or HF readmission at 1 year.

Disproportionate effect on child admissions of the change in Medicines and Healthcare Products Regulatory Agency guidance for management of paracetamol poisoning: an analysis of hospital admissions for paracetamol overdose in England and Scotland.

Objective: The aim of the present study was to assess the effects of the changes in the management of paracetamol overdose recommended by the UK Commission for Human Medicines on rates of hospital admission.

Methods: An interrupted time series analysis was carried out on data for hospital admissions for paracetamol poisoning for England between January 2010 and June 2014, and for Scotland between January 2010 and Sept. 2014.

Prognostic significance of adrenomedullin in patients with heart failure and with myocardial infarction.

We undertook this systematic review to determine the prognostic significance of adrenomedullin (ADM) in patients with heart failure and acute myocardial infarction (AMI). Given the difficulty in measuring mature ADM, its surrogate, midregional proadrenomedullin (MRproADM) has been used in most studies. Systematic search of original published studies through MEDLINE and the Cochrane Collaboration databases restricted to reports in English from January 1, 1993, to June 30, 2014, in humans was undertaken.

Pro-substance p for evaluation of risk in acute myocardial infarction.

Background: Pro-substance P (ProSP) is a stable surrogate marker for labile substance P, which has pro-inflammatory effects, increases platelet aggregation and clot strength, and reduces fibrinolysis.

Objectives: This study assessed whether ProSP was associated with poor prognosis after acute myocardial infarction (AMI) to identify novel pathophysiological mechanisms.

Methods: ProSP was measured in 1,148 AMI patients (825 men, mean age 66.

Proenkephalin and prognosis after acute myocardial infarction.

Objectives: The goal of this research was to assess the prognostic value of proenkephalin (PENK) levels in acute myocardial infarction (AMI) by using N-terminal pro-B-type natriuretic peptide and Global Registry of Acute Coronary Events (GRACE) scores as comparators and to identify levels that might be valuable in clinical decision making.

Background: PENK is a stable analyte of labile enkephalins. Few biomarkers predict recurrent AMI.

The uroguanylin system and human disease.

The uroguanylin system is a newly discovered endocrine/paracrine system that may have a role in the regulation of salt balance, appetite and gut health. The precursor pro-uroguanylin is predominantly synthesized in the gut, although there may be other sites of synthesis, including the kidney tubules. Products from pro-uroguanylin may mediate natriuresis following oral consumption of a salt load through both GC-C (guanylate cyclase C)-dependent and -independent mechanisms, and recent evidence suggests a role in appetite regulation.

Pre-discharge risk stratification in unselected STEMI: is there a role for ST2 or its natural ligand IL-33 when compared with contemporary risk markers?

Background: Soluble ST2 is a marker of cellular stress and injury whose natural ligand is interleukin-33. We investigate, for the first time, the relationship of IL-33 and ST2 with death at 30-days, 1-year and beyond in unselected STEMI patients. We assess the incremental value they offer over GRACE score and NT-proBNP.

Interleukin 33 and ST2 in non-ST-elevation myocardial infarction: comparison with Global Registry of Acute Coronary Events Risk Scoring and NT-proBNP.

Background: Soluble ST2 is a marker of biomechanical strain for which the natural ligand is interleukin 33 (IL-33). They have not been studied together in non-ST-elevation myocardial infarction (NSTEMI). We investigated their relationship with death, heart failure (HF) readmission, and reinfarction combined (termed major adverse cardiac events [MACE]) and, separately, in unselected patients using Global Registry of Acute Coronary Events Risk Scoring (GRACE-RS) and n terminal pro B type natriuretic peptide (NT-proBNP) as benchmark comparators.

C-terminal provasopressin (copeptin) as a prognostic marker after acute non-ST elevation myocardial infarction: Leicester Acute Myocardial Infarction Peptide II (LAMP II) study.

Copeptin, the 39-amino-acid C-terminal portion of provasopressin, has been shown to be an independent predictor for adverse events following STEMI (ST elevation myocardial infarction). We hypothesized that plasma copeptin was an independent predictor for adverse outcomes following acute NSTEMI (non-STEMI) and evaluated whether copeptin added prognostic information to the GRACE (Global Registry of Acute Coronary Events) score compared with NT-proBNP (N-terminal pro-B-type natriuretic peptide). Plasma copeptin and NT-proBNP were measured in 754 consecutive patients admitted to the hospital with chest pain and diagnosed as having NSTEMI in this prospective observational study.

Proteinase 3 and prognosis of patients with acute myocardial infarction.

A multimarker approach may be useful for risk stratification in AMI (acute myocardial infarction) patients, particularly utilizing pathways that are pathophysiologically distinct. Our aim was to assess the prognostic value of PR3 (proteinase 3) in patients post-AMI. We compared the prognostic value of PR3, an inflammatory marker, with an established marker NT-proBNP (N-terminal pro-B-type natriuretic peptide) post-AMI.

Usefulness of plasma tissue inhibitors of metalloproteinases as markers of prognosis after acute myocardial infarction.

Alterations in the balance of matrix metalloproteinase to tissue inhibitor of metalloproteinase (TIMP) are seen after acute myocardial infarction (AMI) and are associated with adverse left ventricular remodeling and prognosis in this setting. We aimed to investigate the association between TIMP levels and the occurrence of major adverse cardiac events (MACEs) after AMI. We measured plasma TIMP-1, -2, and -4 levels in 1,313 patients presenting with AMI.

Prognostic value of mid-regional pro-adrenomedullin levels taken on admission and discharge in non-ST-elevation myocardial infarction: the LAMP (Leicester Acute Myocardial Infarction Peptide) II study.

Objectives: The purpose of this study was to assess the prognostic value of admission and discharge mid-regional pro-adrenomedullin (sAM) levels in non-ST-elevation myocardial infarction (MI) and identify values to aid clinical decision making. N-terminal pro-B-type natriuretic peptide and GRACE (Global Registry of Acute Coronary Events) score were used as comparators.

Background: sAM is a stable precursor of adrenomedullin.

Identification of potential outcome benefit from ACE inhibition after acute coronary syndrome: a biomarker approach using N-terminal proBNP.

Objective: To consider whether patients most likely to benefit from ACE inhibition in routine practice after acute coronary syndrome (ACS) may be identified from plasma natriuretic peptide concentrations.

Design: Observational cohort study.

Setting: Teaching hospital coronary care unit.

Activation of a novel natriuretic endocrine system in humans with heart failure.

Proguanylin and prouroguanylin are the inactive precursors of guanylin and uroguanylin, natriuretic peptides involved in the regulation of sodium balance. Urinary uroguanylin levels have been found previously to be elevated in patients with HF (heart failure). The aim of the present study was to investigate whether plasma proguanylin and prouroguanylin levels are increased in patients with HF and to evaluate their relationship with cardiac and renal function.

Matrix metalloproteinase-2 predicts mortality in patients with acute coronary syndrome.

The aim of the present study was to investigate the predictive value of MMP (matrix metalloproteinase)-2, MMP-3 and MMP-9 levels in patients with acute coronary syndrome for death, readmission with HF (heart failure) or recurrent MI (myocardial infarction) and to compare them with established markers, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and the GRACE (Global Registry of Acute Coronary Events) score. A single blood test was taken 4 days after admission in 1024 consecutive patients with acute MI with end points observed over 519 (134-1059) days [value is median (range)]. MMP-2 and MMP-3 were increased in patients who died (n=111) compared with survivors (P<0.

N-terminal pro-B-type natriuretic peptide complements the GRACE risk score in predicting early and late mortality following acute coronary syndrome.

The GRACE (Global Registry of Acute Coronary Events) risk score has been shown to offer predictive power with regard to death and AMI (acute myocardial infarction) in patients with ACS (acute coronary syndromes). NT-proBNP (N-terminal pro-B-type natriuretic peptide) has also been found to be useful in predicting mortality following ACS. In the present study, we sought to investigate the use of the GRACE score and NT-proBNP levels at predicting risk of early and late deaths following ACS.