A Mark Richards

..To investigate the subacute effects of a sustained intravenous infusion of urocortin-I (Ucn-I) in experimental heart failure (HF)...

..We tested the hypothesis that the rare allele of an ACE2 gene polymorphism was associated with risk factors for and adverse outcome after acute coronary syndrome (ACS) events...

..The place of urotensin II in the chronic trophic responses to cardiac and vascular injury and its possible roles as a neurotransmitter and/or regulator of renal and endocrine function remain largely unexplored...

..Finally, adjustment of therapy for heart failure according to serial measurements of NT-proBNP promises to improve outcomes in comparison with adjusting therapy according to unassisted clinical acumen...

..Recombinant B-type NP is an effective parenteral treatment in decompensated heart failure. These applications of B-type NPs require confirmation before they become established in routine management of heart failure...

..After acute cardiac injury, left ventricular ejection fraction (LVEF) is also of prognostic significance and plays a major role in determining the therapeutic response...

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..Despite many promising candidates requiring fuller investigation, currently, only the natriuretic peptides satisfy these requirements...

..MR antagonism is an important part of the pharmaceutical armamentarium in managing heart failure but must be prescribed with careful case selection, taking note of the evidence of where risks are acceptable and benefits are likely...

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..Because any prospective new treatment is likely to be used in conjunction with standard diuretic therapy, it is necessary to investigate the combined effects of these agents...

..These findings support the concept of adrenomedullin as a protective hormone during hemodynamic compromise with therapeutic potential in heart failure...

..This study aimed to corroborate the association of the AMPD1 C34T polymorphism with survival in larger myocardial infarction (MI) and HF cohorts...

..These results indicate that dual treatment with these two agents is beneficial...

..Apelin also increases circulating levels of a number of vasoactive hormones. Taken together, these results suggest a potential role for apelin in pressure/volume homeostasis...

..These findings support the therapeutic potential for urocortin 2 in heart failure...

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..Urinary betaine excretion positively correlated with plasma homocysteine in outpatients attending a lipid disorders clinic (lipid clinic study). We aimed to confirm this in subjects with established vascular disease...

..We sought to examine the effects of urocortin (UCN) 2 infusion on hemodynamic status, cardiovascular hormones, and renal function in healthy humans...

..Despite the greater falls in blood pressure (and presumably renal perfusion pressure), renal function was maintained at a level similar to that observed with captopril alone...

..The (pro)renin receptor (P)RR is implicated in blood pressure regulation and the pathophysiology of heart failure (HF). The effects of (P)RR blockade in HF have not been previously investigated...

..0; 95% CI: 1.3 to 3.0; P=0.001). This study suggested that angiotensinogen gene variants M235T and T174M may provide prognostic information for long-term survival in heart failure patients...

..We investigated whether aldosterone levels in patients presenting with STEMI or non-STEMI, are predictive of mortality during prolonged follow-up...

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..Our findings indicate that blockade of the TGF-beta signaling pathway results in significant amelioration of deleterious cardiac remodeling after infarction...

..The decreased viability of Npr1(-/-)embryos may result from a combination of cardiomegaly and dysregulated Cx43 protein affecting cardiac contractility...

..However, the effect of rs1333049 on clinical outcomes in patients with established coronary disease has yet to be determined...

..Betaine insufficiency is associated with unfavourable vascular risk profiles in metabolic syndrome patients. We investigated associations between betaine insufficiency and secondary events in acute coronary syndrome patients...

..The association of UCP2 with baseline biochemical and hormonal measurements, including levels of the inflammatory marker myeloperoxidase, was also examined...

..We sought to assess the relationship of antecedent hypertension to neurohormones, ventricular remodeling and clinical heart failure (HF) after myocardial infarction (MI)...

..These data strongly support a use for Ucn1 as a therapeutic option early in the course of the disease...

..Thus, AM-2 may be another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease...

..The threshold for the action of Ucn1 on the natriuretic peptides and endothelin-1 appears to be below that of other actions of Ucn1...

..This study investigated relationships between plasma myeloperoxidase (MPO), protein oxidation markers, and clinical outcome retrospectively in patients after acute myocardial infarction (MI)...

..CONCLUSION: We describe details of a study to test the potential utility of serial measurements of NTproBNP in adjusting the drug treatment of patients with CHF. Projected completion date is 2007...

..These results are the first to show that E(2) stimulates plasma CNP forms and bALP in lambs and adult sheep and raise the possibility that CNP also participates in bone formation in the mature skeleton...

..The effects of AM2 in heart failure have not been investigated previously...

..7%, P < 0.001). Conclusion Ten year rates of mortality and HF are 5-10 times higher when lower eGFR is present together with increased NT-proBNP or depressed LVEF...

..Taken together, differences in magnitude and direction of transorgan gradients for CNP compared with NT-proCNP suggest net generalized cosecretion with differing mechanisms of clearance...

..Fall in plasma CNP but not in NTproCNP in CR adult sheep suggests that CNP degradation (not synthesis) is altered, and contrasts with previous findings in growing lambs where CR reduces both CNP forms...

..In summary, NT-proCNP levels in blood show a strong association with growth velocity and markers of bone formation and may well serve as a useful marker of growth plate activity in humans and other mammals...

..Urocortin 2 (Ucn2) has potent cardiovascular actions and may participate in the pathophysiology of heart failure (HF). The integrated hemodynamic, endocrine, and renal effects of Ucn2 are unknown...

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..ANP and ghrelin were unchanged, and no haemodynamic or renal effects were seen. In conclusion, a brief intravenous infusion of 50 microg of Ucn 1 stimulates corticotropin and cortisol in male volunteers with stable HF...

..We aimed to measure the relationships between plasma and urine betaine and plasma lipids, and the effects of lipid-lowering drugs on these...

..To investigate the role of the endogenous urocortin peptides in heart failure (HF) through blockade of the corticotropin-releasing factor receptor 2 (CRF-R2)...

..853). 4. The results indicate that the homozygous CYP1A1 6235C genotype is associated with greater mortality following the onset of ACS, independent of ethnicity and clinical risk factors, but related to smoking history...

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..The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge)...

..Whether correlations of NTproCNP with linear growth, as found in children and lambs, apply in neonates is unknown...

..We have investigated plasma urocortin 1 as a potential diagnostic marker of heart failure and documented its relationships to symptoms, measures of cardiac function, and concurrent levels of other circulating neurohormones...

..Thus EPO directly enhances cardiac contractility and BNP secretion and alleviates ischemia/reperfusion injury via ET-1-dependent and -independent mechanisms respectively...

..In the meantime, clinicians need to consider the known effects of medications when interpreting plasma levels of the cardiac natriuretic peptides...

..Manipulation of the AM system holds promise as a therapeutic strategy in cardiac disease...

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..This study provides evidence that natriuretic peptides play a pivotal role in preserving volume/electrolyte balance in the early stages of post-MI cardiac dysfunction...

..This is the first report identifying sources of circulating Ucn-1...

..Circulating levels of CNP and NT-CNP were raised in heart failure but to a much lesser degree than ANP and BNP. There was no evidence of net extraction of CNP or NT-CNP across any tissue bed...

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..We describe the first human experience with a permanently implantable, direct left atrial pressure (LAP) monitoring system in ambulatory patients with chronic heart failure...

..Thus, these results clearly point to a role for AM in pressure and volume homeostasis acting, at least in part, by interaction with the renin-angiotensin-aldosterone system (RAAS)...

..The Ile164 variant of the beta2-adrenoceptor has been shown to alter cardiovascular phenotypes and adversely affect survival in heart failure patients...

..However, there is a clear need to identify circulating, specific biomarkers that can detect cardiac ischemia without necrosis...

..Urocortin 1 (Ucn1) and the sympathetic nervous system both participate in cardiac and circulatory regulation, but little is known about their possible interactions...

..The favourable biological properties of the natriuretic peptides have also led to their use as therapeutic agents...

..This encourages further exploration of hormone guidance of anti-heart failure therapy, which could be extended to patients with preserved ejection fraction, in addition to those with established systolic dysfunction...

..In conclusion, cotreatment with adrenomedullin and an endopeptidase inhibitor has beneficial hemodynamic and renal effects in heart failure beyond those of either agent separately...

..How much troponin must change has not been specified. We ascertained whether dynamic changes (δ) in high-sensitivity troponin T (hs-TnT) improved diagnostic and prognostic test performance in the emergency department...

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..CoQ10 depletion may also be a contributory factor for why statin intervention has not improved outcomes in CHF. There is an emerging evidence base in support of CoQ10 as an adjunctive therapy in CHF...

..Measurement of NT-pro-BNP in addition to clinical assessment and echocardiography may allow more reliable follow-up and timing of valve replacement for aortic stenosis...

..There is little recent information regarding outcome and its determinants following cardioversion (CV) for atrial fibrillation (AF) or flutter. This study aims to help improve prediction of cardiac rhythm outcome following CV for AF...

..Effects of eplerenone on LV diastolic function and progression of valve stenosis were also evaluated...

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..Plasma BNP was assessed for its ability to predict echocardiographic abnormality in 100 patients receiving long-term treatment in general practice for a provisional diagnosis of heart failure...

..We sought to determine site(s) of production and clearance of plasma NT-proBNP in the human circulation...

..We characterized the molecular forms of urine NT-proBNP detected by immunoassay...

..The aim of this study was to investigate the relationship between plasma coenzyme Q(10) (CoQ(10)) and survival in patients with chronic heart failure (CHF)...

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..Adjustments in treatment and serial clinical follow-up with NT-proBNP retesting should be considered at frequent intervals until biochemical stabilization or achievement of a maximally tolerated medical program...

..The goal of this study was to determine the bioactivity of urocortin (Ucn) in experimental heart failure (HF)...

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..An improved understanding of the role of adrenomedullin in heart failure might lead to the development of therapeutic agents acting through adrenomedullin receptors...

..Significant arteriovenous gradients were observed across the heart (36%), liver (40%) and kidney (44%). This is the first report to identify the heart, liver and kidney as sources of UII in the circulation...

..We sought to study the individual and integrative role of amino-terminal pro-brain natriuretic peptide (NT-proBNP) and parameters of renal function for prognosis in heart failure...

..CONCLUSIONS: Plasma natriuretic peptide levels are elevated in symptomatic patients with aortic stenosis. Measurement of natriuretic peptides may complement clinical and echocardiographic evaluation of patients with aortic stenosis...

..An inverse relationship between body mass index (BMI); (calculated as weight in kilograms divided by height in meters squared) and NT-proBNP concentrations has been described...

..These results indicate that the suppressive effect of beta blockers on PRA in patients with HF taking ACE inhibitors is temporary, and that there is no significant effect on serum aldosterone levels...

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..Mortality rates in subjects with intermediate NT-pro-BNP concentrations are lower than in those with NT-pro-BNP concentrations diagnostic for HF but are higher than in subjects with NT-pro-BNP concentrations less than the gray zone...

..005) provided prognostic information above and beyond conventional risk markers. In patients with clinically stable, angiographically documented coronary artery disease, plasma BNP levels are independently related to long-term survival...

..In this context, consideration for a more in-depth cardiovascular workup, as well as initiation or intensification of medical therapies with proven benefits might be indicated...