Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients

Struck, Joachim; Chen, Tao; Morgenthaler, Nils G.; Bergmann, Andreas

doi:10.1016/j.peptides.2004.06.019

Cited by 190 publications

(148 citation statements)

References 14 publications

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“…ADM is elevated in response to a variety of stimuli, including sepsis and ventricular pressure/volume overload. [17][18][19][20][21] A double-monoclonal antibody sandwich immunoassay for the measurement of the more stable midregional (MR) fragment of the precursor (pro-ADM) has been identified. 22 Baseline and the change in MR-proADM concentrations after ACS have been shown to be associated with risk of major clinical events, including death.…”

Section: Discussionmentioning

confidence: 99%

Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial

Shah

Marston

Müeller

et al. 2015

Academic Emergency Medicine

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Objectives: Chest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR-proADM) in prediction of mortality and major adverse cardiac events (MACE).Methods: This was a subanalysis of the CHOPIN study, a 16-center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6-month all-cause mortality and the secondary endpoint was 30-day and 6-month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure.Results: MR-proADM performed similarly to troponin (cTnI; c-statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MRproADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6-month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR-proADM, history of coronary artery disease (CAD), and hypertension were predictors of short-term MACE, while history of CAD, hypertension, cTnI, and MR-proADM were predictors of long-term MACE.

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Section: Discussionmentioning

confidence: 99%

Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial

Shah

Marston

Müeller

et al. 2015

Academic Emergency Medicine

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“…The gene encoding for adrenomedullin is located within the short arm of chromosome 11 (2). Measurement of mature ADM as biomarker has been previously hampered by its short plasma half-life of 22 ± 1.6 minutes, the presence of a binding protein called human adrenomedullin binding protein (AMBP-1) identified as complement factor H (3), and the immediate binding of ADM to local receptors, which had rendered its accurate measurement difficult to achieve (3,4). A possible solution to this problem came from the development of assays to identify mid-regional pro-adrenomedullin (MRproADM), which is a more stable non-functional fragment of initial precursor peptide, consisting of 45 to 92 amino acids.…”

Section: Introductionmentioning

confidence: 99%

“…A possible solution to this problem came from the development of assays to identify mid-regional pro-adrenomedullin (MRproADM), which is a more stable non-functional fragment of initial precursor peptide, consisting of 45 to 92 amino acids. MRproADM is secreted in stoichiometric amounts to mature ADM and therefore acts as a reliable surrogate of ADM levels (4). To the best of our knowledge, no study has undertaken a systematic review or meta-analysis of ADM and incident major cardiovascular events or mortality in heart failure patients or acute myocardial infarction patients.…”

Section: Introductionmentioning

confidence: 99%

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

Yuyun

Narayan

2015

The American Journal of Cardiology

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Highlights-This systematic review shows that adrenomedullin is an independent predictor of death in patients with heart failure, as well as MACE and death in patients who have suffered an acute myocardial infarction.-Quantification of this peptide might contribute to improved risk stratification in settings of heart failure and myocardial infarction. ABSTRACTWe undertook this systematic review to determine the prognostic significance of adrenomedullin (ADM) in heart failure and acute myocardial infarction (AMI) patients.Given the difficulty in measuring mature ADM, its surrogate, mid-regional proadrenomedullin (MRproADM), has been used in most studies. 1 nmol/l increase in MRproADM was associated with HR for MACE ranging from 1.78 to 4.10 (CI 1.20 -10.12), while log10 of MRproADM had hazard ratios of 3.63 to 9.75 ) for death across studies in AMI patients. In conclusion, adrenomedullin is an independent predictor of death in patients with heart failure, as well as MACE and death in patients who have suffered an AMI. Quantification of this peptide might contribute to improved risk stratification in settings of heart failure and myocardial infarction.

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“…The data from recent studies suggest that some blood markers, e.g. pro-adrenomedullin (proADM) [6][7][8][9][10][11] or procalcitonin (PCT) [12][13][14][15], mirror the severity of infection and enhance clinical risk scores for short-term prognostication. However, less extensive research has been conducted for a better understanding of factors influencing longterm mortality after initial hospitalisation of CAP patients.…”

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confidence: 99%

Inflammatory responses predict long-term mortality risk in community-acquired pneumonia

Guertler

Wirz²,

Christ‐Crain³

et al. 2010

European Respiratory Journal

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Long-term outcomes in patients surviving community-acquired pneumonia (CAP) are still incompletely understood. This study investigates the association of clinical parameters and blood markers with long-term mortality.We prospectively followed 877 CAP patients from a previous multicentre trial for 18 months follow-up and investigated all-cause mortality following hospital discharge.Overall mortality was 17.3% (95% CI 14.8-19.8%) with a 12.8% (95% CI 10.9-15.0%) mortality incidence rate per year. Initial risk assignment using the Pneumonia Severity Index was accurate during the 18 month follow-up. Multivariable regression models (hazard ratio, 95% CI) designated the following as independent risk factors for long-term mortality: male sex (1.7, 1.2-2.5); chronic obstructive pulmonary disease (1.5, 1.1-2.1); neoplastic disease (2.5, 1.7-3.7); and highest quartile of peak pro-adrenomedullin level (3.3, 1.7-6.2). Initial presentation with temperature .38.7uC (0.4, 0.2-0.6), chills (0.6, 0.4-0.99) and highest quartile of the inflammatory marker C-reactive-protein (0.3, 0.2-0.5) were independent protective factors. A weighted risk score based on these variables showed good discrimination (area under receiver operating characteristic curve 0.78, 95% CI 0.74-0.82).Pronounced clinical and laboratory signs of systemic inflammatory host response upon initial hospital stay were associated with favourable long-term prognosis. Further studies should address whether closer monitoring of high-risk CAP patients after hospital discharge favourably impacts long-term mortality.

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Identification of an Adrenomedullin precursor fragment in plasma of sepsis patients

Cited by 190 publications

References 14 publications

Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial

Midregional Proadrenomedullin Predicts Mortality and Major Adverse Cardiac Events in Patients Presenting With Chest Pain: Results From the CHOPIN Trial

Prognostic Significance of Adrenomedullin in Patients With Heart Failure and With Myocardial Infarction

Inflammatory responses predict long-term mortality risk in community-acquired pneumonia

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