Abstract
Background
Natriuretic peptides are the standard biomarker for risk stratification in cardiovascular
disease. Novel biomarkers of cardiovascular stress might allow refinement in risk
stratification for patients with acute coronary syndrome (ACS). We tested the performance
of these novel biomarkers for cardiovascular risk stratification in patients who presented
with ACS.
Methods
In the AtheroGene study, 873 patients presented with ACS in the emergency department. Biomarkers measured
were: B-type natriuretic peptide (BNP), N-terminal pro BNP (NT-proBNP), midregional
proatrial natriuretic peptide, midregional proadrenomedullin (MR-proADM), copeptin,
and troponin I. The median follow-up time was 4 years and during this time 50 patients
died from cardiac causes.
Results
Cox regression analysis for the continuous variables NT-proBNP and BNP showed a hazard
ratio (HR) of 1.9 and 1.8, respectively, for 1 SD increase (P < 0.001 and P = 0.003) in the fully adjusted model. Novel biomarkers with MR-proADM had an HR of
3.2, followed by midregional proatrial natriuretic peptide with an HR of 1.9 (both
P < 0.001), and copeptin with an HR of 1.6 (P < 0.001). C-index revealed MR-proADM as the best discriminator for identifying patients
with the outcome with a C-index = 0.8, and C-index was 0.72 for NT-proBNP (P for comparison = 0.017). Integrated discrimination improvement for MR-proADM was
0.059 compared with NT-proBNP (P = 0.016), thus providing background that MR-proADM was better to identify persons
with the outcome. Troponin I levels at the time of admission were not significant
for risk stratification.
Conclusions
In patients who present with ACS the novel biomarker, MR-proADM was the best predictor
for outcome. MR-proADM adds modest information and is useful for risk prediction in
ACS patients.
Résumé
Introduction
Les peptides natriurétiques sont les biomarqueurs habituels de la stratification du
risque des maladies cardiovasculaires. Les nouveaux biomarqueurs du stress cardiovasculaire
permettraient d’affiner la stratification du risque des patients atteints d’un syndrome
coronarien aigu (SCA). Nous avons testé la performance de ces nouveaux biomarqueurs
dans la stratification du risque cardiovasculaire chez les patients atteints d’un
SCA.
Méthodes
Dans l’étude AtheroGene, 873 patients atteints d’un SCA se présentaient au service des urgences. Les biomarqueurs
mesurés étaient les suivants : le peptide natriurétique de type B (BNP), le N-terminal
du propeptide natriurétique de type B (NT-proBNP), le peptide mi-régional pro-natriurétique
auriculaire, la pro-adrénomédulline mi-régionale (MR-proADM), la copeptine et la troponine
I. La durée médiane de suivi était de 4 ans. Au cours de cette période, 50 patients
sont morts de causes cardiaques.
Résultats
L’analyse selon le modèle de régression de Cox des variables continues NT-proBNP et
BNP montraient respectivement des rapports de risque (RR) de 1,9 et de 1,8 pour l’augmentation
de 1 unité de l’ET (P < 0,001 et P = 0,003) dans le modèle entièrement ajusté. Les nouveaux biomarqueurs MR-proADM qui
montraient un RR de 3,2 étaient suivis par le peptide mi-régional pro-natriurétique
auriculaire, dont le RR était de 1,9 (P < 0,001 pour les deux), et par la copeptine, dont le RR était de 1,6 (P < 0,001). L’indice C montrait que la MR-proADM, dont l’indice = 0,8, était le meilleur
discriminateur de l’identification des patients, alors que l’indice C du NT-proBNP
était de 0,72 (P pour la comparaison = 0,017). L’amélioration de la discrimination intégrée avec la
MR-proADM était de 0,059 par rapport au NT-proBNP (P = 0,016), ce qui donne par conséquent des informations sur le fait que la MR-proADM
était meilleure pour identifier les personnes avec ce résultat. Les concentrations
de troponine I à l’admission n’étaient pas significatives pour la stratification du
risque.
Conclusions
Chez les patients atteints d’un SCA, le nouveau biomarqueur MR-proADM était le meilleur
prédicteur des résultats. La MR-proADM apporte une information modeste et est utile
pour prédire le risque chez les patients atteints d’un SCA.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Canadian Journal of CardiologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC).Eur Heart J. 2016; 37: 267-315
- Biomarkers and acute coronary syndromes: an update.Eur Heart J. 2014; 35: 552-556
- Sensitive and high sensitivity cardiac troponin I concentrations in the Heart Outcomes Prevention Evaluation (HOPE) study–a high risk population.Clin Chim Acta. 2010; 411: 1832
- High-sensitivity cardiac troponin I measurement for risk stratification in a stable high-risk population.Clin Chem. 2011; 57: 1146-1153
- Clinical performance of two highly sensitive cardiac troponin I assays.Clin Chem. 2009; 55: 109-116
- Incremental prognostic value of biomarkers beyond the GRACE (Global Registry of Acute Coronary Events) score and high-sensitivity cardiac troponin T in non-ST-elevation acute coronary syndrome.Clin Chem. 2013; 59: 1497-1505
- Sensitive troponin assays and N-terminal pro-B-type natriuretic peptide in acute coronary syndrome: prediction of significant coronary lesions and long-term prognosis.Am Heart J. 2013; 165: 716-724
- Midregional proadrenomedullin predicts mortality and major adverse cardiac events in patients presenting with chest pain: results from the CHOPIN trial.Acad Emerg Med. 2015; 22: 554-563
- Serial sampling of copeptin levels improves diagnosis and risk stratification in patients presenting with chest pain: results from the CHOPIN trial.Emerg Med J. 2016; 33: 23-29
- MR-proANP improves prediction of mortality and cardiovascular events in patients with STEMI.Eur J Prev Cardiol. 2015; 22: 693-700
- Copeptin helps in the early detection of patients with acute myocardial infarction: primary results of the CHOPIN trial (Copeptin Helps in the early detection Of Patients with acute myocardial INfarction).J Am Coll Cardiol. 2013; 62: 150-160
- Prognostic performance of multiple biomarkers in patients with non-ST-segment elevation acute coronary syndrome: analysis from the MERLIN-TIMI 36 trial (Metabolic Efficiency With Ranolazine for Less Ischemia in Non-ST-Elevation Acute Coronary Syndromes-Thrombolysis In Myocardial Infarction 36).J Am Coll Cardiol. 2014; 63: 1644-1653
- Short-term mortality risk in emergency department acute heart failure.Acad Emerg Med. 2011; 18: 947-958
- Copeptin as a prognostic factor for major adverse cardiovascular events in patients with coronary artery disease.Int J Cardiol. 2012; 162: 27-32
- Midregional proadrenomedullin for prediction of cardiovascular events in coronary artery disease: results from the AtheroGene study.Clin Chem. 2012; 58: 226-236
- Plasma adrenomedullin as an independent predictor of future cardiovascular events in high-risk patients: comparison with C-reactive protein and adiponectin.Peptides. 2008; 29: 599-605
- Midregional proadrenomedullin and its change predicts recurrent major coronary events and heart failure in stable coronary heart disease patients: the LIPID study.Int J Cardiol. 2014; 172: 411-418
- Copeptin: a biomarker of cardiovascular and renal function.Congest Heart Fail. 2010; 16: S37-S44
- MR-proANP and MR-proADM for risk stratification of patients with acute chest pain.Heart. 2013; 99: 388-395
- Mid-regional pro-atrial natriuretic peptide as a prognostic marker for all-cause mortality in patients with symptomatic coronary artery disease.Clin Sci (Lond). 2012; 123: 601-610
- The utility of pregnancy-associated plasma protein A for determination of prognosis in a cohort of patients with coronary artery disease.Biomark Med. 2015; 9: 731-741
- Risk factors of coronary artery disease in secondary prevention–results from the AtheroGene–study.PLoS One. 2015; 10: e0131434
- Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women.Circulation. 2001; 104: 393-398
- Analyzing survival curves at a fixed point in time.Stat Med. 2007; 26: 4505-4519
- Time-dependent ROC curves for censored survival data and a diagnostic marker.Biometrics. 2000; 56: 337-344
- Inference on correlated discrimination measures in survival analysis: a nonparametric approach.Commun Stat Theory Methods. 2004; 33: 2117-2135
- Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long-term survival after acute myocardial infarction. Comparison with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptide.Circulation. 1996; 93: 1963-1969
- Comparative impact of multiple biomarkers and N-Terminal pro-brain natriuretic peptide in the context of conventional risk factors for the prediction of recurrent cardiovascular events in the Heart Outcomes Prevention Evaluation (HOPE) Study.Circulation. 2006; 114: 201-208
- Early discharge using single cardiac troponin and copeptin testing in patients with suspected acute coronary syndrome (ACS): a randomized, controlled clinical process study.Eur Heart J. 2015; 36: 369-376
- Troponin I concentrations following primary percutaneous coronary intervention predict large infarct size and left ventricular dysfunction in patients with ST-segment elevation acute myocardial infarction.Atherosclerosis. 2003; 168: 181-189
- Cardiac troponin I for prediction of clinical outcomes and cardiac function through 3-month follow-up after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction.Am Heart J. 2015; 169: 257-265.e251
- Long-term stability of endogenous B-type natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP) in frozen plasma samples.Clin Chem Lab Med. 2004; 42: 942-944
- Multiple endothelial biomarkers and noninvasive vascular function in the general population: the Gutenberg Health Study.Hypertension. 2012; 60: 288-295
- Biomarkers from distinct biological pathways improve early risk stratification in medical emergency patients: the multinational, prospective, observational TRIAGE study.Crit Care. 2015; 19: 377
- Novel biomarkers in acute heart failure: MR-pro-adrenomedullin.Clin Chem Lab Med. 2014; 52: 1433-1435
- Midregion prohormone adrenomedullin and prognosis in patients presenting with acute dyspnea: results from the BACH (Biomarkers in Acute Heart Failure) trial.J Am Coll Cardiol. 2011; 58: 1057-1067
- Cardioprotective effects of vasopeptidase inhibitors.Can J Cardiol. 2002; 18: 415-420
- Vasopeptidase inhibition: a novel approach to cardiovascular therapy.Can J Cardiol. 2002; 18: 177-182
Article info
Publication history
Published online: May 19, 2016
Accepted:
May 16,
2016
Received:
January 28,
2016
Footnotes
See page 1476 for disclosure information.
Identification
Copyright
© 2016 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
