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The prognostic value of N-terminal proB-type natriuretic peptide

Nature Clinical Practice Cardiovascular Medicine volume 2, pages 194–201 (2005)Cite this article

Abstract

The heart is not only a pump, but also it is an endocrine organ. Cardiac stretch and overload stimulate the secretion of natriuretic peptides, which have a variety of beneficial actions, such as vasodilation and natriuresis. Cardiac-derived natriuretic peptides, especially B-type natriuretic peptide (BNP), have emerged as useful biomarkers for the diagnosis, and potentially the treatment, of heart failure patients. The inactive amino-terminal fragment of the BNP prohormone (NT-proBNP), which is more stable than mature BNP, has also been recognized as an aid in the diagnosis of left-ventricular systolic dysfunction. Furthermore, elevated NT-proBNP concentrations have been shown to be predictive of poor prognosis in a variety of cardiovascular diseases, suggesting that it could be useful for risk stratification of patients. This review summarizes current literature that has addressed the issue of NT-proBNP as a prognostic tool in heart failure, acute coronary syndromes and other conditions.

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Figure 1: Diagramatic representation of the cleavage of the B-type natriuretic peptide prohormone.
Figure 2: Mortality in hospitalized patients with heart failure as a function of plasma amino-terminal B-type natriuretic peptide prohormone concentrations.
Figure 3: Peto odds ratio fixed model of mortality in the long term and short term in patients with acute coronary syndromes and amino-terminal B-type natriuretic peptide prohormone (or B-type natriuretic peptide in the deLemos study) plasma concentrations above the median.

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References

  1. de Bold AJ et al. (1996) Mechanical and neuroendocrine regulation of the endocrine heart. Cardiovasc Res 31: 7–18

    Article  CAS  Google Scholar 

  2. Grantham JA et al. (1997) BNP: pathophysiological and potential therapeutic roles in acute congestive heart failure. Am J Physiol 272: R1077–R1083

    Article  CAS  Google Scholar 

  3. Tsuruda T et al. (2002) Brain natriuretic Peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. Circ Res 91: 1127–1134

    Article  CAS  Google Scholar 

  4. McCullough PA et al. (2002) B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study. Circulation 106: 416–422

    Article  Google Scholar 

  5. Hobbs RE et al. (1996) Hemodynamic effects of a single intravenous injection of synthetic human brain natriuretic peptide in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol 78: 896–901

    Article  CAS  Google Scholar 

  6. Marcus LS et al. (1996) Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A double-blind, placebo-controlled, randomized crossover trial. Circulation 94: 3184–3189

    Article  CAS  Google Scholar 

  7. Colucci WS et al. (2000) Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. N Engl J Med 343: 246–253

    Article  CAS  Google Scholar 

  8. Goetze JP (2004) Biochemistry of pro-B-type natriuretic peptide-derived peptides: the endocrine heart revisited. Clin Chem 50: 1503–1510

    Article  CAS  Google Scholar 

  9. Pemberton CJ et al. (2000) Deconvolution analysis of cardiac natriuretic peptides during acute volume overload. Hypertension 36: 355–359

    Article  CAS  Google Scholar 

  10. Hunt PJ et al. (1995) The amino-terminal portion of pro-brain natriuretic peptide (Pro-BNP) circulates in human plasma. Biochem Biophys Res Commun 214: 1175–1183

    Article  CAS  Google Scholar 

  11. Pfister R et al. (2004) Use of NT-proBNP in routine testing and comparison to BNP. Eur J Heart Fail 6: 289–293

    Article  CAS  Google Scholar 

  12. Hammerer-Lercher A et al. (2001) Head-to-head comparison of N-terminal pro-brain natriuretic peptide, brain natriuretic peptide and N-terminal pro-atrial natriuretic peptide in diagnosing left ventricular dysfunction. Clin Chim Acta 310: 193–197

    Article  CAS  Google Scholar 

  13. Lainchbury JG et al. (2003) Brain natriuretic peptide and n-terminal brain natriuretic peptide in the diagnosis of heart failure in patients with acute shortness of breath. J Am Coll Cardiol 42: 728–735

    Article  CAS  Google Scholar 

  14. Mueller T et al. (2004) Biochemical diagnosis of impaired left ventricular ejection fraction—comparison of the diagnostic accuracy of brain natriuretic peptide (BNP) and amino terminal proBNP (NT-proBNP). Clin Chem Lab Med 42: 159–163

    CAS  PubMed  Google Scholar 

  15. Hammerer-Lercher A et al. (2004) Natriuretic peptides as markers of mild forms of left ventricular dysfunction: effects of assays on diagnostic performance of markers. Clin Chem 50: 1174–1183

    Article  CAS  Google Scholar 

  16. Mueller T et al. (2004) Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease. Clin Chim Acta 341: 41–48

    Article  CAS  Google Scholar 

  17. Yeo KT et al. (2003) Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay. Clin Chim Acta 338: 107–115

    Article  CAS  Google Scholar 

  18. Costello-Boerrigter LC et al. (2004) NT-proBNP is superior to BNP in the detection of left ventricular systolic dysfunction in the community. Circulation 110: II–368:A1755

    Google Scholar 

  19. Richards AM et al. (2001) Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: prognostic utility and prediction of benefit from carvedilol in chronic ischemic left ventricular dysfunction. Australia-New Zealand Heart Failure Group. J Am Coll Cardiol 37: 1781–1787

    Article  CAS  Google Scholar 

  20. Richards M and Troughton RW (2004) NT-proBNP in heart failure: therapy decisions and monitoring. Eur J Heart Fail 6: 351–354

    Article  CAS  Google Scholar 

  21. O'Brien RJ et al. (2003) Pre-discharge, but not admission, levels of NT-proBNP predict adverse prognosis following acute LVF. Eur J Heart Fail 5: 499–506

    Article  CAS  Google Scholar 

  22. Gardner RS et al. (2003) N-terminal pro-brain natriuretic peptide. A new gold standard in predicting mortality in patients with advanced heart failure. Eur Heart J 24: 1735–1743

    Article  CAS  Google Scholar 

  23. Kirk V et al. (2004) N-terminal proBNP and mortality in hospitalised patients with heart failure and preserved vs. reduced systolic function: data from the prospective Copenhagen Hospital Heart Failure Study (CHHF). Eur J Heart Fail 6: 335–341

    Article  CAS  Google Scholar 

  24. Groenning BA et al. (2004) Diagnostic and prognostic evaluation of left ventricular systolic heart failure by plasma N-terminal pro-brain natriuretic peptide concentrations in a large sample of the general population. Heart 90: 297–303

    Article  CAS  Google Scholar 

  25. Packer M et al. (1996) The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. US Carvedilol Heart Failure Study Group. N Engl J Med 334: 1349–1355

    Article  CAS  Google Scholar 

  26. Merit-HF Study Group (1999) Effect of metoprolol CR/XL in chronic heart failure: metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet 353: 2001–2007

  27. Packer M et al. (2001) Effect of carvedilol on survival in severe chronic heart failure. N Engl J Med 344: 1651–1658

    Article  CAS  Google Scholar 

  28. Luchner A et al. (1998) Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study. J Am Coll Cardiol 32: 1839–1844

    Article  CAS  Google Scholar 

  29. Zugck C et al. (2002) Impact of beta-blocker treatment on the prognostic value of currently used risk predictors in congestive heart failure. J Am Coll Cardiol 39: 1615–1622

    Article  CAS  Google Scholar 

  30. Hartmann F et al. (2004) Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial. Circulation 110: 1780–1786

    Article  CAS  Google Scholar 

  31. Richards AM et al. (1998) Plasma N-terminal pro-brain natriuretic peptide and adrenomedullin: new neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation 97: 1921–1929

    Article  CAS  Google Scholar 

  32. Richards AM et al. (2003) B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction. Circulation 107: 2786–2792

    Article  CAS  Google Scholar 

  33. Jernberg T et al. (2002) N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation. J Am Coll Cardiol 40: 437–445

    Article  CAS  Google Scholar 

  34. Omland T et al. (2002) Prognostic value of N-terminal pro-atrial and pro-brain natriuretic peptide in patients with acute coronary syndromes. Am J Cardiol 89: 463–465

    Article  CAS  Google Scholar 

  35. James SK et al. (2003) N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy. Circulation 108: 275–281

    Article  CAS  Google Scholar 

  36. Jernberg T et al. (2003) N-terminal pro-brain natriuretic peptide in relation to inflammation, myocardial necrosis, and the effect of an invasive strategy in unstable coronary artery disease. J Am Coll Cardiol 42: 1909–1916

    Article  CAS  Google Scholar 

  37. Bazzino O et al. (2004) Relative value of N-terminal probrain natriuretic peptide, TIMI risk score, ACC/AHA prognostic classification and other risk markers in patients with non-ST-elevation acute coronary syndromes. Eur Heart J 25: 859–866

    Article  CAS  Google Scholar 

  38. Omland T et al. (2002) N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation 106: 2913–2918

    Article  CAS  Google Scholar 

  39. Galvani M et al. (2004) N-terminal pro-brain natriuretic peptide on admission has prognostic value across the whole spectrum of acute coronary syndromes. Circulation 110: 128–134

    Article  CAS  Google Scholar 

  40. de Lemos JA et al. (2001) The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 345: 1014–1021

    Article  CAS  Google Scholar 

  41. Galvani M et al. (2004) Natriuretic peptides for risk stratification of patients with acute coronary syndromes. Eur J Heart Fail 6: 327–333

    Article  CAS  Google Scholar 

  42. Zuetenhorst JM et al. (2004) Role of natriuretic peptides in the diagnosis and treatment of patients with carcinoid heart disease. Br J Cancer 90: 2073–2079

    Article  CAS  Google Scholar 

  43. Palladini G et al. (2003) Serum N-terminal pro-brain natriuretic peptide is a sensitive marker of myocardial dysfunction in AL amyloidosis. Circulation 107: 2440–2445

    Article  CAS  Google Scholar 

  44. Olsen MH et al. (2004) N-terminal pro-brain natriuretic peptide predicts cardiovascular events in patients with hypertension and left ventricular hypertrophy: a LIFE study. J Hypertens 22: 1597–1604

    Article  CAS  Google Scholar 

  45. Kucher N et al. (2003) Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism. Circulation 107: 1576–1578

    Article  Google Scholar 

  46. Pruszczyk P et al. (2003) N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism. Eur Respir J 22: 649–653

    Article  CAS  Google Scholar 

  47. Gerber IL et al. (2003) Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis. Circulation 107: 1884–1890

    Article  Google Scholar 

  48. Weber M et al. (2004) Relation of N-terminal pro-B-type natriuretic peptide to severity of valvular aortic stenosis. Am J Cardiol 94: 740–745

    Article  CAS  Google Scholar 

  49. Bergler-Klein J et al. (2004) Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation 109: 2302–2308

    Article  CAS  Google Scholar 

  50. Sutton TM et al. (2003) Plasma natriuretic peptide levels increase with symptoms and severity of mitral regurgitation. J Am Coll Cardiol 41: 2280–2287

    Article  CAS  Google Scholar 

  51. Herrmann Z et al. (2003) The influence of renal function on NT-proBNP levels in various disease groups. Clin Lab 49: 649–656

    CAS  PubMed  Google Scholar 

  52. McCullough PA et al. (2003) B-type natriuretic peptides: a diagnostic breakthrough for clinicians. Rev Cardiovasc Med 4: 72–80

    PubMed  Google Scholar 

  53. Apple FS et al. (2004) Multi-biomarker risk stratification of N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, and cardiac troponin T and I in end-stage renal disease for all-cause death. Clin Chem 50: 2279–2285

    Article  CAS  Google Scholar 

  54. Wei Y et al. (2000) Corin, a transmembrane cardiac serine protease, acts as a pro-atrial natriuretic peptide-converting enzyme. Proc Natl Acad Sci USA 97: 8525–8529

    Article  Google Scholar 

  55. Jiang W et al. (2005) Changes in production and metabolism of brain natriuretic peptide in rats with myocardial necrosis Eur J Pharmacol 507: 153–162

    Article  CAS  Google Scholar 

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Acknowledgements

We thank Linda C Combs for her assistance in the preparation of this review and Dr Guido Boerrigter for useful suggestions.

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Authors and Affiliations

  1. Mayo Clinic and Mayo Clinic College of Medicine,

    Lisa C Costello-Boerrigter & John C Burnett Jr

  2. Mayo Clinic Cardiovascular Research Center,

    Lisa C Costello-Boerrigter & John C Burnett Jr

  3. Mayo Clinic College of Medicine, Rochester, MN, USA

    Lisa C Costello-Boerrigter & John C Burnett Jr

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  1. Lisa C Costello-Boerrigter
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Correspondence to Lisa C Costello-Boerrigter.

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Competing interests

John C Burnett Jr has received a research grant from Roche Diagnostics Ltd.

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Costello-Boerrigter, L., Burnett, J. The prognostic value of N-terminal proB-type natriuretic peptide. Nat Rev Cardiol 2, 194–201 (2005). https://doi.org/10.1038/ncpcardio0156

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