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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.

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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