Amino-terminal Pro-brain Natriuretic Peptide Testing - Recent Lessons Learned

Login or register to view PDF.
Citation
US Cardiology, 2006;3(1):49-50

Pages

The use of natriuretic peptide testing has dramatically risen recently, in recognition of the value of these blood tests for assisting in the evaluation of patients with suspected heart failure (HF). B-type natriuretic peptide (BNP) is formed as a consequence of production of a 108-amino-acid precursor peptide that is synthesised within the cardiomyocyte; this 'pro-BNP108ÔÇÖ is subsequently cleaved at the time of release of the peptide by the cardiomyocyte into two fragments: the 32-amino-acid BNP and the 76-amino-acid amino-terminal portion (NT-proBNP). BNP has numerous biologic effects in the body, including induction of diuresis and natriuresis, vasodilation and downregulation of the renin-angiotensin-aldosterone system. These effects bespeak of the potential usefulness of measurement of BNP or NT-proBNP in disease states such as HF.

The first US Food and Drug Administration (FDA)- approved BNP assay became available in 2001. Subsequently, automated assays for NT-proBNP received approval in 2002 and, since then, testing for the natriuretic peptides has been shown to be exceptionally useful for numerous clinical applications, including the evaluation of the patient complaining of dyspnea, as elevated concentrations of these markers have been shown to be present in patients with acute HF, a diagnosis that is typically difficult to secure using standard clinical methods.

Since the earliest experiences with BNP and NT-proBNP, much has been learned about the utility of these tests for evaluation of patients with suspected or proven HF. This review will provide a brief comparison of the methods for measuring BNP and NT-proBNP, and then will focus on the recent lessons learned, in particular regarding the great utility of NT-proBNP for evaluating and managing the patient with suspected or proven HF.

Comparing BNP with NT-proBNP
Analytical Differences

As would be expected, the analytical methods for testing both BNP and NT-proBNP differ considerably, and as such it is not surprising that considerable differences between the two markers exist with respect to optimal methods for their testing. It has been shown that recoverable levels of BNP fall rapidly after phlebotomy,1 which likely reflects on-going activity of neutral endopeptidases in the blood sample or activation of the kallikrein system in the tube within which the blood sample is collected.2 Indeed, a recent study using exquisitely accurate mass spectral techniques actually demonstrated that among HF patients with extremely high concentrations of 'BNP32ÔÇÖ (as assessed by a point-of-care immunoassay for the marker), no detectable intact BNP actually existed in the samples.3

Pages

References
  1. Yeo K T, Wu A H, Apple F S, et al., Multicenter evaluation of the Roche NT-proBNP assay and comparison to the Biosite Triage BNP assay , Clin Chim Acta (2003);338(1-2): pp. 107-115.
    Crossref | PubMed
  2. Shimizu H, Aono K, Masuta K, et al., Degradation of human brain natriuretic peptide (BNP) by contact activation of blood coagulation system , Clin Chim Acta (2001);305(1-2): pp. 181-186.
    Crossref | PubMed
  3. Hawkridge A M, Heublein, D M, Bergen H R 3rd, et al., Quantitative mass spectral evidence for the absence of circulating brain natriuretic peptide (BNP-32) in severe human heart failure , Proc Natl Acad Sci U S A (2005);102(48): pp. 17442-17447.
    Crossref | PubMed
  4. Lainchbury J G, Campbell E, Frampton C M, et al., 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 (2003);42(4): pp. 728-735.
    Crossref | PubMed
  5. Mueller T, Gegenhuber A, Poelz W, et al., Head-to-head comparison of the diagnostic utility of BNP and NT-proBNP in symptomatic and asymptomatic structural heart disease , Clin Chim Acta (2004);341(1-2): pp. 41-48.
    Crossref | PubMed
  6. Mueller T, Gegenhuber A, Poelz W, et al., Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure , Heart (2005);91(5): pp. 606-612.
    Crossref | PubMed
  7. Hunt S A, Abraham W T, Chin M H, et al., ACC/AHA 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure in the Adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure): developed in collaboration with the American College of Chest Physicians and the International Society for Heart and Lung Transplantation: endorsed by the Heart Rhythm Society , Circulation (2005);112(12): pp. e154-e235.
    Crossref | PubMed
  8. Tang W H, Girod J P, Lee M J, et al., Plasma B-type natriuretic peptide levels in ambulatory patients with established chronic symptomatic systolic heart failure , Circulation (2003);108(24): pp. 2964-2966.
    Crossref | PubMed
  9. Maisel A S, McCord J, Nowak R M, et al., Bedside B-Type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational Study , J Am Coll Cardiol (2003);41(11): pp. 2010-2017.
    Crossref
  10. O'Donoghue M, Chen A, Baggish A L, et al., The effects of ejection fraction on N-terminal ProBNP and BNP levels in patients with acute CHF: analysis from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) study , J Card Fail (2005);11(5 Suppl): pp. S9-S14.
    Crossref | PubMed
  11. Januzzi J L Jr, Camargo C A, Anwaruddin S, et al., The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study , Am J Cardiol (2005);95(8): pp. 948-954.
    Crossref | PubMed
  12. Januzzi J L, van Kimmenade R, Lainchbury J, et al., NT-proBNP testing for diagnosis and short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the International Collaborative of NT-proBNP Study , Eur Heart J (2006);27(3): pp. 330-337.
    Crossref | PubMed
  13. McCullough P A, Nowak R M, McCord J, et al., B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study , Circulation (2002);106(4): pp. 416-422.
    Crossref
  14. Anwaruddin S, Lloyd-Jones D M, Baggish A, et al., Renal function, congestive heart failure, and amino-terminal pro-brain natriuretic peptide measurement: results from the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) Study , J Am Coll Cardiol (2006);47(1): pp. 91-97.
    Crossref | PubMed
  15. James S K, Lindahl B, Siegbahn A, et al., 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 (2003);108(3): pp. 275-281.
    Crossref | PubMed
  16. Jernberg T, Lindahl B, Siegbahn A, et al., 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 (2003);42(11): pp. 1909-1916.
    Crossref | PubMed
  17. Heeschen C, Hamm C W, Mitrovic V, et al., N-terminal pro-B-type natriuretic peptide levels for dynamic risk stratification of patients with acute coronary syndromes , Circulation (2004);110(20): pp. 3206-3012.
    Crossref | PubMed
  18. Kucher N, Printzen G, Doernhoefer T et al., Low pro-brain natriuretic peptide levels predict benign clinical outcome in acute pulmonary embolism , Circulation (2003);107(12): pp. 1576-1578.
    Crossref | PubMed
  19. Binder L, Pieske B, Olschewski M, et al., N-terminal pro-brain natriuretic peptide or troponin testing followed by echocardiography for risk stratification of acute pulmonary embolism , Circulation (2005);112(11): pp. 1573-1579.
    Crossref | PubMed
  20. Januzzi J L Jr, Sakhuja R, O'Donoghue M, et al., Utility of amino-terminal pro-brain natriuretic peptide testing for prediction of 1-year mortality in patients with dyspnea treated in the emergency department , Arch Intern Med (2006);166(3): pp. 315-320.
    Crossref | PubMed
  21. Baggish A, Cameron R, Anwaruddin S, et al., A clinical and biochemical critical pathway for the evaluation of patients with suspected acute congestive heart failure: the ProBNP Investigation of Dyspnea in the Emergency Department (PRIDE) algorithm , Crit Pathways in Cardiol (2004);3: pp. 171-176.
  22. Bettencourt P, Azevedo A, Pimenta J, et al., N-terminal-pro-brain natriuretic peptide predicts outcome after hospital discharge in heart failure patients , Circulation (2004);110(15): pp. 2168-2174.
    Crossref | PubMed