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Circulation. 1998;97:1921-1929

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(Circulation. 1998;97:1921-1929.)
© 1998 American Heart Association, Inc.


Clinical Investigation and Reports

Plasma N-Terminal Pro–Brain Natriuretic Peptide and Adrenomedullin

New Neurohormonal Predictors of Left Ventricular Function and Prognosis After Myocardial Infarction

A. Mark Richards, MD, PhD; M. Gary Nicholls, MD; Tim G. Yandle, PhD; Chris Frampton, PhD; Eric A. Espiner, MD; John G. Turner, MD; Rona C. Buttimore, RN; John G. Lainchbury, MB, ChB; John M. Elliott, MB, ChB, PhD; Hamid Ikram, MD, PhD; Ian G. Crozier, MD; ; David W. Smyth, MD

From the Departments of Cardiology, Endocrinology, and Nuclear Medicine, Christchurch Hospital and Department of Medicine, Christchurch School of Medicine, Christchurch, New Zealand.

Correspondence to Prof A.M. Richards, Department of Medicine, Christchurch School of Medicine, Riccarton Ave, PO Box 4345, Christchurch, New Zealand. E-mail bgriffin{at}chmeds.ac.nz

Background—Newly discovered circulating peptides, N-terminal pro–brain natriuretic peptide (N-BNP) and adrenomedullin (ADM), were examined for prediction of cardiac function and prognosis and compared with previously reported markers in 121 patients with myocardial infarction.

Methods and Results—The association between radionuclide left ventricular ejection fraction (LVEF) and N-BNP at 2 to 4 days (r=-.63, P<.0001) and 3 to 5 months (r=-.58, P<.0001) after infarction was comparable to that for C-terminal BNP and far stronger than for ADM (r=-.26, P<.01), N-terminal atrial natriuretic peptide (N-ANP), C-terminal ANP, cGMP, or plasma catecholamine concentrations. For prediction of death over 24 months of follow-up, an early postinfarction N-BNP level >=160 pmol/L had sensitivity, specificity, positive predictive value, and negative predictive values of 91%, 72%, 39%, and 97%, respectively, and was superior to any other neurohormone measured and to LVEF. Only 1 of 21 deaths occurred in a patient with an N-BNP level below the group median (Kaplan-Meier survival analysis, P<.00001). For prediction of heart failure (left ventricular failure), plasma N-BNP >= 145 pmol/L had sensitivity (85%) and negative predictive value (91%) comparable to the other cardiac peptides and was superior to ADM, plasma catecholamines, and LVEF. By multivariate analysis, N-BNP but not ADM provided predictive information for death and left ventricular failure independent of patient age, sex, LVEF, levels of other hormones, and previous history of heart failure, myocardial infarction, hypertension, or diabetes.

Conclusions—Plasma N-BNP measured 2 to 4 days after myocardial infarction independently predicted left ventricular function and 2-year survival. Stratification of patients into low- and high-risk groups can be facilitated by plasma N-BNP or BNP measurements, and one of these could reasonably be included in the routine clinical workup of patients after myocardial infarction.


Key Words: brain natriuretic peptide • atrial natriuretic factor • peptides • myocardial infarction • ventricles • prognosis




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Eur. Heart J., September 1, 2004; 25(17): 1486 - 1493.
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Clin. Chem.Home page
M. Ala-Kopsala, J. Magga, K. Peuhkurinen, J. Leipala, H. Ruskoaho, J. Leppaluoto, and O. Vuolteenaho
Molecular Heterogeneity Has a Major Impact on the Measurement of Circulating N-Terminal Fragments of A- and B-Type Natriuretic Peptides
Clin. Chem., September 1, 2004; 50(9): 1576 - 1588.
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J. P. Goetze
Biochemistry of Pro-B-Type Natriuretic Peptide-Derived Peptides: The Endocrine Heart Revisited
Clin. Chem., September 1, 2004; 50(9): 1503 - 1510.
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Diabetes CareHome page
M. Magnusson, O. Melander, B. Israelsson, A. Grubb, L. Groop, and S. Jovinge
Elevated Plasma Levels of Nt-proBNP in Patients With Type 2 Diabetes Without Overt Cardiovascular Disease
Diabetes Care, August 1, 2004; 27(8): 1929 - 1935.
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Eur J Heart FailHome page
A. Cochet, M. Zeller, Y. Cottin, C. Robert-Valla, A. Lalande, I. L'Huilllier, A. Comte, P. M. Walker, J. Desgres, J.-E. Wolf, et al.
The extent of myocardial damage assessed by contrast-enhanced MRI is a major determinant of N-BNP concentration after myocardial infarction
Eur J Heart Fail, August 1, 2004; 6(5): 555 - 560.
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J Am Coll CardiolHome page
J. L. Mega, D. A. Morrow, J. A. de Lemos, M. S. Sabatine, S. A. Murphy, N. Rifai, C. M. Gibson, E. M. Antman, and E. Braunwald
B-type natriuretic peptide at presentation and prognosis in patients with ST-segment elevation myocardial infarction: An ENTIRE-TIMI-23 substudy
J. Am. Coll. Cardiol., July 21, 2004; 44(2): 335 - 339.
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Clin. Chem.Home page
A. Hammerer-Lercher, W. Ludwig, G. Falkensammer, S. Muller, E. Neubauer, B. Puschendorf, O. Pachinger, and J. Mair
Natriuretic Peptides as Markers of Mild Forms of Left Ventricular Dysfunction: Effects of Assays on Diagnostic Performance of Markers
Clin. Chem., July 1, 2004; 50(7): 1174 - 1183.
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B. R. Palmer, C. M. Frampton, A. M. Richards, V. A. Cameron, and T. Nakayama
Absence of a NPR-A Gene Functional Deletion Allele in a Postmyocardial Infarction Cohort From New Zealand
Circ. Res., May 28, 2004; 94(10): e86 - e86.
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CirculationHome page
J. Bergler-Klein, U. Klaar, M. Heger, R. Rosenhek, G. Mundigler, H. Gabriel, T. Binder, R. Pacher, G. Maurer, and H. Baumgartner
Natriuretic Peptides Predict Symptom-Free Survival and Postoperative Outcome in Severe Aortic Stenosis
Circulation, May 18, 2004; 109(19): 2302 - 2308.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
J. P. Goetze, W. Yongzhong, J. F Rehfeld, E. Jorgensen, and J. Kastrup
Coronary angiography transiently increases plasma pro-B-type natriuretic peptide
Eur. Heart J., May 1, 2004; 25(9): 759 - 764.
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J. Magga, M. Puhakka, S. Hietakorpi, K. Punnonen, P. Uusimaa, J. Risteli, O. Vuolteenaho, H. Ruskoaho, and K. Peuhkurinen
Atrial natriuretic peptide, B-type natriuretic peptide, and serum collagen markers after acute myocardial infarction
J Appl Physiol, April 1, 2004; 96(4): 1306 - 1311.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
A. Bayes-Genis, M. Santalo-Bel, E. Zapico-Muniz, L. Lopez, C. Cotes, J. Bellido, R. Leta, P. Casan, and J. Ordonez-Llanos
N-terminal probrain natriuretic peptide (NT-proBNP) in the emergency diagnosis and in-hospital monitoring of patients with dyspnoea and ventricular dysfunction
Eur J Heart Fail, March 15, 2004; 6(3): 301 - 308.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
T. Jernberg, S. James, B. Lindahl, M. Stridsberg, P. Venge, and L. Wallentin
NT-proBNP in unstable coronary artery disease--experiences from the FAST, GUSTO IV and FRISC II trials
Eur J Heart Fail, March 15, 2004; 6(3): 319 - 325.
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Eur J Heart FailHome page
M. Galvani, D. Ferrini, and F. Ottani
Natriuretic peptides for risk stratification of patients with acute coronary syndromes
Eur J Heart Fail, March 15, 2004; 6(3): 327 - 333.
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Eur J Heart FailHome page
V. Kirk, M. Bay, J. Parner, K. Krogsgaard, T.M. Herzog, S. Boesgaard, C. Hassager, O.W. Nielsen, J. Aldershvile, and H. Nielsen
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, March 15, 2004; 6(3): 335 - 341.
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Eur J Heart FailHome page
F. Hartmann, M. Packer, A. J.S. Coats, M. B. Fowler, H. Krum, P. Mohacsi, J. L. Rouleau, M. Tendera, A. Castaigne, J. Trawinski, et al.
NT-proBNP in severe chronic heart failure: rationale, design and preliminary results of the COPERNICUS NT-proBNP substudy
Eur J Heart Fail, March 15, 2004; 6(3): 343 - 350.
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Eur J Heart FailHome page
M. Richards and R. W. Troughton
NT-proBNP in heart failure: therapy decisions and monitoring
Eur J Heart Fail, March 15, 2004; 6(3): 351 - 354.
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J Am Coll CardiolHome page
J. M. Tapanainen, K. S. Lindgren, T. H. Makikallio, O. Vuolteenaho, J. Leppaluoto, and H. V. Huikuri
Natriuretic peptides as predictors of non-sudden and sudden cardiac death after acute myocardial infarction in the beta-blocking era
J. Am. Coll. Cardiol., March 3, 2004; 43(5): 757 - 763.
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HeartHome page
B A Groenning, I Raymond, P R Hildebrandt, J C Nilsson, M Baumann, and F Pedersen
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, March 1, 2004; 90(3): 297 - 303.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
D. Logeart, G. Thabut, P. Jourdain, C. Chavelas, P. Beyne, F. Beauvais, E. Bouvier, and A. C. Solal
Predischarge B-type natriuretic peptide assay for identifying patients at high risk of re-admission after decompensated heart failure
J. Am. Coll. Cardiol., February 18, 2004; 43(4): 635 - 641.
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J Am Coll CardiolHome page
R. W. Troughton, D. L. Prior, J. J. Pereira, M. Martin, A. Fogarty, A. Morehead, T. G. Yandle, A. M. Richards, R. C. Starling, J. B. Young, et al.
Plasma B-type natriuretic peptide levels in systolic heart failure: importance of left ventricular diastolic function and right ventricular systolic function
J. Am. Coll. Cardiol., February 4, 2004; 43(3): 416 - 422.
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ChestHome page
S. de Denus, C. Pharand, and D. R. Williamson
Brain Natriuretic Peptide in the Management of Heart Failure: The Versatile Neurohormone
Chest, February 1, 2004; 125(2): 652 - 668.
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Anesth. Analg.Home page
E. Berendes, C. Schmidt, H. Van Aken, M. G. Hartlage, M. Rothenburger, S. Wirtz, H. H. Scheld, G. Brodner, and M. Walter
A-Type and B-Type Natriuretic Peptides in Cardiac Surgical Procedures
Anesth. Analg., January 1, 2004; 98(1): 11 - 19.
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A. Clerico and M. Emdin
Diagnostic Accuracy and Prognostic Relevance of the Measurement of Cardiac Natriuretic Peptides: A Review
Clin. Chem., January 1, 2004; 50(1): 33 - 50.
[Abstract] [Full Text] [PDF]


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HypertensionHome page
S. P. Wright, T. C.R. Prickett, R. N. Doughty, C. Frampton, G. D. Gamble, T. G. Yandle, N. Sharpe, and M. Richards
Amino-Terminal Pro-C-Type Natriuretic Peptide in Heart Failure
Hypertension, January 1, 2004; 43(1): 94 - 100.
[Abstract] [Full Text] [PDF]


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H. D. White and J. K. French
Use of brain natriuretic peptide levels for risk assessment in non-ST-elevation acute coronary syndromes
J. Am. Coll. Cardiol., December 3, 2003; 42(11): 1917 - 1920.
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Arch SurgHome page
A. E. Luckey, C. J. Parsa, and A. H. Harken
Reversible Cardiac Sympathectomy by High Thoracic Epidural Anesthesia Improves Regional Left Ventricular Function in Patients Undergoing Coronary Artery Bypass Grafting--Invited Critique
Arch Surg, December 1, 2003; 138(12): 1291 - 1291.
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Am. J. Respir. Crit. Care Med.Home page
J. C. T. Pepperell, N. A. Maskell, D. R. Jones, B. A. Langford-Wiley, N. Crosthwaite, J. R. Stradling, and R. J. O. Davies
A Randomized Controlled Trial of Adaptive Ventilation for Cheyne-Stokes Breathing in Heart Failure
Am. J. Respir. Crit. Care Med., November 1, 2003; 168(9): 1109 - 1114.
[Abstract] [Full Text] [PDF]


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Eur Respir JHome page
P. Pruszczyk, M. Kostrubiec, A. Bochowicz, G. Styczynski, M. Szulc, M. Kurzyna, A. Fijalkowska, A. Kuch-Wocial, I. Chlewicka, and A. Torbicki
N-terminal pro-brain natriuretic peptide in patients with acute pulmonary embolism
Eur. Respir. J., October 1, 2003; 22(4): 649 - 653.
[Abstract] [Full Text] [PDF]


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Eur Heart JHome page
M.R Cowie, P Jourdain, A Maisel, U Dahlstrom, F Follath, R Isnard, A Luchner, T McDonagh, J Mair, M Nieminen, et al.
Clinical applications of B-type natriuretic peptide (BNP) testing
Eur. Heart J., October 1, 2003; 24(19): 1710 - 1718.
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Eur Heart JHome page
R.S. Gardner, F. Ozalp, A.J. Murday, S.D. Robb, and T.A. McDonagh
N-terminal pro-brain natriuretic peptide: A new gold standard in predicting mortality in patients with advanced heart failure
Eur. Heart J., October 1, 2003; 24(19): 1735 - 1743.
[Abstract] [Full Text] [PDF]


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J Am Coll CardiolHome page
J. G. Lainchbury, E. Campbell, C. M. Frampton, T. G. Yandle, M. G. Nicholls, and A. M. Richards
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., August 20, 2003; 42(4): 728 - 735.
[Abstract] [Full Text] [PDF]


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HeartHome page
C Fisher, C Berry, L Blue, J J Morton, and J McMurray
N-terminal pro B type natriuretic peptide, but not the new putative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure
Heart, August 1, 2003; 89(8): 879 - 881.
[Abstract] [Full Text] [PDF]


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Eur J Heart FailHome page
R. J. O'Brien, I. B. Squire, B. Demme, J. E. Davies, and L. L. Ng
Pre-discharge, but not admission, levels of NT-proBNP predict adverse prognosis following acute LVF
Eur J Heart Fail, August 1, 2003; 5(4): 499 - 506.
[Abstract] [Full Text] [PDF]


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CirculationHome page
D. A. Morrow and E. Braunwald
Future of Biomarkers in Acute Coronary Syndromes: Moving Toward a Multimarker Strategy
Circulation, July 22, 2003; 108(3): 250 - 252.
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CirculationHome page
S. K. James, B. Lindahl, A. Siegbahn, M. Stridsberg, P. Venge, P. Armstrong, E. S. Barnathan, R. Califf, E. J. Topol, M. L. Simoons, 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, July 22, 2003; 108(3): 275 - 281.
[Abstract] [Full Text] [PDF]


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HeartHome page
I Raymond, B A Groenning, P R Hildebrandt, J C Nilsson, M Baumann, J Trawinski, and F Pedersen
The influence of age, sex and other variables on the plasma level of N-terminal pro brain natriuretic peptide in a large sample of the general population
Heart, July 1, 2003; 89(7): 745 - 751.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
R. W. Troughton, C. M. Frampton, T. G. Yandle, E. A. Espiner, G. Nicholls, and M. Richards
Plasma Amino-Terminal B-Type Natriuretic Peptide Measured by Elecsys 2010 Assay in a Trial of Hormone-guided Treatment for Heart Failure
Clin. Chem., July 1, 2003; 49(7): 1212 - 1215.
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