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J Am Coll Cardiol, 2002; 40:976-982
© 2002 by the American College of Cardiology Foundation
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CLINICAL STUDY: BIOMARKERS

Plasma brain natriuretic peptide concentration: impact of age and gender

Margaret M. Redfield, MD*,*, Richard J. Rodeheffer, MD*, Steven J. Jacobsen, MD, PhD{dagger}, Douglas W. Mahoney, MS{ddagger}, Kent R. Bailey, PhD{ddagger} and John C. Burnett, Jr, MD*

* Division of Cardiovascular Diseases, and Sections of, Rochester, Minnesota, USA
{dagger} Health Science Research and, Rochester, Minnesota, USA
{ddagger} Biostatistics, Mayo Clinic and Foundation, Rochester, Minnesota, USA

Manuscript received March 4, 2002; accepted May 31, 2002.

* Reprint requests and correspondence: Dr. Margaret M. Redfield, Guggenheim 9, Mayo Clinic, 200 First Street, Southwest, Rochester, Minnesota 55905, USA.
redfield.margaret{at}mayo.edu

OBJECTIVES: We wished to examine the effects of age and gender on plasma brain natriuretic peptide (BNP) concentration in a population-based study.

BACKGROUND: Measurement of BNP concentration is approved for use in the diagnosis of heart failure and may aid in the detection of left ventricular dysfunction. Although BNP is approved for clinical use, there are few data regarding the range of BNP observed in persons without cardiovascular disease or cardiac dysfunction. These data are essential for the interpretation of BNP.

METHODS: In 2,042 randomly selected residents of Olmsted County, Minnesota, >44 years old, BNP (Shionogi and Biosite assays), Doppler echocardiography, and medical record review were performed. A normal subset of subjects (n = 767) in sinus rhythm without cardiovascular, renal, or pulmonary disease or diabetes; on no cardiovascular medications; and with normal systolic, diastolic, and valvular function was identified.

RESULTS: Within the normal subset, the distribution of BNP differed by age, gender, and assay system. With both assays, BNP increased significantly with age and was significantly higher in women than men, leading to age-, gender-, and assay-specific reference ranges. Receiver operating characteristic analysis for the ability of BNP to detect an ejection fraction ≤40% was performed in each age/gender stratum in the entire cohort (n = 2,042) and confirmed that discriminatory values for BNP for detection of reduced ejection fraction were higher in women and older persons and were different between the two assays.

CONCLUSIONS: Interpretation of BNP should include consideration of age-, gender-, and assay-specific partition values.

Abbreviations and Acronyms
  BNP
  brain natriuretic peptide
  CHF
  congestive heart failure
  CI
  confidence interval
  E/A
  early-to-late filling velocities
  EF
  ejection fraction
  HRT
  hormone replacement therapy
  LV
  left ventricular
  ROC
  receiver operating characteristic
  2-D
  two-dimensional




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M. Kubanek, I. Malek, J. Kautzner, M. Hegarova, M. Wiendl, P. Lupinek, L. Karasova, and V. Lanska
The value of B-type natriuretic peptide and big endothelin-1 for detection of severe pulmonary hypertension in heart transplant candidates
Eur J Heart Fail, December 1, 2005; 7(7): 1149 - 1155.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
G. I.W. Galasko, A. Lahiri, S. C. Barnes, P. Collinson, and R. Senior
What is the normal range for N-terminal pro-brain natriuretic peptide? How well does this normal range screen for cardiovascular disease?
Eur. Heart J., November 1, 2005; 26(21): 2269 - 2276.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. M. Redfield, S. J. Jacobsen, B. A. Borlaug, R. J. Rodeheffer, and D. A. Kass
Age- and Gender-Related Ventricular-Vascular Stiffening: A Community-Based Study
Circulation, October 11, 2005; 112(15): 2254 - 2262.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
C. W. Knudsen, T. Omland, P. Clopton, A. Westheim, A. H.B. Wu, P. Duc, J. McCord, R. M. Nowak, J. E. Hollander, A. B. Storrow, et al.
Impact of Atrial Fibrillation on the Diagnostic Performance of B-Type Natriuretic Peptide Concentration in Dyspneic Patients: An Analysis From the Breathing Not Properly Multinational Study
J. Am. Coll. Cardiol., September 6, 2005; 46(5): 838 - 844.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
M. Kupari, H. Turto, J. Lommi, M. Makijarvi, and H. Parikka
Transcardiac gradients of N-terminal B-type natriuretic peptide in aortic valve stenosis
Eur J Heart Fail, August 1, 2005; 7(5): 809 - 814.
[Abstract] [Full Text] [PDF]

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 Mayo Clin Proc.Home page
P. M. McKie and J. C. Burnett Jr
B-Type Natriuretic Peptide as a Biomarker Beyond Heart Failure: Speculations and Opportunities
Mayo Clin. Proc., August 1, 2005; 80(8): 1029 - 1036.
[Abstract] [PDF]

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 HypertensionHome page
A. Luchner, C. Hengstenberg, H. Lowel, G. A.J. Riegger, H. Schunkert, and S. Holmer
Effect of Compensated Renal Dysfunction on Approved Heart Failure Markers: Direct Comparison of Brain Natriuretic Peptide (BNP) and N-Terminal Pro-BNP
Hypertension, July 1, 2005; 46(1): 118 - 123.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
T.v. Lukowicz, M. Fischer, H.W. Hense, A. Doring, J. Stritzke, G. Riegger, H. Schunkert, and A. Luchner
BNP as a marker of diastolic dysfunction in the general population: Importance of left ventricular hypertrophy
Eur J Heart Fail, June 1, 2005; 7(4): 525 - 531.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
D. Detaint, D. Messika-Zeitoun, J.-F. Avierinos, C. Scott, H. Chen, J. C. Burnett Jr, and M. Enriquez-Sarano
B-Type Natriuretic Peptide in Organic Mitral Regurgitation: Determinants and Impact on Outcome
Circulation, May 10, 2005; 111(18): 2391 - 2397.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
B. Bar-Oz, A. Lev-Sagie, I. Arad, L. Salpeter, and A. Nir
N-Terminal pro-B-Type Natriuretic Peptide Concentrations in Mothers just before Delivery, in Cord Blood, and in Newborns
Clin. Chem., May 1, 2005; 51(5): 926 - 927.
[Full Text] [PDF]

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 HeartHome page
G I W Galasko, R Senior, and A Lahiri
Ethnic differences in the prevalence and aetiology of left ventricular systolic dysfunction in the community: the Harrow heart failure watch
Heart, May 1, 2005; 91(5): 595 - 600.
[Abstract] [Full Text] [PDF]

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 HeartHome page
T Mueller, A Gegenhuber, W Poelz, and M Haltmayer
Diagnostic accuracy of B type natriuretic peptide and amino terminal proBNP in the emergency diagnosis of heart failure
Heart, May 1, 2005; 91(5): 606 - 612.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
M. Ala-Kopsala, H. Ruskoaho, J. Leppaluoto, L. Seres, R. Skoumal, M. Toth, F. Horkay, and O. Vuolteenaho
Single Assay for Amino-Terminal Fragments of Cardiac A- and B-Type Natriuretic Peptides
Clin. Chem., April 1, 2005; 51(4): 708 - 718.
[Abstract] [Full Text] [PDF]

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 NEJMHome page
I. S. Wittstein, D. R. Thiemann, J. A.C. Lima, K. L. Baughman, S. P. Schulman, G. Gerstenblith, K. C. Wu, J. J. Rade, T. J. Bivalacqua, and H. C. Champion
Neurohumoral Features of Myocardial Stunning Due to Sudden Emotional Stress
N. Engl. J. Med., February 10, 2005; 352(6): 539 - 548.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
R. Schnabel, H. J. Rupprecht, K. J. Lackner, E. Lubos, C. Bickel, J. Meyer, T. Munzel, F. Cambien, L. Tiret, S. Blankenberg, et al.
Analysis of N-terminal-pro-brain natriuretic peptide and C-reactive protein for risk stratification in stable and unstable coronary artery disease: results from the AtheroGene study
Eur. Heart J., February 1, 2005; 26(3): 241 - 249.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
J. A. Silva, A. W. Chan, C. J. White, T. J. Collins, J. S. Jenkins, J. P. Reilly, and S. R. Ramee
Elevated Brain Natriuretic Peptide Predicts Blood Pressure Response After Stent Revascularization in Patients With Renal Artery Stenosis
Circulation, January 25, 2005; 111(3): 328 - 333.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
A. M. Pritchett, D. W. Mahoney, S. J. Jacobsen, R. J. Rodeheffer, B. L. Karon, and M. M. Redfield
Diastolic dysfunction and left atrial volume: A population-based study
J. Am. Coll. Cardiol., January 4, 2005; 45(1): 87 - 92.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
J. P. Goetze, J. F. Rehfeld, R. Videbaek, L. Friis-Hansen, and J. Kastrup
B-type natriuretic peptide and its precursor in cardiac venous blood from failing hearts
Eur J Heart Fail, January 1, 2005; 7(1): 69 - 74.
[Abstract] [Full Text] [PDF]

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 Eur J Heart FailHome page
J. Hogenhuis, A. A. Voors, T. Jaarsma, H. L. Hillege, F. Boomsma, and D. J. van Veldhuisen
Influence of age on natriuretic peptides in patients with chronic heart failure: a comparison between ANP/NT-ANP and BNP/NT-proBNP
Eur J Heart Fail, January 1, 2005; 7(1): 81 - 86.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
J. Nordmeyer, S. Eder, S. Mahmoodzadeh, P. Martus, J. Fielitz, J. Bass, N. Bethke, H. R. Zurbrugg, R. Pregla, R. Hetzer, et al.
Upregulation of Myocardial Estrogen Receptors in Human Aortic Stenosis
Circulation, November 16, 2004; 110(20): 3270 - 3275.
[Abstract] [Full Text] [PDF]

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 Arch Intern MedHome page
J. McCord, B. J. Mundy, M. P. Hudson, A. S. Maisel, J. E. Hollander, W. T. Abraham, P. G. Steg, T. Omland, C. W. Knudsen, K. R. Sandberg, et al.
Relationship Between Obesity and B-Type Natriuretic Peptide Levels
Arch Intern Med, November 8, 2004; 164(20): 2247 - 2252.
[Abstract] [Full Text] [PDF]

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 J. Appl. Physiol.Home page
M. Jayachandran, H. Okano, R. Chatrath, W. G. Owen, J. P. McConnell, and V. M. Miller
Sex-specific changes in platelet aggregation and secretion with sexual maturity in pigs
J Appl Physiol, October 1, 2004; 97(4): 1445 - 1452.
[Abstract] [Full Text] [PDF]

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 Eur Heart JHome page
T. Jernberg, S. James, B. Lindahl, N. Johnston, M. Stridsberg, P. Venge, and L. Wallentin
Natriuretic peptides in unstable coronary artery disease
Eur. Heart J., September 1, 2004; 25(17): 1486 - 1493.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
A. S. Jaffe, F. S. Apple, and L. Babuin
Why We Don't Know the Answer May Be More Important than the Specific Question
Clin. Chem., September 1, 2004; 50(9): 1495 - 1497.
[Full Text] [PDF]

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 J Am Coll CardiolHome page
R. J. Rodeheffer
Measuring plasma B-type natriuretic peptide in heart failure: Good to go in 2004?
J. Am. Coll. Cardiol., August 18, 2004; 44(4): 740 - 749.
[Abstract] [Full Text] [PDF]

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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.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. Galvani, F. Ottani, L. Oltrona, D. Ardissino, G. F. Gensini, A. P. Maggioni, P. M. Mannucci, N. Mininni, M. D. Prando, M. Tubaro, et al.
N-Terminal Pro-Brain Natriuretic Peptide on Admission Has Prognostic Value Across the Whole Spectrum of Acute Coronary Syndromes
Circulation, July 13, 2004; 110(2): 128 - 134.
[Abstract] [Full Text] [PDF]

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 CirculationHome page
M. M. Redfield, R. J. Rodeheffer, S. J. Jacobsen, D. W. Mahoney, K. R. Bailey, and J. C. Burnett Jr
Plasma Brain Natriuretic Peptide to Detect Preclinical Ventricular Systolic or Diastolic Dysfunction: A Community-Based Study
Circulation, June 29, 2004; 109(25): 3176 - 3181.
[Abstract] [Full Text] [PDF]

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 J Am Coll CardiolHome page
M. R. Mehra, P. A. Uber, M. H. Park, R. L. Scott, H. O. Ventura, B. C. Harris, and E. D. Frohlich
Obesity and suppressed B-type natriuretic peptide levels in heart failure
J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1590 - 1595.
[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.
[Abstract] [Full Text] [PDF]


 
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