Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter April 29, 2014

Age- and gender-specific brain natriuretic peptide (BNP) reference ranges in primary care

  • Josephine M. Keyzer EMAIL logo , Johannes J. Hoffmann , Lianne Ringoir , Karin C. Nabbe , Jos W. Widdershoven and Victor J. Pop

Abstract

Background: Chronic heart failure is a common disease with a high morbidity and mortality. In primary care, brain natriuretic peptide (BNP) is used for excluding heart failure. The Dutch and European Society of Cardiology heart failure guidelines apply two BNP cut-off levels without making distinction for gender and age. The aim of our study was to establish BNP reference ranges for use in primary care.

Methods: We investigated BNP values of 9447 eligible subjects in a primary care laboratory. For establishing the reference ranges in various age and gender classes we used the Bhattacharya method.

Results: Analysis of variance demonstrated that BNP data were significantly dependent on age and gender (p<0.001 and p=0.002, respectively), with the age effect being the strongest. Further, we found that the reference ranges were significantly higher than the cut-off values used in the heart failure guidelines, particularly in elderly subjects. For example, the proportion of individuals with a BNP value higher than the 29 pmol/L cut-off increased from approximately 5% in the youngest group to no less than about 50% in the oldest subjects.

Conclusions: BNP reference ranges need to be age- and gender-specific. When applying a single cut-off, many healthy subjects, especially the elderly, would be falsely diagnosed as having elevated BNP, and referred for further unnecessary diagnostics.


Corresponding author: Josephine M. Keyzer, Department of Medical and Clinical Psychology, CoRPS, Tilburg University, PO Box 90153, 5000 LE Tilburg, The Netherlands, Phone: +31 618049590, E-mail:

Acknowledgments

We thank the Beloce Foundation, a primary care scientific non-profit foundation of the southeast of the Netherlands, for their kind support to analyze the data. Thanks for data collection by the ICT department of Diagnostiek voor U, especially Wil Staps.

Conflict of interest statement

Authors’ conflict of interest disclosure: The authors stated that there are no conflicts of interest regarding the publication of this article. Research funding played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

Research funding: None declared.

Employment or leadership: J. Hoffmann is a scientific employee of Abbott Diagnostics. The other authors have nothing to disclose.

Honorarium: None declared.

References

1. Poole-Wilson PA. Chronic heart failure: cause, pathophysiology, prognosis, clinical manifestations, investigations. In: Julian DG, Gamm AJ, Fox FK, Hall RJ, Poole-Wilson PA, editors. Diseases of the heart. London: Bailliere-Tindall, 1989:24–36.Search in Google Scholar

2. Mosterd A, Hoes AW. Clinical epidemiology of heart failure. Heart 2007;93:1137–46.10.1136/hrt.2003.025270Search in Google Scholar

3. Bleumink GS, Knetsch AM, Sturkenboom MC, Straus SM, Hofman A, Deckers JW, et al. Quantifying the heart failure epidemic: prevalence, incidence rate, lifetime risk and prognosis of heart failure The Rotterdam Study. Eur Heart J 2004;25:1614–9.10.1016/j.ehj.2004.06.038Search in Google Scholar

4. Engelfriet PM, Hoogenveen RT, Poos MJ, Blokstra A, van Baal PH, Verschuren WM. Heart failure: epidemiology, risk factors and future. RIVM rapport 260401006. Bilthoven: RIVM, 2012. Available from: http://www.rivm.nl/bibliotheek/rapporten/260401006.html. Accessed August 30, 2013.Search in Google Scholar

5. Stewart S, MacIntyre K, Hole DJ, Capewell S, McMurray JJ. More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 2001;3:315–22.10.1016/S1388-9842(00)00141-0Search in Google Scholar

6. Stewart S, Ekman I, Ekman T, Oden A, Rosengren A. Population impact of heart failure and the most common forms of cancer: a study of 1 162 309 hospital cases in Sweden (1988 to 2004). Circ Cardiovasc Qual Outcomes 2010;3:573–80.10.1161/CIRCOUTCOMES.110.957571Search in Google Scholar

7. Jhund PS, Macintyre K, Simpson CR, Lewsey JD, Stewart S, Redpath A, et al. Long-term trends in first hospitalization for heart failure and subsequent survival between 1986 and 2003: a population study of 5.1 million people. Circulation 2009;119: 515–23.10.1161/CIRCULATIONAHA.108.812172Search in Google Scholar

8. Mosterd A, Reitsma JB, Grobbee DE. ACE inhibition and hospitalisation rates for heart failure, the Netherlands 1980–1999. The end of an epidemic? Heart 2002;87:388–92.Search in Google Scholar

9. Slobbe LC, Smit JM, Groen J, Poos MJ, Kommer GJ. Cost of illness in the Netherlands 2007: trends in healthcare expenditure 1999–2010. RIVM rapport 270751023. Bilthoven: RIVM, 2011. Available from: http://www.rivm.nl/bibliotheek/rapporten/270751023.html. Accessed August 30, 2013.Search in Google Scholar

10. De Bold AJ, Borenstein HB, Veress AT, Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci 1981;28:89–94.10.1016/0024-3205(81)90370-2Search in Google Scholar

11. Yandle TG. Biochemistry of natriuretic peptides. J Intern Med 1994;235:561–76.10.1111/j.1365-2796.1994.tb01263.xSearch in Google Scholar

12. Davidson NC, Struthers AD. Brain natriuretic peptide. J Hypertens 1994;12:329–36.Search in Google Scholar

13. Maisel AS, Krishnaswamy P, Nowak RM, McCord J, Hollander JE, Duc P, et al. Rapid measurement of B-type natriuretic peptide in the emergency diagnosis of heart failure. N Engl J Med 2002;347:161–7.10.1056/NEJMoa020233Search in Google Scholar

14. Davis M, Espiner E, Richards G, Billings J, Town I, Neill A, et al. Plasma brain natriuretic peptide in assessment of acute dyspnoea. Lancet 1994;343:440–4.10.1016/S0140-6736(94)92690-5Search in Google Scholar

15. Struthers AD. Ten years of natriuretic peptide research: a new dawn for their diagnostic and therapeutic use? Br Med J 1994;308:1615–9.10.1136/bmj.308.6944.1615Search in Google Scholar PubMed PubMed Central

16. Cowie MR, Struthers AD, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, et al. Value of natriuretic peptides in assessment of patients with possible new heart failure in primary care. Lancet 1997;350:1349–53.10.1016/S0140-6736(97)06031-5Search in Google Scholar

17. Sagnella GA. Measurement and significance of circulating natriuretic peptides in cardiovascular disease. Clin Sci 1998;95:519–29.10.1042/cs0950519Search in Google Scholar

18. Sagnella GA. Measurement and importance of plasma brain natriuretic peptide and related peptides. Ann Clin Biochem 2001;38:83–93.10.1258/0004563011900317Search in Google Scholar

19. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the task force for the diagnosis and treatment of acute and chronic heart failure 2012 of the European Society of Cardiology. Developed in collaboration with the heart failure association (HFA) of the ESC. Eur Heart J 2012;33:1787–847.Search in Google Scholar

20. Hoes AW, Voors AA, Rutten FH, Van Lieshout J, Janssen PG, Walma EP. NHG-standaard Hartfalen. 2e herziening. Huisarts Wet 2010;53:368–89.Search in Google Scholar

21. Raymond I, Groenning BA, Hildebrandt PR, Nilsson JC, Baumann M, Trawinski J, et al. 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 2003;89:745–51.10.1136/heart.89.7.745Search in Google Scholar

22. DeFilippi C, van Kimmenade RR, Pinto YM. Amino-terminal pro-B-type natriuretic peptide testing in renal disease. Am J Cardiol 2008;101:82–8.10.1016/j.amjcard.2007.11.029Search in Google Scholar

23. McCullough PA, Kuncheria J, Mathur VS. Diagnostic and therapeutic utility of B-type natriuretic peptide in patients with renal insufficiency and decompensated heart failure. Rev Cardiovasc Med 2003;4:3–12.Search in Google Scholar

24. McCullough PA, Sandberg KR. B-type natriuretic peptide and renal disease. Heart Fail Rev 2003;8:335–8.10.1023/A:1026187013370Search in Google Scholar

25. Vickery S, Price CP, John RI, Abbas NA, Webb MC, Kempson ME, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD: relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis 2005;46: 610–20.10.1053/j.ajkd.2005.06.017Search in Google Scholar

26. Siebenhofer A, Ng LL, Plank J, Berghold A, Hodl R, Pieber TR. Plasma N-terminal pro-brain natriuretic peptide in type 1 diabetic patients with and without diabetic nephropathy. Diabet Med 2003;20:535–9.10.1046/j.1464-5491.2003.00948.xSearch in Google Scholar

27. Tanabe A, Naruse M, Wasada T, Naruse K, Yoshimoto T, Omori Y, et al. Effects of acute hyperinsulinemia on plasma atrial and brain natriuretic peptide concentrations. Eur J Endocrinol 1995;132:693–8.10.1530/eje.0.1320693Search in Google Scholar

28. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic peptide concentration: impact of age and gender. J Am Coll Cardiol 2002;40:976–82.10.1016/S0735-1097(02)02059-4Search in Google Scholar

29. Wang TJ, Larson MG, Levy D, Leip EP, Benjamin EJ, Wilson PW, et al. Impact of age and sex on plasma natriuretic peptide levels in healthy adults. Am J Cardiol 2002;90:254–8.10.1016/S0002-9149(02)02464-5Search in Google Scholar

30. Ringoir L, Pedersen SS, Widdershoven JW, Pouwer F, Keyzer JM, Romeijnders A, et al. Beta-blockers and depression in elderly hypertension patients in primary care. Family Medicine (in press).Search in Google Scholar

31. Mongia SK, La’ulu SL, Apple FS, Ler R, Murakami MM, Roberts WL. Performance characteristics of the Architect brain natriuretic peptide (BNP) assay: a two site study. Clin Chim Acta 2008;391:102–5.10.1016/j.cca.2008.01.026Search in Google Scholar PubMed

32. Bhattacharya CG. A simple method of resolution of a distribution into Gaussian components. Biometrics 1967;23:115–35.10.2307/2528285Search in Google Scholar

33. Baadenhuijsen H, Smit JC. Indirect estimation of clinical chemical reference intervals from total hospital patient data: application of a modified Bhattacharya procedure. J Clin Chem Lab Med 1985;23:829–39.10.1515/cclm.1985.23.12.829Search in Google Scholar PubMed

34. Knudsen CW, Riis JS, Finsen AV, Eikvar L, Müller C, Westheim A, et al. Diagnostic value of a rapid test for B-type natriuretic peptide in patients presenting with acute dyspnoe: effect of age and gender. Eur J Heart Fail 2004;6:55–62.10.1016/j.ejheart.2003.10.006Search in Google Scholar PubMed

Received: 2013-9-20
Accepted: 2014-3-31
Published Online: 2014-4-29
Published in Print: 2014-9-1

©2014 by De Gruyter

Downloaded on 23.4.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2013-0791/html
Scroll to top button