European Heart Journal Advance Access originally published online on July 21, 2005
European Heart Journal 2005 26(21):2269-2276; doi:10.1093/eurheartj/ehi410
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What is the normal range for N-terminal pro-brain natriuretic peptide? How well does this normal range screen for cardiovascular disease?
1Department of Cardiovascular Medicine, Northwick Park Hospital, Watford Road, Harrow, Middlesex HA1 3UJ, UK
2Department of Chemical Pathology, St George's Hospital, London, UK
Received 17 October 2004; revised 30 April 2005; accepted 16 June 2005; online publish-ahead-of-print 21 July 2005.
* Corresponding author. Tel: +44 20 8869 2547/8; fax: +44 20 8864 0075. E-mail address: roxy.senior{at}virgin.net
See page 2220 for the editorial comment on this article (doi:10.1093/eurheartj/ehi470)
Aims To define the N-terminal pro-brain natriuretic peptide (NTpBNP) normal range, assessing its cardiovascular screening characteristics in general population and higher risk subjects.
Methods and results A total of 2320 subjects (1392 general population and 928 high-risk) 
45 years old, selected randomly from seven community practices, were invited to undergo clinical assessment and echocardiography and to assess NTpBNP serum levels. Of these, 1205 attended. The NTpBNP normal range was calculated and its cardiovascular screening characteristics were assessed. Age (P<0.0001) and female gender (P<0.0001) independently predicted NTpBNP levels in normal subjects. In the general population, age- and gender-stratified normal NTpBNP levels gave a negative-predictive value (NPV) of 99% in excluding left ventricular systolic dysfunction, atrial fibrillation, and valvular heart disease, and a positive predictive value of 56% in detecting any cardiovascular disease assessed. In high-risk subjects, these values were 98 and 62%, respectively. Ninety-five per cent of subjects with NTpBNP levels over four times the normal had significant cardiovascular disease with the others having renal dysfunction.
Conclusion Normal NTpBNP levels should be stratified by age and gender. Normal NTpBNP levels give high NPV in excluding significant cardiovascular disease. Most subjects with raised NTpBNP levels and almost all subjects with NTpBNP levels over four times the normal have significant cardiovascular disease.
Key Words: Natriuretic peptides • Screening • Left ventricular systolic dysfunction • Atrial fibrillation • Valvular heart disease • Heart failure
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