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

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.Keywords: Bhattacharya statistics; brain natriuretic peptide (BNP); chronic heart failure; primary care; reference ranges