Best Practices for NT-proBNP Reference Values: Findings from the CLEAN Assessment

Abstract

The natriuretic peptides, B-type natriuretic peptide (BNP) and NT-proBNP that have emerged as tools 
for diagnosing congestive heart failure (CHF) are affected by age and renal insufficiency (RI). NT
proBNP is used in rejecting CHF and as a marker of risk for patients with acute coronary syndromes. 
This observational study was undertaken to evaluate the reference value for interpreting NT-proBNP 
concentrations. The hypothesis is that increasing concentrations of NT-proBNP are associated with the 
effects of multiple co-morbidities, not merely CHF, resulting in altered volume status or myocardial 
filling pressures. NT-proBNP was measured in a population with normal trans-thoracic 
echocardiograms (TTE) and free of anemia or renal impairment. Study participants were seen in acute 
care for symptoms of shortness of breath suspicious for CHF requiring evaluation with cardiac NT
proBNP assay. The median NT-proBNP for patients under 50 years is 60.5 pg/ml with an upper limit of 
462 pg/ml, and for patients over 50 years the median was 272.8 pg/ml with an upper limit of 998.2 pg/ml. 
We suggest that NT-proBNP levels can be more accurately interpreted only after removal of the major 
co-morbidities that affect an increase in this peptide in serum. The PRIDE study guidelines should be 
applied until presence or absence of comorbidities is diagnosed. With no comorbidities, the reference 
range for normal over 50 years of age remains steady at ~1000 pg/ml. The effect shown in previous 
papers likely is due to increasing concurrent comorbidity with age.