N-terminal pro-brain natriuretic peptide (NT-proBNP) in healthy blood donors and in patients from general practitioners with and without a diagnosis of cardiac disease

Abstract

Background: The natriuretic peptides and especially the N-terminal pro-brain natriuretic peptide (NT-proBNP) are increased in conditions with cardiac ventricular volume and pressure overload. Early stages of ventricular volume and pressure overload are often without signs and symptoms and therefore difficult to diagnose. On the contrary, a normal level of a natriuretic peptide excludes congestive heart failure as a cause of dyspnea with high probability. In addition, natriuretic peptide levels predict the risk of death and cardiovascular events after adjustment for traditional risk factors. A few studies suggest that age, gender and renal function may influence circulating natriuretic peptide levels. This study was therefore initiated to a) assess reference values for the N-terminal pro-brain natriuretic peptide (NT-proBNP) in a group of blood donors and healthy elderly individuals and to relate these levels to age, sex, and creatinine and b) to measure the levels of NT-proBNP in a population of patients presenting to general practitioners and to check the quality of the diagnoses congestive heart failure and dyspnea of other causes (heart failure patients usually present with breathlessness but the low specificity of dyspnea often leads to misdiagnoses). Finally, the percentage of patients with other diagnoses and elevated NT-proBNP as an indicator of an increased cardiovascular risk or up to now unknown cardiac disease was determined.

Study design and methods: N=1981 blood donors, N=283 individuals from general practitioners (GP) without cardiac disease and N=570 consecutive patients from GPs were recruited and tested for the presence of NT-proBNP using a newly developed electrochemiluminescence immunoassay run on an automated analyzer (Elecsys, Roche Diagnostics).

Results: NT-proBNP was detected at relatively homogenous levels in all individuals below the age of 50 years. NT-proBNP values increased with increasing age which was due to the increasing number of outliers in that group. Females had higher NT-proBNP levels than males.

Conclusions: Based on the assumption that individuals below the age of 50 years are healthy, reference values based on the 97.5th percentile were established. These values were considered to be normal. The presented data and data from the literature suggest that also in the elderly population a cut-off level of 125 pg/ml is useful either to exclude cardiac dysfunction in symptomatic individuals or to risk stratify elderly individuals in terms of the necessity for intervention.