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

Objective: To identify potentially confounding variables for the interpretation of plasma N-terminal pro brain natriuretic peptide (NT-proBNP). Design: Randomly selected subjects filled in a heart failure questionnaire and underwent pulse and blood pressure measurements, ECG, echocardiography, and blood sampling. Setting: Subjects were recruited from four Copenhagen general practices located in the same urban area and were examined in a Copenhagen University Hospital. Patients: 382 women and 290 men in four age groups: 50-59 years (n=174); 60-69 years (n=204); 70-79 years (n=174); and >80 years (n=120). Main outcome measures: Associations between the plasma concentration of NT-proBNP and a range of clinical variables. Results: In the undivided study sample, female sex (p<0.0001), greater age (p<0.0001), increasing dyspnoea (p=0.0001), diabetes mellitus (p=0.01), valvar heart disease (p=0.002), low heart rate (p<0.0001), left ventricular ejection fraction <= 45% (p<0.0001), abnormal ECG (p<0.0001), high log(10)[plasma creatinine] (p=0.0009), low log,0[plasma glycosylated haemoglobin A1c] (p=0.0004), and high log(10)[urine albumin] (p<0.0001) were independently associated with a high plasma log(10)[plasma NT-proBNP] by multiple linear regression analysis. Conclusions: A single reference interval for the normal value of NT-proBNP is unlikely to suffice. There are several confounders for the interpretation of a given NT-proBNP concentration and at the very least adjustment should be made for the independent effects of age and sex.