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

Abstract

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 < or = 45% (p < 0.0001), abnormal ECG (p < 0.0001), high log10[plasma creatinine] (p = 0.0009), low log10[plasma glycosylated haemoglobin A1c] (p = 0.0004), and high log10[urine albumin] (p < 0.0001) were independently associated with a high plasma log10[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.

Figure 1

Plasma concentrations of N-terminal pro brain natriuretic peptide in men and women in the study sample. Horizontal bars indicate geometric mean concentrations. Definition of “normal” subject: no congestive heart failure, no ischaemic heart disease, no history of hypertension, no diabetes, no lung disease, no cardiovascular drugs treatment, left ventricular ejection fraction of ⩾ 60%, blood pressure < 140/90 mm Hg, and a normal ECG. NT-proBNP, N-terminal pro brain natriuretic peptide.

Figure 2

Plasma concentrations of N-terminal pro brain natriuretic peptide in different age and sex groups in the undivided study sample. Horizontal bars indicate geometric mean concentrations.

Figure 3

Plasma concentrations of N-terminal pro brain natriuretic peptide in different age and sex groups in the subjects defined as “normal” in the study sample. Horizontal bars indicate geometric mean concentrations. Definition of normal subject: no congestive heart failure, no ischaemic heart disease, no history of hypertension, no diabetes, no lung disease, no cardiovascular drug treatment, left ventricular ejection fraction of ⩾ 60%, blood pressure < 140/90 mm Hg, and a normal ECG.