title: Reference limits for N-terminal-pro-B-type natriuretic peptide in healthy individuals (from the Framingham Heart Study).
abstract: N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) is a commonly measured cardiovascular biomarker in ambulatory and hospital settings. Nonetheless, there are limited data regarding "normal" ranges for NT-pro-BNP in healthy subjects, despite the importance of such information for interpreting natriuretic peptide measurements. In this study, a healthy reference sample free of cardiovascular disease from the Framingham Heart Study Generation 3 cohort was examined; there were 2,285 subjects (mean age 38 years, 56% women). Plasma NT-pro-BNP levels were measured using the Roche Diagnostics Elecsys 2010 assay, and reference values (2.5th, 50th, and 97.5th quantiles) were determined using empiric and quantile regression methods. Gender, age, blood pressure, and body mass index accounted for approximately 33% of the interindividual variability in NT-pro-BNP in the reference sample. NT-pro-BNP values were substantially higher in women compared to men at every age, and levels increased with increasing age for both genders. Using quantile regression, the upper reference values (97.5th quantile) for NT-pro-BNP were 42.5 to 106.4 pg/ml in men (depending on age) and 111.0 to 215.9 pg/ml in women. Intraindividual variability was assessed in an additional 12 healthy subjects, who had serial NT-pro-BNP measurements over 1 month. Intraclass correlation was 0.85, indicating that most of the variability in NT-pro-BNP concentrations was among rather than within subjects. However, the reference change value was 100%, suggesting that small proportional differences in NT-pro-BNP could be attributable to analytic variability. In conclusion, the reference limits obtained from this large, healthy, community-based sample may aid in the evaluation of NT-pro-BNP concentrations measured for clinical and research purposes.
authors.affiliation: Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Fradley
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Elizabeth
authors.initials: E
authors.lastname: McCabe
authors.forename: Erin
authors.initials: E
authors.lastname: Coglianese
authors.forename: Ravi V
authors.initials: RV
authors.lastname: Shah
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000367:Age Factors; D001794:Blood Pressure; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood*; D010446:Peptide Fragments / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis; D012494:Sampling Studies; D012737:Sex Factors
chemical_list: D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain