The 97.5th percentile upper reference limit (97.5th URL) of N-terminal prob-type natriuretic peptide (NT-proBNP) is influenced by multiple factors and depends on the inclusion criteria of apparently healthy people. In this study, the reference upper limit of NT-proBNP was established on apparently healthy people in Beijing area with abnormal hs-cTn as the exclusion criterion.

According to the latest expert consensus recommendation standards of natriuretic peptide in the detection and clinical application of heart failure published by the Clinical Application Group of Cardiac Bio-Markers of the International Union of Clinical Chemistry, 1 635 healthy people without abnormal appearance of routine indicators such as sex, age, glycated hemoglobin, estimated glomerular filtration rate and medical history were collected. After excluding participants with potential myocardial injury according to hs-cTnI and/or hs-cTnT concentration>99th URL, NT-proBNP 97.5th URL was established in healthy subjects aged 21-40 years (n=205), 41-50 years (n=535), 51-60 years (n=556) and >60 years (n=339) based on non-parametric statistics.

The level of NT-proBNP was positively correlated with age (r=0.254, P<0.001). The levels of NT-proBNP were positively correlated with hs-cTnI, hs-cTnT in males (r=0.377 and r=0.429, both P<0.001). The levels of NT-proBNP were also positively correlated with hs-cTnI, hs-cTnT in females (r=0.132 and r=0.296, both P<0.001). When hs-cTn>99th URL was used as the criterion to exclude patients with potential myocardial injury, among apparently healthy people aged 21-40 years old, 41-50 years old, 51-60 years old and >60 years old, male NT-proBNP 97.5th URL was 81.9 (90%CI 60.0-588.8), 141.2 (90%CI 100.0-263.6), 272.0 (90%CI 193.0-494.0) and 547.9 (90%CI 311.2-738.6), respectively; For females, the rates were 227.5 (90%CI 81.9-360.8), 153.2 (90%CI 128.2-239.5), 300.6 (90%CI 211.0-376.4) and 395.8 (90%CI 242.3-543.5) ng/L, respectively.

This study confirmed that hs-cTn>99th URL can be used as an apparent population screening criterion for natriuretic peptide reference interval studies, which is helpful to remove conventional means to include individuals with occult myocardial injury in apparently healthy patients, so as to establish a more rigorous healthy cohort and establishing solid normal NT-proBNP reference interval.

Troponin; N-terminal pro-B-type natriuretic peptide; Reference range