Reference ranges for NT-proBNP (N-terminal pro-B-type natriuretic peptide) and risk factors for higher NT-proBNP concentrations in a large general population cohort

Welsh, P. et al. (2022) Reference ranges for NT-proBNP (N-terminal pro-B-type natriuretic peptide) and risk factors for higher NT-proBNP concentrations in a large general population cohort. Circulation: Heart Failure, 15(10), pp. 957-967. (doi: 10.1161/CIRCHEARTFAILURE.121.009427) (PMID:36098049) (PMCID:PMC9561238)

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Background: Demographic differences in expected NT-proBNP (N-terminal pro-B-type natriuretic peptide) concentration are not well established. We aimed to establish reference ranges for NT-proBNP and explore the determinants of moderately elevated NT-proBNP under the universal definition of heart failure criteria. Methods: This is a cross-sectional study. NT-proBNP was measured in serum from 18 356 individuals without previous cardiovascular disease in the Generation Scotland Scottish Family Health Study. Age- and sex-stratified medians and 97.5th centiles were generated. Sex stratified risk factors for moderately elevated NT-proBNP (≥125 pg/mL) were investigated. Results: In males, median (97.5th centile) NT-proBNP concentration at age <30 years was 21 (104) pg/mL, rising to 38 (195) pg/ml at 50 to 59 years, and 281 (6792) pg/mL at ≥80 years. In females, median NT-proBNP at age <30 years was 51 (196) pg/mL, 66 (299) pg/mL at 50 to 59 years, and 240 (2704) pg/mL at ≥80 years. At age <30 years, 9.8% of females and 1.4% of males had elevated NT-proBNP, rising to 76.5% and 81.0%, respectively, at age ≥80 years. After adjusting for risk factors, an NT-proBNP ≥125 pg/mL was more common in females than males (OR, 9.48 [95% CI, 5.60–16.1]). Older age and smoking were more strongly associated with elevated NT-proBNP in males than in females (Psex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (Psex interaction=0.007). Cconclusions: An NT-proBNP ≥125 pg/mL is common in females without classical cardiovascular risk factors as well as older people. If NT-proBNP becomes widely used for screening in the general population, interpretation of NT-proBNP levels will require that age and sex-specific thresholds are used to identify patients with potential pathophysiology.

Item Type:Articles
Additional Information:Roche Diagnostics supported this study through provision of free reagents and a grant. Generation Scotland received support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Dr Mills is supported by a British Heart Foundation Senior Clinical Research Fellowship (FS/16/14/32023). Dr Januzzi is supported in part by the Hutter Family Professorship Chair. Drs McMurray and Sattar are supported by British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217. D.M. Kimenai was supported by Health Data Research UK, which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation‚ and the Wellcome Trust.
Glasgow Author(s) Enlighten ID:Lang, Professor Ninian and Sattar, Professor Naveed and Campbell, Dr Ross and Welsh, Professor Paul and McMurray, Professor John and Petrie, Professor Mark and Mooney, Dr Leanne
Authors: Welsh, P., Campbell, R. T., Mooney, L., Kimenai, D. M., Hayward, C., Campbell, A., Porteous, D., Mills, N., Lang, N. N., Petrie, M. C., Januzzi, J. L., McMurray, J. J.V., and Sattar, N.
College/School:College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
Journal Name:Circulation: Heart Failure
Publisher:American Heart Association
ISSN (Online):1941-3297
Published Online:13 September 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Circulation: Heart Failure 15(10): 957-967
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
190082Generation ScotlandAnna DominiczakOffice of the Chief Scientific Adviser (CSO)CZD/16/6MVLS - College Senior Management
303944BHF Centre of ExcellenceColin BerryBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science