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

Paul Welsh; Ross T Campbell; Leanne Mooney; Dorien M. Kimenai; Caroline Hayward; Archie Campbell; David Porteous; Nicholas L Mills; Ninian Lang; Mark C. Petrie; James L Januzzi; John J. V. McMurray; Naveed A. Sattar

doi:10.1161/CIRCHEARTFAILURE.121.009427

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

Paul Welsh^*, Ross T Campbell, Leanne Mooney, Dorien M. Kimenai, Caroline Hayward, Archie Campbell, David Porteous, Nicholas L Mills, Ninian Lang, Mark C. Petrie, James L Januzzi, John J. V. McMurray, Naveed A. Sattar

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract / Description of output

Background
Demographic differences in expected NT-proBNP 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 (≥125pg/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 50-59 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 50-59 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 ≥125pg/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 (p for sex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (p for sex interaction 0.007).
Conclusions

An NT-proBNP ≥125pg/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.

Original language	English
Article number	e009427
Number of pages	11
Journal	Circulation: Heart failure
Volume	15
Early online date	13 Sept 2022
DOIs	https://doi.org/10.1161/CIRCHEARTFAILURE.121.009427
Publication status	E-pub ahead of print - 13 Sept 2022

Keywords / Materials (for Non-textual outputs)

NT-proBNP
risk factors
heart failure
sex
age

Access to Document

10.1161/CIRCHEARTFAILURE.121.009427

Circ-HF GS_Manuscript R2_final_nofc-mergedAccepted author manuscript, 357 KB
CIRCHEARTFAILURE.121.009427Final published version, 803 KBLicence: Creative Commons: Attribution (CC-BY)

High-Sensitivity Cardiac Troponin and Coronary Heart Disease
Mills, N.
UK-based charities
2/02/16 → 1/02/21
Project: Research

Cite this

Welsh, P., Campbell, R. T., Mooney, L., Kimenai, D. M., Hayward, C., Campbell, A., Porteous, D., Mills, N. L., Lang, N., Petrie, M. C., Januzzi, J. L., McMurray, J. J. V., & Sattar, N. A. (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, Article e009427. Advance online publication. https://doi.org/10.1161/CIRCHEARTFAILURE.121.009427

@article{dd5b2b5ca020495aa2f9921f452a3b1f,

title = "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",

abstract = "BackgroundDemographic differences in expected NT-proBNP 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.MethodsThis 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 (≥125pg/ml) were investigated.ResultsIn males, median [97.5th centile] NT-proBNP concentration at age <30 years was 21 [104] pg/ml, rising to 38 [195] pg/ml at 50-59 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 50-59 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 ≥125pg/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 (p for sex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (p for sex interaction 0.007).ConclusionsAn NT-proBNP ≥125pg/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.",

keywords = "NT-proBNP, risk factors, heart failure, sex, age",

author = "Paul Welsh and Campbell, {Ross T} and Leanne Mooney and Kimenai, {Dorien M.} and Caroline Hayward and Archie Campbell and David Porteous and Mills, {Nicholas L} and Ninian Lang and Petrie, {Mark C.} and Januzzi, {James L} and McMurray, {John J. V.} and Sattar, {Naveed A.}",

note = "Funding 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. The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the article. Funding Information: Dr Welsh reports grant income from Roche Diagnostics within this work and grant income from AstraZeneca, Boehringer Ingelheim, and Novartis, and speaker fees from Novo Nordisk, outside the submitted work. Dr Sattar has received grant and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis; grant from Roche Diagnostics; and personal fees from Abbott Laboratories‚ Afimmune, Amgen, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi outside the submitted work. Dr Januzzi is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical end point committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr McMurray reports payments to his employer, University of Glasgow, for work on clinical trials, consulting, lecturing, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos, as well as personal lecture fees from Abbott, Hikma, Sun Pharmaceuticals, and Servier. Dr Mills has received honoraria from Abbott Diagnostics, Siemens Healthineers, and Singulex, and the University of Edinburgh has received research grants from Abbott Diagnostics and Siemens Healthineers. All other authors declare no conflicts. Publisher Copyright: {\textcopyright} 2022 Lippincott Williams and Wilkins. All rights reserved.",

year = "2022",

month = sep,

day = "13",

doi = "10.1161/CIRCHEARTFAILURE.121.009427",

language = "English",

volume = "15",

journal = "Circulation: Heart failure",

issn = "1941-3289",

publisher = "Lippincott Williams and Wilkins",

}

Welsh, P, Campbell, RT, Mooney, L, Kimenai, DM , Hayward, C , Campbell, A , Porteous, D , Mills, NL, Lang, N, Petrie, MC, Januzzi, JL, McMurray, JJV & Sattar, NA 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, vol. 15, e009427. https://doi.org/10.1161/CIRCHEARTFAILURE.121.009427

TY - JOUR

T1 - 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

AU - Welsh, Paul

AU - Campbell, Ross T

AU - Mooney, Leanne

AU - Kimenai, Dorien M.

AU - Hayward, Caroline

AU - Campbell, Archie

AU - Porteous, David

AU - Mills, Nicholas L

AU - Lang, Ninian

AU - Petrie, Mark C.

AU - Januzzi, James L

AU - McMurray, John J. V.

AU - Sattar, Naveed A.

N1 - Funding 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. The funders had no role in the design and conduct of the study, in the collection, analysis, and interpretation of the data, and in the preparation, review, or approval of the article. Funding Information: Dr Welsh reports grant income from Roche Diagnostics within this work and grant income from AstraZeneca, Boehringer Ingelheim, and Novartis, and speaker fees from Novo Nordisk, outside the submitted work. Dr Sattar has received grant and personal fees from AstraZeneca, Boehringer Ingelheim, and Novartis; grant from Roche Diagnostics; and personal fees from Abbott Laboratories‚ Afimmune, Amgen, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novo Nordisk, Pfizer, and Sanofi outside the submitted work. Dr Januzzi is a Trustee of the American College of Cardiology; is a board member of Imbria Pharmaceuticals; has received grant support from Abbott Diagnostics, Applied Therapeutics, Innolife, and Novartis; has received consulting income from Abbott Diagnostics, Boehringer Ingelheim, Janssen, Novartis, and Roche Diagnostics; and participates in clinical end point committees/data safety monitoring boards for AbbVie, Siemens, Takeda, and Vifor. Dr McMurray reports payments to his employer, University of Glasgow, for work on clinical trials, consulting, lecturing, and other activities from Alnylam, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardurion, Cytokinetics, Dal-Cor, GlaxoSmithKline, Ionis, KBP Biosciences, Novartis, Pfizer, and Theracos, as well as personal lecture fees from Abbott, Hikma, Sun Pharmaceuticals, and Servier. Dr Mills has received honoraria from Abbott Diagnostics, Siemens Healthineers, and Singulex, and the University of Edinburgh has received research grants from Abbott Diagnostics and Siemens Healthineers. All other authors declare no conflicts. Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.

PY - 2022/9/13

Y1 - 2022/9/13

N2 - BackgroundDemographic differences in expected NT-proBNP 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.MethodsThis 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 (≥125pg/ml) were investigated.ResultsIn males, median [97.5th centile] NT-proBNP concentration at age <30 years was 21 [104] pg/ml, rising to 38 [195] pg/ml at 50-59 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 50-59 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 ≥125pg/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 (p for sex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (p for sex interaction 0.007).ConclusionsAn NT-proBNP ≥125pg/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.

AB - BackgroundDemographic differences in expected NT-proBNP 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.MethodsThis 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 (≥125pg/ml) were investigated.ResultsIn males, median [97.5th centile] NT-proBNP concentration at age <30 years was 21 [104] pg/ml, rising to 38 [195] pg/ml at 50-59 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 50-59 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 ≥125pg/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 (p for sex interaction <0.001, 0.07, respectively). Diabetes was inversely associated with odds of elevated NT-proBNP in females only (p for sex interaction 0.007).ConclusionsAn NT-proBNP ≥125pg/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.

KW - NT-proBNP

KW - risk factors

KW - heart failure

KW - sex

KW - age

U2 - 10.1161/CIRCHEARTFAILURE.121.009427

DO - 10.1161/CIRCHEARTFAILURE.121.009427

M3 - Article

SN - 1941-3289

VL - 15

JO - Circulation: Heart failure

JF - Circulation: Heart failure

M1 - e009427

ER -

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

Abstract / Description of output

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

High-Sensitivity Cardiac Troponin and Coronary Heart Disease

Cite this