Multiple cardiac biomarkers to improve prediction of cardiovascular events: Findings from the Generation Scotland Scottish Family Health Study

Paul Welsh; Dorien M. Kimenai; Anoop S. V. Shah; Danni A. Gadd; Riccardo E Marioni; Mark Woodward; Cathie L M Sudlow; Archie Campbell; John G F Cleland; Pierpaolo Pellicori; Caroline Hayward; Nicholas L Mills; Naveed Sattar

doi:10.1093/clinchem/hvad205

Multiple cardiac biomarkers to improve prediction of cardiovascular events: Findings from the Generation Scotland Scottish Family Health Study

Paul Welsh^*, Dorien M. Kimenai, Anoop S. V. Shah, Danni A. Gadd, Riccardo E Marioni, Mark Woodward, Cathie L M Sudlow, Archie Campbell, John G F Cleland, Pierpaolo Pellicori, Caroline Hayward, Nicholas L Mills, Naveed Sattar

^*Corresponding author for this work

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

Abstract

Background: Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific combined cardiac biomarker approach for cardiovascular risk prediction.
Methods: In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 factors.
Results: The study population comprised 18,383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to base model was for women GDF-15 and for men NT-proBNP (change in c-index: +0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination.
Conclusions: A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.

Original language	English
Journal	Clinical Chemistry
DOIs	https://doi.org/10.1093/clinchem/hvad205
Publication status	Published - 9 Dec 2023

Keywords / Materials (for Non-textual outputs)

Biomarkers
cardiovascular
risk factors
general population

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Multiple cardiac biomarkers_WELSH_DOA27102023_AFV
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Accepted author manuscript, 431 KBLicence: Creative Commons: Attribution (CC-BY)

High-Sensitivity Cardiac Troponin Beyond the Acute Coronary Syndrome
Mills, N. (Principal Investigator), Anand, A. (Co-investigator), Chapman, A. (Co-investigator), Ferry, A. (Co-investigator), Newby, D. (Co-investigator), Strachan, F. (Co-investigator) & Tsanas, T. (Co-investigator)
UK-based charities
1/06/20 → 31/05/25
Project: Research
High-sensitivity Cardiac Troponin In The Prevention Of Cardiovascular Disease
Shah, A. (Principal Investigator), Mills, N. (Co-investigator) & Newby, D. (Co-investigator)
UK-based charities
1/08/19 → 31/07/20
Project: Research
Quantitative Traits in Health and Disease
Haley, C. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Cite this

Welsh, P., Kimenai, D. M., Shah, A. S. V., Gadd, D. A., Marioni, R. E., Woodward, M., Sudlow, C. L. M., Campbell, A., Cleland, J. G. F., Pellicori, P., Hayward, C., Mills, N. L., & Sattar, N. (2023). Multiple cardiac biomarkers to improve prediction of cardiovascular events: Findings from the Generation Scotland Scottish Family Health Study. Clinical Chemistry. https://doi.org/10.1093/clinchem/hvad205

@article{909f97f5290340eca8228f4993e42c86,

title = "Multiple cardiac biomarkers to improve prediction of cardiovascular events: Findings from the Generation Scotland Scottish Family Health Study",

abstract = "Background: Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific combined cardiac biomarker approach for cardiovascular risk prediction. Methods: In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 factors.Results: The study population comprised 18,383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to base model was for women GDF-15 and for men NT-proBNP (change in c-index: +0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination. Conclusions: A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.",

keywords = "Biomarkers, cardiovascular, risk factors, general population",

author = "Paul Welsh and Kimenai, {Dorien M.} and Shah, {Anoop S. V.} and Gadd, {Danni A.} and Marioni, {Riccardo E} and Mark Woodward and Sudlow, {Cathie L M} and Archie Campbell and Cleland, {John G F} and Pierpaolo Pellicori and Caroline Hayward and Mills, {Nicholas L} and Naveed Sattar",

note = "Funding Roche Diagnostics supported this study through provision of free reagents and a grant for measurement of NT-proBNP, CRP and GDF-15. Troponin measurements and analysis were supported by a Stratified Medicine Grant from the Chief Scientist Office of the Scottish Government Health Directorates (ASM/14/1). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). DMK is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/IBSRF/23/25161). CH is supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease). NLM is supported by the British Heart Foundation through a Chair Award (CH/F/21/90010), Programme Grant (RG/20/10/34966), and a Research Excellent Award (RE/18/5/34216). ASVS is supported by the British Heart Foundation through an Intermediate Clinical Research Fellowship (FS/19/17/34172). The funders had no role in the study and the decision to submit this work to be considered for publication",

year = "2023",

month = dec,

day = "9",

doi = "10.1093/clinchem/hvad205",

language = "English",

journal = "Clinical Chemistry",

issn = "0009-9147",

publisher = "Oxford University Press",

}

Welsh, P, Kimenai, DM, Shah, ASV, Gadd, DA, Marioni, RE, Woodward, M, Sudlow, CLM , Campbell, A, Cleland, JGF, Pellicori, P, Hayward, C , Mills, NL & Sattar, N 2023, 'Multiple cardiac biomarkers to improve prediction of cardiovascular events: Findings from the Generation Scotland Scottish Family Health Study', Clinical Chemistry. https://doi.org/10.1093/clinchem/hvad205

TY - JOUR

T1 - Multiple cardiac biomarkers to improve prediction of cardiovascular events

T2 - Findings from the Generation Scotland Scottish Family Health Study

AU - Welsh, Paul

AU - Kimenai, Dorien M.

AU - Shah, Anoop S. V.

AU - Gadd, Danni A.

AU - Marioni, Riccardo E

AU - Woodward, Mark

AU - Sudlow, Cathie L M

AU - Campbell, Archie

AU - Cleland, John G F

AU - Pellicori, Pierpaolo

AU - Hayward, Caroline

AU - Mills, Nicholas L

AU - Sattar, Naveed

N1 - Funding Roche Diagnostics supported this study through provision of free reagents and a grant for measurement of NT-proBNP, CRP and GDF-15. Troponin measurements and analysis were supported by a Stratified Medicine Grant from the Chief Scientist Office of the Scottish Government Health Directorates (ASM/14/1). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). DMK is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/IBSRF/23/25161). CH is supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease). NLM is supported by the British Heart Foundation through a Chair Award (CH/F/21/90010), Programme Grant (RG/20/10/34966), and a Research Excellent Award (RE/18/5/34216). ASVS is supported by the British Heart Foundation through an Intermediate Clinical Research Fellowship (FS/19/17/34172). The funders had no role in the study and the decision to submit this work to be considered for publication

PY - 2023/12/9

Y1 - 2023/12/9

N2 - Background: Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific combined cardiac biomarker approach for cardiovascular risk prediction. Methods: In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 factors.Results: The study population comprised 18,383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to base model was for women GDF-15 and for men NT-proBNP (change in c-index: +0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination. Conclusions: A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.

AB - Background: Many studies have investigated whether single cardiac biomarkers improve cardiovascular risk prediction for primary prevention but whether a combined approach could further improve risk prediction is unclear. We aimed to test a sex-specific combined cardiac biomarker approach for cardiovascular risk prediction. Methods: In the Generation Scotland Scottish Family Health Study, N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor-15 (GDF-15), cardiac troponin I (cTnI), cardiac troponin T (cTnT), and C-reactive protein (CRP) were measured in stored serum using automated immunoassays. Sex-specific Cox models that included SCORE2 risk factors evaluated addition of single and combined biomarkers for prediction of major adverse cardiovascular events (MACE). Combined biomarker models were compared to a baseline model that included SCORE2 factors.Results: The study population comprised 18,383 individuals (58.9% women, median age of 48 years [25th-75th percentile, 35-58 years]). During the median follow up of 11.6 (25th-75th percentile, 10.8-13.0) years, MACE occurred in 942 (5.1%) individuals. The greatest increase in discrimination with addition of individual biomarkers to base model was for women GDF-15 and for men NT-proBNP (change in c-index: +0.010 for women and +0.005 for men). For women, combined biomarker models that included GDF-15 and NT-proBNP (+0.012) or GDF-15 and cTnI (+0.013), but not CRP or cTnT, further improved discrimination. For men, combined biomarker models that included NT-proBNP and GDF-15 (+0.007), NT-proBNP and cTnI (+0.006), or NT-proBNP and CRP (+0.008), but not cTnT, further improved discrimination. Conclusions: A combined biomarker approach, particularly the use of GDF-15, NT-proBNP and cTnI, further refined cardiovascular risk estimates.

KW - Biomarkers

KW - cardiovascular

KW - risk factors

KW - general population

U2 - 10.1093/clinchem/hvad205

DO - 10.1093/clinchem/hvad205

M3 - Article

SN - 0009-9147

JO - Clinical Chemistry

JF - Clinical Chemistry

ER -

Multiple cardiac biomarkers to improve prediction of cardiovascular events: Findings from the Generation Scotland Scottish Family Health Study

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

High-Sensitivity Cardiac Troponin Beyond the Acute Coronary Syndrome

High-sensitivity Cardiac Troponin In The Prevention Of Cardiovascular Disease

Quantitative Traits in Health and Disease

Cite this