Welsh, P. et al. (2023) Multiple cardiac biomarkers to improve prediction of cardiovascular events: findings from the Generation Scotland Scottish Family Health Study. Clinical Chemistry, 70(2), pp. 403-413. (doi: 10.1093/clinchem/hvad205) (PMID:38069915)
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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 risk 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 the 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.
| Item Type: | Articles |
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| Additional Information: | 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). D.M. Kimenai is supported by a British Heart Foundation Intermediate Basic Science Research Fellowship (FS/IBSRF/23/25161), and by Health Data Research UK, which receives its funding from HDR UK Ltd (HDR5012) 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 Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Foundation, and the Wellcome Trust. C. Hayward is supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease). N.L. Mills 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). A.S.V. Shah is supported by the British Heart Foundation through an Intermediate Clinical Research Fellowship (FS/19/17/34172). C.L.M. Sudlow received a £5M Wellcome Trust (major research funding charity) longitudinal studies award to University of Edinburgh 2019–2024 for enhancement, extension, and maintenance of the Generation Scotland study (PI). D.A. Gadd is funded by the Wellcome Trust 4-year PhD in Translational Neuroscience—training the next generation of basic neuroscientists to embrace clinical research [108890/Z/15/Z]. M. Woodward is supported by the Australian National Health and Medical Research Council (APP1149987, APP1174120). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Woodward, Professor Mark and Cleland, Professor John and Sattar, Professor Naveed and Welsh, Professor Paul and Pellicori, Dr Pierpaolo |
| Authors: | 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., and Sattar, N. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Clinical Chemistry |
| Publisher: | Oxford University Press |
| ISSN: | 0009-9147 |
| ISSN (Online): | 1530-8561 |
| Copyright Holders: | Copyright © The Authors 2023 |
| First Published: | First published in Clinical Chemistry 70(2):403–413 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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