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Licensed Unlicensed Requires Authentication Published by De Gruyter August 18, 2022

Reference ranges for GDF-15, and risk factors associated with GDF-15, in a large general population cohort

  • Paul Welsh EMAIL logo , Dorien M. Kimenai , Riccardo E. Marioni , Caroline Hayward , Archie Campbell , David Porteous , Nicholas L. Mills , Stephen O’Rahilly and Naveed Sattar

Abstract

Objectives

Growth differentiation factor (GDF)-15 is attracting interest as a biomarker in several areas of medicine. We aimed to evaluate the reference range for GDF-15 in a general population, and to explore demographics, classical cardiovascular disease risk factors, and other cardiac biomarkers associated with GDF-15.

Methods

GDF-15 was measured in serum from 19,462 individuals in the Generation Scotland Scottish Family Health Study. Associations of cardiometabolic risk factors with GDF-15 were tested using adjusted linear regression. Among 18,507 participants with no heart disease, heart failure, or stroke, and not pregnant, reference ranges (median and 97.5th centiles) were derived by decade age bands and sex.

Results

Among males in the reference range population, median (97.5th centile) GDF-15 concentration at age <30 years was 537 (1,135) pg/mL, rising to 931 (2,492) pg/mL at 50–59 years, and 2,152 (5,972) pg/mL at ≥80 years. In females, median GDF-15 at age <30 years was 628 (2,195) pg/mL, 881 (2,323) pg/mL at 50–59 years, and 1847 (6,830) pg/mL at ≥80 years. Among those known to be pregnant, median GDF-15 was 19,311 pg/mL. After adjustment, GDF-15 was higher in participants with adverse cardiovascular risk factors, including current smoking (+26.1%), those with previous heart disease (+12.7%), stroke (+17.1%), heart failure (+25.3%), and particularly diabetes (+60.2%). GDF-15 had positive associations with cardiac biomarkers cardiac troponin I, cardiac troponin T, and N-terminal pro B-type natriuretic peptide (NT-proBNP).

Conclusions

These data define reference ranges for GDF-15 for comparison in future studies, and identify potentially confounding risk factors and mediators to be considered in interpreting GDF-15 concentrations.


Corresponding author: Dr. Paul Welsh, BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA, UK, Phone: +0141 330 2569, E-mail:

Funding source: Roche Diagnostics

Funding source: Medical Research Council

Award Identifier / Grant number: U. MC_UU_00007/10

Funding source: Scottish Funding Council

Award Identifier / Grant number: HR03006

Funding source: British Heart Foundation

Award Identifier / Grant number: CH/F/21/90010

Award Identifier / Grant number: RE/18/5/34216

Award Identifier / Grant number: RE/18/6/34217

Award Identifier / Grant number: RG/20/10/34966

Funding source: Health Data Research UK

Award Identifier / Grant number: HDR-5012

Funding source: Chief Scientist Office of the Scottish Government Health Directorates

Award Identifier / Grant number: CZD/16/6

Acknowledgments

We thank: Philip Stewart, Elaine Butler, Emma Dunning and Josephine Cooney (University of Glasgow) for excellent technical support; all the families who took part; the GPs and Scottish School of Primary Care for their help in recruitment; and the Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. The authors thank Liz Coyle, University of Glasgow, for her assistance in the preparation of this article.

  1. Research funding: 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]. CH is supported by a Medical Research Council Programme Grant (U. MC_UU_00007/10). NLM is supported by a Chair Award (CH/F/21/90010), a Programme Grant (RG/20/10/34966) and a Research Excellence Award (RE/18/5/34216) from the British Heart Foundation. NS is supported by British Heart Foundation Centre of Research Excellence Grant (RE/18/6/34217). DMK is 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.

  2. Author contributions: PW and NS conceived and designed the study. AC conducted data acquisition. PW carried out the statistical analysis. PW and NS wrote the original manuscript. All authors contributed to the interpretation of the data and critical revision of the manuscript for important intellectual content and approved the final draft. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interests: PW reports grant income from Roche Diagnostics, AstraZeneca, Boehringer Ingelheim, and Novartis, outside the submitted work. REM has received speaker fees from Illumina and is an advisor to the Epigenetic Clock Development Foundation. NLM has received research grants to the University of Edinburgh from Abbott Diagnostics and Siemens Healthineers that are not related to the current work and has acted as a consultant for Abbott Diagnostics, Siemens Healthineers, Roche, and LumiraDx. SO has provided remunerated consultancy services to Pfizer, AstraZeneca, Novo Nordisk and ERX Pharmaceuticals. NS has consulted for Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi; and received grant support paid to his University from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics outside the submitted work. All other authors declare no conflicts.

  4. Informed consent: Informed consent was obtained from all individuals included in this study.

  5. Ethical approval: The research related to human use has been complied with all the relevant national regulations, institutional policies and in accordance with the tenets of the Helsinki Declaration, and ethical approval was obtained from Research Ethics Committees in Scotland along with the necessary NHS R&D approval.

  6. Data availability: The datasets generated during and/or analysed during the current study are available from the GS access committee https://www.ed.ac.uk/generation-scotland/for-researchers/access on reasonable request.

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Received: 2022-02-15
Accepted: 2022-08-01
Published Online: 2022-08-18
Published in Print: 2022-10-26

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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