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. 2022 Aug 18;60(11):1820-1829.
doi: 10.1515/cclm-2022-0135. Print 2022 Oct 26.

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

Paul Welsh  1 , Dorien M Kimenai  2 , Riccardo E Marioni  3 , Caroline Hayward  4 , Archie Campbell  3 , David Porteous  3 , Nicholas L Mills  2   5 , Stephen O'Rahilly  6   7 , Naveed Sattar  1
Affiliations

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

Paul Welsh et al. Clin Chem Lab Med. .

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.

Keywords: biochemical markers; guidelines; reference ranges.

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Conflict of interest statement

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.

Figures

Figure 1:
Figure 1:
Histogram of GDF-15 distribution, separately in males (clear bars) and females (green bars), in 18,507 participants without heart disease, heart failure, or stroke, and not known to be pregnant.
Figure 2:
Figure 2:
Association between age and the 50th centile (males light blue, females orange) and the 97.5th centile (males dark blue, females red) of GDF-15 in a continuous model. Coloured areas are 95% CI. Modelled in 18,507 participants without heart disease, heart failure, or stroke, and not known to be pregnant.
See this image and copyright information in PMC

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