Plasma levels of growth differentiation factor 15 are associated with future risk of venous thromboembolism
Open accessAbstract
Growth differentiation factor 15 (GDF-15), a marker of inflammation and oxidative stress, has emerged as a biomarker for arterial cardiovascular disease. However, the association between GDF-15 and venous thromboembolism (VTE) remains uncertain. We therefore investigated the association between plasma GDF-15 levels and future risk of incident VTE and explored the potential of a causal association using Mendelian randomization (MR). We conducted a population-based nested case-control study comprising 416 VTE patients and 848 age- and sex-matched controls derived from the Tromsø Study. Logistic regression was used to calculate odds ratios (ORs) for VTE across GDF-15 quartiles. For the MR, we used data from the International Network on Venous Thrombosis (INVENT) consortium to examine whether single nucleotide polymorphisms (SNPs) associated with GDF-15 levels with genome-wide significance were related to VTE. We found that the ORs for VTE increased across GDF-15 quartiles (Ptrend = .002). Participants with GDF-15 values in the highest quartile (≥358 pg/mL) had an OR for VTE of 2.05 (95% confidence interval, 1.37-3.08) compared with those with GDF-15 in the lowest quartile (<200 pg/mL) in the age- and sex-adjusted model. ORs remained essentially the same after further adjustment for body mass index, smoking, hormone therapy, physical activity, and C-reactive protein. Similar results were obtained for provoked/unprovoked events, deep vein thrombosis, and pulmonary embolism. GDF-15 levels, as predicted by the SNPs, were not associated with VTE in MR. Our results indicate that high GDF-15 levels are associated with increased risk of VTE, but MR suggests that this association is not causal.
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The association between GDF-15 levels and VTE was independent of D-dimer and von Willebrand factor.
“Importantly, the association between GDF-15 levels and VTE was independent of D-dimer and von Willebrand factor, which are well-established biomarkers for thrombosis (35).”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [35]
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- Authors
- Hansen, E.-S., Hindberg, K., Latysheva, N., Aukrust, P., Ueland, T., Hansen, J.-B., Brækkan, S. K., Morelli, V. M., & the INVENT Consortium
- Affiliations
- UiT The Arctic University of Norway (NO)
- Oslo University Hospital (NO)
- University of Oslo (NO)
- University Hospital of North Norway (NO)
- ORCID
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2020-10-15
- Volume
- 136
- Issue
- 16
- Pages
- 1863-1870
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W3042076497
- Cited by
- 22
- References
- 48
- Citations by year
- 2026: 6 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 1 · 2021: 6 · 2020: 1
- FWCI
- 2.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Blood (publishedVersion)
- PubMed (publishedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, other-oa)
- Funders
- Stiftelsen Kristian Gerhard Jebsen
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Keywords
- growth differentiation factor 15, venous thromboembolism, deep vein thrombosis, pulmonary embolism, biomarkers, inflammation, oxidative stress, Mendelian randomization, genetic variants, causal relationship, Tromsø Study
- MeSH terms
- Disease Susceptibility, Female, Humans, Male, Prognosis, Risk Factors, Biomarkers, Odds Ratio, Case-Control Studies, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Venous Thromboembolism, Growth Differentiation Factor 15
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