Lipids & metabolic liver disease
Growth differentiation factor-15 and the incidence, bidirectional progression, and risk prediction of atherosclerotic cardiovascular disease and metabolic dysfunction-associated steatotic liver disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3
Authors' conclusion
GDF-15 may serve as a promising biomarker for cardiovascular-kidney-liver-metabolic syndrome risk stratification and management.
Study context
- Population
- UK Biobank participants with cardiovascular-kidney-metabolic (CKM) syndrome stages 0–3 (AHA criteria); mean age 56.16 years, 57.32% female
- Participants
- 29,697 participants
- Exposure
- GDF-15 per 1-unit increase
- Outcome
- Incident ASCVD, MASLD and their comorbidity
Methodological detailsUK Biobank, Fine-Gray competing risk regression, multi-state Markov model
- UK Biobank
- Fine-Gray competing risk regression
- Multi-state Markov model
Main finding
As reported in the abstract
Incident ASCVD, MASLD and comorbidity per 1-unit increase in GDF-15
Estimate (95% CI)P value
GDF-15 per 1-unit increase
HR (ASCVD) 1.25(1.15–1.36)
P = 1.35 × 10-7GDF-15 per 1-unit increase
HR (MASLD) 1.62(1.41–1.86)
P = 2.06 × 10-11GDF-15 per 1-unit increase
HR (comorbidity) 1.62(1.32–2.18)
P = 4.36 × 10-7Per 1-unit increase, as printed
- Developed atherosclerotic cardiovascular disease (ASCVD)
- 2,786
- Developed MASLD
- 456
Observational data: associations, not effects.
Further findings
10-year cumulative incidence of ASCVD and MASLD by GDF-15 level
- ASCVD, top 10% GDF-15
- 15.75%
- MASLD, top 10% GDF-15
- 2.03%
- ASCVD, top 5% GDF-15
- 20.05%
- MASLD, top 5% GDF-15
- 2.32%
- GDF-15 predicted bidirectional progression between ASCVD and MASLD
Cross-sectional associations
- Higher GDF-15 associated with poorer CKM health; strongest associations with renal function markers, then insulin resistance indices
Risk prediction
- Adding GDF-15 to PREVENT, SCORE2, FLI, FIB-4 and ARPI gave modest improvements in discrimination, reclassification and prediction error, particularly for ASCVD
- GDF-15 had high relative importance (SHAP, likelihood ratio (LR)) and in several settings outperformed established biomarkers
Original publication
Growth differentiation factor-15 and the incidence, bidirectional progression, and risk prediction of atherosclerotic cardiovascular disease and metabolic dysfunction-associated steatotic liver disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0–3. Cardiovasc Diabetol. Published 12 June 2026. doi:10.
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