Diagnostic or prognostic study
Combined clinical, metabolomic, and polygenic scores for cardiovascular risk prediction
- Prognostic cohort study
- population modelling
Authors' conclusion
Combining NMR metabolomic, polygenic, and clinical biomarkers with SCORE2 enhanced prediction of first-onset CVD and could have substantial population health benefit if applied at scale.
Study context
- Population
- UK Biobank participants aged 40–69 without previous cardiovascular disease (CVD), diabetes or lipid-lowering treatment8,919 incident CVD cases
- Participants
- 297,463 participants
- Comparison
- SCORE2 plus clinical biomarkers, nuclear magnetic resonance (NMR) metabolomic scores and polygenic risk scores (PRS) vs SCORE2 alone
- Outcome
- 10-year fatal and non-fatal CVD; risk discrimination by Harrel's C-index
- Follow-up
- 10 years
Performance
As reported in the abstract
Risk discrimination (C-index)
SCORE2
0.719
C-index
Each group vs SCORE2ΔC-index (CI)
SCORE2 + clinical biomarkers
0.014(0.012–0.015)
SCORE2 + NMR metabolomic scores
0.010(0.009–0.012)
SCORE2 + PRS
0.009(0.008–0.011)
SCORE2 + combinationlargest improvement
0.024(0.022–0.027)
Further findings
Risk discrimination with each biomarker set added individually to SCORE2 (SCORE2 C-index 0.719)
- 11 clinical biomarkers, ΔC-index
- 0.014 [0.012-0.015]
- NMR metabolomic biomarker scores, ΔC-index
- 0.010 [0.009-0.012]
- PRSs, ΔC-index
- 0.009; [0.008-0.011]
Risk stratification (categorical net reclassification index), combined biomarkers
- Net case reclassification
- 16.66% (15.50%-17.81%)
Modelled CVD events prevented per 100 000 screened, biomarkers added to SCORE2 for targeted risk reclassification
- ΔCVDprevented
- 184 [174-194]
- CVD events prevented per 100 000 screened, from 229 to 413
- Statins prescribed per CVD event prevented essentially maintained
- population modelling
Original publication
Combined clinical, metabolomic, and polygenic scores for cardiovascular risk prediction. Eur Heart J. Published 15 December 2025. doi:10.1093/eurheartj/ehaf947
Summarised from the published abstract; every number is checked against it