Valvular & structural heart disease
Plasma metabolomics uncovers key metabolites and enhances prediction of aortic stenosis: insights from prospective cohort and Mendelian randomisation studies
Authors' conclusion
Our study identified 39 metabolites with causal associations with AS risk, particularly apolipoprotein B-containing lipoproteins. The derived 12-metabolite panel significantly improved AS risk prediction, demonstrating the potential of NMR-based metabolomics to enhance AS risk stratification and targeted prevention.
Study context
- Population
- Participants with plasma nuclear magnetic resonance (NMR)-based metabolomic profiling (168 metabolites), followed for incident aortic stenosisSample sizes printed only for the prediction-model sets · training set 146,252 · testing set 62,678 · external validation cohort 21,546
- Exposure
- Clinical risk factors-based Cox regression model with the 12 metabolites added vs clinical risk factors alone, for aortic stenosis (AS) risk prediction
- Outcome
- Incident AS
- Follow-up
- Median 13.7 years
Methodological detailsNMR-based metabolomics, LASSO regression, external validation cohort
- NMR-based metabolomics
- LASSO regression
- External validation cohort
Main finding
As reported in the abstract
AS events
2562
Metabolites significantly associated with AS risk in observational analyses (after adjustment and multiple-testing correction)
77 of 168
Metabolites causally associated with AS risk in MR analyses, including apolipoprotein B, apolipoprotein B-containing lipoprotein particles and lipid constituents within lipoprotein subclasses
39
Observational data: associations, not effects.
Secondary outcomes
Incident AS-related interventions or deaths (secondary outcome) · median follow-up of 13.7 years
- AS-related interventions or deaths
- 1039
- All of the 39 metabolites were associated with incident AS-related interventions or deaths
AS risk prediction: clinical risk factors model with vs without 12 LASSO-selected metabolites
- Metabolites identified by LASSO in the training set
- 12
- C index, testing set
- 0.780 to 0.791
- C index, external validation cohort
- 0.764 to 0.786
- Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) significantly improved
Original publication
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