Valvular & structural heart disease
Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis
Authors' conclusion
These findings identify MMP12 as a potential novel circulating biomarker of AS risk and C1QTNF1 as a new putative target to prevent AS progression.
Study context
- Population
- ARIC study participants in mid-life (V3) and late-life (V5); replication in Cardiovascular Health StudyV3
- Participants
- 11,430 participants
- Outcome
- Proteins associated with AVmax and dimensionless index by echocardiography (V5) and with incident AV-related hospitalization (after V3)
Methodological detailsSomaScan aptamer-affinity assay (4,877 plasma proteins), cross-sectional and prospective analyses, independent replication sample, Mendelian randomization, AV tissue gene expression
- SomaScan aptamer-affinity assay (4,877 plasma proteins)
- Cross-sectional and prospective analyses
- Independent replication sample
- Mendelian randomization
- AV tissue gene expression
Main finding
As reported in the abstract
Proteins associated with AVmax, dimensionless index and incident AV-related hospitalization
- Proteins cross-sectionally associated with AVmax and dimensionless index at V5 and with risk of incident AV-related hospitalization after V3
- 52
Observational data: associations, not effects.
Further findings
Moderate or severe aortic stenosis (AS) (replication, Cardiovascular Health Study, n = 3,413)
- Proteins significantly associated with adjudicated moderate or severe AS, incl. MMP12, C1QTNF1 and growth differentiation factor-15
- 6
MMP12: AVmax progression, AV calcification, AV tissue expression · 6 years
- MMP12 associated with greater increase in AVmax over 6 years, greater AV calcification, and greater expression in calcific vs normal or fibrotic AV tissue
Mendelian randomization: AS and AVmax
- C1QTNF1 had consistent potential causal effects on both AS and AVmax
Original publication
Large-Scale Proteomics Identifies Novel Biomarkers and Circulating Risk Factors for Aortic Stenosis. J Am Coll Cardiol. Published 6 February 2024. doi:10.
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