Valvular & structural heart disease
Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis
Authors' conclusion
While aortic stenosis genetic risk was independent from clinical risk factors and performed comparably to all other risk factors besides age, genetic risk resulted in only a small improvement in overall aortic stenosis risk discrimination beyond age and clinical risk factors.
Study context
- Population
- Individuals from Million Veteran Program (MVP) and UK Biobank meeting a validated AS case/control definition, and Thrombolysis in Myocardial Infarction (TIMI) trial participants without preexisting aortic valve replacementMVP 147,104
- Exposure
- AS PRS vs established clinical risk factors for AS risk estimation
- Outcome
- AS (ICD or CPT codes in UK Biobank and MVP; safety event data in TIMI trials)
Methodological detailsMVP, UK Biobank and 6 TIMI trials, Analysis January 2022 to December 2023
- MVP, UK Biobank and 6 TIMI trials
- Analysis January 2022 to December 2023
Main finding
As reported in the abstract
AS, per 1 SD PRS
AS PRS (per 1 SD)Estimate (95% CI)P value
MVP testing sample
OR 1.41(1.37–1.45)
P = 4.6 × 10-116TIMI trials
HR 1.44(1.27–1.62)
P = 3.2 × 10-9Per 1 SD, as printed
Observational data: associations, not effects.
Further findings
Risk discrimination (C index)
- MVP: clinical risk factors
- 0.78
- MVP: risk factors + AS PRS
- 0.79
- TIMI: clinical risk factors
- 0.71
- TIMI: risk factors + AS PRS
- 0.73
- Improvement with PRS added
- 0.01 to 0.02
Combined clinical and genetic risk within an age range
- Additive; increased gradient of AS risk
- 3- to 4-fold
Original publication
Novel Polygenic Risk Score and Established Clinical Risk Factors for Risk Estimation of Aortic Stenosis. JAMA Cardiol. Published 1 April 2024. doi:10.
Summarised from the published abstract; every number is checked against it