Valvular & structural heart disease
Rare Genetic Variants in LDLR , APOB , and PCSK9 Are Associated With Aortic Stenosis
Authors' conclusion
Rare genetic variants that confer lifelong higher or lower LDL-C levels are associated with substantially increased and decreased risk of AS, respectively.
Study context
- Population
- Unrelated participants of UK Biobank and All of Us with sequencing data and electronic health records421,049 UK Biobank (UKB) + 195,519 All of Us
- Comparison
- LDLR carriers vs APOB or PCSK9 carriers
- Outcome
- Diagnosed aortic stenosis (AS)
Methodological detailsUK Biobank and All of Us, meta-analysis
- UK Biobank and All of Us
- Meta-analysis
Pooled result
As reported in the abstract
AS
Odds ratio (95% CI)P value
LDLR carriers
3.52(2.39–5.20)
P = 2.3e-10APOB or PCSK9 carriers
0.49(0.31–0.75)
P = 0.001Further pooled results
Aortic valve replacement
| Comparison | OR (95% CI) | P value | |
|---|---|---|---|
| LDLR carriersMeta-analysis | 3.78 (2.26–6.32) | P = 4.0e-7 | |
| APOB or PCSK9 carriersMeta-analysis | 0.54 (0.30–0.97) | P = 0.04 | |
| 0.10.31310Odds ratio (log scale) |
| Outcome | Estimate | P value |
|---|---|---|
| Mean LDL-C (UKB)LDLR carriers | difference +42.6 mg/dL | P = 4.4e-237 |
| Mean LDL-C (UKB)APOB or PCSK9 carriers | difference −32.3 mg/dL | P < 5e-324 |
| Peak aortic valve velocity (UKB imaging substudy)LDLR carriers | difference +12.2 cm/s | P = 1.6e-5 |
| Peak aortic valve velocity (UKB imaging substudy)PCSK9 carriers | difference −6.9 cm/s | P = 0.022 |
- Peak aortic valve velocity (UKB imaging substudy): 57 371 imaging substudy participants
Original publication
Rare Genetic Variants in LDLR , APOB , and PCSK9 Are Associated With Aortic Stenosis. Circulation. Published 2 September 2024. doi:10.
Summarised from the published abstract; every number is checked against it