Elevated Lipoprotein(a) and Risk of Aortic Valve Stenosis in the General Population
Key result
Elevated Lp(a) is linked to ~190% higher risk of aortic valve stenosis.
- HR 2.9
- 95% CI 1.8-4.9
- P<0.001
- n=77,680
Why the study?
The etiologic basis of aortic valve stenosis is unclear, though recent data have implicated an LPA genetic variant associated with lipoprotein(a) levels.
Do elevated lipoprotein(a) levels and corresponding LPA risk genotypes increase the risk of aortic valve stenosis in the general population?
Population
77,680 Danish participants from 2 general population studies
Comparison
Elevated lipoprotein(a) levels and LPA risk genotypes vs lower levels and non-risk genotypes
Design
Prospective observational and Mendelian randomization study
Follow-up
As long as 20 years
Authors
Discussion
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Member takes
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
STSotirios TsimikasCardiovascular medicine researcher, UC San Diego
“Kamstrup et al. confirm and extend the findings of Thanassoulis et al. by showing that elevated Lp(a) levels (>74 mg/dl, representing ∼10% to 15% of the general population) were independently associated with CAVS, predicting a 3-fold increased risk. Consistent with genetic causality, carriers of LPA SNPs rs10455872 and rs3798220 and of low number of KIV-2 repeats, all of which are associated with higher Lp(a) levels, were also associated with CAVS. The enhanced risk was driven by high Lp(a) levels and not an independent risk of the LPA SNPs.”
Implication
Elevated Lp(a) levels and corresponding genetic variants are prospectively associated with a significantly increased risk of aortic valve stenosis in the general population.
Key Points
- This study aims to determine the association between elevated lipoprotein(a) levels and the risk of aortic valve stenosis (AVS) with corresponding genetic variants.
- Combined data from two prospective general population studies (n=77,680) over 20 years.
- Conducted Mendelian randomization analysis with observational components.
- Evaluated associations with multivariable adjusted hazard ratios.
- For >90 mg/dl Lp(a), the hazard ratio for AVS was 2.9 (95% CI: 1.8 to 4.9), p<0.001.
- Genetic relative risk for AVS was 1.6 (95% CI: 1.2 to 2.1) per 10-fold increase in Lp(a) levels.
- Elevated Lp(a) levels correlated with minor allele carriers of rs10455872 and rs3798220.
Study Design
Type
Observational (n=77,680)
Multicenter
Yes
Structured PICO
Do elevated lipoprotein(a) levels and corresponding LPA risk genotypes increase the risk of aortic valve stenosis in the general population?
P
Population
77,680 Danish participants from two prospective general population cohorts followed for up to 20 years, during which 454 were diagnosed with aortic valve stenosis.
E
Exposure
Elevated lipoprotein(a) levels and corresponding LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism)
C
Comparator
Lower lipoprotein(a) levels (e.g., <22nd percentile, <5 mg/dl)
O
Outcome
Aortic valve stenosis (AVS)hard clinical
Main Result
Hazard Ratio: 2.9 (95% CI 1.8–4.9)
p-value: p=<0.001
Elevated Lp(a) levels and corresponding genetic variants are prospectively associated with a significantly increased risk of aortic valve stenosis in the general population.
Cite This Study
Kamstrup et al. (2013) conducted an observational in Aortic valve stenosis (n=77,680). Elevated Lipoprotein(a) levels vs. Lipoprotein(a) levels <5 mg/dl was evaluated on Aortic valve stenosis (HR 2.9, 95% CI 1.8-4.9, p=<0.001). Elevated Lipoprotein(a) levels >90 mg/dl were associated with a nearly threefold increased risk of aortic valve stenosis compared to levels <5 mg/dl (HR 2.9; 95% CI 1.8-4.9; P<0.001 for trend).