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Lp(a) and Calcific Aortic Valve Stenosis Progression
Quick Takes
- Elevated Lp(a) concentrations were associated not only with incident aortic stenosis but also with more rapid hemodynamic aortic stenosis progression as assessed by the peak velocity and mean gradient.
- Lp(a) may therefore represent an important potential therapeutic target in aortic stenosis.
- Additional prospective studies are indicated to assess whether effective Lp(a) lowering might delay aortic stenosis progression in patients with elevated baseline concentrations.
Study Questions:
What is the association between plasma lipoprotein(a) [Lp(a)] concentrations and hemodynamic progression in patients with aortic stenosis?
Methods:
The investigators included patients with aortic stenosis from five longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the United Kingdom. Of 757 total patients, data on plasma Lp(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024. Cohort-specific plasma Lp(a) concentration tertiles was exposure of interest. The main outcome measure was hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area. A general linear model was used to compare the association of exposure to elevated Lp(a) levels (top vs. bottom tertile) with peak aortic jet velocity progression.
Results:
Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (standard deviation) age was 65.2 (13.1) years. Patients in the top Lp(a) tertile demonstrated 41% (estimate, 1.41; 95% confidence interval [CI], 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma Lp(a) concentrations were treated as a continuous variable.
Conclusions:
The authors report that higher plasma Lp(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis.
Perspective:
This study reports that elevated Lp(a) concentrations were associated not only with incident aortic stenosis but also with more rapid hemodynamic aortic stenosis progression as assessed by the peak velocity and mean gradient. Lp(a) may therefore represent an important potential therapeutic target in aortic stenosis. Additional prospective studies are indicated to assess whether this association is causal and whether effective Lp(a) lowering might delay aortic stenosis progression in patients with elevated baseline concentrations.
Clinical Topics: Dyslipidemia, Valvular Heart Disease, Advanced Lipid Testing, Lipid Metabolism
Keywords: Lipoprotein(a), Aortic Valve Stenosis
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