Aortic stenosis
JAMA Cardiology meta-analysis of 710 patients finds top-tertile Lp(a) drives 41-57% faster echocardiographic progression of aortic stenosis (JAMA Cardiol 2024)
Original title: Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis
This systematic review and meta-analysis pooled five longitudinal aortic stenosis cohorts from Canada and the UK (March 2001 to March 2023), including 710 of 757 total patients with both Lp(a) measurements and echocardiographic progression data (70% male, mean age 65.2 years). Patients in the top Lp(a) tertile showed 41% faster annualised progression of peak aortic jet velocity (estimate 1.41, 95% CI 1.13-1.75) and 57% faster progression of mean transvalvular gradient (estimate 1.57, 95% CI 1.18-2.10) than those in the bottom tertile, with no heterogeneity across cohorts and similar results when Lp(a) was analysed continuously. Progression of aortic valve area itself did not differ significantly between groups (estimate 1.23, 95% CI 0.71-2.12). With no pharmacological treatment currently available to slow aortic stenosis progression, this multi-cohort evidence strengthens the case for testing Lp(a)-lowering therapy as a way to slow haemodynamic disease progression.
Original abstract
Importance: There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial.
Objective: To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis.
Design, Settings And Participants: The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(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.
Exposure: Cohort-specific plasma lipoprotein(a) concentration tertiles.
Main Outcomes And Measures: Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area.
Results: Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% 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 lipoprotein(a) concentrations were treated as a continuous variable.
Conclusions And Relevance: In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.