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Meta-Analysis
. 2024 Sep 1;9(9):835-842.
doi: 10.1001/jamacardio.2024.1882.

Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis

Benoit J Arsenault  1   2 , Krithika Loganath  3 , Arnaud Girard  1 , Simona Botezatu  3   4 , Kang H Zheng  5   6 , Evangelos Tzolos  3 , Kathia Abdoun  1 , Lionel Tastet  1 , Romain Capoulade  7 , Nancy Côté  1 , Neil Craig  3 , Kwan L Chan  8 , James W Tam  9 , Koon K Teo  10 , Christian Couture  1 , Marie-Annick Clavel  1   2 , Patrick Mathieu  1   11 , Sébastien Thériault  1   12 , Erik S G Stroes  5 , David E Newby  3 , Sotirios Tsimikas  13 , Philippe Pibarot  1   2 , Marc R Dweck  3
Affiliations
Meta-Analysis

Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis

Benoit J Arsenault et al. JAMA Cardiol. .

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.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Arsenault reported grants from Silence Therapeutics, Eli Lilly, and Pfizer and personal fees from Silence Therapeutics, Eli Lilly, and Novartis during the conduct of the study. Dr Capoulade reported personal fees from Novartis during the conduct of the study. Dr Craig reported grants from Medical Research Council Clinical Research Training Fellowship outside the submitted work. Dr Chan reported grants from the Canadian Institutes of Health Research during the conduct of the study. Dr Clavel reported grants from Edwards Lifesciences, Medtronic, and Pi-Cardia outside the submitted work. Dr Stroes reported personal fees (advisory board/lecturing fees paid to institution) from Amgen, Sanofi, Novartis, Ionis, and NovoNordisk outside the submitted work. Dr Tsimikas reported grants from Novartis and other Ionis (stock), Kleanthi (ownership), and Oxitiope (ownership) during the conduct of the study; in addition, Dr Tsimikas had a patent for University of California San Diego issued. Dr Pibarot reported grants from Novartis Echo Core Lab analyses for the HORIZON CAVS trial during the conduct of the study as well as grants from Edwards Lifesciences Echo Core Lab Analyses for transcatheter valve therapies, Medtronic (preclinical in vitro analyses for TVT devices), and Pi-Cardia (Echo Core Lab analyses for TVTs) outside the submitted work. Dr Dweck reported personal fees from Novartis and Silence therapeutics during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association Between Exposure to Elevated Lipoprotein(a) Levels and Peak Aortic Jet Velocity (Vpeak) Progression in Patients From 5 Cohorts
Effect sizes and meta-analysis represent the effect of the comparison between the top lipoprotein(a) tertile with the bottom lipoprotein(a) tertile (A) or the correlation coefficients (Pearson r) between lipoprotein(a) and Vpeak progression (B). ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; COR, correlation; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; RoF, Ring of Fire; ROM, ratio of means; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Figure 2.
Figure 2.. Association Between Exposure to Elevated Lipoprotein(a) Levels and Mean Transvalvular Gradients Progression in Patients From 5 Cohorts
Effect sizes and meta-analysis represent the effect of the comparison between the top lipoprotein(a) tertile with the bottom lipoprotein(a) tertile (A) or the correlation coefficients (Pearson r) between lipoprotein(a) and mean transvalvular gradients progression (B). ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; COR, correlation; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; RoF, Ring of Fire; ROM, ratio of means; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Figure 3.
Figure 3.. Annualized Peak Aortic Jet Velocity (Vpeak) Progression Rates in Patients From 5 Cohorts by Lipoprotein(a) Tertile
Annualized peak aortic jet velocity in m/s/y in patients with aortic stenosis separated into lipoprotein(a) tertiles are reported as mean (SD) changes. ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; SALTIRE, Scottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
Figure 4.
Figure 4.. Annualized Mean Transvalvular Gradients Progression Rates in Patients From 4 Cohorts by Lipoprotein(a) Tertiles
Annualized mean transvalvular gradients in mm Hg/y in patients with aortic stenosis separated into lipoprotein(a) tertiles are reported as mean (SD) changes. ASTRONOMER indicates Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin; PROGRESSA, Metabolic Determinants of the Progression of Aortic Stenosis; SALTIRE2, Study Investigating the Effect of Drugs Used to Treat Osteoporosis on the Progression of Calcific Aortic Stenosis.
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Supplementary concepts