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Brief Report
December 2018

Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial

Author Affiliations
  • 1Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec City, Québec, Canada
  • 2L’institut du thorax, Institut National de la Santé et de la Recherche Medicale, Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire Nantes, University of Nantes, Nantes, France
  • 3Vascular Medicine Program, University of California, San Diego, La Jolla
  • 4Ottawa Heart Institute, University of Ottawa, Ottawa, Ontario, Canada
JAMA Cardiol. 2018;3(12):1212-1217. doi:10.1001/jamacardio.2018.3798
Key Points

Question  Is the association of increased lipoprotein(a) and oxidized phospholipid levels with a faster rate of calcific aortic valve stenosis progression a linear or a threshold association?

Findings  In a secondary analysis of the ASTRONOMER trial following up a cohort of 220 patients with mild to moderate aortic stenosis, a significant linear association was found between plasma levels of lipoprotein(a) and oxidized phospholipids on apolipoprotein B and apolipoprotein(a) and a faster rate of aortic stenosis progression.

Meanings  By documenting the linear association of lipoprotein(a) and its content of oxidized phospholipids with faster progression of calcific aortic stenosis, this study has pathophysiological and clinical implications for these patients.


Importance  Several studies have reported an association of levels of lipoprotein(a) (Lp[a]) and the content of oxidized phospholipids on apolipoprotein B (OxPL-apoB) and apolipoprotein(a) (OxPL-apo[a]) with faster calcific aortic valve stenosis (CAVS) progression. However, whether this association is threshold or linear remains unclear.

Objective  To determine whether the plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) have a linear association with a faster rate of CAVS progression.

Design, Setting, and Participants  This secondary analysis of a randomized clinical trial tested the association of baseline plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) with the rate of CAVS progression. Participants were included from the ASTRONOMER (Effects of Rosuvastatin on Aortic Stenosis Progression) trial, a multicenter study conducted in 23 Canadian sites designed to test the effect of statin therapy (median follow-up, 3.5 years [interquartile range, 2.9-4.5 years]). Patients with mild to moderate CAVS defined by peak aortic jet velocity ranging from 2.5 to 4.0 m/s were recruited; those with peak aortic jet velocity of less than 2.5 m/s or with an indication for statin therapy were excluded. Data were collected from January 1, 2002, through December 31, 2005, and underwent ad hoc analysis from April 1 through September 1, 2018.

Interventions  After the randomization process, patients were followed up by means of echocardiography for 3 to 5 years.

Main Outcomes and Measures  Progression rate of CAVS as assessed by annualized progression of peak aortic jet velocity.

Results  In this cohort of 220 patients (60.0% male; mean [SD] age, 58 [13] years), a linear association was found between plasma levels of Lp(a) (odds ratio [OR] per 10-mg/dL increase, 1.10; 95% CI, 1.03-1.19; P = .006), OxPL-apoB (OR per 1-nM increase, 1.06; 95% CI, 1.01-1.12; P = .02), and OxPL-apo(a) (OR per 10-nM increase, 1.16; 95% CI, 1.05-1.27; P = .002) and faster CAVS progression, which is marked in younger patients (OR for Lp[a] level per 10-mg/dL increase, 1.19 [95% CI, 1.07-1.33; P = .002]; OR for OxPL-apoB level per 1-nM increase, 1.06 [95% CI, 1.02-1.17; P = .01]; and OR for OxPL-apo[a] level per 10-nM increase, 1.26 [95% CI, 1.10-1.45; P = .001]) and remained statistically significant after comprehensive multivariable adjustment (β coefficient, ≥ 0.25; SE, ≤ 0.004 [P ≤ .005]; OR, ≥1.10 [P ≤ .007]).

Conclusions and Relevance  This study demonstrates that the association of Lp(a) levels and its content in OxPL with faster CAVS progression is linear, reinforcing the concept that Lp(a) levels should be measured in patients with mild to moderate CAVS to enhance management and risk stratification.

Trial Registration  ClinicalTrials.gov Identifier: NCT00800800