Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis
Romain Capoulade, Kwan L Chan, Calvin Yeang, Patrick Mathieu, Yohan Bossé, Jean G Dumesnil, James W Tam, Koon K Teo, Ablajan Mahmut, Xiaohong Yang, Joseph L Witztum, Benoit J Arsenault, Jean-Pierre Després, Philippe Pibarot, Sotirios Tsimikas, Romain Capoulade, Kwan L Chan, Calvin Yeang, Patrick Mathieu, Yohan Bossé, Jean G Dumesnil, James W Tam, Koon K Teo, Ablajan Mahmut, Xiaohong Yang, Joseph L Witztum, Benoit J Arsenault, Jean-Pierre Després, Philippe Pibarot, Sotirios Tsimikas
Abstract
Background: Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a).
Objectives: This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events.
Methods: OxPL on apolipoprotein B-100 (OxPL-apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up.
Results: AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL-apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL-apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death.
Conclusions: Elevated Lp(a) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS. (Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800).
Keywords: Doppler echocardiography; aortic valve replacement; lipoprotein; peak aortic jet velocity.
Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
Source: PubMed