Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis

Authors: Capoulade, Romain; Chan, Kwan L.; Yeang, Calvin; Mathieu, PatrickBossé, YohanDumesnil, Jean G.; Tam, James W.; Teo, Koon Kang; Mahmut, Ablajan; Yang, Xiaohong; Witztum, Joseph L.; Arsenault, BenoitDesprés, Jean-PierrePibarot, Philippe; Tsimikas, Sotirios
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: þ0.26 0.26 vs. þ0.17 0.21 m/s/year; p ¼ 0.005) and OxPL-apoB (þ0.26 0.26 m/s/year vs. þ0.17 0.21 m/s/year; p ¼ 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.
Document Type: Article de recherche
Issue Date: 15 September 2015
Open Access Date: Restricted access
Document version: VoR
Permalink: http://hdl.handle.net/20.500.11794/6628
This document was published in: Journal of the American College of Cardiology, Vol. 66 (11), 1236 (2015)
Elsevier Biomedical
Alternative version: 10.1016/j.jacc.2015.07.020
Collection:Articles publiés dans des revues avec comité de lecture

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