Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis
Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis
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DOI：
10.1016/j.jacc.2015.07.020
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发表时间：
2015-09-15
影响因子：
24
通讯作者：
Tsimikas, Sotirios
中科院分区：
文献类型：
--
作者：
Capoulade, Romain;Chan, Kwan L.;Tsimikas, Sotirios
背景脂蛋白（a）（Lp[a]）升高与主动脉瓣狭窄（AS）相关。氧化磷脂（OxPL）是心瓣膜细胞钙化的关键介质，由脂蛋白（a）携带，本研究旨在确定脂蛋白（a）和OxPL是否与动脉粥样硬化的血流动力学进展和动脉粥样硬化相关事件有关。检测了220例轻中度AS患者血清Lp（a）水平及反映Lp（a）生物学活性的载脂蛋白B（OxPL-apoB）。主要终点是AS的进展率，通过多普勒超声心动图测量的主动脉瓣峰值喷射速度的年增加，以m/s/年为单位;次要终点是在3.5 ± 1.2年的随访期间需要进行主动脉瓣置换术和心源性死亡。（峰值主动脉喷射速度：+0.26 +/- 0.26 vs. +0.17 +/- 0.21 m/s/年; p = 0.005）和OxPL-apoB（+0.26 +/- 0.26 m/s/年vs. +0.17 +/- 0.21 m/s/年; p = 0.01）。多变量校正后，Lp（a）或OxPL-apoB水平升高仍是AS进展较快的独立预测因素。校正年龄、性别和基线AS严重程度后，Lp（a）或OxPL-apoB水平处于前三分位的患者主动脉瓣置换和心源性死亡风险增加。这些发现支持了Lp（a）通过其相关OxPL介导AS进展的假设，并为降低Lp（a）和OxPL-apoB降低AS治疗的随机试验提供了理论基础。(C)2015年由美国心脏病学会基金会。
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. (C) 2015 by the American College of Cardiology Foundation.