Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients
Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients
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DOI：
10.1016/j.atherosclerosis.2014.10.028
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发表时间：
2014-12-01
期刊：
影响因子：
5.3
通讯作者：
Drexel, Heinz
中科院分区：
文献类型：
--
作者：
Muendlein, Axel;Saely, Christoph H.;Drexel, Heinz
背景：在动物研究中，血管生成素样蛋白4 （ANGPTL4）与包括血脂异常和动脉粥样硬化在内的心脏代谢紊乱有关；然而，在人类中，它对代谢特征和心血管风险的影响尚不清楚。方法：我们研究了490名接受冠状动脉造影的患者血浆ANGPTL4水平与代谢综合征（统一的共识定义）、血管造影确定的冠状动脉疾病（CAD）以及未来心血管事件风险的关系，以评估稳定的CAD。此外，我们研究了ANGPTL4基因标记单核苷酸多态性rs4076317、rs2278236、rs1044250和rs11672433以及变异rs116843064 （E40K）对包括上述490例受试者在内的983例冠状动脉造影患者心血管风险的影响。结果：代谢综合征患者血浆ANGPTL4水平明显高于无代谢综合征患者（26.0 +/- 19.4 ng/ml vs. 22.2 +/- 19.7 ng/ml; p = 0.008）。未发现ANGPTL4与冠脉动脉粥样硬化之间有显著相关性。然而，血浆ANGPTL4在单因素（HR1.45 [1.16-1.82], p = 0.001）和标准心血管危险因素校正后（hr1.26 [1.01-1.58], p = 0.045）均能显著预测未来心血管事件。同样，rs4076317、rs2278236和rs1044250显著影响未来心血管事件的风险（调整后hr分别为0.70 [0.54-0.90],p = 0.005、0.76 [0.61-0.94],p = 0.012、1.30 [1.03-1.62],p = 0.025）。结论：血浆ANGPTL4水平和ANGPTL4变异可以独立于传统心血管危险因素预测心血管事件。2014爱思唯尔爱尔兰有限公司版权所有。
Background: Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear. Methods: We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angio-graphically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects. Results: Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 +/- 19.4 ng/ml vs. 22.2 +/- 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angio-graphically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16-1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01-1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54-0.90]; p = 0.005, 0.76 [0.61-0.94]; p = 0.012, and 1.30 [1.03-1.62]; p = 0.025, respectively). Conclusions: We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors. (C) 2014 Elsevier Ireland Ltd. All rights reserved.