Serum-Based Oxylipins Are Associated with Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients.
Serum-Based Oxylipins Are Associated with Outcomes in Primary Prevention Implantable Cardioverter Defibrillator Patients.
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DOI：
10.1371/journal.pone.0157035
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Cheng A
中科院分区：
文献类型：
--
作者：
Zhang Y;Guallar E;Blasco-Colmenares E;Harms AC;Vreeken RJ;Hankemeier T;Tomaselli GF;Cheng A
收缩性心力衰竭患者有室性心律失常和全因死亡的风险。关于这些事件背后的机制知之甚少。我们试图更好地了解氧脂素（一种来源于多不饱和脂肪酸氧化的脂质代谢物）是否与一级预防植入式心律转复除颤器（ICD）接受者的这些结局相关。在来自PROSE-ICD研究的479名个体中，分析了基线血清，并定量分析了35种已知生物学相关的氧脂素代谢产物。使用考克斯比例风险模型评价ICD电击与室性心律失常和全因死亡率的相关性。6种氧脂素，17，18-DiHETE（HR = 0.83，95% CI 0.70 - 0.99，根据氧脂平水平的SD变化），19，20-DiHDPA（HR = 0.79，95% CI 0.63至0.98），5，6-DiHETrE（HR = 0.73，95% CI 0.58至0.91），8，9-DiHETrE（HR = 0.76，95% CI 0.62 - 0.95），9，10-DiHOME（HR = 0.81，95% CI 0.65 - 1.00）和PGF 1 α（HR = 1.33，95% CI 1.04 - 1.71）与适当ICD电击的风险相关。此外，4种氧脂素与前体的比例，15 S-HEPE/ FA（20：5-ω3）、17，18-DiHETE / FA（20：5-ω3）、19，20-DiHDPA / FA（20：5-ω3）和5S-HEPE / FA（20：5-ω3）与全因死亡风险呈正相关。在一级预防ICD患者的前瞻性队列中，我们使用代谢分析技术确定了几种与适当休克和死亡率相关的新型氧化脂质标志物。这些发现可能为该患者人群中导致不良事件的潜在生物学途径提供新的见解。
Individuals with systolic heart failure are at risk of ventricular arrhythmias and all-cause mortality. Little is known regarding the mechanisms underlying these events. We sought to better understand if oxylipins, a diverse class of lipid metabolites derived from the oxidation of polyunsaturated fatty acids, were associated with these outcomes in recipients of primary prevention implantable cardioverter defibrillators (ICDs). Among 479 individuals from the PROSE-ICD study, baseline serum were analyzed and quantitatively profiled for 35 known biologically relevant oxylipin metabolites. Associations with ICD shocks for ventricular arrhythmias and all-cause mortality were evaluated using Cox proportional hazards models. Six oxylipins, 17,18-DiHETE (HR = 0.83, 95% CI 0.70 to 0.99 per SD change in oxylipin level), 19,20-DiHDPA (HR = 0.79, 95% CI 0.63 to 0.98), 5,6-DiHETrE (HR = 0.73, 95% CI 0.58 to 0.91), 8,9-DiHETrE (HR = 0.76, 95% CI 0.62 to 0.95), 9,10-DiHOME (HR = 0.81, 95% CI 0.65 to 1.00), and PGF1α (HR = 1.33, 95% CI 1.04 to 1.71) were associated with the risk of appropriate ICD shock after multivariate adjustment for clinical factors. Additionally, 4 oxylipin-to-precursor ratios, 15S-HEPE / FA (20:5-ω3), 17,18-DiHETE / FA (20:5-ω3), 19,20-DiHDPA / FA (20:5-ω3), and 5S-HEPE / FA (20:5-ω3) were positively associated with the risk of all-cause mortality. In a prospective cohort of patients with primary prevention ICDs, we identified several novel oxylipin markers that were associated with appropriate shock and mortality using metabolic profiling techniques. These findings may provide new insight into the potential biologic pathways leading to adverse events in this patient population.