Data_Sheet_2_Plasma Oxylipins: A Potential Risk Assessment Tool in Atherosclerotic Coronary Artery Disease.docx

Background: While oxylipins have been linked to coronary artery disease (CAD), little is known about their diagnostic and prognostic potential.
Objective: We tested whether plasma concentration of specific oxylipins may discriminate among number of diseased coronary arteries and predict median 5-year outcomes in symptomatic adults.
Methods: Using a combination of high-performance liquid chromatography (HPLC) and quantitative tandem mass spectrometry, we conducted a targeted analysis of 39 oxylipins in plasma samples of 23 asymptomatic adults with low CAD risk and 74 symptomatic adults (≥70% stenosis), aged 38–87 from the Greater Portland, Oregon area. Concentrations of 22 oxylipins were above the lower limit of quantification in >98% of adults and were compared, individually and in groups based on precursors and biosynthetic pathways, in symptomatic adults to number of diseased coronary arteries [(1) n = 31; (2) n = 23; (3) n = 20], and outcomes during a median 5-year follow-up (no surgery: n = 7; coronary stent placement: n = 24; coronary artery bypass graft surgery: n = 26; death: n = 7).
Results: Plasma levels of six quantified oxylipins decreased with the number of diseased arteries; a panel of five oxylipins diagnosed three diseased arteries with 100% sensitivity and 70% specificity. Concentrations of five oxylipins were lower and one oxylipin was higher with survival; a panel of two oxylipins predicted survival during follow-up with 86% sensitivity and 91% specificity.
Conclusions: Quantification of plasma oxylipins may assist in CAD diagnosis and prognosis in combination with standard risk assessment tools.

背景：尽管氧脂素（oxylipins）已被证实与冠状动脉粥样硬化性心脏病（coronary artery disease, CAD）相关，但目前学界对其诊断与预后潜力的认知仍较为有限。
研究目的：本研究旨在探究特定氧脂素的血浆浓度是否可区分冠状动脉病变支数，并预测有症状成年患者的中位5年预后结局。
研究方法：本研究采用高效液相色谱（high-performance liquid chromatography, HPLC）与定量串联质谱联用技术，对来自俄勒冈州大波特兰地区的97名成年受试者的血浆样本进行靶向分析，其中包括23名CAD风险较低的无症状成年人，以及74名存在症状且冠状动脉狭窄程度≥70%的成年患者，受试者年龄跨度为38~87岁。在超过98%的受试者中，22种氧脂素的浓度高于定量下限；研究人员基于前体物质与生物合成途径，将有症状患者的这些氧脂素分别及分组后，与冠状动脉病变支数（单支病变：n=31；双支病变：n=23；三支病变：n=20）以及中位5年随访结局进行对比分析。随访结局包括未行手术（n=7）、冠状动脉支架置入术（n=24）、冠状动脉旁路移植术（n=26）以及死亡（n=7）。
研究结果：血浆中6种定量氧脂素的水平随冠状动脉病变支数增加而降低；由5种氧脂素组成的检测组合对三支冠状动脉病变的诊断灵敏度为100%，特异度为70%。与存活患者相比，死亡患者体内5种氧脂素的浓度更低，另有1种氧脂素的浓度更高；由2种氧脂素组成的检测组合对随访期间的生存结局具有预测价值，其灵敏度为86%，特异度为91%。
研究结论：血浆氧脂素的定量检测，可与标准风险评估工具联用，辅助冠状动脉粥样硬化性心脏病的诊断与预后评估。