The present study explored patterns of circulating metabolites and proteins that can predict future risk for ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). We conducted a prospective nested case-control study in northern Sweden in individuals who developed STEMI (N = 50) and NSTEMI (N = 50) within 5 years and individually matched controls (N = 100). Fasted plasma samples were subjected to multiplatform mass spectrometry-based metabolomics and multiplex protein analyses. Multivariate analyses were used to elucidate infarction-specific metabolite and protein risk profiles associated with future incident STEMI and NSTEMI. We found that altered lysophosphatidylcholine (LPC) to lysophosphatidylethanolamine (LPE) ratio predicted STEMI and NSTEMI events in different ways. In STEMI, lysophospholipids (mainly LPEs) were lower, whereas in NSTEMI, lysophospholipids (mainly LPEs) were higher. We found a similar response for all detected lysophospholipids but significant alterations only for those containing linoleic acid (C18:2, p < 0.05). Patients with STEMI had higher secretoglobin family 3A member 2 and tartrate-resistant acid phosphate type 5 and lower platelet-derived growth factor subunit A, which are proteins associated with atherosclerosis severity and plaque development mediated via altered phospholipid metabolism. In contrast, patients with NSTEMI had higher levels of proteins associated with inflammation and macrophage activation, including interleukin 6, C-reactive protein, chemerin, and cathepsin X and D. The STEMI risk marker profile includes factors closely related to the development of unstable plaque, including a higher LPC:LPE ratio, whereas NSTEMI is characterized by a lower LPC:LPE ratio and increased inflammation.

中文翻译：

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溶血磷脂作为ST抬高型心肌梗死（STEMI）和非ST抬高型心肌梗死（NSTEMI）的预测标记

本研究探索了循环代谢物和蛋白质的模式，这些模式可以预测未来ST抬高型心肌梗塞（STEMI）和非ST抬高型心肌梗塞（NSTEMI）的风险。我们在瑞典北部进行了一项前瞻性巢式病例对照研究，研究对象是在5年内患上STEMI（N = 50）和NSTEMI（N = 50）的个体，并分别配对了对照（N = 100）。对禁食的血浆样品进行基于多平台质谱的代谢组学和多重蛋白分析。使用多变量分析来阐明与未来STEMI和NSTEMI事件相关的梗塞特异性代谢物和蛋白质风险谱。我们发现，改变溶血磷脂酰胆碱（LPC）与溶血磷脂酰乙醇胺（LPE）的比例可以不同方式预测STEMI和NSTEMI事件。在STEMI中 溶血磷脂（主要为LPEs）较低，而在NSTEMI中，溶血磷脂（主要为LPEs）较高。我们发现，所有检测到的溶血磷脂都具有相似的响应，但只有包含亚油酸的那些（C18：2，p＜0.05）。STEMI患者具有较高的分泌血红蛋白家族3A成员2和抗酒石酸盐酸性5型和较低的血小板衍生生长因子亚基A，这些蛋白与动脉粥样硬化严重程度和通过磷脂代谢改变介导的斑块形成有关。相比之下，NSTEMI患者的炎症和巨噬细胞活化相关蛋白水平较高，包括白介素6，C反应蛋白，凯莫瑞以及组织蛋白酶X和D。STEMI危险标志物谱包括与不稳定斑块发展密切相关的因素，包括较高的LPC：LPE比，而NSTEMI的特征是较低的LPC：LPE比和增加的炎症。