1 Baker Heart and Diabetes Institute Melbourne Australia.
2 Department of Cardiology The Alfred Hospital Melbourne Australia.
J Am Heart Assoc. 2019 Jun 4;8(11):e011792. doi: 10.1161/JAHA.118.011792.
Background Although acute coronary syndromes (ACS) are a major cause of morbidity and mortality, relationships with biologically active lipid species potentially associated with plaque disruption/erosion in the context of their lipoprotein carriers are indeterminate. The aim was to characterize lipid species within lipoprotein particles which differentiate ACS from stable coronary artery disease. Methods and Results Venous blood was obtained from 130 individuals with de novo presentation of an ACS (n=47) or stable coronary artery disease (n=83) before coronary catheterization. Lipidomic measurements (533 lipid species; liquid chromatography electrospray ionization/tandem mass spectrometry) were performed on whole plasma as well as 2 lipoprotein subfractions: apolipoprotein A1 (apolipoprotein A, high-density lipoprotein) and apolipoprotein B. Compared with stable coronary artery disease, ACS plasma was lower in phospholipids including lyso species and plasmalogens, with the majority of lipid species differing in abundance located within high-density lipoprotein (high-density lipoprotein, 113 lipids; plasma, 73 lipids). Models including plasma lipid species alone improved discrimination between the stable and ACS groups by 0.16 (C-statistic) compared with conventional risk factors. Models utilizing lipid species either in plasma or within lipoprotein fractions had a similar ability to discriminate groups, though the C-statistic was highest for plasma lipid species (0.80; 95% CI, 0.75-0.86). Conclusions Multiple lysophospholipids, but not cholesterol, featured among the lipids which were present at low concentration within high-density lipoprotein of those presenting with ACS. Lipidomics, when applied to either whole plasma or lipoprotein fractions, was superior to conventional risk factors in discriminating ACS from stable coronary artery disease. These associative mechanistic insights elucidate potential new preventive, prognostic, and therapeutic avenues for ACS which require investigation in prospective analyses.
尽管急性冠状动脉综合征（ACS）是发病率和死亡率的主要原因，但与脂蛋白载体中潜在与斑块破裂/侵蚀相关的生物活性脂质种类的关系尚不确定。本研究旨在描述区分 ACS 与稳定型冠状动脉疾病的脂蛋白颗粒中的脂质种类。
在冠状动脉造影前，从 130 例新发 ACS（n=47）或稳定型冠状动脉疾病（n=83）患者中采集静脉血。对全血浆以及 2 种脂蛋白亚组分（载脂蛋白 A1（载脂蛋白 A，高密度脂蛋白）和载脂蛋白 B）进行脂质组学测量（533 种脂质；液相色谱电喷雾电离/串联质谱法）。与稳定型冠状动脉疾病相比，ACS 患者的血浆磷脂含量较低，包括溶血磷脂和血浆甘油磷脂，大多数脂质种类的丰度差异位于高密度脂蛋白（高密度脂蛋白，113 种脂质；血浆，73 种脂质）。与传统危险因素相比，仅包括血浆脂质种类的模型可使稳定和 ACS 组之间的区分度提高 0.16（C 统计量）。使用血浆或脂蛋白部分中的脂质种类的模型具有相似的分组区分能力，尽管血浆脂质种类的 C 统计量最高（0.80；95%CI，0.75-0.86）。
在 ACS 患者的高密度脂蛋白中，多种溶血磷脂而非胆固醇存在于低浓度的脂质中。脂质组学应用于全血浆或脂蛋白部分时，在区分 ACS 与稳定型冠状动脉疾病方面优于传统危险因素。这些关联的机制见解阐明了 ACS 的潜在新的预防、预后和治疗途径，需要在前瞻性分析中进行研究。
