Diaz Sílvia O, Sánchez-Quesada José Luis, de Freitas Victor, Leite-Moreira Adelino, Barros António S, Reis Ana
Cardiovascular Research and Development Center, Department of Surgery and Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Cardiovascular Biochemistry, Biomedical Research Institute IIB Sant Pau, Sant Antoni Ma Claret, 167, Barcelona, CIBERDEM, ISCIII, Spain.
Anal Chim Acta. 2021 Jan 15;1142:189-200. doi: 10.1016/j.aca.2020.10.037. Epub 2020 Oct 30.
Cardiovascular diseases (CVD) remain the biggest cause of deaths worldwide and a major socio-economic impact to society. In this work, we conducted an unbiased exploratory analysis of the large-scale lipidome in human plasma samples from patients with fatal and non-fatal CVD from large cohorts. The exploratory analysis included data from 10,349 individuals from 20 countries in Asia, Australasia, Europe and North America (ADVANCE cohort), and thus representative of the worldwide population. Through the analysis of hazard ratios (HR), we found 306 lipids relevant in CV Death and 294 lipids relevant in CV Events of which 262 lipids were common to fatal and non-fatal events followed over time (3, 5 and 8 years). Our exploratory analysis reveals that, over time, the plasma lipid signature found in non-fatal CVD events is similar to that preceding CVD death. Among the common lipid signature, we found that sphingolipids (HexCer, SM, Cer and other glycosphingolipids) and phospholipids (PC and PE) were strongly associated with CVD events outcome, while polyunsaturated plasmenyl PC and PE lipids were inversely associated with CV outcome. The restricted panel of specific lipids has the potential to improve CVD risk stratification and management, and significantly reduce the time involved in the analysis and data treatment in low-resolution MS instruments making plasma lipidomics a cost-efficient approach for clinical scenario. In our view, once standardized clinical, analytical and data reporting guidelines are implemented worldwide, lipid-based discriminators can be routinely applied in the CVD risk stratification and improve the performance of current clinical, biochemical and imaging diagnostic tools assisting the decision-making process particularly in patients with multiple co-morbidities.
心血管疾病（CVD）仍然是全球最大的死亡原因，对社会具有重大的社会经济影响。在这项研究中，我们对来自大型队列中致命性和非致命性CVD患者的人类血浆样本中的大规模脂质组进行了无偏探索性分析。该探索性分析纳入了来自亚洲、澳大拉西亚、欧洲和北美的20个国家的10349名个体的数据（ADVANCE队列），因此代表了全球人群。通过对风险比（HR）的分析，我们发现306种脂质与心血管死亡相关，294种脂质与心血管事件相关，其中262种脂质在致命性和非致命性事件中随时间推移（3年、5年和8年）是共同的。我们的探索性分析表明，随着时间的推移，在非致命性CVD事件中发现的血浆脂质特征与CVD死亡前的特征相似。在共同的脂质特征中，我们发现鞘脂（神经酰胺己糖苷、鞘磷脂、神经酰胺和其他糖鞘脂）和磷脂（磷脂酰胆碱和磷脂酰乙醇胺）与CVD事件结局密切相关，而多不饱和缩醛磷脂酰胆碱和磷脂酰乙醇胺脂质与心血管结局呈负相关。特定脂质的受限面板有可能改善CVD风险分层和管理，并显著减少低分辨率质谱仪分析和数据处理所需的时间，使血浆脂质组学成为一种经济高效的临床方法。我们认为，一旦在全球范围内实施标准化的临床、分析和数据报告指南，基于脂质的判别指标就可以常规应用于CVD风险分层，并提高当前临床、生化和影像学诊断工具的性能，特别是在患有多种合并症的患者中协助决策过程。
