Exploratory analysis of large-scale lipidome in large cohorts: are we any closer of finding lipid-based markers suitable for CVD risk stratification and management?

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.