Insights into the prognosis of lipidomic dysregulation for death risk in patients with coronary artery disease

Qin, Min; Zhu, Qian; Lai, Weihua; Ma, Qilin; Liu, Chen; Chen, Xiaoping; Zhang, Yuelin; Wang, Zixian; Chen, Hui; Yan, Hong; Lei, Heping; Zhang, Shuyao; Dong, Xuekui; Wang, Hong; Huang, Min; Lian, Qizhou; Zhong, Shilong

BACKGROUND: Dyslipidaemia contributes to the progression of coronary artery disease (CAD) toward adverse outcomes. Plasma lipidomic measure may improve the prognostic performances of clinical endpoints of CAD. Our research is designed to identify the correlations between plasma lipid species and the risks of death, major adverse cardiovascular event (MACE) and left ventricular (LV) remodeling in patients with CAD. METHODS: A total of 1569 Chinese patients with CAD, 1011 single‐centre patients as internal training cohort, and 558 multicentre patients as external validation cohort, were enrolled. The concentration of plasma lipids in both cohorts was determined through widely targeted lipidomic profiling. Least absolute shrinkage and selection operator Cox and multivariate Cox regressions were used to develop prognostic models for death and MACE, respectively. RESULTS: Ten (Cer(d18:1/20:1), Cer(d18:1/24:1), PE(30:2), PE(32:0), PE(32:2), PC(O‐38:2), PC(O‐36:4), PC(16:1/22:2), LPC(18:2/0:0) and LPE(0:0/24:6)) and two (Cer(d18:1/20:1) and LPC(20:0/0:0)) lipid species were independently related to death and MACE, respectively. Cer(d18:1/20:1) and Cer(d18:1/24:1) were correlated with LV remodeling (P < .05). The lipidic panel incorporating 10 lipid species and two traditional biomarkers for predicting 5‐year death risk represented a remarkable higher discrimination than traditional model with increased area under the curve from 76.56 to 83.65%, continuous NRI of 0.634 and IDI of 0.131. Furthermore, the panel was successfully used in differentiating multicentre patients with low, middle, or high risks (P < .0001). Further analysis indicated that the number of double bonds of phosphatidyl choline and the content of carbon atoms of phosphatidyl ethanolamines were negatively associated with death risk. CONCLUSIONS: Improvement in the prediction of death confirms the effectiveness of plasma lipids as predictors to risk classification in patients with CAD. The association between the structural characteristics of long‐chain polyunsaturated fatty acids and death risk highlights the need for mechanistic research that characterizes the role of individual lipid species in disease pathogenesis.