Ceramides and risk of major adverse cardiovascular events: A meta-analysis of longitudinal studies

BACKGROUND: Recent cohort studies evaluated the association between some previously identified high-risk ceramides [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] and risk of major adverse cardiovascular events in adult population. OBJECTIVE: The objective of this meta-analysis was to investigate the magnitude of such associations. METHODS: We searched publication databases using appropriate keywords to identify cohort studies (published up to July 30, 2019), in which association between previously identified high-risk ceramides and major adverse cardiovascular events was reported. Data from eligible studies were extracted and meta-analysis was performed using random-effects modeling. RESULTS: Seven cohort studies with aggregate data on 29,818 individuals (2736 new cases of cardiovascular events over a median follow-up of 6 years) were included. Higher plasma levels of Cer(d18:1/16:0) (random effects hazard ratio [HR] per standard deviation 1.21, 95% confidence interval [CI] 1.11-1.32, I-2 = 88%), Cer(d18:1/18:0) (HR 1.19, 95% CI 1.10-1.27, I-2 = 68%), and Cer(d18:1/24:1) (HR 1.17, 95% CI 1.08-1.27, I-2 = 83%) were associated with major adverse cardiovascular events. Conversely, no association with plasma levels of Cer(d18:1/22:0) (HR 1.14 95% CI 0.88-1.47, I-2 = 88%) and Cer(d18:1/24:0) (HR 0.97, 95% CI 0.89-1.05, I-2 = 73%) was found. Subgroup analyses did not substantially modify the findings. CONCLUSIONS: Higher plasma levels of Cer(d18:1/16:0), Cer(d18:1/18:0) and Cer(d18:1/24:1) were associated with major adverse cardiovascular events, whereas plasma levels of Cer(d18:1/22:0) and Cer(d18:1/24:0) were not. Additional research is required to elucidate the different role of ceramides on pathways involved in cardiovascular disease. (C) 2020 National Lipid Association. All rights reserved.