Manuel Gonzalez-Plascencia, Idalia Garza-Veloz, Virginia Flores-Morales, Margarita L. Martinez-Fierro
Ceramides are bioactive sphingolipids increasingly recognized as mediators of cardiometabolic disease and residual cardiovascular risk. Accumulating evidence from experimental and clinical studies indicates that specific ceramide species contribute to insulin resistance, endothelial dysfunction, myocardial injury, and adverse cardiovascular outcomes. In particular, long-chain ceramides (C16:0, C18:0, C20:0 Cer) are consistently associated with myocardial infarction, heart failure, and cardiovascular mortality, whereas very-long-chain ceramides (C22:0, C24:0 Cer) exhibit neutral or potentially protective associations. This narrative review integrates biochemical, experimental, and clinical evidence to examine ceramide metabolism, molecular diversity, and their emerging role as biomarkers for cardiovascular risk stratification. We also discuss ceramide-based risk scores and their potential clinical utility beyond traditional lipid parameters. Understanding the structure-function relationships of ceramides may support the development of novel diagnostic and therapeutic strategies in cardiovascular prevention.