Ceramides as Biomarkers of Risk Prediction and Prognosis in Cardiovascular and Other Diseases: Are We There Yet?

Cardiovascular disease (CVD) is the leading cause of death worldwide, yet roughly 70% of major adverse cardiovascular events occur in statin-treated patients with optimized Low-density lipoprotein cholesterol (LDL-C), a gap that cholesterol-based risk panels do not close. Ceramides are bioactive sphingolipids whose plasma species and ratios carry risk information absent from standard lipid panels, and ceramide-based scores (CERT and CERT2) are already in clinical use. Whether this value extends beyond CVD is unclear. We reviewed ceramide species and ratios as biomarkers for disease prediction, prognosis, and disease activity across cardiovascular, metabolic, autoimmune rheumatic, inflammatory bowel, pulmonary, kidney, and oncologic contexts, searching PubMed and Scopus from January 1990 to June 2026 and extending the search for the historical literature. In CVD, CERT and CERT2 predicted cardiovascular events and mortality independently of LDL cholesterol, including in statin-treated and kidney disease populations. In metabolic and autoimmune rheumatic disease, ceramide profiles tracked cardiovascular risk and disease activity. In inflammatory bowel disease, chronic obstructive pulmonary disease, and most cancers, the evidence is mechanistically strong but limited to single-cohort or observational studies. Ceramides are emerging biomarkers that complement, not replace, established risk tools. Broader clinical use requires prospective validation, diverse cohorts, standardized assays, and demonstrated cost-effectiveness.