Prognostic Value of Ceramide-Based Lipid Scores in Cardiovascular Disease and Heart Failure: Insights From CERT1, CERT2, and Ceramide Ratios
Sidhartha Gautam SenapatiIntroduction:
Residual cardiovascular risk persists despite optimal control of traditional risk factors. Ceramide-based lipid scores have emerged as novel biomarkers that may improve prognostic assessment in Cardiovascular Disease (CVD) and Heart Failure (HF).
Methods:
The literature was reviewed using PubMed, Embase, and the Cochrane Library, with all records up to October 2025 included. Terms like ceramide, ceramide ratios, CERT1, CERT2, lipidomics, cardiovascular disease, and heart failure were searched. The focus of the study was on prospective cohort studies, randomized trial substudies, and external validation analyses that linked ceramide-based scores to cardiovascular outcomes. Studies that only used experimental or preclinical models were excluded. If multiple papers came from the same group of patients, the most thorough or reliable ones were selected. Because of differences in how scores were constructed, tested, and reported, the findings were summarized qualitatively rather than conducted as a meta-analysis.
Results:
In several studies, ceramide-based scores were consistently linked to worse cardiovascular outcomes, even after accounting for standard risk factors. CERT2 performed well in both people without heart disease and those with existing conditions. In the STABILITY trial, CERT2 predicted cardiovascular death (HR 1.47, 95% CI 1.35–1.59) and hospitalizations for Heart Failure (HR 1.56, 95% CI 1.39–1.76). Adding ceramide ratios, especially C16:0/C24:0, to existing models improved risk prediction, with net reclassification improvements up to 0.17. On the other hand, higher C24:0/C16:0 ratios were linked to lower risks of death from any cause or from heart disease. These results were similar in older adults, people with diabetes, and community groups.
Discussion:
Ceramide-based scores reflect metabolic risks that standard lipid tests do not show. They offer extra information for predicting outcomes in different clinical situations, including heart failure.
Conclusion:
Ceramide-based lipid scores, especially CERT2 and some ceramide ratios, provide extra value for predicting cardiovascular risk beyond traditional factors. However, most evidence so far only shows associations, not cause and effect, so their use in everyday clinical care is still under investigation. More studies in different groups and randomized trials are needed before these scores can be used regularly in practice.