AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Dynamic Changes in Plasma Ceramides as Predictors of Mortality Risk: Evidence from the SHIP Longitudinal Study
By Ferris C, Peterson LR, Cresci S et al.
Background: Plasma ceramides are emerging as new biomarkers for cardiovascular disease. Ceramides are complex lipids with a sphingoid base linked to fatty acyl chains of varying lengths that play key roles in cellular processes including apoptosis and inflammation. Higher ratios of very long chain species (e.g. C24:0 and C22:0) to long chain species (e.g. C16:0) have been shown to be inversely associated with incident CAD, heart failure, and all-cause mortality. It is unknown whether changes in plasma ceramides over time are predictive of differences in risk of mortality. To investigate this, we examined the relationship between dynamic changes in ceramide ratios and survival using data from the Study of Health in Pomerania (SHIP) cohort. Hypothesis: We hypothesized that participants with increasing C24:0/C16:0 over time would have greater survival compared to participants with decreasing C24:0/C16:0. Methods: The SHIP cohort consisted of 3,300 participants in Northeast Germany with common CVD factors. Liquid chromatography-tandem mass spectrometry was used to analyze C16:0, C22:0 and C24:0 ceramides at two times points, SHIP-1 and SHIP-2. We calculated changes in plasma ceramides and ratios (C24:0/C16:0, C22:0/C16:0) of participants who survived at least 8 years after SHIP-2 to compare with those who died earlier (median: 9.62 vs. 5.34 years) using 1:1 matching of risk profiles (Mahalanobis distance). The multivariable matching included age, sex, blood pressure, diabetes, smoking, eGFR, NT-proBNP, total cholesterol-HDL ratio and all ceramides at SHIP-1. We performed Kaplan-Meier and Cox regression model analyses using baseline and follow up data (median timepoint of 9.75 years). Results: We found that, despite having lower baseline C24:0/C16:0 levels, participants who had an increase in C24:0/C16:0 between SHIP-1 and -2 had greater survival probability over time compared to those whose C24:0/C16:0 decreased ( Figure 1, p= 0.00015). Participants who had increases compared to those with decreases in C22:0/C16:0 also had greater survival (p=0.00019). Increases in C22:0 and C24:0 individually demonstrated increased survival probability compared to participants with decreases in C22:0 and C24:0 (p=0.00851, p=0.00042). There was no significant difference in survival between participants whose C16:0 increased or decreased over time (p=0.41). We also found that after adjusting for standard CVD risk factors, decreases in C24:0/C16:0 were associated with all-cause mortality (HR 1.82; 95% CI 1.36-2.44;P<0.0001); however, decreases in C16:0 alone was not (HR 1.08; 95% CI 0.79-1.46; p=0.063). Conclusions: In this community-based cohort, changes in ceramide ratios over time were significantly correlated with risk for mortality and survival time. These results implicate potentially important role for interventions that increase plasma levels of very long chain ceramides.