CIRCULATING CERAMIDES AND CARDIOVASCULAR OUTCOMES IN A REAL-WORLD SETTING, USING MAYO CLINIC ELECTRONIC MEDICAL RECORDS
Author(s)
Erin L. Ferguson, MPH, PhD, Paul Brendel, PhD, William Gordon, PhD, Caislin L. Firth, PhD;
Valo Health, Lexington, MA, USA
Valo Health, Lexington, MA, USA
OBJECTIVES: Ceramides are lipids implicated in inflammation and accumulate in tissues of patients with cardiovascular disease (CVD). Multiple clinical cohorts have linked elevated ceramide levels, independent of low-density lipoprotein cholesterol (LDL-C), to CVD. A gap exists in understanding the role of ceramides in CVD in general patient populations. This study evaluated associations between ceramide risk scores, LDL-C, and incident CVD outcomes and mortality in electronic health records.
METHODS: We included adults seen at Mayo Clinic with a ceramide risk score panel (i.e. baseline) between 2016-2024. We included ceramides as a linear and categorical (low:0-2, moderate:3-6, increased:7-9, and highest risk:10-12) feature, and used LDL-C measures within 3 months of ceramide panel. We assessed incident CV outcomes (e.g. major adverse cardiovascular events, heart failure) and all-cause mortality. We modeled each outcome separately, using time-to-event Cox proportional hazards, censoring at death or observation end (April 2025). We adjusted models for comorbidity and demographic covariates and used an interaction term of ceramide and LDL-C to test whether LDL-C levels modified ceramide-outcome associations.
RESULTS: Patients (n=5,778) had an average ceramide risk score of 3.55 (SD: 2.96) with 3.8% (n=218) in the highest risk group. The highest ceramide risk score group had an increased hazard of mortality relative to low-risk group (HR= 3.82, 95% CI: 1.67-8.74), when controlled for LDL-C. Ceramides, as a linear or categorical feature, were not associated with incident cardiovascular events, though confidence intervals were wide. LDL-C levels were associated with heart failure (HR per 10 mg/dL = 1.06, 1.03-1.08) but not mortality (HR= 0.96, 0.88-1.06) when adjusted for ceramide score. There was no significant interaction between LDL-C and ceramide scores.
CONCLUSIONS: Elevated ceramide scores were associated with mortality and not CV outcomes. The relationships between ceramide scores, subsequent medical interventions or treatment initiation, and CVD risk will be investigated in future work.
METHODS: We included adults seen at Mayo Clinic with a ceramide risk score panel (i.e. baseline) between 2016-2024. We included ceramides as a linear and categorical (low:0-2, moderate:3-6, increased:7-9, and highest risk:10-12) feature, and used LDL-C measures within 3 months of ceramide panel. We assessed incident CV outcomes (e.g. major adverse cardiovascular events, heart failure) and all-cause mortality. We modeled each outcome separately, using time-to-event Cox proportional hazards, censoring at death or observation end (April 2025). We adjusted models for comorbidity and demographic covariates and used an interaction term of ceramide and LDL-C to test whether LDL-C levels modified ceramide-outcome associations.
RESULTS: Patients (n=5,778) had an average ceramide risk score of 3.55 (SD: 2.96) with 3.8% (n=218) in the highest risk group. The highest ceramide risk score group had an increased hazard of mortality relative to low-risk group (HR= 3.82, 95% CI: 1.67-8.74), when controlled for LDL-C. Ceramides, as a linear or categorical feature, were not associated with incident cardiovascular events, though confidence intervals were wide. LDL-C levels were associated with heart failure (HR per 10 mg/dL = 1.06, 1.03-1.08) but not mortality (HR= 0.96, 0.88-1.06) when adjusted for ceramide score. There was no significant interaction between LDL-C and ceramide scores.
CONCLUSIONS: Elevated ceramide scores were associated with mortality and not CV outcomes. The relationships between ceramide scores, subsequent medical interventions or treatment initiation, and CVD risk will be investigated in future work.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EPH3
Topic
Epidemiology & Public Health
Disease
No Additional Disease & Conditions/Specialized Treatment Areas, SDC: Cardiovascular Disorders (including MI, Stroke, Circulatory)