Ceramides surpass LDL-cholesterol in predicting cardiovascular mortality in patients with as well as in patients without the metabolic syndrome

Abstract Introduction The power of cardiovascular risk prediction is biased by comorbidities (e.g. metabolic syndrome, MetS), medical treatment, and age, which impact cholesterol levels. When applying LDL-C, the true risk of such confounded patients is often underestimated. However, it is unclear whether this likewise applies to other lipid markers, in particular ceramides. Purpose The purpose of this study was to investigate the power of ceramides for cardiovascular risk prediction. Methods In this prospective cohort study, we recorded cardiovascular mortality for 16 years in 1306 patients. Their median age was 67 years, all had a high preexisting cardiovascular risk, 53% were taking statins, and 44% had the MetS. Results Ceramide levels, CERT1 and CERT2 scores but not LDL-C differed significantly between patients with and without MetS. A Cox regression analysis adjusting for age, sex, history of smoking, hypertension, BMI and statin use revealed that LDL-C failed to predict cardiovascular mortality in patients with was well as in patients without the MetS. In contrast, ceramide-based markers were able to significantly predict cardiovascular mortality after stratification and multivariate adjustment in both subgroups. Conclusion We thus propose that ceramide-based predictors rather than LDL-C should be applied for a more accurate cardiovascular risk prediction in high risk patients with as well as in those without the MetS.