The ceramide ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) have recently been reported to be associated with cardiovascular risk. Data on their power to predict cardiovascular events in patients with type 2 diabetes (T2DM) are sparse, and it is unknown whether they prospectively predict cardiovascular events independently from the presence of coronary artery disease (CAD) at baseline. These issues are addressed in the present study. We measured the above-mentioned serum ceramide ratios in a cohort of 894 patients in whom the presence of CAD was determined angiographically. Prospectively, we recorded cardiovascular events over a mean follow-up time of 9.2±3.2 years. At baseline, the ratios Cer(d18:1/16:0)/Cer(d18:1/24:0), Cer(d18:1/18:0)/Cer(d18:1/24:0) and Cer(d18:1/24:1)/Cer(d18:1/24:0) were significantly higher in T2DM patients (n=239) than in patients without T2DM (0.11 vs. 0.10, p=0.011; 0.46 vs. 0.39, p<0.001; and 0.46 vs. 0.41, p<0.001), but did not differ significantly between patients with CAD (n=491) and those without CAD. Prospectively, vascular events occurred in 110 (47%) of the patients with T2DM and in 212 (33%) of nondiabetic patients (p<0.001). For the ratio Cer(d18:1/16:0)/Cer(d18:1/24:0) a significant association with cardiovascular events in T2DM patients could be demonstrated univariately (standardized HR 1.23 [1.07-1.41], p=0.003), and after adjustment for age, gender, BMI, smoking, LDL cholesterol, HDL cholesterol, hypertension, statin intake, and also the for the CAD status at baseline (standardized adjusted HR 1.28 [1.10-1.50], p=0.002). We conclude that ceramide ratios have the potential to predict cardiovascular events in patients with T2DM, independent from their baseline CAD status. Further research addressing the selection of optimal ceramide species for risk prediction appears warranted.
A. Leiherer: None. A. Muendlein: None. C.H. Saely: None. R. Laaksonen: None. M. Laaperi: None. A. Vonbank: None. B. Larcher: None. A. Mader: None. P. Fraunberger: None. H. Drexel: None.