P4497Serum ceramides and type 2 diabetes are mutually independent predictors of cardiovascular events in patients with peripheral artery disease

Abstract Introduction: Ceramides are enriched in atherosclerotic plaques, and a set of circulating ceramides including Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0) has recently emerged as predictors of cardiovascular outcomes in coronary artery disease patients. Hypothesis: We hypothesize that they have the power to predict cardiovascular events in patients with peripheral artery disease (PAD). Methods: We measured the serum concentrations of the above mentioned ceramides in a cohort of 380 patients with sonographically proven PAD, of whom 107 had type 2 diabetes (T2DM). Prospectively, we recorded 221 cardiovascular events over a mean follow-up time of 6.3±2.3 years. Results: Cardiovascular event risk was higher in T2DM patients than in those who did not have diabetes (69 vs. 52%, p=0.001). The ceramides Cer(18:1/16:0) and Cer(18:1/24:1) and the respective ratios Cer(18:1/16:0) / Cer(18:1/24:0) and Cer(18:1/24:1) / Cer(18:1/24:0) were significant predictors of cardiovascular events both univariately and after multivariate adjustment including the presence of T2DM (figure). Conversely, T2DM predicted cardiovascular events independently from the investigated ceramides (adjusted HR 1.76 [1.31-2.35], p<0.001). Conclusions: We conclude that the investigated ceramides and T2DM are mutually independent predictors of cardiovascular events in PAD patients.