Abstract 19495: Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial

Background: Although in vitro studies and investigations in animal models and small clinical populations have suggested that ceramides may represent an intermediate link between over-nutrition and certain pathological mechanisms underlying cardiovascular disease (CVD), no prospective studies have investigated plasma ceramides and risk of CVD. Methods: The analytic population consisted of 980 participants from the PREDIMED trial, including 230 incident cases of CVD and 787 randomly selected participants at baseline, followed for up to 7.4 years. Participants were randomly assigned to a Mediterranean diet (MedDiet) supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or a control diet. Plasma ceramide concentrations were measured on a liquid chromatography tandem mass spectrometry metabolomics platform. The primary outcome was a composite of non-fatal acute myocardial infarction, non-fatal stroke, or cardiovascular death. Results: The multivariable HRs comparing the extreme quartiles of plasma concentrations of C16:0, C22:0, C24:0 and C24:1 ceramides were 2.39 (95% CI, 1.49-3.83, P for trend P for interaction =0.01). Participants with a higher ceramide score and assigned to either of the two intervention groups showed similar CVD risk to those with a lower ceramide score, whereas participants with a higher ceramide score and assigned to the control group presented significantly higher CVD risk. Changes in ceramide concentration were not significantly different between MedDiet and control groups during the first year of follow-up. Conclusions: Our study documented a novel positive association between baseline plasma ceramide concentrations and incident CVD. In addition, a Mediterranean dietary intervention may mitigate potential deleterious effects of elevated plasma ceramide concentrations on CVD.