Increased levels of circulating fatty acids are associated with protective effects against future cardiovascular events in non-diabetics.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality worldwide, particularly in individuals with diabetes. The current study objective was to determine the circulating metabolite profiles associated with the risk of future cardiovascular events, with emphasis on diabetes status. Non-targeted metabolomics analysis was performed by LC-HRMS in combination with targeted quantification of eicosanoids and endocannabinoids. Plasma from 375 individuals from the IMPROVE pan-European cohort were included in a case-control study design. Following data processing, the three metabolite datasets were concatenated to produce a single dataset of 267 identified metabolites. Factor analysis identified six factors that described 26.6% of the variability in the given set of predictors. An association with cardiovascular events was only observed for one factor following adjustment (p=0.026). From this factor, we identified a free fatty acid signature (n=10 lipids, including saturated, monounsaturated, and polyunsaturated fatty acids) that was associated with lower risk of future cardiovascular events in non-diabetics only (OR=0.65, 0.27-0.80 95% CI, p=0.030), whereas no association was observed among diabetic individuals. These observations support the hypothesis that increased levels of circulating omega-6 and omega-3 fatty acids are associated with protective effects against future cardiovascular events. However, these effects were only observed in the non-diabetic population, further highlighting the need for patient stratification in clinical investigations.