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J Proteome Res. 2018 Feb 2;17(2):870-878. doi: 10.1021/acs.jproteome.7b00671. Epub 2018 Jan 22.

Increased Levels of Circulating Fatty Acids Are Associated with Protective Effects against Future Cardiovascular Events in Nondiabetics.

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Division of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet , 17177 Stockholm, Sweden.
Cardiovascular Medicine Unit, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet and Department of Cardiology, Karolinska University Hospital Solna , 17176 Stockholm, Sweden.
Department of Medical Biotechnology and Translational Medicine, Università degli Studi di Milano , 20133 Milan, Italy.
Centro Cardiologico Monzino, I.R.C.C.S. , 20138 Milan, Italy.
Cardiovascular Genetics, Institute of Cardiovascular Science, University College of London , London WC1E 6BT, United Kingdom.
Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine , 70100 Kuopio, Finland.
Department of Cardiology, Karolinska University Hospital Solna , 17176 Stockholm, Sweden.
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet , 17177 Stockholm, Sweden.
Department of Medicine, University Medical Center Groningen , 9713 GZ Groningen, The Netherlands.
Assistance Publique - Hopitaux de Paris ; Service Endocrinologie-Metabolisme, Groupe Hôpitalier Pitie-Salpetriere, Unités de Prévention Cardiovasculaire, 75004 Paris, France.
Institute of Public Health and Clinical Nutrition, University of Eastern Finland , Kuopio Campus, 70211 Kuopio, Finland.
Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia , Perugia 06132, Italy.


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. Nontargeted 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 was included in a case-control study design. Following data processing, the three metabolite data sets were concatenated to produce a single data set 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 nondiabetics 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 nondiabetic population, further highlighting the need for patient stratification in clinical investigations.


cardiovascular disease; diabetes; eicosanoids; endocannabinoids; fatty acids; metabolomics

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