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

M.A. Kamleh, O. McLeod, A. Checa, D. Baldassarre, F. Veglia, K. Gertow, S.E. Humphries, R. Rauramaa, U. De Faire, A.J. Smit, P. Giral, S. Kurl, E. Mannarino, E. Tremoli, A. Silveira, J. Örvik, A. Hamsten, C.E. Wheelock

Research output: Contribution to journalArticlepeer-review


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. © 2017 American Chemical Society.
Original languageEnglish
Pages (from-to)870-878
Number of pages9
JournalJournal of Proteome Research
Issue number2
Publication statusPublished - 2018


  • 15 hydroxyicosatetraenoic acid
  • 5 hydroxyicosatetraenoic acid
  • 5,8,11 icosatrienoic acid
  • adrenic acid
  • angiotensin receptor antagonist
  • antidiabetic agent
  • antihypertensive agent
  • antilipemic agent
  • antithrombocytic agent
  • arachidonic acid
  • dihomo gamma linolenic acid
  • docosahexaenoic acid
  • endocannabinoid
  • fatty acid derivative
  • gamma linolenic acid
  • hydroxymethylglutaryl coenzyme A reductase inhibitor
  • icosanoid
  • insulin
  • linoleic acid
  • monounsaturated fatty acid
  • n palmitoyl taurine
  • n stearoyl taurine
  • oleic acid
  • omega 3 fatty acid
  • omega 6 fatty acid
  • palmitic acid
  • palmitoleic acid
  • polyunsaturated fatty acid
  • saturated fatty acid
  • stearic acid
  • unclassified drug
  • biological marker
  • oxylipin, adult
  • aged
  • antihypertensive therapy
  • Article
  • cardiovascular disease
  • cardiovascular risk
  • case control study
  • cohort analysis
  • controlled study
  • diabetes mellitus
  • disease association
  • factor analysis
  • fatty acid analysis
  • female
  • futurology
  • heart protection
  • high risk patient
  • human
  • hypertension
  • insulin treatment
  • liquid chromatography-mass spectrometry
  • longitudinal study
  • low risk patient
  • major clinical study
  • male
  • metabolite
  • metabolomics
  • observational study
  • predictor variable
  • priority journal
  • quantitative analysis
  • blood
  • middle aged
  • prognosis
  • protection
  • risk factor, Aged
  • Biomarkers
  • Cardiovascular Diseases
  • Case-Control Studies
  • Diabetes Mellitus
  • Eicosanoids
  • Endocannabinoids
  • Factor Analysis, Statistical
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Female
  • Humans
  • Male
  • Middle Aged
  • Oxylipins
  • Prognosis
  • Protective Factors
  • Risk Factors


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