title: Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort.
abstract: OBJECTIVE
  Ceramides are molecular lipids implicated in apoptosis, inflammation, obesity, and insulin resistance. An earlier study reported that ceramides were associated with fatal outcome among patients with coronary heart disease. Here, we examined whether ceramides are associated with major adverse cardiovascular events (MACEs) among apparently healthy individuals.
  
  
  RESULTS
  FINRISK 2002 is a population-based risk factor survey, which recruited men and women aged 25 to 74 years. The cohort was followed up until the end of 2014. We quantified 4 circulating ceramides, Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:0), and Cer(d18:1/24:1), in 8101 serum samples by a targeted liquid chromatography-tandem mass spectrometry assay. Primary outcome of interest was incident MACE (n=813). Secondary analyses were performed for MACE death (n=116) without previous nonfatal MACE and for recurrent MACE (n=226) among survivors of a previous incident MACE. We used Cox proportional hazard models adjusted for the Framingham covariates to determine the association of ceramides with the outcomes. Of the ceramide species, Cer(d18:1/18:0) had the strongest association with incident MACE and the highest unadjusted hazard ratio of 1.31 (95% confidence interval, 1.21-1.41), which remained significant at 1.21 (95% confidence interval, 1.11-1.33) after Framingham risk factor adjustments. The hazard ratios were generally stronger for recurrent and fatal events than for first events. Clinical net reclassification improvement was 7.5% (P=6.9×10-5) for Cer(d18:1/18:0).
  
  
  CONCLUSIONS
  Distinct serum ceramides are associated with the risk of incident MACE in apparently healthy individuals. These results should encourage more detailed analyses of ceramides in cardiovascular pathobiology and suggest new biomarkers of MACE risk.
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Marko
authors.initials: M
authors.lastname: Sysi-Aho
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Mika
authors.initials: M
authors.lastname: Hilvo
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Dimple
authors.initials: D
authors.lastname: Kauhanen
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Reini
authors.initials: R
authors.lastname: Hurme
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Kim
authors.initials: K
authors.lastname: Ekroos
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.).
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
authors.affiliation: From the Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.); Zora Biosciences Oy, Espoo, Finland (M.S.-A., M.H., D.K., R.H., K.E., R.L.); Medical School, University of Tampere, Finland (R.L.); and Finnish Clinical Biobank, University Hospital of Tampere, Finland (R.L.). reijo.laaksonen@zora.fi.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D002518:Ceramides / Q000097:blood*; D002853:Chromatography, Liquid; D015897:Comorbidity; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008019:Life Style; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015995:Prevalence; D011379:Prognosis; D016016:Proportional Hazards Models; D012008:Recurrence; D018570:Risk Assessment; D012307:Risk Factors; D053719:Tandem Mass Spectrometry; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D002518:Ceramides
keywords: cardiovascular diseases; ceramides; lipidomics; lipids; metabolomics; risk factors