Circulating Ceramides Predict Cardiovascular Outcomes in the Population-Based FINRISK 2002 Cohort

Aki S. Havulinna, Marko Sysi-Aho, M. Hilvo, Dimple Kauhanen, Reini Hurme, Kim Ekroos, Veikko Salomaa, Reijo Laaksonen

Research output: Contribution to journalArticleScientificpeer-review

172 Citations (Scopus)

Abstract

bjective—
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.

Approach and 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.
Original languageEnglish
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume36
Issue number12
DOIs
Publication statusPublished - Dec 2016
MoE publication typeA1 Journal article-refereed

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