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Circulating Sphingolipids and All-Cause Mortality: The Strong Heart Family Study.

Amanda M Fretts1,2, Paul N Jensen2,3, Colleen M Sitlani2,3

  • 1Department of Epidemiology University of Washington Seattle WA USA.

Journal of the American Heart Association
|June 21, 2024
PubMed
Summary

Ceramides and sphingomyelins with different fatty acid chain lengths show varying associations with mortality. Shorter chains (16:0) increase mortality risk, while longer chains (20:0, 22:0, 24:0) are linked to decreased mortality risk.

Keywords:
American Indianceramidesmortalitysphingolipidssphingomyelins

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Area of Science:

  • Biochemistry
  • Genetics
  • Epidemiology

Background:

  • Ceramide and sphingomyelin associations with mortality are chain-length dependent.
  • Previous research suggests varying impacts based on fatty acid chain length.
  • This study investigates these associations in an American Indian population.

Purpose of the Study:

  • To examine the associations of eight ceramide and sphingomyelin species with all-cause mortality.
  • To determine if fatty acid chain length modifies the association between sphingolipids and mortality.
  • To analyze data from the Strong Heart Family Study (SHFS) participants.

Main Methods:

  • Analysis of 2688 participants from the Strong Heart Family Study (SHFS).
  • Measurement of plasma ceramide and sphingomyelin species with saturated fatty acids (16:0, 20:0, 22:0, 24:0) using liquid chromatography and mass spectrometry.
  • Follow-up for 18.8 years (2001-2020) and assessment of mortality associations using Cox models.

Main Results:

  • Ceramides and sphingomyelins with a 16:0 fatty acid were positively associated with mortality (e.g., Cer-16 HR=1.68, SM-16 HR=1.80).
  • Ceramides and sphingomyelins with longer fatty acids (20:0, 22:0, 24:0) were inversely associated with mortality (e.g., Cer-24 HR=0.67, SM-24 HR=0.59).
  • Significant associations were observed across all measured ceramide and sphingomyelin species.

Conclusions:

  • The direction and magnitude of ceramide and sphingomyelin associations with mortality are dependent on the fatty acid chain length.
  • Fatty acid chain length is a critical determinant of the prognostic value of sphingolipids.
  • Findings highlight the complex role of sphingolipid metabolism in cardiovascular health and mortality.