Plasma C20-Sphingolipids predict cardiovascular events independently from conventional cardiovascular risk factors in patients undergoing coronary angiography

Atherosclerosis. 2015 May;240(1):216-21. doi: 10.1016/j.atherosclerosis.2015.03.011. Epub 2015 Mar 14.


Aims: Sphingolipids are emerging as novel players in the pathogenesis of atherosclerosis and cardiovascular disease. Serine palmitoyltransferase (SPT) catalyzes the first and rate-limiting step in the de novo synthesis of sphingolipids--the condensation of palmitoyl-CoA and L-Serine. In addition to these canonical substrates, SPT can also metabolize other acyl-CoAs and amino acids, thus generating a variety of atypical sphingoid bases. In this study, we investigated the association of these atypical sphingoid bases with the presence of angiographically characterized coronary artery disease (CAD) as well as their ability to predict the incidence of cardiovascular events.

Methods and results: 349 subjects, who underwent coronary angiography for the evaluation of established or suspected stable CAD, were enrolled in the study at baseline and followed up for cardiovascular events over a period of 8 years (median 7.7 years). The sphingoid base profile in the extracted plasma sphingolipids were determined by LC/MS after acid-base hydrolysis. Plasma levels of C18SAdiene were found to be significantly lower in CAD patients at baseline, while levels for C16SA, C16SO, C17SO, C18SA, C18SO, and C19SO and 1-deoxy sphingoid bases were not different. In the prospective analysis C20SO significantly predicted cardiovascular events (standardized adjusted HR=1.20, CI 95% [1.03-1.41]; p=0.022) after adjusting for traditional risk factors, the use of lipid-lowering drugs and angiographically-determined CAD at baseline.

Conclusion: Plasma C20SO levels are independent predictive biomarkers for cardiovascular events, even after adjusting for cardiovascular risk factors including coronary stenosis.

Keywords: Atypical sphingolipids; C(20)Sphingosine; Coronary artery disease; Myocardial infarction; Predictive biomarker; Risk factor; Serine-palmitoyltransferase; Stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Chromatography, Liquid
  • Coronary Angiography*
  • Coronary Artery Disease / blood*
  • Coronary Artery Disease / diagnostic imaging*
  • Coronary Artery Disease / etiology
  • Coronary Artery Disease / mortality
  • Coronary Artery Disease / therapy
  • Coronary Stenosis / blood*
  • Coronary Stenosis / diagnosis
  • Coronary Stenosis / diagnostic imaging*
  • Coronary Stenosis / etiology
  • Coronary Stenosis / mortality
  • Coronary Stenosis / therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Incidence
  • Kaplan-Meier Estimate
  • Male
  • Mass Spectrometry
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications
  • Middle Aged
  • Myocardial Infarction / etiology
  • Myocardial Infarction / mortality
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Sphingolipids / blood*
  • Stroke / etiology
  • Stroke / mortality
  • Time Factors
  • Up-Regulation


  • Biomarkers
  • Sphingolipids