title: Plasma C20-Sphingolipids predict cardiovascular events independently from conventional cardiovascular risk factors in patients undergoing coronary angiography.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Plasma C20SO levels are independent predictive biomarkers for cardiovascular events, even after adjusting for cardiovascular risk factors including coronary stenosis.
authors: Institute for Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland; Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
authors: Alaa
authors: A
authors: Othman
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors: Christoph H
authors: CH
authors: Saely
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors: Axel
authors: A
authors: Muendlein
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.
authors: Alexander
authors: A
authors: Vonbank
authors: Vorarlberg Institute for Vascular Investigation and Treatment (VIVIT), Feldkirch, Austria; Department of Medicine and Cardiology, Academic Teaching Hospital Feldkirch, Feldkirch, Austria; Private University of the Principality of Liechtenstein, Triesen, Liechtenstein; Drexel University College of Medicine, Philadelphia, PA, USA.
authors: Heinz
authors: H
authors: Drexel
authors: Institute for Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland; Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
authors: Arnold
authors: A
authors: von Eckardstein
authors: Institute for Clinical Chemistry, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland; Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. Electronic address: thorsten.hornemann@usz.ch.
authors: Thorsten
authors: T
authors: Hornemann
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002853:Chromatography, Liquid; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D023921:Coronary Stenosis / Q000097:blood* / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000209:etiology / Q000401:mortality / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008297:Male; D013058:Mass Spectrometry; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013107:Sphingolipids / Q000097:blood*; D020521:Stroke / Q000209:etiology / Q000401:mortality; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D013107:Sphingolipids
keywords: Atypical sphingolipids; C(20)Sphingosine; Coronary artery disease; Myocardial infarction; Predictive biomarker; Risk factor; Serine-palmitoyltransferase; Stroke