title: Plasma concentrations of molecular lipid species in relation to coronary plaque characteristics and cardiovascular outcome: Results of the ATHEROREMO-IVUS study.
abstract: OBJECTIVE
  Previous lipidomics analyses have demonstrated that several lipid molecules in plasma are associated with fatal outcome in patients with coronary artery disease (CAD). This study aims to investigate the associations of previously identified high risk lipid molecules in plasma with coronary plaque characteristics derived from intravascular ultrasound virtual histology (IVUS-VH) imaging, with coronary lipid core burden index (LCBI) on near-infrared spectroscopy (NIRS), and with one year cardiovascular outcome in patients with CAD.
  
  
  METHODS
  Between 2008 and 2011, IVUS-VH imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography for acute coronary syndrome (ACS) or stable CAD. NIRS imaging was additionally performed in 191 patients. Plasma concentrations of molecular lipids were measured with mass spectrometry.
  
  
  RESULTS
  Several cholesteryl ester, ceramide and lactosylceramide species and ceramide ratios were associated with vulnerable plaque characteristics on IVUS-VH and NIRS imaging and with 1-year major adverse cardiac events (MACE, defined as all-cause mortality, ACS and unplanned coronary revascularization). In particular, ceramide d18:1/16:0 was consistently associated with higher necrotic core fraction on IVUS-VH (p = 0.001), higher LCBI (p = 0.024) on NIRS and higher MACE rate (adjusted HR 1.79 per standard deviation increase in log-transformed lipid concentration, 95%CI 1.24-2.59, p = 0.002).
  
  
  CONCLUSIONS
  Several molecular lipid species, and particularly ceramide(d18:1/16:0), are associated with the fraction of necrotic core tissue and lipid core burden in coronary atherosclerosis, and are predictive for 1-year clinical outcome after coronary angiography. These molecular lipids may improve risk stratification in CAD and may also be interesting therapeutic targets for the treatment of atherosclerotic disease.
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands; ICIN Netherlands Heart Institute, Utrecht, the Netherlands.
authors.forename: Jin M
authors.initials: JM
authors.lastname: Cheng
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Suoniemi
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: Isabella
authors.initials: I
authors.lastname: Kardys
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Terhi
authors.initials: T
authors.lastname: Vihervaara
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: Sanneke P M
authors.initials: SP
authors.lastname: de Boer
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: K Martijn
authors.initials: KM
authors.lastname: Akkerhuis
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Marko
authors.initials: M
authors.lastname: Sysi-Aho
authors.affiliation: Zora Biosciences, Espoo, Finland.
authors.forename: Kim
authors.initials: K
authors.lastname: Ekroos
authors.affiliation: Cardialysis, Rotterdam, the Netherlands.
authors.forename: Hector M
authors.initials: HM
authors.lastname: Garcia-Garcia
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: Rohit M
authors.initials: RM
authors.lastname: Oemrawsingh
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Regar
authors.affiliation: Department of Internal Medicine II - Cardiology, University of Ulm Medical Centre, Ulm, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardialysis, Rotterdam, the Netherlands; Imperial College, International Center of Circulatory Health, London, United Kingdom.
authors.forename: Patrick W
authors.initials: PW
authors.lastname: Serruys
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands.
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: van Geuns
authors.affiliation: Erasmus MC, Department of Cardiology, Rotterdam, the Netherlands; Cardiovascular Research School Erasmus University Rotterdam, Rotterdam, the Netherlands. Electronic address: h.boersma@erasmusmc.nl.
authors.forename: Eric
authors.initials: E
authors.lastname: Boersma
authors.affiliation: Zora Biosciences, Espoo, Finland; University Hospital, Tampere, Finland; Medical School University of Tampere, Finland. Electronic address: reijo.laaksonen@zora.fi.
authors.forename: Reijo
authors.initials: R
authors.lastname: Laaksonen
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy; D000368:Aged; D015415:Biomarkers / Q000097:blood; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000097:blood* / Q000000981:diagnostic imaging* / Q000401:mortality / Q000628:therapy; D003331:Coronary Vessels / Q000000981:diagnostic imaging* / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008055:Lipids / Q000097:blood*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009204:Myocardial Revascularization; D009336:Necrosis; D009426:Netherlands; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012307:Risk Factors; D012422:Rupture, Spontaneous; D019265:Spectroscopy, Near-Infrared; D018084:Ultrasonography, Interventional
chemical_list: D015415:Biomarkers; D008055:Lipids
keywords: Atherosclerosis; Intravascular ultrasound; Lipids; Near-infrared spectroscopy; Prognosis