title: Relationship of serum inflammatory biomarkers with plaque inflammation assessed by FDG PET/CT: the dal-PLAQUE study.
abstract: OBJECTIVE
  This study sought to longitudinally investigate the relationship between a broad spectrum of serum inflammatory biomarkers and plaque inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).
  
  
  BACKGROUND
  Both plaque inflammation and serum biomarkers of inflammation are associated with atherothrombotic events; however, the relationship between them is unclear.
  
  
  METHODS
  We conducted a post hoc analysis of the dal-PLAQUE (A Randomized Placebo-Controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors), a randomized, placebo-controlled study of dalcetrapib, a cholesteryl ester transfer protein inhibitor, in 130 patients with coronary heart disease, or coronary heart disease risk equivalents on stable lipid-lowering therapy. Baseline and change after 3-month follow-up in inflammatory biomarker levels and baseline and change after 3-month follow-up in aorta and carotid (18)F-FDG PET/CT (mean maximum target-to-background ratio of the most diseased segment [TBRmds]) were analyzed.
  
  
  RESULTS
  Baseline myeloperoxidase positively correlated with baseline carotid TBRmds (rho = 0.25, p = 0.02). This correlation remained at the 3-month follow-up and was independent of traditional cardiovascular disease risk factors. Baseline lipoprotein-associated phospholipase A2 mass correlated with aorta TBRmds (rho = 0.21, p = 0.03). However, this correlation disappeared at the 3-month follow-up and was not independent of cardiovascular disease risk factors. There was no association between change from baseline in myeloperoxidase or lipoprotein-associated phospholipase A2 mass and change from baseline in aorta and carotid TBRmds. Baseline and change from baseline in high sensitivity C-reactive protein, interleukin 6, soluble P-selectin, soluble E-selectin, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and matrix-metalloproteinase 3 and 9 did not correlate with baseline or change from baseline in carotid or aorta TBRmds.
  
  
  CONCLUSIONS
  Our data show that, in patients with coronary heart disease or at high risk of coronary heart disease on stable lipid-lowering therapy, circulating myeloperoxidase levels are associated with carotid plaque inflammation. (A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors [dal-PLAQUE]; NCT00655473).
authors.affiliation: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Duivenvoorden
authors.affiliation: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Venkatesh
authors.initials: V
authors.lastname: Mani
authors.affiliation: George Institute, University of Sydney, Sydney, Australia.
authors.forename: Mark
authors.initials: M
authors.lastname: Woodward
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: David
authors.initials: D
authors.lastname: Kallend
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Suchankova
authors.affiliation: Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York.
authors.forename: Valentin
authors.initials: V
authors.lastname: Fuster
authors.affiliation: Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: James H F
authors.initials: JHF
authors.lastname: Rudd
authors.affiliation: Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Tawakol
authors.affiliation: Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York; Peter Munk Cardiac Centre and Li Ka Shing Knowledge Institute, Toronto, Ontario, Canada.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Farkouh
authors.affiliation: Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York, New York; Cardiovascular Institute, Mount Sinai School of Medicine, New York, New York. Electronic address: zahi.fayad@mssm.edu.
authors.forename: Zahi A
authors.initials: ZA
authors.lastname: Fayad
mesh_terms: D000577:Amides; D001011:Aorta / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology; D001018:Aortic Diseases / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000187:drug effects / Q000276:immunology; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000276:immunology; D004311:Double-Blind Method; D004952:Esters; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use; D018836:Inflammation Mediators / Q000097:blood*; D008137:Longitudinal Studies; D064847:Multimodal Imaging; D009195:Peroxidase / Q000097:blood; D058226:Plaque, Atherosclerotic; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds / Q000627:therapeutic use; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000577:Amides; D015415:Biomarkers; D004952:Esters; D000960:Hypolipidemic Agents; D018836:Inflammation Mediators; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds; D019788:Fluorodeoxyglucose F18; C411602:dalcetrapib; D009195:Peroxidase
keywords: (18)F-FDG PET/CT; IL-6; Lp-PLA(2); MMP; MPO; TBR(mds); atherosclerosis; fluorodeoxyglucose F 18 positron emission tomography; fluorodeoxyglucose F 18 positron emission tomography/computed tomography; high-sensitivity C-reactive protein; hsCRP; inflammatory biomarkers; interleukin 6; lipoprotein-associated phospholipase A(2); matrix metalloproteinase; myeloperoxidase; sE-selectin; sICAM; sP-selectin; sVCAM; soluble E-selectin; soluble P-selectin; soluble intracellular adhesion molecule; soluble vascular cell adhesion molecule; target-to-background ratio of the most diseased segment