title: Biological variation of established and novel biomarkers for atherosclerosis: Results from a prospective, parallel-group cohort study.
abstract: BACKGROUND
  Biomarkers are a promising tool for the management of patients with atherosclerosis, but their variation is largely unknown. We assessed within-subject and between-subject biological variation of biomarkers in peripheral artery disease (PAD) patients and healthy controls, and defined which biomarkers have a favorable variation profile for future studies.
  
  
  METHODS
  Prospective, parallel-group cohort study, including 62 patients with stable PAD (79% men, 65±7years) and 18 healthy control subjects (44% men, 57±7years). Blood samples were taken at baseline, and after 3-, 6-, and 12-months. We calculated within-subject (CVI) and between-subject (CVG) coefficients of variation and intra-class correlation coefficient (ICC).
  
  
  RESULTS
  Mean levels of D-dimer, hs-CRP, IL-6, IL-8, MMP-9, MMP-3, S100A8/A9, PAI-1, sICAM-1, and sP-selectin levels were higher in PAD patients than in healthy controls (P≤.05 for all). CVI and CVG of the different biomarkers varied considerably in both groups. An ICC≥0.5 (indicating moderate-to-good reliability) was found for hs-CRP, D-Dimer, E-selectin, IL-10, MCP-1, MMP-3, oxLDL, sICAM-1 and sP-selectin in both groups, for sVCAM in healthy controls and for MMP-9, PAI-1 and sCD40L in PAD patients.
  
  
  CONCLUSIONS
  Single biomarker measurements are of limited utility due to large within-subject variation, both in PAD patients and healthy subjects. D-dimer, hs-CRP, MMP-9, MMP-3, PAI-1, sP-selectin and sICAM-1 are biomarkers with both higher mean levels in PAD patients and a favorable variation profile making them most suitable for future studies.
authors.affiliation: Division of Angiology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland. Electronic address: rolf.engelberger@chuv.ch.
authors.forename: Rolf P
authors.initials: RP
authors.lastname: Engelberger
authors.affiliation: Clinical Trial Unit Bern, Department of Clinical Research, and Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
authors.forename: Andreas
authors.initials: A
authors.lastname: Limacher
authors.affiliation: Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
authors.forename: Nils
authors.initials: N
authors.lastname: Kucher
authors.affiliation: Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Baumann
authors.affiliation: Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
authors.forename: Günther
authors.initials: G
authors.lastname: Silbernagel
authors.affiliation: F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Renée
authors.initials: R
authors.lastname: Benghozi
authors.affiliation: Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
authors.forename: Dai-Do
authors.initials: DD
authors.lastname: Do
authors.affiliation: Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
authors.forename: Torsten
authors.initials: T
authors.lastname: Willenberg
authors.affiliation: Swiss Cardiovascular Center, Division of Clinical and Interventional Angiology Inselspital, University Hospital and University of Bern, Switzerland.
authors.forename: Iris
authors.initials: I
authors.lastname: Baumgartner
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers
keywords: Atherosclerosis; Biological variation; Biomarkers; Inflammation; Peripheral vascular disease