title: The inverse association of incident cardiovascular disease with plasma bilirubin is unaffected by adiponectin.
abstract: OBJECTIVE
  Bilirubin may protect against atherosclerotic cardiovascular disease (CVD). The heme oxygenase pathway is crucial for bilirubin generation, and is stimulated by adiponectin. We tested the relationship of plasma bilirubin with adiponectin, and determined whether the association of incident CVD with bilirubin is modified by adiponectin.
  
  
  METHODS
  A community-based prospective nested case-control study (PREVEND cohort) was carried out in 87 non-diabetic men who developed a first cardiovascular event (cases) and 94 controls during a median follow-up of 6.1 (2.8-10.6) years.
  
  
  RESULTS
  In all subjects combined, bilirubin was positively related to adiponectin (r = 0.205, P = 0.006). Age-adjusted incident CVD was inversely associated with bilirubin (hazard ratio (HR): 0.80 (95% CI 0.65-0.99), P = 0.048), independently of adiponectin (HR: 0.78 (95% CI 0.63-0.97), P = 0.027). Adiponectin did not modify the association of CVD with bilirubin (interaction term: P = 0.65). After additional adjustment for CVD risk factors, neither the association of incident CVD with bilirubin nor with adiponectin remained significant (P > 0.20 for both), and there was again no interaction between bilirubin and adiponectin on CVD risk (P = 0.67).
  
  
  CONCLUSIONS
  Bilirubin is related to adiponectin, but the association of bilirubin with CVD risk is largely unaffected by adiponectin.
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands. Electronic address: r.p.f.dullaart@umcg.nl.
authors.forename: Robin P F
authors.initials: RP
authors.lastname: Dullaart
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands; Department of Vascular Medicine, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Jeltje
authors.initials: J
authors.lastname: Boersema
authors.affiliation: Department of Vascular Medicine, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Joop D
authors.initials: JD
authors.lastname: Lefrandt
authors.affiliation: Department of Endocrinology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Bruce H R
authors.initials: BH
authors.lastname: Wolffenbuttel
authors.affiliation: Department of Nephrology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
mesh_terms: D052242:Adiponectin / Q000097:blood*; D000328:Adult; D000368:Aged; D001663:Bilirubin / Q000097:blood*; D002318:Cardiovascular Diseases / Q000209:etiology*; D016022:Case-Control Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D052242:Adiponectin; D001663:Bilirubin
keywords: Adiponectin; Bilirubin; Cardiovascular disease; Prospective nested case–control study