title: Association of bilirubin with coronary artery calcification and cardiovascular events in the general population without known liver disease: the Heinz Nixdorf Recall study.
abstract: BACKGROUND
  Bilirubin is a product of heme oxygenase and an antioxidant per se. In selected cohorts and patient studies, bilirubin was associated with decreased risk for cardiovascular events. We aimed to determine the association of serum bilirubin with coronary artery calcification (CAC) and incident cardiovascular disease in the unselected general population.
  
  
  METHODS
  Participants without prior coronary heart or liver disease were drawn from the population-based Heinz Nixdorf Recall study. CAC was measured from electron beam computed tomography and quantified using the Agatston method. Incident major cardiovascular events (coronary events, stroke, cardiovascular death) were assessed during follow-up. The association of bilirubin with CAC score and incident events was calculated using regression analysis.
  
  
  RESULTS
  A total of 3,553 subjects (mean age 59.4 years, 44 % male) were included. Bilirubin was inversely correlated with CAC in men [estimated % change in (CAC + 1) per each gender-specific standard deviation of bilirubin [95 % confidence interval (CI): -6.1 (-11.6; -1.7) %, p = 0.032] but less so in women [-3.6 (-7.7; 0.2) %, p = 0.065], when adjusting for age only. With adjustment for traditional cardiovascular risk factors, the association was less pronounced [men: -2.5 (-7.5; 2.6) %, p = 0.35, women: -0.2 (-4.1; 3.5) %, p = 0.9]. Likewise, higher bilirubin by one standard deviation was associated with 19 % lower frequency of incident cardiovascular events in age- and gender-adjusted Cox regression analysis [hazard ratio (95 % CI): 0.81 (0.68; 0.96), p = 0.014]; this effect was slightly attenuated after adjustment for traditional cardiovascular risk factors [0.87 (0.73; 1.04), p = 0.13].
  
  
  CONCLUSIONS
  Our data from a general population suggest that a potential protective role of bilirubin in the atherosclerosis process is largely secondary to a more beneficial risk factor profile.
authors.affiliation: Department of Cardiology, West German Heart Center, University of Duisburg-Essen, Hufelandstr. 55, 45147, Essen, Germany, amir-abbas.mahabadi@uk-essen.de.
authors.forename: Amir A
authors.initials: AA
authors.lastname: Mahabadi
authors.forename: Nils
authors.initials: N
authors.lastname: Lehmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Möhlenkamp
authors.forename: Hagen
authors.initials: H
authors.lastname: Kälsch
authors.forename: Marcus
authors.initials: M
authors.lastname: Bauer
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Susanne
authors.initials: S
authors.lastname: Moebus
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000367:Age Factors; D000368:Aged; D050197:Atherosclerosis / Q000473:pathology; D001663:Bilirubin / Q000097:blood*; D002114:Calcinosis / Q000175:diagnosis / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000503:physiopathology*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012044:Regression Analysis; D012307:Risk Factors; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D001663:Bilirubin