title: Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial.
abstract: OBJECTIVE
  An inverse relationship between (serum) total bilirubin and risk of cardiovascular disease has been reported previously, but longitudinal data on overweight and obese patients are lacking. We have investigated the relationship between total bilirubin and cardiovascular adverse events in a large group of patients with risk factors for cardiovascular disease who were enrolled in a large weight loss trial.
  
  
  RESULTS
  Data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, including almost 10.000 overweight/obese high cardiovascular risk patients, were used. The relationship between total bilirubin level at screening and the primary outcome (i.e. non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death) for the entire study period was investigated using Cox proportional hazards models. The population was divided into four groups based on total bilirubin levels (normal range 5-25 μmol/L). Time-dependent Cox analyses were also performed to adjust for weight loss over time. Initial analyses adjusted for sex, age and treatment allocation showed significantly reduced hazard ratios of 0.80 (95% confidence interval 0.68-0.94), 0.73 (0.62-0.86) and 0.77 (0.65-0.91), for the three higher total bilirubin groups: >8 and ≤10 μmol/L, >10 and ≤13 μmol/L and >13 μmol/L (5-95 interpercentile range for total bilirubin at screening; 6-19 μmol/L), compared to the lowest total bilirubin group ≤8 μmol/L. When adjusting for classical cardiovascular risk factors, estimates increased towards unity. Additional adjustment for indicators of liver function did not alter the results. A time-dependent Cox model, adjusted for weight loss, demonstrated a similar trend.
  
  
  CONCLUSIONS
  Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.
authors.affiliation: Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark. Electronic address: madsejorgensen@gmail.com.
authors.forename: M E
authors.initials: ME
authors.lastname: Jørgensen
authors.affiliation: Department of Health Science and Technology, Aalborg University, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Torp-Pedersen
authors.affiliation: Centre for Cardiovascular Prevention & Outcomes, UCL Institute of Cardiovascular Sciences, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Finer
authors.affiliation: Boden Institute, University of Sydney, NSW, Australia.
authors.forename: I
authors.initials: I
authors.lastname: Caterson
authors.affiliation: London School of Hygiene and Tropical Medicine, London, UK.
authors.forename: W P T
authors.initials: WP
authors.lastname: James
authors.affiliation: Special Vocational College for handicapped Persons, Mainz, Germany.
authors.forename: U F
authors.initials: UF
authors.lastname: Legler
authors.affiliation: Department of Cardiology, Gentofte Hospital, University of Copenhagen, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Andersson
mesh_terms: D000368:Aged; D001663:Bilirubin / Q000097:blood*; D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality / Q000517:prevention & control; D015331:Cohort Studies; D004311:Double-Blind Method; D005260:Female; D006323:Heart Arrest / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D015994:Incidence; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009203:Myocardial Infarction / Q000453:epidemiology / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D009765:Obesity / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D050177:Overweight / Q000097:blood / Q000503:physiopathology* / Q000628:therapy; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D015854:Up-Regulation; D015431:Weight Loss
chemical_list: D001663:Bilirubin
keywords: Bilirubin; Cardiovascular disease; SCOUT