Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial

Abstract Background and aims 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. Methods and 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. Conclusion Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.