Elevated serum bilirubin may significantly reduce coronary heart disease risk in females: A prospective cohort study

Background and aims: There is still inconsistent evidence over the protective effect of total bilirubin on the development of coronary heart disease (CHD). Therefore, we aimed to investigate the association between bilirubin in population subtypes and the risks of CHD between different gender and menstruation subgroups.

Methods and results: In this prospective cohort study, 29,750 participants free of CHD with an average age of 47 ± 14 years were recruited at baseline; of these, 720 CHD first-attack cases were collected after 7-years of follow up. The covariate-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) of CHD with 95% confidence intervals (CIs). The serum bilirubin concentration was quarterly stratified based on the distribution of healthy population without CHD onset. The HRs of incident CHD decreased with elevated bilirubin in females (ρ trend<0.05), but not males. In postmenopausal females, compared with the lowest quartile of total bilirubin, the adjusted HRs for the third and fourth quartiles were 0.64 (95% CI: 0.45, 0.93) and 0.59 (95% CI: 0.42, 0.86), the adjusted HRs in the third and fourth quartiles of direct bilirubin were 0.56 (0.39, 0.82) and 0.56 (0.38, 0.81), and for indirect bilirubin, corresponding HR in the highest quartile was 0.56 (0.38, 0.83).

Conclusion: Elevated serum bilirubin was inversely associated with adjusted HRs of CHD in females, especially postmenopausal females. The relationship between elevated direct bilirubin and reduced HRs of CHD may be closer than indirect bilirubin in postmenopausal females.