Higher serum bilirubin is associated with decreased risk for early familial coronary artery disease

Mildly increased serum bilirubin has recently been suggested as a protective factor, possibly reducing the risk of coronary artery disease (CAD) by acting as an antioxidant. We tested this hypothesis by examining serum bilirubin concentrations and other coronary risk factors in 120 men and 41 women with early familial CAD and 155 control subjects. At screening, both cases and control subjects were 38 to 68 years old. Early familial CAD patients had experienced myocardial infarction, coronary artery bypass grafting, or coronary angioplasty by age 55 years for men and 65 for women and had another sibling similarly affected. The average total serum bilirubin concentration was 8.9 +/- 6.1 mu mol/L in cases and 12.4 +/- 8.1 mu mol/L in control subjects (P=.0001 for difference). In univariate analysis stratified by sex, serum bilirubin was strongly and inversely related to CAD risk, with relative odds of 0.4 to 0.1 (relative to the lowest quintile, P=.04 to .00001) in both men and women as bilirubin increased into the upper two quintiles. Multiple logistic regression analysis was performed including age, sex, smoking, body mass index, diabetes, hypertension, plasma measured LDL cholesterol, HDL cholesterol, triglycerides, and serum bilirubin as potential risk factors. Bilirubin entered as an independent protective factor with an odds ratio of 0.25 (P=.0015) for an increase of 17 mu mol/L (1 mg/dL). The standardized logistic regression coefficient for bilirubin was -.33 compared with -.34 for HDL, suggesting that the protective effect of bilirubin on CAD risk in the population is comparable to that of HDL cholesterol. A history of cigarette smoking was associated with significantly lower serum bilirubin concentration and appeared to attenuate the protective effect of bilirubin.