Bilirubin concentration, UGT1A1*28 polymorphism, and coronary artery disease.

An inverse association between serum bilirubin and cardiovascular disease has been shown in numerous retrospective and prospective studies (1–8) as well as in a metaanalysis study (9 ). Schwertner et al. (1 ) first reported that fasting serum bilirubin concentrations are inversely related to coronary artery stenosis in men. Low serum bilirubin concentrations were found to be associated with an increased risk of coronary artery disease (CAD), whereas bilirubin concentrations near the upper end of the reference interval were associated with a low risk of CAD. The strength of the association between bilirubin and CAD was similar to that of smoking, systolic blood pressure, and HDL-cholesterol. Hopkins et al. (2 ) confirmed the findings in a retrospective case-controlled study of men and women with early familial CAD. Individuals in the top quintile of serum bilirubin concentrations had an 80% reduction in CAD risk compared with individuals in the lowest quintile. Low bilirubin concentrations also have been found in individuals with peripheral vascular disease (PVD) (3 ) and ischemic heart disease (IHD) (6–8). Several prospective studies have shown that low serum bilirubin predicts future cardiovascular disease. In 1995, Breimer et al. (6 ) performed a prospective study of 7685 middle-aged men enrolled in the British Regional Heart Study (BRHS) and found that both low and high bilirubin concentrations were associated with an increased risk of CAD. In a prospective study of serum bilirubin and myocardial infarction (MI) in the Framingham Offspring Study (7 ), higher total serum bilirubin concentrations were associated with a lower risk of MI, CAD, and any cardiovascular disease event in men; in contrast, there was only suggestive evidence for a lower CAD risk in women.