Bilirubin is one of the natural anti-oxidants. But reports on human anti-atherosclerotic effect of mild serum bilirubin elevation are controversial according to age, gender of subjects or adopted markers of atherosclerosis, and many of these reports are cross-sectional studies. We studied the effect of mild serum bilirubin elevation on intima-media thickness (IMT) longitudinally, and cross-sectionally compared the association by age or gender.Design and Method:
We followed 743 subjects longitudinally (571 subjects with equal or less than 1.0 mg/dl of serum bilirubin, 172 subjects with more than 1.0 mg/dl) up to 5 years with carotid max IMT as a marker of atherosclerosis and increase of max IMT more than 1.1 mm as endpoint. Event-free ratio was compared between groups by Kaplan-Meier method. In the cross-sectional study, Pearson's correlation coefficient between serum bilirubin and max IMT was compared in total subjects (4633 people who had medical check-up), male group (1713 subjects), female group (1615 subjects), very elderly group (older than 80 years), elderly group (65–79 years), middle-aged group (40–64 years), and younger group (younger than 39 years). Serum AST was also compared with serum bilirubin or abdominal circumference in these groups.Results:
In the longitudinal study, max IMT increase was significantly delayed in the elevated bilirubin group (P < 0.001). In the cross-sectional study, No association between max IMT and serum bilirubin was found in the total subject. Significant positive correlations between max IMT and serum bilirubin level was found in the male and middle-aged groups (P < 0.05 for both). Significant negative correlation was found only in very elderly group (P < 0.05). In the middle-aged group, serum AST level positively correlated with serum bilirubin level (P < 0.05) and abdominal circumference (P < 0.001).Conclusions:
Metabolic syndrome can mask anti-atherosclerotic effect of bilirubin as a confounding factor by elevating serum bilirubin due to fatty liver and by aggravating atherosclerosis due to increased abdominal fat.