Association between Total Cholesterol and the Direct to Total Bilirubin Ratio in Serum

Abstract

Background: Bilirubin and cholesterol are associated with cardiovascular disease, though the relationship between these metabolites has not been fully investigated. Methods: Healthy subjects were enrolled. Annual cross-sectional assessment (year; 2012, 2016) and retrospective longitudinal assessment (year; 2012 to 2016) were performed. The subjects with receiving statin treatment were analyzed separately. Bilirubin ratio was defined as direct (or conjugated) bilirubin divided by the total bilirubin level in serum. Then, differences among the measurement principles were examined (year; 2017). Results: Bilirubin ratio measured by the vanadate oxidation method (VA) was strongly correlated with the total cholesterol level in both the non-statin group (2012: r = −0.753, n = 740; 2016: r = −0.763, n = 792; all p < 0.001) and the statin group (2012: r = −0.825, n = 39; 2016: r = −0.855, n = 43; all p < 0.001). The percent change of the bilirubin ratio from 2012 to 2016 was negatively proportional to that of total cholesterol (r = −0.634, n = 538; p < 0.001). A comparison of the two different methods in 305 participants in 2017 showed that the correlation was stronger with the VA than with the bilirubin oxidase method (BOD), (VA: r = −0.759, p < 0.001; BOD: r = −0.160, p = 0.005). In a laboratory experiment, the addition of cholesterol to human serum reduced the bilirubin ratio in both methods. Conclusion: A strong association between cholesterol and the ratio of direct to total bilirubin was revealed.