Relation of Conjugated Bilirubin Concentrations to the Presence of Coronary Artery Calcium

Whether conjugated bilirubin concentration, resulting from hepatic UDP-glucuronosyltransferase 1 A1 activity, is associated with cardiovascular disease is unknown. Our aim was to investigate the relation between serum conjugated bilirubin concentrations and coronary artery calcium score (CACS) as a measure of preclinical atherosclerosis. Data were analyzed from an occupational cohort of 14,583 subjects who underwent a cardiac computed tomographic estimation of CACS and measurements of risk factors. Logistic regression was used to describe associations between bilirubin concentrations and CACS. The proportion of subjects with a CACS >0 (total: men = 1,351, women = 111) decreased across increasing conjugated bilirubin quartiles (men p <0.001, women p = 0.005). After adjustment for age, gender, waist, systolic blood pressure, smoking, exercise, alcohol, homeostatic model assessment of insulin resistance, glucose, triglyceride, high- and low-density lipoprotein cholesterols, high-sensitivity C-reactive protein, lipoprotein (a), ferritin, fatty liver, cerebrovascular accident, coronary artery disease, hypertension, and diabetes, there was an inverse independent association between conjugated bilirubin and CACS >0 (odds ratio 0.76, 95% confidence interval 0.64 to 0.92, p = 0.004, for top vs bottom quartile). After further adjustment for estimated glomerular filtration rate, the odds ratio was 0.83 (95% confidence interval 0.69 to 0.99), p = 0.04. Exclusion of subjects with a high bilirubin (total >1.3 mg/dl) did not attenuate the association. In conclusion, there was a strong inverse and independent relation between conjugated bilirubin and CACS. The mechanism behind this association is not clear and may not be causal, but the effects of glucuronidation on cardiovascular disease risk should be tested.