Bilirubin Improves Risk Prediction of Cardiovascular Death

Diabetes is one of the most prevalent disorders worldwide and cardiovascular (CV) disease is the leading cause of mortality and morbidity in diabetic patients. Therefore, improvements in risk prevention and adequate treatment are needed in these high-risk subjects.

Previous studies have shown that elevated serum bilirubin concentrations might protect against atherosclerosis, yet it remains unclear whether higher serum bilirubin concentrations work in favor of the cardiovascular system in patients with type 2 diabetes.


A team of scientists led by those at the National Yang-Ming University (Taipei, Taiwan, ROC) enrolled 2,936 subjects with type 2 diabetes (1,009 males and 1,927 females; mean age of 62.7 ± 11 years). The goal of the study was to investigate the association between serum bilirubin and subsequent development of cardiovascular death among asymptomatic diabetic patients.

Blood samples were obtained from all patients after an overnight fast of more than 12 hours. Total bilirubin was measured using a Hitachi 7600 chemistry analyzer with a vanadate oxidation method. Lipid profiles including triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) cholesterol, serum total bilirubin, albumin, creatinine, aspartate transaminase (AST), alanine transaminase (ALT, and glucose were also measured at the same time.

The team followed the patients for 5.4 ± 3.0 years, and there were 218 deaths including 95 cardiovascular deaths. The occurrence of CV death and all-cause death were negatively correlated with increasing serum bilirubin quintiles and actual bilirubin values. Serum bilirubin was negatively associated with incident cardiovascular death and all-cause death. The addition of bilirubin for cardiovascular death increased the C-statistic from 0.713 to 0.729 and showed an integrated discrimination improvement (IDI) of 0.012 with 8.57% improvement in net reclassification analysis.

The authors concluded that higher serum concentrations of bilirubin are associated with a decreased risk of developing CV and all-cause death in diabetic patients. Bilirubin improved the risk prediction of cardiovascular death but provided only a slightly better prediction of all-cause death than conventional risk factors. The study was published in the January 2019 issue of the journal Clinica Chimica Acta.

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