Serum bilirubin improves the risk predictions of cardiovascular and total death in diabetic patients

Su Chan Chen, Chih Pei Lin, Hsiu Chuan Hsu, Jiah Hwang Shu, Ying Liang, Pai Feng Hsu, Yuan Jen Wang, Yaw Zon Ding, Teh Ling Liou, Ying Wen Wang, Yung Chang Chang, Wan Leong Chan, Jaw Wen Chen, Shing Jong Lin, Hsin Bang Leu

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


Background: Bilirubin is a potential endogenous inhibitor of atherosclerosis. We investigated the association of bilirubin and cardiovascular (CV) and all-cause mortality including potential improvements in bilirubin risk reclassification in asymptomatic diabetic patients. Methods: We enrolled 2936 asymptomatic diabetic subjects. The serum bilirubin was measured, and future CV and all-cause death were the primary endpoints. Results: The follow-up period was 5.4 ± 3.0 y. 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 (hazard ratio: 0.26, 95% CI, 0.11–0.61, p =.01) and all-cause death (hazard ratio: 0.30, 95% CI, 0.17–0.51, p ≤.001). The addition of bilirubin for cardiovascular death increased the C-statistic from 0.713 (95% CI, 0.664–0.762) to 0.729 (95% CI, 0.681–0.776) (P =.008) and showed an integrated discrimination improvement (IDI) of 0.012 (P <.0171) with 8.57% improvement in net reclassification analysis (P =.0224). These results suggest additional predictive value is possible via total bilirubin levels for future CV deaths in diabetic patients. In terms of all-death, the addition of bilirubin significantly increased the C-statistic (from 0.769 to 0.78, P =.0064)—a 3.52% net reclassification improvement (P =.0307). It did not improve the IDI (p =.1505). Conclusions: 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.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalClinica Chimica Acta
Publication statusPublished - Jan 2019
Externally publishedYes


  • Atherosclerosis
  • Cardiovascular death
  • Cardiovascular disease
  • Diabetes mellitus
  • Net reclassification-improvement
  • Total bilirubin

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Biochemistry, medical


Dive into the research topics of 'Serum bilirubin improves the risk predictions of cardiovascular and total death in diabetic patients'. Together they form a unique fingerprint.

Cite this