Bilirubin is negatively associated with hemoglobin a(1c) independently of other cardiovascular risk factors in apparently healthy Japanese men and women.

BACKGROUND Serum total bilirubin (TB) is a potent antioxidant and may be a negative risk factor of cardiovascular disease. In non-diabetic adults, hemoglobin A(1c) (HbA(1c)), but not fasting plasma glucose, is an independent risk factor of cardiovascular disease. METHODS AND RESULTS Linear regression using TB as a dependent variable and cardiovascular risk factors, including HbA(1c), as independent variables, linear regression using HbA(1c) as a dependent variable and other cardiovascular risk factors, including TB, as independent variables, and logistic regression using the highest decile (≥ 5.4%) of HbA(1c) as a dependent variable and TB and other cardiovascular risk factors as independent variables were performed for 893 apparently healthy male smokers, 1,607 male nonsmokers, and 1,680 women. The standardized regression coefficient of HbA(1c) for TB and that of TB for HbA(1c) was -0.12 (P = 0.007) and -0.06 (P = 0.02), respectively, in the smokers, -0.20 (P < 0.0001) and -0.07 (P < 0.0001), respectively, in the nonsmokers, and -0.21 (P < 0.0001) and -0.14 (P < 0.0001), respectively, in the women. The odds ratio of 1 SD increment in TB for HbA(1c) ≥ 5.4% was not significant in the smokers, 0.67 (P = 0.002) in the nonsmokers, and 0.55 (P<0.0001) in the women. CONCLUSIONS Bilirubin was negatively associated with HbA(1c) independently of other cardiovascular risk factors in apparently healthy Japanese men and women. The association was weak in male smokers.