Low Serum Bilirubin Level as an Independent Predictor of Stroke Incidence

Abstract

Bilirubin is not only a waste end-product but also an antioxidant. Bilirubin is known to be associated with decrease in cardiovascular risk in men, but its relationship to stroke was not clearly understood. Serum bilirubin concentrations were measured in 78 724 health examinees (41 054 men, aged 30-89 years) from 1994 to 2001. The subjects with potential hepatobiliary diseases or Gilbert syndrome were excluded from analysis. Stroke incidence outcome was collected from hospital records of admission attributable to stroke from 1994 to 2007. Serum bilirubin measurements were divided into 4 levels: 0 to 10.2, 10.3 to 15.3, 15.4 to 22.1, and 22.2 to 34.2 micromol/L. The number of stroke cases was 1137 in men and 827 in women. In Cox proportional hazard models, participants with a higher level of bilirubin showed lower hazard ratios in men with ischemic stroke after adjustment for multiple confounding factors compared to the lowest level of bilirubin (hazard ratio [HR], 0.72; 95% CI, 0.58-0.90 in level 3; HR, 0.66; 95% CI, 0.49-0.89 in level 4; P for trend=0.016). The risk of all stroke types also decreased as bilirubin levels increased (HR, 0.81; 95% CI, 0.68-0.97 in level 3; HR, 0.74; 95% CI, 0.58-0.94 in level 4; P for trend=0.0071). However, these associations were not seen in hemorrhagic stroke or in women. These findings suggest that serum bilirubin might have some protective function against stroke risk in men.