Protective and Indicating Effect of Indirect Bilirubin in Intracranial or Extracranial Artery Atherosclerotic Stenosis Progresses

Background: Bilirubin is the metabolic end-product of heme degradation by heme oxy-genase (HO), which has recently been shown to act as an antioxidant which can protect against atherosclerosis. This study explored the relationship between serum bilirubin levels and different degrees of atherosclerotic stenosis in intracranial or extracranial arteries. Methods: The study included 189 patients undergoing digital subtraction angiography (DSA) diagnosed as being normal or having been confirmed as atherosc lerotic stenosis in the intracranial or extracranial arteries. The patients were allocated to normal, mild (<50% diameter stenosis), moderate (50% - 69% stenosis), severe (70% - 99% stenosis) and occlusion groups according to the severity of stenosis proved by DSA. Blood samples were collected to determine bilirubin concentrations and other biochemical indicators of atherosclerosis. Univariate and multivariate analyses were performed to evaluate the associations between disease severity and biomarkers. Results: Indirect bilirubin (Ibil) concentrations increased in parallel with the increasing severity of atherosclerotic stenosis in the intracranial or extracranial arteries, but decreased in patients with occluded cranial vessels. Multivariate analysis showed that Ibil levels were significantly higher in patients with severe stenosis group than in those with mild stenosis (OR, 1.464; 95% CI, 1.050 - 2.042; P = 0.024). However, Ibil levels were significantly lower in patients with occlusion than in those with severe stenosis (OR, 0.790; 95% CI, 0.684 - 0.913; P = 0.001). Conclusions: Ibil appears to have a protective effect against the development of atherosclerotic stenosis in intracranial or extracranial arteries. The biosynthesis of Ibil increases with stenosis progresses but decreases once occlusion occurs.