The Association Between Serum Bilirubin And Intracranial Atherosclerotic Stenosis

Objective: In recent years,the incidence of cerebrovascular events has gradually increased,and ischemic stroke accounts for a large proportion.As intracranial atherosclerotic stenosis(ICAS)is one of the most common causes of stroke,exploring the factors related to ICAS has become a top priority.It is well known that advanced age,diabetes,hypertension and dyslipidemia are important causes of ICAS.Bilirubin has long been considered as a potential toxicant with high concentrations in the human body,but there is strong research data indicating that bilirubin has antioxidant,anti-inflammatory and cell protection functions.The current research results mostly point out that improving serum bilirubin level may utilize its anti-oxidation and anti-inflammation functions to delay the progression of atherosclerosis,thus playing a role in reducing the risk of ischemic events.However,most of these studies are about the relationship between bilirubin and coronary artery,while there are relatively few studies on serum bilirubin level and ICAS,so the relationship between ICAS and serum bilirubin level is not clear.The purpose of this study was to investigate the effect of bilirubin levels on ICAS in a non-stroke population.Methods: This study enrolled 753 patients over 40 years old who underwent magnetic resonance angiography(MRA)(non-stroke patients who visited the Department of Neurology at Qingdao Municipal Hospital from January 2014 to June 2018 and healthy subjects who visited the health examination center),including 601 patients without intracranial atherosclerotic stenosis as control group and 152 patients with intracranial atherosclerotic stenosis as case group.Among the 753 participants,they were divided into two subgroups according to age.We defined older than 65 years old as the aged group,with 422 cases,and 65 years old and under as the middle-aged group,with 331 cases.In this study,ICAS is defined as the presence of one or more atherosclerotic stenosis greater than 50% in the following important intracranial vascular segments,including the intracranial segments of the internal carotid and vertebral arteries,the basilar artery,the middle cerebral artery(M1,M2),the anterior cerebral artery(A1,A2)and the posterior cerebral artery(P1,P2).Multiple regression model was used to analyze the relationship between bilirubin and ICAS in the total population and in different age subgroups.In the multivariate Logistic regression analysis,age,gender,systolic blood pressure,hypertension,diabetes,coronary atherosclerotic heart disease,smoking,alcohol consumption,triglyceride and total cholesterol were included in the regression model as covariables.Results: Total bilirubin(TBIL),direct bilirubin(DBIL)and indirect bilirubin(IBIL)in Non-ICAS patients were significantly higher than those in ICAS patients.Multivariate regression analysis showed that,TBIL(OR = 0.93,95%CI = 0.87-0.99,p = 0.018),DBIL(OR = 0.66,95%CI = 0.48-0.89,p = 0.007)and IBIL(OR = 0.92,95%CI = 0.86-0.99,p = 0.030)were proved to be the independent protective factors for intracranial atherosclerotic stenosis in a non-stroke setting.In the total population,the fourth quartile of TBIL(OR = 0.40,95%CI = 0.23-0.79,p = 0.001),DBIL(OR = 0.54,95%CI = 0.30-0.96,p = 0.037)and IBIL(OR = 0.50,95%CI = 0.28-0.86,p = 0.013)are at low risk of Intracranial atherosclerotic stenosis.In the age subgroup,there was no significant correlation between TBIL,DBIL and IBIL and ICAS in subjects ≤ 65 years old.In the subjects over 65 years old,TBIL TBIL(OR = 0.92,95%CI = 0.86-1.00,p = 0.044),DBIL(OR = 0.65,95%CI = 0.44-0.96,p = 0.031)and IBIL(OR = 0.92,95%CI = 0.83-1.00,p =0.058)were significantly correlated with ICAS.Conclusion: The results suggest that the increase of serum TBIL,DBIL and IBIL levels is related to the reduction of ICAS risk.And the protective effect is more significant in the elderly people over 65 years old.