Serum bilirubin levels are associated with poor functional outcomes in patients with acute ischemic stroke or transient ischemic attack

Quping Ouyang,Xia Meng,Qin Xu,Hao Li,Anxin Wang,Pan Chen,Yingting Zuo,Zhimeng Liu,Yongjun Wang,Xue Tian

doi:10.1186/s12883-021-02398-z

Abstract

BackgroundThe prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. We aimed to investigate the association between serum bilirubin, including total bilirubin (TBIL), direct bilirubin (DBIL) and indirect bilirubin (IBIL) and poor functional outcomes in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA).MethodsAll patients with AIS or TIA were recruited from the Third China National Stroke Registry. The poor functional outcomes included modified Rankin Scale (mRS) score 2–6 and 3–6 at 3 months and 1 year. Multivariable logistic regression was used to investigate the associations of TBIL, DBIL, and IBIL with poor functional outcomes.ResultsAmong 11,121 enrolled patients, the median (interquartile range) of TBIL, DBIL, and IBIL was 13.30 (9.90–17.70), 3.80 (2.70–5.30), and 9.30 (6.70–12.80) µmol/L. After adjustment for conventional confounding factors, patients in the highest TBIL quartile had the highest proportion of mRS score 2–6 at 3 months (odds ratio [OR], 1.37; 95 % confidence interval [CI], 1.19–1.59) and 1 year (OR, 1.31; 95 % CI, 1.13–1.52), and mRS score 3–6 at 3 months (OR, 1.33; 95 % CI, 1.11–1.59) and 1 year (OR, 1.28; 95 % CI, 1.07–1.53), when compared to patients in the lowest TBIL quartile. Similar results were observed for DBIL and IBIL. We also found J-shaped associations between serum bilirubin levels and each outcome.ConclusionsElevated levels of serum bilirubin were significantly associated with poor functional outcomes in patients with AIS or TIA at 3 months and 1 year.

Highlights

The prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties
Some supported a positive association between serum bilirubin and poor functional outcomes, suggesting that serum bilirubin may be a highly toxic substance when high concentrations accumulated within biological tissues [2,3,4,5]
For modified Rankin Scale (mRS) score 2–6 at 3 months as the outcome of interest, the C statistics by the conventional model can significantly improve by addition of total bilirubin (TBIL)

Summary

Introduction

The prognostic value of serum bilirubin in stroke is controversial, since bilirubin has both neuroprotective and neurotoxic properties. While other data supported a negative or a null significant association, suggesting that bilirubin harbors powerful antioxidant properties, higher levels of serum bilirubin might offer a therapeutic advantage in oxidative stress-mediated diseases, such as ischemic stroke [6,7,8,9,10]. This appear paradox between the strong basic evidence and the failure in translation to humans brings great confusion. Possible reasons for the discrepancy may be the small sample size in previous studies and the absence of long-term follow up

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