Abstract
BACKGROUND: Circulating total bilirubin is a biomarker of ischemic stroke and may serve as a potential prognostic factor. It is imperative to systemically evaluate the correlation between circulating total bilirubin and risk for stroke. This systematic review and meta-analysis investigated the relationship between total serum bilirubin and risk for stroke. METHODS: Studies published before 30 June 2017 were searched in four databases (PubMed, EMBASE, Web of Science and Cochrane Central). Additional studies were searched by reviewing references and contacting authors. Cohort, cross-sectional and case-control studies in adults that examined the association between serum total bilirubin and stroke were included irrespective of language and date of publication. The primary outcome of this study was ischemic stroke, and the secondary outcome was stroke. Abstract and full-text were reviewed by two independent reviewers, and disagreement was resolved by consulting a third reviewer. Data were extracted by two independent reviewers using a pre-designed data collection form. RESULTS: Eleven observational studies (5 prospective and 6 cross-sectional studies) involving 131,450 subjects were included for analysis. In four studies with 83,380 subjects, the relationship between circulating total bilirubin and ischemic stroke was investigated, ischemic stroke was found in 2,496 patients, and the total odds ratio (OR) of the highest bilirubin and the lowest bilirubin for the occurrence of ischemic stroke was 0.66 (95% CI: 0.58-0.74). Eleven studies with 131,450 subjects explored the correlation between bilirubin and stroke, stroke was reported in 5,060 patients, and the total OR of the highest bilirubin and the lowest bilirubin for the occurrence of stroke was 0.73 (95% CI: 0.68-0.79). A stratified analysis based on the gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females. CONCLUSIONS: The available studies support an inverse association between circulating total bilirubin and risk for ischemic stroke and stroke in males. Prospective studies with large sample size are needed to establish the role of circulating bilirubin in the prevention of stroke.