Baseline Serum Bilirubin and Risk of First Stroke in Hypertensive Patients

Abstract

Background Data on the association between serum bilirubin and the risk of stroke are limited and inconclusive. We aimed to evaluate the association between serum bilirubin and the risk of first stroke and to examine any possible effect modifiers in hypertensive patients. Methods and Results Our study was a post hoc analysis of the CSPPT (China Stroke Primary Prevention Trial). A total of 19 906 hypertensive patients were included in the final analysis. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% CIs for the risk of first stroke associated with serum bilirubin levels. The median follow‐up period was 4.5 years. When serum total bilirubin was assessed as tertiles, the adjusted HR of first ischemic stroke for participants in tertile 3 (12.9–34.1 μmol/L) was 0.75 (95% CI, 0.59–0.96), compared with participants in tertile 1 (<9.3 μmol/L). When direct bilirubin was assessed as tertiles, a significantly lower risk of first ischemic stroke was also found in participants in tertile 3 (2.5–24.8 μmol/L) (adjusted HR, 0.77; 95% CI, 0.60–0.98), compared with those in tertile 1 (<1.6 μmol/L). However, there was no significant association between serum total bilirubin (tertile 3 versus 1: adjusted HR, 1.45; 95% CI, 0.89–2.35) or direct bilirubin (tertile 3 versus 1: adjusted HR, 1.27; 95% CI, 0.76–2.11) and first hemorrhagic stroke. Conclusions In this sample of Chinese hypertensive patients, there was a significant inverse association between serum total bilirubin or direct bilirubin and the risk of first ischemic stroke.

Association between bilirubin levels and risk of stroke: a systematic review and meta-analysis

“…Finally, a total of 11 independent cohort studies (published in nine articles) were included in the meta-analysis (figure 1). 10–12 14 18–20 34 35…”

“…Eleven independent cohort studies examining the relationship between bilirubin levels and stroke risk (7835 cases among 263 596 individuals) were published between 2009 and 2020 (online supplemental table 2). Among these, two studies were primarily conducted in the USA,11 14 four in Asian countries (China and Korea) 10 18–20 and three in European countries 12 34 35. The size of individuals ranged from 316 (in the study conducted by Liu et al 19) to 96 381 (in the study conducted by Marconi et al 14).…”

“…The median follow-up time varied from 1.89 to 14 years. Of the 11 cohort studies, 8 reported outcomes for ischaemic stroke,10 14 18–20 34 7 reported outcomes for total stroke10–12 18 20 35 and 2 provided data for both stroke subtypes 10 18. Regarding the assessment of study quality, all articles were considered of high quality according to the NOS (online supplemental table 3).…”

“…However, the number of studies in previous meta-analyses was limited. Since 2015, five new studies examining the relationship between bilirubin levels and stroke have been reported 13 14 18–20. We therefore aimed to conduct an up-to-date meta-analysis assessing the consistency and strength of this association in cohort studies.…”

Longitudinal Associations Between Serum Bilirubin Level and Carotid Atherosclerosis Plaque in a Health Screening Population

“…Studies have reported that decreased bilirubin levels are associated with asymptomatic intracranial atherosclerosis 32 and cerebral infarction. 58 Exploring the relationship between bilirubin and CAS can inspire clinicians on cerebral infarction prevention and treatment. The levels of TBIL and UCB were negatively correlated with the CAS process, and the association of UCB was stronger, whereas the level of CB was positively correlated with CAS.…”