Abstract
OBJECTIVES: To explore the relationship between total bilirubin (TBil) and stroke risk in older patients with obstructive sleep apnea syndrome (OSAS). METHODS: A total of 1,007 patients with OSAS without stroke history aged ≥ 60 years and with complete serum TBil records were enrolled in this study. The median follow-up was 42 months. Participants were divided into four groups based on the quartile of the baseline serum TBil concentration. Multivariate Cox proportional hazards analysis and restricted cubic spline (RCS) were used to investigate the association of TBil with the incidence of new-onset stroke. RESULTS: The PRIMARY part: the third quantile TBil level group had the lowest prevalence of stroke among the four groups. The RCS functions depicted a J-type curve relationship between TBil (3.3-33.3 µmol/L) and stroke (nonlinear P < 0.05). When the TBil level was in the range of 3.3 to 11.5 µmol/L, the possible protective influence of bilirubin against stroke in patients with OSAS enhanced with an increasing TBil level. However, when the TBil level exceeded 11.5 µmol/L and gradually increased, the effect of TBil on stroke risk became more and more pronounced. The SECONDARY part: for every 1 µmol/L increase in TBil levels in the range of 11.5 to 33.3 µmol/L, the risk of stroke in patients with OSAS increased by 16.2% (P < 0.001). In addition, there was a higher risk in women with OSAS (hazard ratio (HR)=1.292, 95% confidence interval (95%CI): 1.093-1.528; P = 0.003). Moreover, an increased TBil level alone was significantly associated with stroke in subjects aged < 75 years (HR: 1.190, 95%CI: 1.069-1.324), patients with mild-to-moderate OSAS (HR: 1.215, 95%CI: 1.083-1.364), and individuals without atrial fibrillation (AF) (HR: 1.179, 95%CI: 1.083-1.285) within a TBil level in the range of 11.5 to 33.3 µmol/L. CONCLUSIONS: Both lower and higher bilirubin levels may increase the risk of stroke in older persons with OSAS, and there was a J-type dose-response relationship. The risk of stroke was lowest when the TBil level was approximately 11.5 µmol/L.