Gao Y, Zhao L B, Li K, Su X, Li X, Li J, Zhao Z, Wang H, He Z, Fang F, Xu W, Qian X, Fan L, Liu L
Lin Liu, MD, Department of Pulmonary and Critical Care Medicine of the Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital, Beijing 100853, China. Email:
J Nutr Health Aging. 2023;27(9):692-700. doi: 10.1007/s12603-023-1965-2.
To explore the relationship between total bilirubin (TBil) and stroke risk in older patients with obstructive sleep apnea syndrome (OSAS).
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.
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.
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.
探讨老年阻塞性睡眠呼吸暂停综合征（OSAS）患者总胆红素（TBil）与中风风险之间的关系。
本研究共纳入1007例年龄≥60岁、无中风病史且有完整血清TBil记录的OSAS患者。中位随访时间为42个月。根据基线血清TBil浓度的四分位数将参与者分为四组。采用多变量Cox比例风险分析和受限立方样条（RCS）分析来研究TBil与新发中风发生率之间的关联。
主要部分：四分位数TBil水平分组中，第三四分位数TBil水平组的中风患病率在四组中最低。RCS函数描绘了TBil（3.3 - 33.3 μmol/L）与中风之间的J型曲线关系（非线性P < 0.05）。当TBil水平在3.3至11.5 μmol/L范围内时，胆红素对OSAS患者中风的潜在保护作用随TBil水平升高而增强。然而，当TBil水平超过11.5 μmol/L并逐渐升高时，TBil对中风风险的影响越来越明显。次要部分：在11.5至33.3 μmol/L范围内，TBil水平每升高1 μmol/L，OSAS患者中风风险增加16.2%（P < 0.001）。此外，OSAS女性患者中风风险更高（风险比（HR）=1.292，95%置信区间（95%CI）：1.093 - 1.528；P = 0.003）。而且，在TBil水平为11.5至33.3 μmol/L范围内，仅TBil水平升高就与年龄<75岁的受试者中风显著相关（HR：1.190，95%CI：1.069 - 1.324）、轻度至中度OSAS患者中风显著相关（HR：1.215，95%CI：1.083 - 1.364）以及无房颤（AF）个体中风显著相关（HR：1.179，95%CI：1.083 - 1.285）。
较低和较高的胆红素水平都可能增加老年OSAS患者的中风风险，且存在J型剂量反应关系。当TBil水平约为11.5 μmol/L时，中风风险最低。
