Zhao Kun, Wang Rui, Chen Rongrong, Liu Jialei, Ye Qing, Wang Kai, Li Juebao
Department of Rehabilitation Medicine, Center for Rehabilitation Medicine, Rehabilitation & Sports Medicine Research Institute of Zhejiang Province, Zhejiang Provincial People's Hospital, Affiliated People's Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, China.
Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Front Neurosci. 2023 Feb 14;17:1122235. doi: 10.3389/fnins.2023.1122235. eCollection 2023.
Bilirubin has anti-inflammatory, antioxidant, and neuroprotective properties, but the association between bilirubin and stroke remains contentious. A meta-analysis of extensive observational studies on the relationship was conducted.
Studies published before August 2022 were searched in PubMed, EMBASE, and Cochrane Library. Cohort, cross-sectional and case-control studies that examined the association between circulating bilirubin and stroke were included. The primary outcome included the incidence of stroke and bilirubin quantitative expression level between stroke and control, and the secondary outcome was stroke severity. All pooled outcome measures were determined using random-effects models. The meta-analysis, subgroup analysis, and sensitivity analysis were performed using Stata 17.
A total of 17 studies were included. Patients with stroke had a lower total bilirubin level (mean difference = -1.33 μmol/L, 95% CI: -2.12 to -0.53, < 0.001). Compared with the lowest bilirubin level, total odds ratio (OR) of the highest bilirubin for the occurrence of stroke was 0.71 (95% CI: 0.61-0.82) and ischemic stroke was 0.72 (95% CI: 0.57-0.91), especially in cohort studies with accepted heterogeneity ( = 0). Serum total and direct bilirubin levels were significantly and positively associated with stroke severity. A stratified analysis based on gender showed that the total bilirubin level in males correlated with ischemic stroke or stroke, which was not noted in females.
While our findings suggest associations between bilirubin levels and stroke risk, existing evidence is insufficient to establish a definitive association. Better-designed prospective cohort studies should further clarify pertinent questions (PROSPERO registration number: CRD42022374893).
胆红素具有抗炎、抗氧化和神经保护特性，但胆红素与中风之间的关联仍存在争议。对关于该关系的大量观察性研究进行了荟萃分析。
在PubMed、EMBASE和Cochrane图书馆中检索2022年8月之前发表的研究。纳入了检查循环胆红素与中风之间关联的队列研究、横断面研究和病例对照研究。主要结局包括中风的发病率以及中风与对照组之间胆红素的定量表达水平，次要结局是中风严重程度。所有汇总结局指标均使用随机效应模型确定。使用Stata 17进行荟萃分析、亚组分析和敏感性分析。
共纳入17项研究。中风患者的总胆红素水平较低（平均差异=-1.33μmol/L，95%可信区间：-2.12至-0.53，P<0.001）。与最低胆红素水平相比，最高胆红素水平发生中风的总比值比（OR）为0.71（95%可信区间：0.61-0.82），缺血性中风为0.72（95%可信区间：0.57-0.91），尤其是在异质性可接受（I²=0）的队列研究中。血清总胆红素和直接胆红素水平与中风严重程度显著正相关。基于性别的分层分析表明，男性的总胆红素水平与缺血性中风或中风相关，而女性未观察到这种情况。
虽然我们的研究结果表明胆红素水平与中风风险之间存在关联，但现有证据不足以确立明确的关联。设计更好的前瞻性队列研究应进一步阐明相关问题（PROSPERO注册号：CRD42022374893）。
