Data_Sheet_1_The Nonlinear Relationship Between Total Bilirubin and Coronary Heart Disease: A Dose-Response Meta-Analysis.PDF

Background: Evidence suggests that the total bilirubin has a protective effect on coronary heart disease (CHD), but the dose-response relationship remains controversial, and there is no meta-analysis to assess the relationship.
Methods: As of October 1, 2021, relevant literature was selected from four databases (PubMed, Web of Science, Cochrane Library, and Embase) by using a retrieval strategy. The dose-response curve between the total bilirubin and CHD was fitted by a restricted cubic spline. Stata 12.0 was used for statistical analysis.
Results: A total of 170,209 (6,342 cases) participants from 7 prospective studies were analyzed in our meta-analysis. We calculated the pooled relative risks (RRs) and 95% CIs for the association between serum bilirubin level and risk of CHD using random-effects models. Compared with the first quantile, the bilirubin level in the third quantile had a protective effect on the risk of CHD (RR, 0.90; 95% CI, 0.82–0.99). The restricted cubic spline functions depicted a U-type curve relationship between bilirubin (3.42–49 μmol/L) and CHD (Plinear < 0.001). When the bilirubin level was in the range of 3.42–13μmol/L, the protective effect of bilirubin on CHD was enhanced with increasing bilirubin levels. When the bilirubin level exceeded 13μmol/L, the protective effect of bilirubin weakened, and a dangerous effect gradually appeared with further increases in bilirubin levels.
Conclusions: Compared with a low bilirubin level, a high bilirubin level has a protective effect on the risk of CHD, and there was a U-shaped dose-response relationship between them.

背景：现有研究证据表明，总胆红素（total bilirubin）对冠状动脉心脏病（coronary heart disease, CHD）具有保护作用，但二者的剂量-反应关系仍存在争议，目前尚无荟萃分析对该关联进行评估。
方法：截至2021年10月1日，本研究通过制定检索策略，从PubMed、Web of Science、Cochrane图书馆及Embase四大数据库中筛选相关文献。采用限制性立方样条（restricted cubic spline）拟合总胆红素与CHD之间的剂量-反应曲线，并使用Stata 12.0软件完成统计学分析。
结果：本项荟萃分析共纳入7项前瞻性研究，涉及170209名参与者（其中6342例CHD病例）。本研究采用随机效应模型，计算了血清胆红素水平与CHD发病风险关联的合并相对风险（relative risks, RRs）及95%置信区间（95% CIs）。与第一分位组相比，第三分位组的胆红素水平对CHD发病风险具有保护作用（RR=0.90；95%CI：0.82~0.99）。限制性立方样条分析显示，胆红素水平（3.42~49 μmol/L）与CHD发病风险呈U型曲线关联（线性检验P<0.001）。当胆红素水平处于3.42~13μmol/L区间时，其对CHD的保护作用随胆红素水平升高而增强；当胆红素水平超过13μmol/L时，其保护作用逐渐减弱，且随胆红素水平进一步升高，逐渐显现出有害效应。
结论：与低水平胆红素相比，高水平胆红素对CHD发病风险具有保护作用，二者之间存在U型剂量-反应关联。