Department of Public Health and Preventive Medicine, School of Medicine, 47885Jinan University, Guangzhou, China.
Georgia Prevention Institute, Department of Population Health Sciences, Medical College of Georgia, 1421Augusta University, Augusta, GA, USA.
Angiology. 2022 Nov-Dec;73(10):911-919. doi: 10.1177/00033197211059693. Epub 2022 Jan 11.
The association between bilirubin (BIL) and cardiovascular disease (CVD) remains controversial. We performed a meta-analysis of prospective studies to evaluate this association in the general population. We searched PubMed, EMBASE, Web of Science, Cochrane, and Scopus databases through to September 2021. The Newcastle-Ottawa Quality Assessment Scale was used to assess study quality. The pooled effect estimate was calculated by the fixed-effect model or random-effect model. We included 12 prospective studies (368 567 participants). The pooled risk ratio of CVD for the lowest vs highest groups of BIL levels was .75 (95% CI: .58-.97) with high heterogeneity (I = 87.5%, < .001). Similar associations were observed for coronary heart disease and stroke. We further performed a "dose-response" meta-analysis, and a significant U-shaped relationship between circulating (most values were serum bilirubin, but a few were plasma bilirubin) BIL and CVD ( < .01) was observed. The lowest risk of CVD events was observed in participants with a BIL of 17-20 µmol/L in serum and/or plasma. In conclusion, there was a U-shaped dose-response relationship between BIL and CVD, especially for men. Further studies are needed to confirm our findings and identify the mechanisms involved as well as any prognostic or therapeutic potential.
胆红素（BIL）与心血管疾病（CVD）之间的关联仍存在争议。我们进行了一项荟萃分析，以评估一般人群中这种关联。我们通过PubMed、EMBASE、Web of Science、Cochrane 和 Scopus 数据库搜索至 2021 年 9 月。使用纽卡斯尔-渥太华质量评估量表评估研究质量。通过固定效应模型或随机效应模型计算汇总效应估计值。我们纳入了 12 项前瞻性研究（368567 名参与者）。最低组与最高组 BIL 水平的 CVD 风险比为.75（95%CI：.58-.97），异质性较高（I = 87.5%，<.001）。对于冠心病和中风也观察到了类似的关联。我们进一步进行了“剂量-反应”荟萃分析，观察到循环胆红素（大多数值为血清胆红素，但有少数为血浆胆红素）与 CVD 之间存在显著的 U 形关系（<.01）。在血清和/或血浆中胆红素水平为 17-20μmol/L 的参与者中，CVD 事件的风险最低。总之，BIL 与 CVD 之间存在 U 形剂量反应关系，尤其是男性。需要进一步的研究来证实我们的发现，并确定所涉及的机制以及任何预测或治疗潜力。
