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REVIEW article

Front. Endocrinol.

Sec. Cardiovascular Endocrinology

Volume 16 - 2025 | doi: 10.3389/fendo.2025.1451465

This article is part of the Research TopicRe-visiting Risk Factors for Cardiometabolic Diseases: Towards a New Epidemiological FrontierView all 34 articles

Association between serum bilirubin levels and carotid atherosclerosis: A systematic review and meta-analysis

Provisionally accepted
Bao-E  YanBao-E Yan1,2Ying  LiYing Li1Min-Jie  ZhuMin-Jie Zhu2Qian-Jun  WangQian-Jun Wang2Jing  XiaoJing Xiao1Yan  ZhangYan Zhang1Chun-Yan  ZhangChun-Yan Zhang1Jing  ZhouJing Zhou2*Tuo  HanTuo Han1*
  • 1Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
  • 2Department of Cardiovascular Medicine, Affiliated Hospital of Yan'an University, Yan'an, China

The final, formatted version of the article will be published soon.

OBJECTIVE: Carotid atherosclerosis (CAS) is a significant factor contributing to cardiovascular events and poses a major public health concern. There are still many controversies about the association between serum bilirubin and CAS. This study aims to provide a systematic review and meta-analysis to examine the association between serum bilirubin levels and carotid atherosclerosis.METHODS: An electronic literature search was performed using PubMed, Web of Science and Embase up to December 2023. Articles were screened based on predefined inclusion criteria and assessed for risk of bias and quality of evidence utilizing the Newcastle-Ottawa Scale and GRADE tool. Pooled mean differences were calculated using a random effects model. Subgroup and metaregression analyses were performed to identify potential sources of heterogeneity.RESULTS: Nine studies involving 7,023 participants were included in this meta-analysis. The results indicated that patients with carotid atherosclerosis exhibited lower levels of total bilirubin compared to those without (SMD -3.42, 95% CI [-5.18, -1.67]), with a statistically significant difference (z=-3.819, P<0.001). Moreover, a significant inverse association was found between total bilirubin levels and the risk of carotid atherosclerosis (OR 0.79, 95% CI [0.71, 0.88], P<0.001, I²=78.2%). However, substantial heterogeneity was observed (I²=98.0%, P<0.001). Subgroup and meta-regression analyses indicated that sample size and the severity of carotid atherosclerotic lesions might contribute to the heterogeneity observed across studies. The GRADE assessment was low.CONCLUSION: Lower serum bilirubin levels are associated with an increased risk of carotid atherosclerosis. This meta-analysis offers new insights into the development of diagnostic biomarkers and therapeutic targets. Further prospective cohort studies are necessary to validate our conclusions.https://www.crd.york.ac.uk/prospero/, identifier CRD42024498887.

Keywords: carotid atherosclerosis, Carotid Intima-Media Thickness, carotid plaque, Bilirubin, Meta-analysis

Received: 19 Jun 2024; Accepted: 02 Jun 2025.

Copyright: © 2025 Yan, Li, Zhu, Wang, Xiao, Zhang, Zhang, Zhou and Han. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Jing Zhou, Department of Cardiovascular Medicine, Affiliated Hospital of Yan'an University, Yan'an, China
Tuo Han, Department of Cardiovascular Medicine, Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi, China

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