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- 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
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.