ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardiovascular Epidemiology and Prevention
This article is part of the Research TopicThe Role of Environmental and Metabolic Factors in Global Cardiovascular HealthView all 12 articles
Temporal relationship between inflammation and metabolic disorders and its influence on atherosclerotic cardiovascular disease
Provisionally accepted
Zhihui LIU1Huayu Sun1Hongmin Liu1Jintao Tao1Yutong Wu2Yixiu Chen1Yicheng Liao1Mo Zhang1Yufeng Bian1Renjie Fu1Yajing Liang1Wenchao Yao3
Shouling Wu1*
Yuntao Wu1*- 1Kailuan General Hospital, Tangshan, China
- 2University of Toronto, Toronto, Canada
- 3North China University of Science and Technology, Tangshan, China
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Background: The temporal sequence between inflammation and metabolic disorders in the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) remains unclear. This study investigated the directional relationship between high-sensitivity C-reactive protein (hsCRP) and continuous metabolic syndrome score (cMetS) and their joint effect on ASCVD. Methods: A prospective cohort study was conducted in two phases: 1) A cross-lagged panel model analyzed the bidirectional relationship between hsCRP and cMetS in 62,296 participants. 2) After excluding participants with pre-existing ASCVD, the cohort was categorized into four groups based on cumulative exposure to hsCRP and cMetS to assess the risk of ASCVD and its subtypes using Cox proportional hazards models. Results: A bidirectional relationship was found between hsCRP and cMetS. However, the path from baseline hsCRP to follow-up cMetS (β2=0.05661) was significantly stronger than the reverse path (β1=0.05361). In the joint exposure analysis, compared to the lowest exposure group (G1), groups G2, G3, and G4 showed progressively higher risks of ASCVD with adjusted hazard ratios of 1.45, 1.80, and 2.17, respectively. Significant interactions were observed with age and 10-year ASCVD risk (P for interaction <0.01). The relative risk increase was more pronounced in participants aged <60 years and those classified as low-risk. Conclusion: Inflammation and metabolic disorders have a bidirectional relationship, with a stronger temporal pathway suggesting inflammation precedes metabolic dysfunction. Concurrent exposure to both significantly elevates ASCVD risk, particularly in individuals under 60 and those traditionally considered at low risk.
Keywords: Inflammation, C-Reactive Protein, metabolic disorders, Temporal relationship, longitudinal study
Received: 13 Jul 2025; Accepted: 28 Nov 2025.
Copyright: © 2025 LIU, Sun, Liu, Tao, Wu, Chen, Liao, Zhang, Bian, Fu, Liang, Yao, Wu and Wu. 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:
Shouling Wu
Yuntao Wu
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