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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Cardiac Rhythmology
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1446610
This article is part of the Research Topic New Challenges in Arrhythmology View all 4 articles

Lipid-lowering drugs, circulating inflammatory factors, and atrial fibrillation: a mediation Mendelian randomization study

Provisionally accepted
Guangyang Ou Guangyang Ou 1Yi Zhang Yi Zhang 2Huzhi Cai Huzhi Cai 3*Kunpeng Yao Kunpeng Yao 1*Zerui Qiu Zerui Qiu 1*Yaowu Chen Yaowu Chen 1*Yang Yang Yang Yang 1*Xinyu Chen Xinyu Chen 1,3*
  • 1 Hunan University of Chinese Medicine, Changsha, China
  • 2 Department of Urology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • 3 The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China

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

    Background: Previous studies have shown an association between lipid-lowering drugs, circulating inflammatory factors, and atrial fibrillation (AF), but the specific effects of lipid-lowering drugs on AF and whether they can be mediated by circulating inflammatory factors remain unclear.We collected 10 genetic variants encoding lipid-lowering drug targets and AF (LDLR, HMGCR, PCSK9, NPC1L1, APOB, APOB, ABCG5, ABCG8, LPL, APOC3, and PPARA) based on genome-wide association study (GWAS) summary statistics. Drug target Mendelian randomization (MR) was used to explore the causal relationship between lipid-lowering drugs and AF. In addition, we performed a mediation analysis of 91 circulating inflammatory factors to explore potential mediators. Sensitivity analyses were performed to verify the reliability of the MR Results by MR-Egger intercept test, Cochran Q test and leave-one-out test.The results of IVW method showed that LPL agonist had a protective effect on AF(OR = 0. 854, 95%CI: 0.816-0.894, P = 1.844E-11). However, the other nine lipid-lowering drug targets had no significant effect on AF. Notably, we found a mediator role of Fibroblast Growth Factor 5 (FGF5) in the protective effect of LPL agonist on AF with a mediator ratio of 9.22%. Sensitivity analyses supported the robustness of our findings, indicating a possible mediating pathway by which LPL agonists affect the risk of AF. Our study provides new insights into the complex interactions among lipid-lowering agents, circulating inflammatory factors and AF, and also identified a potential mediating role of FGF5 in the pathogenesis of AF. Our findings highlight the potential of LPL agonists and targeting specific inflammatory factors for therapeutic intervention in AF, providing promising avenues for future research and clinical strategies for the management and prevention of AF.

    Keywords: Lipid-lowering drugs, LPL agonist, Atrial Fibrillation, circulating inflammatory factors, Fibroblast Growth Factor 5, drug treatment, Mendelian randomization study

    Received: 10 Jun 2024; Accepted: 14 Oct 2024.

    Copyright: © 2024 Ou, Zhang, Cai, Yao, Qiu, Chen, Yang and Chen. 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:
    Huzhi Cai, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, China
    Kunpeng Yao, Hunan University of Chinese Medicine, Changsha, China
    Zerui Qiu, Hunan University of Chinese Medicine, Changsha, China
    Yaowu Chen, Hunan University of Chinese Medicine, Changsha, China
    Yang Yang, Hunan University of Chinese Medicine, Changsha, China
    Xinyu Chen, Hunan University of Chinese Medicine, Changsha, 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.