Chen Bohang, Wang Chuqiao, Li Wenjie
The First Clinical Medical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
Department of Cardiovascular Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning, China.
Front Cardiovasc Med. 2024 Apr 9;11:1385223. doi: 10.3389/fcvm.2024.1385223. eCollection 2024.
Although several observational studies have linked serum albumin to cardiovascular disease and considered it as an important biomarker, little is known about whether increasing or maintaining serum albumin levels can effectively improve the prognosis of patients with atrial fibrillation. Therefore, this study aims to further explore the causal relationship between serum albumin and atrial fibrillation and its potential mechanism.
Using data from large-scale genome-wide association studies, we conducted a two-sample Mendelian randomization (MR) analysis and a mediation MR analysis, using serum albumin as the exposure variable and atrial fibrillation as the outcome variable. We included 486 serum metabolites as potential mediating factors. To increase the robustness of the analysis, we applied five statistical methods, including inverse variance weighted, weighted median, MR-Egger, simple mode, and weighted mode. Validate the MR results using Bayesian weighted Mendelian randomization method.
The results of the MR analysis indicate a significant inverse association between genetically predicted serum albumin concentration (g/L) and the risk of atrial fibrillation (Beta = -0.172, OR = 0.842, 95% CI: 0.753-0.941, = 0.002). Further mediation MR analysis revealed that serum albumin may mediate the causal relationship with atrial fibrillation by affecting two serum metabolites, docosatrienoate and oleate/vaccenate, and the mediating effect was significant. In addition, all our instrumental variables showed no heterogeneity and level-multiplicity in the MR analysis. To verify the stability of the results, we also conducted a sensitivity analysis using the leave-one-out method, and the results further confirmed that our findings were robust and reliable. Finally, we conducted a validation using the Bayesian weighted Mendelian randomization method, which demonstrated the reliability of our causal inference results.
This study strongly demonstrates the causal relationship between serum albumin and reduced risk of atrial fibrillation through genetic methods, and reveals the key mediating role of two serum metabolites in this relationship. These findings not only provide a new perspective for our understanding of the role of serum albumin in atrial fibrillation, but also provide new ideas for the prevention and treatment strategies of atrial fibrillation.
尽管多项观察性研究已将血清白蛋白与心血管疾病联系起来，并将其视为一种重要的生物标志物，但对于提高或维持血清白蛋白水平是否能有效改善房颤患者的预后，人们知之甚少。因此，本研究旨在进一步探讨血清白蛋白与房颤之间的因果关系及其潜在机制。
利用大规模全基因组关联研究的数据，我们进行了两样本孟德尔随机化（MR）分析和中介MR分析，以血清白蛋白作为暴露变量，房颤作为结局变量。我们纳入了486种血清代谢物作为潜在的中介因素。为了提高分析的稳健性，我们应用了五种统计方法，包括逆方差加权法、加权中位数法、MR-Egger法、简单模式法和加权模式法。使用贝叶斯加权孟德尔随机化方法验证MR结果。
MR分析结果表明，基因预测的血清白蛋白浓度（g/L）与房颤风险之间存在显著的负相关（β = -0.172，OR = 0.842，95%CI：0.753 - 0.941，P = 0.002）。进一步的中介MR分析显示，血清白蛋白可能通过影响两种血清代谢物二十二碳三烯酸和油酸/反式油酸来介导与房颤的因果关系，且中介效应显著。此外，我们所有的工具变量在MR分析中均未显示出异质性和水平多重性。为了验证结果的稳定性，我们还使用留一法进行了敏感性分析，结果进一步证实我们的发现是稳健可靠的。最后，我们使用贝叶斯加权孟德尔随机化方法进行了验证，这证明了我们因果推断结果的可靠性。
本研究通过基因方法有力地证明了血清白蛋白与降低房颤风险之间的因果关系，并揭示了两种血清代谢物在这种关系中的关键中介作用。这些发现不仅为我们理解血清白蛋白在房颤中的作用提供了新的视角，也为房颤的预防和治疗策略提供了新的思路。
