Xie Sisi, Kutalik Zoltan, Thomas Aurélien, Perrais Maïwenn, Vaucher Julien, Marques-Vidal Pedro
Department of Medicine, Internal Medicine, Lausanne University Hospital (CHUV) and University of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland.
Department of Computational Biology, University of Lausanne, 1015, Lausanne, Switzerland.
Biol Trace Elem Res. 2025 Apr 2. doi: 10.1007/s12011-025-04581-6.
Dyslipidemia is an important public health issue. Copper may influence lipid metabolism, possibly via inflammation, but the mechanisms remain unclear. This study aimed to assess the association between urinary copper concentrations and blood lipids (total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG)), and the possible mediating role of inflammation, assessed via high-sensitivity C-reactive protein (hs-CRP). We conducted a cross-sectional, population-based study using baseline data from Switzerland's CoLaus|PsyCoLaus cohort. Urinary copper was measured from spot urine using inductively coupled plasma mass spectrometry and adjusted for creatinine. Lipid markers and hs-CRP were measured using standardized biochemical assays. Multiple linear regression assessed associations, and mediation effects were evaluated using the SGmediation2 package. A total of 6284 adults (mean age 52.6 years, 53.4% female) were included. Urinary copper was positively associated with TG (beta=0.08, 95%CI 0.04, 0.12) and negatively associated with HDL-C (- 0.04, 95%CI - 0.07, - 0.003). Additionally, urinary copper was positively associated with hs-CRP (0.51, 95%CI 0.42, 0.60), which in turn was positively associated with TG (0.05, 95%CI 0.04, 0.06) and negatively associated with HDL-C (- 0.04, 95%CI - 0.05, - 0.03). Mediation analysis revealed that urinary copper exerts partial indirect effects on TG (mediation effect 31.4%) and HDL-C (56.9%) through hs-CRP. hs-CRP partially mediated the associations between urinary copper and HDL-C and TG, with a robust effect for TG but statistical uncertainty for HDL-C. No mediation was observed for TC or LDL-C. These findings suggest hs-CRP's role in lipid metabolism, especially in TG regulation.
血脂异常是一个重要的公共卫生问题。铜可能通过炎症影响脂质代谢，但其机制尚不清楚。本研究旨在评估尿铜浓度与血脂（总胆固醇（TC）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）和甘油三酯（TG））之间的关联，以及通过高敏C反应蛋白（hs-CRP）评估的炎症可能的中介作用。我们利用瑞士CoLaus|PsyCoLaus队列的基线数据进行了一项基于人群的横断面研究。使用电感耦合等离子体质谱法从随机尿样中测量尿铜，并根据肌酐进行校正。使用标准化生化检测方法测量脂质标志物和hs-CRP。多元线性回归评估关联，并使用SGmediation2软件包评估中介效应。共纳入6284名成年人（平均年龄52.6岁，53.4%为女性）。尿铜与TG呈正相关（β=0.08，95%CI 0.04，0.12），与HDL-C呈负相关（-0.04，95%CI -0.07，-0.003）。此外，尿铜与hs-CRP呈正相关（0.51，95%CI 0.42，0.60），而hs-CRP又与TG呈正相关（0.05，95%CI 0.04，0.06），与HDL-C呈负相关（-0.04，95%CI -0.05，-0.03）。中介分析显示，尿铜通过hs-CRP对TG（中介效应31.4%）和HDL-C（56.9%）产生部分间接影响。hs-CRP部分介导了尿铜与HDL-C和TG之间的关联，对TG的影响较强，但对HDL-C的影响存在统计不确定性。未观察到TC或LDL-C的中介作用。这些发现表明hs-CRP在脂质代谢中发挥作用，尤其是在TG调节方面。
