Urinary Copper Is Associated with Dyslipidemia, and This Association Is Mediated by Inflammation

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.