Serum Copper-to-Zinc Ratio and Oxidative Stress Are Associated with Anemia in Older Adults with Cardiovascular-Kidney-Metabolic Syndrome

作者：Bruschetta G, Gembillo G, Lo Cicero L, D'Ascola A, Bruno F, Corsonello A, Santoro D, Di Rosa M, Soraci L · 发表于：International journal of molecular sciences · 年份：2026 · DOI：10.3390/ijms27135840 · 被引用次数：74 · 研究领域：Oxidative Stress、Copper、Zinc、Anemia、Cardio-Renal Syndrome、Metabolic Syndrome、Humans、Biomarkers、Female、Male、Aged

Chronic oxidative stress is a molecular hallmark of cardiovascular-kidney-metabolic (CKM) syndrome, yet its contribution to CKM-associated anemia beyond erythropoietin deficiency and iron restriction is poorly characterized. The serum copper-to-zinc (Cu/Zn) ratio reflects impaired Cu/Zn-SOD1 antioxidant capacity and inflammatory trace-element imbalance, but its relationships with circulating redox biomarkers and its hematological relevance in CKM syndrome has never been explored in a community-dwelling cohort of older adults. We analyzed 2391 NHANES 2011-2016 participants ≥ 50 years of age with CKM stage I-IV. To explore whether the serum Cu/Zn ratio was associated with oxidative stress and immunomodulatory biomarkers as well as with the odds of anemia, we used survey-weighted Spearman correlations, linear regression (outcome: hemoglobin), and logistic regression (outcome: anemia); multivariate models were adjusted for a panel of antioxidant or immunomodulatory biomarkers (selenium, vitamin D), pro-oxidant biomarkers (lead, cadmium, cotinine, uric acid), red cell distribution width (RDW) as a composite biomarker of erythrocyte stress, neutrophil-to-lymphocyte ratio (NLR), CKM stage, and comorbidities. The molecular targets of the nine biomarkers were mapped onto a protein-protein interaction network using the STRING database v12.0 to contextualize regression findings within a systems biology framework. Anemia was present in 205 participants (8.6%). The Cu/Zn ratio was inverse...