Associations of Serum Trace-Element Concentrations with Selected Blood Biomarkers: A Secondary Cross-Sectional Analysis of the SPES Cohort

Trace elements have nutritional and toxicological roles relevant to lipid metabolism and inflammation. In a secondary cross-sectional study, we examined 19 serum elements and blood biomarkers in 4026 adults from the SPES community biomonitoring programme in Campania, Italy. Low-density lipoprotein cholesterol (LDL-C) and neutrophil-to-lymphocyte ratio (NLR) were co-primary outcomes; systemic immune–inflammation index (SII) was secondary. Adjusted models used multiple imputation and false-discovery-rate (FDR) correction. Selenium, copper and zinc showed positive LDL-C associations among directly quantified concentrations, whereas the mercury association depended on assay availability and quantification. Models with untransformed LDL-C estimated differences of approximately 1–4 mg/dL per element-specific interquartile increase in log concentration. Copper and zinc estimates were smaller in an exploratory joint model. For mercury, LDL-C was higher with quantifiable rather than below-quantification concentrations, but the gradient within the quantified range was uncertain. All four primary-model LDL-C associations met both outcome-specific and combined co-primary FDR thresholds; no primary linear NLR association did. Copper, cobalt, molybdenum and antimony were associated with higher SII after outcome-specific FDR correction, with less consistent results across sensitivity analyses. These modest LDL-C differences warrant prospective investigation; the cross-sectional associations do not establish causal or individual clinical effects.