EXPOSURE TO METAL MIXTURES AND MONOCYTE TO HIGH-DENSITY LIPOPROTEIN CHOLESTEROL RATIO IN OCCUPATIONAL WORKERS: A CROSS-SECTIONAL STUDY IDENTIFYING KEY METALS AND NONLINEAR DOSE-RESPONSE RELATIONSHIPS

Abstract

Metal exposure has been implicated in the dysregulation of inflammation and lipid metabolism, with the monocyte to high-density lipoprotein cholesterol ratio (MHR) serving as a composite biomarker integrating these two pathways. However, the association between metal mixture exposure and MHR in occupational populations remains poorly understood. In this cross-sectional study of 700 workers from the Manganese Exposed Workers Healthy Cohort, we investigated relationships between 20 blood cell metals and MHR. LASSO regression identified 13 metals associated with MHR. In multi-metal generalized linear models, magnesium (β=0.402, 95% CI: 0.119–0.685), titanium (β=0.068, 95% CI: 0.000–0.136), copper (β=0.331, 95% CI: 0.082–0.580), rubidium (β=0.261, 95% CI: 0.053–0.468), and cadmium (β=0.056, 95% CI: 0.010–0.103) were significantly positively associated with MHR, while iron showed a significant negative association (β=-0.659, 95% CI: -0.976– -0.342). Significant dose-response relationships were observed for magnesium, iron, rubidium, and cadmium (all P_trend<0.05). Restricted cubic spline analysis revealed a U-shaped curve for cadmium (P_non-linear=0.023) and an inverted U-shaped curve for rubidium (P_non-linear=0.007). Weighted quantile sum regression showed a marginally significant positive association between metal mixture exposure and MHR (β=0.014, P=0.086), with rubidium (weight 0.247), cadmium (0.209), and titanium (0.144) as core contributing metals. Our findings suggest that exposure to multiple metals, particularly rubidium, cadmium, and titanium, may be associated with elevated MHR in occupational populations, with nonlinear dose-response relationships. However, the mixture association was marginally significant (P=0.086) and needs confirmation.