Analysis of the association between mixed exposure to multiple metals and comorbidity of hypertension and abnormal bone mass: Baseline data from the Chinese multi-ethnic cohort study (CMEC)

Abstract

Comorbidity represents an increasingly significant public health challenge. While numerous studies have confirmed the association between metals and both hypertension and osteopenia, the relationship between the multi-faceted effects of mixed metal exposure and the comorbidity of hypertension with abnormal bone mass, as well as age-specific associations, remains unclear. This study utilized baseline data from the China Multi-Ethnic Cohort Study, investigating 9870 Chinese ethnic minorities (Dong and Miao) aged 30-79 years. We measured 17 urinary metal levels using inductively coupled plasma mass spectrometry. The study employed Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression and Bayesian Kernel Machine Regression (BKMR) models to explore the association between urinary metals and comorbidity of hypertension and abnormal bone mass risk. In single-metal models, urinary nickel and zinc levels showed positive correlations with hypertension-related bone mass reduction risk, with ORs and 95 % CIs of 1.23 (1.01, 1.50) and 1.56 (1.27, 1.90), respectively. LASSO regression identified 11 urinary metals (aluminum, cobalt, chromium, copper, iron, manganese, lithium, lead, strontium, vanadium, and zinc) associated with hypertension and abnormal bone mass comorbidity. These selected metals were incorporated into subsequent analyses. BKMR analysis revealed an overall negative effect of metal mixtures on hypertension and abnormal bone mass comorbidity when all metals were fixed at their 50th percentiles. Vanadium and lithium showed negative correlations with the comorbidity. In subgroup analyses, age-stratified groups demonstrated consistent overall negative effects of metal mixtures on the comorbidity. Notably, in individuals over 60 years old, aluminum additionally exhibited a negative association alongside vanadium. Interactions were observed among metals in mixed exposures. Increasing urinary aluminum concentrations attenuated the negative correlation between manganese and hypertension-bone mass abnormality comorbidity. Similarly, increasing manganese concentrations weakened the positive association between urinary zinc and the comorbidity. In individuals under 60 years old, consistent with the general population, increasing urinary aluminum concentrations at P₅₀ levels of other metals diminished the protective effect of manganese against hypertension-bone mass abnormality comorbidity. Interactions were identified between aluminum and lithium, and between manganese and zinc. This study provides substantial evidence linking mixed urinary metal exposure to hypertension and bone mass comorbidity, exploring the multifaceted effects of mixed metal exposure. These findings contribute to a deeper understanding of the role of metal exposure in chronic disease comorbidity, offering a scientific foundation and new directions for preventing and controlling hypertension and bone mass comorbidity, as well as informing public health policy formulation from an environmental metal perspective.

Keywords: Abnormal bone mass; Comorbidity; Hypertension; Multi-metal mixed exposure；BKMR model.