Integrated Environmental Cadmium Exposure, Plaque Calcium Content, and Lifestyle Factors Improve Prediction of Carotid Plaque Echogenicity: An Exposome-Oriented Approach

Cadmium exposure has been implicated in the development of atherosclerosis, yet its relationship with carotid plaque composition and echogenicity remains poorly understood. A better understanding of the environmental and biological factors influencing plaque characteristics may facilitate more accurate stratification of patients at high risk of ischemic stroke. The aim of this study was to evaluate the relationships between environmental cadmium exposure, plaque calcium content, lifestyle-related factors, and carotid plaque echogenicity, and to assess their combined value for predicting a highly echogenic carotid plaque phenotype. This cross-sectional study included 80 patients with advanced carotid atherosclerosis undergoing carotid endarterectomy. Cadmium concentrations were simultaneously determined in blood, urine, and surgically excised carotid plaques, whereas calcium concentrations were measured in plaque tissue, serum, and urine using atomic absorption spectrometry. Carotid plaque echogenicity was assessed preoperatively using ultrasound-derived Gray-Scale Median (GSM), and multivariable logistic regression models were developed to predict a highly echogenic, stable plaque phenotype. Current smokers exhibited significantly higher blood and urinary cadmium concentrations than never smokers, while urinary cadmium remained elevated after smoking cessation, reflecting cumulative exposure. Plaque calcium content showed the strongest positive association with GSM, whereas cadmium concentrations in blood, urine, and plaque tissue were not independently associated with continuous GSM. Higher fruit and vegetable intake was also positively associated with plaque echogenicity. Integrating cadmium biomarkers, plaque calcium content, smoking-related variables, and dietary factors substantially improved prediction of GSM ≥ 75, achieving excellent discrimination (AUC = 0.870) with 85.0% classification accuracy. These findings suggest that carotid plaque echogenicity reflects the combined influence of local tissue mineralization, environmental exposures, and lifestyle-related factors. This integrative approach may improve our understanding of carotid plaque biology and support future strategies for risk assessment and clinical stratification of patients with carotid atherosclerosis.