Abstract Body (Do not enter title and authors here): Background: Cardiovascular disease (CVD) is a leading cause of morbidity and mortality globally. Toxic metals are widespread environmental contaminants and may play a role in the development of CVD. However, individuals are typically exposed to metal mixtures rather than single elements, and few studies have examined the combined effect of such exposures using advanced mixture modeling. To evaluate the associations between blood levels of five toxic metals and five CVDs using both single and mixture toxic metal exposure.
Methods: We used data from the 2015–2023 National Health and Nutrition Examination Survey. Blood concentrations of lead, cadmium, mercury, selenium, and manganese are examined in the presence of congestive heart failure, coronary heart disease, angina, heart attack, and stroke. Multivariable logistic regression models and weighted quantile sum (WQS) regression adjust for sociodemographic, behavioral, and dietary confounders.
Results: We included 15,000 U.S. adults aged 20 years and older. 48.33% were male, with 34% identifying as Black and 14% Hispanic. CVD prevalence ranged from 2.5% (angina) to 4.7% (stroke). Mean blood concentrations were 1.24 µg/dL for lead and 0.48 µg/L for cadmium. In adjusted single-metal models, cadmium was consistently and positively associated with greater odds of CVD outcomes, including angina (OR: 1.26, 95% CI: 1.04–1.54), heart attack (OR: 1.43, 95% CI: 1.17–1.76), and stroke (OR: 1.16, 95% CI: 0.99–1.37). Lead and mercury showed varied associations across outcomes, and selenium was marginally protective in some models. In WQS mixture models, significant associations were observed for coronary heart disease (WQS estimate = 0.2585, 95% CI: 0.1066–0.4104, p = 0.0009). For other outcomes (stroke, heart attack), WQS mixture effects were not statistically significant. Cadmium contributed the greatest weight to the metal mixture across most outcomes (e.g., 63.5% for CHF, 67.6% for stroke), with manganese contributing notably to coronary heart disease (weight: 76.9%).
Conclusions: Cadmium is a major contributor to the observed associations between metal exposure and cardiovascular diseases in U.S. adults. While mixture modeling revealed a significant effect for coronary heart disease, cadmium dominated the mixture components in most outcomes. Further prospective studies are recommended to understand the role of the toxic metal exposures, especially Cadmium, in CVD prevalence.