Investigating the Interplay of Toxic Metals and Essential Elements in Cardiovascular Disease

Cardiovascular diseases (CVDs) are the leading cause of mortality globally, accounting for approximately one-third of all deaths. Exposure to toxic metals poses significant risks to cardiovascular health, contributing to the development of CVDs. Essential elements are crucial for maintaining cardiovascular function; however, imbalances or deficiencies in these elements can exacerbate the risk and progression of CVDs. Understanding the interactions between toxic metals and essential elements is crucial for elucidating their impact on cardiovascular health. This study aims to examine the individual and combined effects of toxic metals-lead (Pb), cadmium (Cd), and mercury (Hg)-along with essential elements-manganese (Mn), iron (Fe), and selenium (Se)-on CVDs. We explored the effects of toxic metals and essential elements using data from the National Health and Nutrition Examination Survey (NHANES, 2017-2018). We conducted descriptive analyses and applied advanced statistical methods, including Bayesian kernel machine regression (BKMR), weighted quantile sum regression (WQSR), and quantile g-computation, to assess the associations between these toxic metals and essential elements on key cardiovascular-related biomarkers. The results revealed distinct patterns of influence across the toxic metals and essential elements. Spearman correlation showed a stronger association among toxic metals than essential elements. Bayesian kernel machine regression (BKMR) and posterior inclusion probability (PIP) analysis identified lead, mercury, iron, and selenium as key contributors to CVD risk, with lead strongly linked to high-density lipoprotein (HDL), diastolic blood pressure (DBP), and systolic blood pressure (SBP). Selenium was linked to low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol. Univariate and bivariate analyses confirmed lead and mercury's strong associations with triglycerides and blood pressure, while lead, selenium, and iron were linked to different cholesterol outcomes. Single-variable analysis revealed an interaction between individual exposures and combined exposures. The overall exposure effect assessing the impact of all exposures combined on CVD markers revealed a steady positive association with triglycerides, total cholesterol, LDL, non-HDL cholesterol, and DBP, with HDL and SBP increasing from the 65th percentile. Quantile g-computation and WQSR confirmed lead's consistent positive association across all outcomes, with variations among other toxic metals and essential elements. In conclusion, our study suggests that toxic metals and essential elements are important factors in CVD outcomes, with different metals and elements associated with variations in specific biomarkers.