Single and Combined Associations of Plasma and Urine Essential Trace Elements (Zn, Cu, Se, and Mn) with Cardiovascular Risk Factors in a Mediterranean Population

Abstract

Trace elements are micronutrients that are required in very small quantities through diet but are crucial for the prevention of acute and chronic diseases. Despite the fact that initial studies demonstrated inverse associations between some of the most important essential trace elements (Zn, Cu, Se, and Mn) and cardiovascular disease, several recent studies have reported a direct association with cardiovascular risk factors due to the fact that these elements can act as both antioxidants and pro-oxidants, depending on several factors. This study aims to investigate the association between plasma and urine concentrations of trace elements and cardiovascular risk factors in a general population from the Mediterranean region, including 484 men and women aged 18–80 years and considering trace elements individually and as joint exposure. Zn, Cu, Se, and Mn were determined in plasma and urine using an inductively coupled plasma mass spectrometer (ICP-MS). Single and combined analysis of trace elements with plasma lipid, blood pressure, diabetes, and anthropometric variables was undertaken. Principal component analysis, quantile-based g-computation, and calculation of trace element risk scores (TERS) were used for the combined analyses. Models were adjusted for covariates. In single trace element models, we found statistically significant associations between plasma Se and increased total cholesterol and systolic blood pressure; plasma Cu and increased triglycerides and body mass index; and urine Zn and increased glucose. Moreover, in the joint exposure analysis using quantile g-computation and TERS, the combined plasma levels of Zn, Cu, Se (directly), and Mn (inversely) were strongly associated with hypercholesterolemia (OR: 2.03; 95%CI: 1.37–2.99; p < 0.001 per quartile increase in the g-computation approach). The analysis of urine mixtures revealed a significant relationship with both fasting glucose and diabetes (OR: 1.91; 95%CI: 1.01–3.04; p = 0.046). In conclusion, in this Mediterranean population, the combined effect of higher plasma trace element levels (primarily Se, Cu, and Zn) was directly associated with elevated plasma lipids, whereas the mixture effect in urine was primarily associated with plasma glucose. Both parameters are relevant cardiovascular risk factors, and increased trace element exposures should be considered with caution.

Association of multiple blood metals with thyroid function in general adults: A cross−sectional study

“…Currently, there is no consensus on which of the statistical methods is the best for mixture analysis. The purpose of QGC is to specifically address the inherent complexities of high-dimensional mixture data and to estimate the joint effect of the analyzed chemicals ( 24 ). BKMR can be used to find the nonlinear exposure–response relationship with other metals fixed at certain levels.…”

Recent advances in the application of ionomics in metabolic diseases

“…For example, high Mn exposure could decrease the risk of high triglycerides ( 225 ), while elevated blood/serum levels of toxic heavy metals (such as Hg, As, and Pb) may increase the risk of different types of hyperlipidemia ( 226 – 228 ). Very recently, Barragán et al examined the associations of plasma essential trace elements with hyperlipidemia in a Mediterranean population, which demonstrated that plasma Mg concentrations and combined effect of plasma Zn, Cu, and Se levels had a positive association with hypercholesterolemia whereas plasma Mn concentrations would have negative effects on the amount of plasma lipids ( 229 , 230 ). A U-shaped link was suggested to exist between plasma Se levels and hypercholesterolemia, indicating that both low and high Se concentrations might have negative effects on plasma lipids ( 230 ).…”

A simple, rapid method for simultaneous determination of multiple elements in serum by using an ICP-MS equipped with collision cell

“…Clinical analysis of heavy metal elements in human samples, such as serum, can provide information about occupational exposure, intake, and toxicity of heavy metals and can also be used for the diagnosis of some diseases [ 7 – 10 ]. With the development of environmental epidemiology and exposure omics, researchers have become increasingly interested in the relationship between trace elements and chronic non-communicable diseases in the general population [ 11 – 13 ], which requires the establishment of a series of element detection methods.…”