Associations of serum zinc and copper concentrations within cardiovascular and neurological traits

Globally, cardiovascular disease (CVD) is the leading cause of death and has been linked to major depressive disorder (MDD). Imbalances in the homeostasis of the essential trace elements zinc and copper have been linked to both pathologies, with the underlying mechanisms being not yet fully understood. Therefore, this doctoral thesis aimed to investigate the associations of serum zinc and copper concentrations within cardiovascular and neurological traits. 

At first, serum zinc and copper levels were related to (sub-)clinical CVD. In 244 individuals with a prevalent CVD diagnosis serum zinc concentrations were significantly higher than in 694 community-dwelling controls, whereas serum copper concentrations did not differ between these groups. In multivariable-adjusted statistical models, higher serum zinc and copper concentrations were associated with a higher odds of having CVD. Furthermore, in controls, higher zinc and copper concentrations were associated with increases in augmentation index in multivariable-adjusted statistical models. Moreover, circulating copper concentrations were directly associated with pulse wave velocity and this association was non-linear. 

Secondly, serum zinc and copper concentrations were related to magnetic resonance imaging measurements of brain (micro-)structure, such as total grey and white matter volume, white matter lesions and global fractional anisotropy. 595 individuals diagnosed with MDD had significantly lower serum zinc and higher serum copper concentrations than 445 community-dwelling controls. In controls, higher serum zinc levels were directly and linearly associated with increases in global fractional anisotropy and with total white matter volume in a non-linear manner in multivariable-adjusted statistical models. Furthermore, in participants with prevalent MDD, we observed that higher serum copper concentrations were inversely associated with total white matter volume. 

These findings support previous observations and suggest that metabolic imbalances of zinc and copper are involved in cardiovascular pathophysiology and neuromodulatory mechanisms. Given the growing global burden of both conditions, further studies are needed to elucidate the underlying complex mechanisms.