Exploring the interplay between valvular and serum zinc and copper levels and disease markers in aortic stenosis

Abstract

Aortic stenosis (AS) is a progressive condition characterized by valve calcification and significant morbidity, often requiring invasive intervention. The AS pathophysiology is multifaceted, with evidence suggesting a role for trace elements. However, whether zinc (Zn) and copper (Cu) are associated with valve calcification is unclear. This exploratory study assessed the Zn and Cu levels in the serum and aortic valves of AS patients undergoing surgical valve replacement and explored the relationships between trace elements and clinical and biochemical parameters to better understand their potential roles in AS pathophysiology. An inverse relationship was observed between serum Zn levels and systolic pressure gradients across the valve (p < 0.0001). Zn accumulation was identified in calcified aortic valves, suggesting a systemic redistribution of Zn during disease progression. The valvular Cu/Zn ratio was reversed (<1) compared to that in serum. The lipoprotein(a), an inflammatory marker, was positively correlated with serum Cu levels (p = 0.0007) and the Cu/Zn ratio (p = 0.02). However, no direct association was found between valvular Cu content and the AS severity. The findings suggest that Zn depletion in serum, coupled with its accumulation in calcified valves, reflects a disease-driven redistribution mechanism that may serve a protective role against calcification progression. Additionally, the study highlights a potential interplay between Cu metabolism and inflammatory processes in AS. Further research is required to determine whether therapeutic modulation of Zn levels could offer benefits in AS management.