Serum copper, copper-zinc ratio and the risk of sudden cardiac death and all-cause death: a prospective cohort study

Abstract Sudden cardiac death (SCD) constitutes a major global health burden, contributing to about 20% of deaths in Western countries. In addition to the associated economic and health impacts of SCD, the genetic predispositions to SCD-associated risk factors make identification of biomarkers for screening or therapeutic management of SCD to be crucial. Copper (Cu) and Zinc (Zn) are essential micronutrients and trace elements involved in various homeostatic mechanisms in humans, including inflammation, immunity, and oxidation-reduction reactions. However, the potential association of Cu and Cu/Zn ratio and risk of SCD in a prospective study is not established. We therefore examined the association between serum Cu levels, Cu/Zn ratio and the risk of SCD and all-cause death in Finnish men. Methods We used a prospective study from eastern Finland, comprising 1889 men aged 42–60 years without history of coronary heart disease at baseline ((1984–1989). The baseline serum Cu and Zn concentrations were determined using Atomic Absorption Spectrometer. Serum Cu/Zn ratio were categorized into quartiles: ≤1.03; >1.03 to ≤1.18; >1.18 to ≤1.34; and >1.34. Associations of serum Cu, Cu/Zn ratio and risk of SCD and all-cause death were analyzed using multivariable Cox models. Results After a median follow-up of 26 years, 147 SCD cases and 848 all-cause deaths were recorded. The hazard ratios (HR, and 95% CI) per unit increase in serum Cu levels for SCD and all-cause death were 2.51 (1.00–6.28) and 2.37 (1.60–3.51) respectively, after adjustment for age, C-reactive protein, total cholesterol, body mass index, systolic blood pressure, smoking status, and history of type 2 diabetes. Using the first quartile of Cu/Zn ratio as the referent, the HR and 95% CIs for SCD and all-cause death in the fourth quartiles were 1.32 (0.84–2.09) and 1.35 (1.11–1.64) respectively. Men in the highest quartile of Cu/Zn ratio, compared with those in the lowest quartile, had higher risk of all-cause death. Conclusion Serum Cu level, per unit increment, was directly associated with risk of SCD and all-cause death in middle-aged Finnish men. There was linear association between Cu/Zn ratio and risk of all-cause death. Serum Cu can possibly be a prognostic marker or risk factor for SCD and all-cause death, while Cu/Zn ratio may be a marker for all-cause death. However, the exact mechanisms need further exploration. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): North Savo Regional Fund