Serum copper-to-zinc ratio is associated with heart failure and improves risk prediction in middle-aged and older Caucasian men: A prospective study

Background and aims Serum copper (Cu) and zinc (Zn) may play a role in the development of adverse cardiovascular outcomes including heart failure (HF). Serum Cu/Zn-ratio has been shown to be a risk indicator for cardiovascular disease, but its relationship with HF has not been previously investigated. We aimed to assess the association between Cu/Zn-ratio and incident HF risk using a prospective cohort study. Methods and results Study participants were recruited in eastern Finland with baseline examinations carried out between March 1998 and December 2001. Serum levels of Cu and Zn were measured using atomic absorption spectrometry in 1866 men aged 42–61 years without a history of HF at baseline. Multivariable-adjusted hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident HF. During 26.5 years median follow-up, 365 HF cases occurred. Restricted cubic splines suggested linear relationships of serum Cu/Zn-ratio, Cu and Zn with HF risk. A unit increase in Cu/Zn-ratio was associated with an increased HF risk in analysis adjusted for several potential confounders including nutritional factors such as total energy intake, intake of fruits, berries and vegetables, and red meat (HR 1.63; 95% CI 1.06–2.51). The corresponding multivariable-adjusted HRs (95% CIs) for serum Cu and Zn were 2.42 (1.32–4.44) and 1.34 (0.50–3.63), respectively. Addition of Cu/Zn-ratio to a HF risk prediction model was associated with improved risk prediction. Conclusion In middle-aged and older Finnish men, increased serum Cu/Zn-ratio is associated with an increased risk of HF in a linear dose-response fashion and might improve HF risk assessment.