Association between copper levels and heart failure: a meta-analysis

Background and Objectives: Copper dyshomeostasis can lead to many diseases, including cardiovascular disease. However, there are conflicting reports on the relationship between serum copper levels and heart failure (HF). To explore the relationship between serum copper levels and HF by performing a meta-analysis. Methods and Study Design: The PubMed and ScienceDirect databases until June 2019 were searched for reports on the association between serum copper levels and HF. Results: A total of thirteen studies including 1504 subjects were chosen for the meta-analysis. The pooled analysis indicated that patients with HF had higher copper levels than the control subjects [standardized mean difference (SMD), 0.982; 95% confidence interval (CI), (0.679, 1.285)]. Subgroup analysis stratified by different geographic locations found that HF patients had higher copper levels than the control subjects in Asia and Europe [Asia: SMD, 0.948 and 95% CI, (0.569, 1.327); Europe: SMD, 1.275 and 95% CI, (0.633, 1.917)], but not in America [America: SMD, 0.637 and 95% CI, (-0.109, 1.383)]. Additionally, subgroup analysis revealed that patients with ischemic cardiomyopathy (ICM) [SMD, 1.171; 95% CI, (0.717, 1.624)], idiopathic dilated cardiomyopathy (IDCM) [SMD, 0.569; 95% CI, (0.097, 1.042)] and other types of HF [SMD, 1.152; 95% CI, (0.594, 1.710)] all had higher copper levels than controls. Further subgroup analysis stratified by Newcastle-Ottawa Scale (NOS) scores also found higher serum copper levels in patients with HF than controls within each subgroup. Conclusions: Our meta-analysis identified a significant association between high copper levels and HF.