Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis Muñoz-Bravo, Carlos Lozano Lorca, Macarena Kouiti, Malak González-Palacios Torres, Carla Barrios Rodríguez, Rocío Jiménez Moleón, José Juan Serum copper Cardiovascular disease Cardiovascular mortality Stroke Myocardial infarction Meta-analysis Cardiovascular events Background: Despite the fact that several studies have investigated the association between serum copper levels (S-Cu) and the risk of cardiovascular diseases, this relationship remains unclear. The aims of this study were to investigate the association between S-Cu and risk of major adverse cardiovascular events (MACE), including total stroke, ischemic stroke, hemorrhagic stroke, myocardial infarction and cardiovascular mortality, and identify potential sources of results heterogeneity. Methods: We carried out a systematic review and meta-analysis. The selection criteria were: (1) Observational studies (cohort studies, case-control studies and hybrid studies); (2) Studies containing quantitative data about the relationship between S-Cu and risk of MACE; (3) Estimating association measures; and (4) Studies written in English, French or Spanish. Overall pooled Odds ratio (pOR) and 95% confidence intervals (95% CI) of MACE for the highest vs. lowest S-Cu category were calculated using random-effects models. Results: Sixteen studies with a total of 41,322 participants were included in the meta-analysis: 10 prospective cohort studies, 5 nested case-control studies and 1 case-control study. Comparing highest vs. lowest category, high S-Cu levels were associated with total stroke (pOR: 1.49, 95% CI 1.22–1.82; I2=0%, p=0.54), myocardial infarction (pOR: 1.31, 95% CI 1.17–1.46; I2=0.0%, p=0.92) and cardiovascular mortality (pOR: 1.60, 95% CI 1.39–1.86; I2=0.0%, p=0.54). Subgroup analysis showed that studies with a hybrid design had higher risks for cardiovascular mortality (pOR: 3.42, 95% CI 1.98–5.92) and ischemic stroke (pOR: 1.54, 95% CI 1.30–1.83). Conclusion: High S-Cu levels were associated with an increased risk of total stroke, myocardial infarction and cardiovascular mortality. Hybrid studies seems to modify the strength of the association between S-Cu and the risk of cardiovascular mortality and ischemic stroke 2023-09-01T10:24:01Z 2023-09-01T10:24:01Z 2023-06-27 journal article Muñoz-Bravo C, Soler-Iborte E, Lozano- Lorca M, Kouiti M, González-Palacios Torres C, Barrios-Rodríguez R and Jiménez-Moleón JJ (2023) Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis. Front. Cardiovasc. Med. 10:1217748. [doi: 10.3389/fcvm.2023.1217748] https://hdl.handle.net/10481/84185 10.3389/fcvm.2023.1217748 eng http://creativecommons.org/licenses/by/4.0/ open access Atribución 4.0 Internacional Frontiers