Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis

Carlos Muñoz-Bravo; Eva Soler-Iborte; Macarena Lozano-Lorca; Malak Kouiti; Carla González-Palacios Torres; Rocío Barrios-Rodríguez; José Juan Jiménez-Moleón

doi:10.3389/fcvm.2023.1217748

Serum copper levels and risk of major adverse cardiovascular events: a systematic review and meta-analysis

Front Cardiovasc Med. 2023 Jun 27:10:1217748. doi: 10.3389/fcvm.2023.1217748. eCollection 2023.

Authors

Carlos Muñoz-Bravo^{1

2}, Eva Soler-Iborte³, Macarena Lozano-Lorca^{4

5}, Malak Kouiti^{4

6}, Carla González-Palacios Torres⁴, Rocío Barrios-Rodríguez^{4

5

7}, José Juan Jiménez-Moleón^{4

5

7}

Affiliations

¹ Department of Public Health and Psychiatry, School of Medicine, University of Málaga, Málaga, Spain.
² Biomedical Research Institute of Malaga (IBIMA), Málaga, Spain.
³ Department of Public Health, Hospital Universitario San Cecilio, Spain Biohealth Research Institute in Granada (ibs.GRANADA), Granada, Spain.
⁴ Department of Preventive Medicine and Public Health, Universidad de Granada, Granada, Spain.
⁵ Instituto de Investigación Biosanitaria Ibs.GRANADA, Granada, Spain.
⁶ Laboratory of Health Sciences and Technologies, Higher Institute of Health Sciences, Hassan First University of Settat, Settat, Morocco.
⁷ Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain.

Abstract

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.

Systematic review registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022370782], identifier [CRD42022370782].

Keywords: cardiovascular disease; cardiovascular mortality; major adverse cardiovascular events; meta-analysis; myocardial infarction; serum copper; stroke.

Publication types

Review