Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial Muñoz-Bravo, Carlos Olmedo Palma, Pablo Gil Hernández, Fernando Serum copper Trace elements Cardiovascular disease Infarction Stroke PREDIMED This research was funded by the official funding agency for biomedical research of the Spanish government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial (RTIC G03/140; RTIC RD 06/0045 “PREDIMED”), and JR14/00008, and through Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), and by grants from Centro Nacional de Investigaciones Cardiovasculares (CNIC06/2007), the Fondo de Investigación Sanitaria–Fondo Europeo de Desarrollo Regional (Proyecto de Investigación (PI04-2239, PI05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI10/02658, PI11/01647, P11/02505 and PI13/00462), the Ministerio de Ciencia e Innovación (Recursos y teconologia agroalimentarias (AGL)-2009-13906-C02 and AGL2010-22319-C03 and AGL2013-49083C3-1-R), the Ministerio de Economía y Competitividad-Fondos FEDER-Instituto de Salud Carlos III (UNGR15-CE-3380), the Fundación Mapfre 2010, the Consejería de Salud de la Junta de Andalucía (PI0105/2007), the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, the Generalitat Valenciana (Generalitat Valenciana Ayuda Complementatia GVACOMP) 06109, GVACOMP2010-181, GVACOMP2011-151), Conselleria de Sanitat y AP; Atención Primaria (CS) 2010-AP-111, and CS2011-AP-042), Regional Government of Navarra (P27/2011), and Centre Català de la Nutrició de l'Institut d'Estudis Catalans. Hojiblanca and Patrimonio Communal Olivarero donated extra-virgin olive oil; the California Walnut Commission donated walnuts; Borges donated almonds; La Morella Nuts donated hazelnuts. The authors would like to thank the Universidad de Malaga/ Consorcio de Bibliotecas Universitarias de Andalucía (CBUA) for funding the Open Access fees for the publication. The authors would like to thank the Aula de Dieta Mediterránea y Vida Saludable de la Real Academia de Medicina de Andalucía Oriental, Ceuta y Melilla for its financial support in the analytical determination of copper levels. Background and aim: Certain trace elements have been associated with increased cardiovascular risk. The aim of this study was to evaluate the association between serum copper (S -Cu) levels and the risk of a first event of cardiovascular disease (CVD) in a population of older adults with high cardiovascular risk. Methods and results: We conducted a case-control study nested within the PREDIMED trial. During a median follow-up of 4.8 years, a total of 207 incident cases diagnosed with CVD were matched for sex, age, and intervention group with 436 controls. Personal interviews, reviews of medical records, and validated questionnaires were used to assess known CVD risk factors. Biological serum samples were collected annually. Inductively coupled plasma mass spectrometry analysis was used to determine S-Cu levels. Adjusted odds ratios were calculated using multivariate conditional logistic regression models. All participants had S-Cu levels within the reference values, 750 mg/L to 1450 mg/L. Among men, but not among women, the mean S-Cu concentration was higher in cases 1014.1 mg/L than in controls 959.3 mg/L; (p = 0.004). In men, the multivariable-adjusted odds ratio for CVD was 2.36 (95% CI 1.07-5.20 for the comparison of the highest vs. the lowest quartile; p for trend = 0.02), in women, it was 0.43 (95% CI 0.11-1.70; p for trend = 0.165). Conclusion: In older Spanish men with high cardiovascular risk, a significant association was observed between high S-Cu levels, but still within the reference values, and an increased risk of a first event of CVD. Our findings suggest a sex difference in CVD risk and S-Cu levels. To confirm this relationship and to analyze the differences observed between men and women, further studies are needed. 2023-12-05T11:36:45Z 2023-12-05T11:36:45Z 2023-11 journal article C. Muñoz-Bravo et al. Association between serum copper levels and risk of cardiovascular disease: A nested case-control study in the PREDIMED trial. Nutrition, Metabolism & Cardiovascular Diseases (2023) 33, 2199e2208. [https://doi.org/10.1016/j.numecd.2023.07.008] https://hdl.handle.net/10481/86037 10.1016/j.numecd.2023.07.008 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier