Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study
Background and aim Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association...
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| Format: | info:eu-repo/semantics/article |
| Language: | eng |
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Elsevier
2023
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| Online Access: | https://hdl.handle.net/10171/66786 |
| _version_ | 1793400092859826176 |
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| author | Santos, J.L. (José Luis) Ruiz-Canela, M. (Miguel) Razquin, C. (Cristina) Clish, C.B. (Clary B.) Guasch-Ferre, M. (Marta) Babio, N. (Nancy) Corella, D. (Dolores) Gomez-Gracia, E. (Enrique) Fiol, M. (Miquel) Estruch, R. (Ramón) Lapetra, J. (José) Fito, M. (Montserrat) Aros, F. (Fernando) Serra-Majem, L. (Luis) Liang, L. (Liming) Martínez, M.A. (María Ángeles) Toledo, E. (Estefanía) Salas-Salvado, J. (Jordi) Hu, F.B. (Frank B.) Martinez-Gonzalez, M.A. (Miguel Ángel) |
| author_facet | Santos, J.L. (José Luis) Ruiz-Canela, M. (Miguel) Razquin, C. (Cristina) Clish, C.B. (Clary B.) Guasch-Ferre, M. (Marta) Babio, N. (Nancy) Corella, D. (Dolores) Gomez-Gracia, E. (Enrique) Fiol, M. (Miquel) Estruch, R. (Ramón) Lapetra, J. (José) Fito, M. (Montserrat) Aros, F. (Fernando) Serra-Majem, L. (Luis) Liang, L. (Liming) Martínez, M.A. (María Ángeles) Toledo, E. (Estefanía) Salas-Salvado, J. (Jordi) Hu, F.B. (Frank B.) Martinez-Gonzalez, M.A. (Miguel Ángel) |
| author_sort | Santos, J.L. (José Luis) |
| collection | DSpace |
| description | Background and aim
Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions.
Methods and results
Case-cohort study from the PREDIMED trial involving participants aged 55–80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20–1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12–1.58) for fumarate and 1.47 (95%CI:1.21–1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32–1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention.
Conclusion
Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. |
| format | info:eu-repo/semantics/article |
| id | oai:dadun.unav.edu:10171-66786 |
| institution | Universidad de Navarra |
| language | eng |
| publishDate | 2023 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oai:dadun.unav.edu:10171-667862023-07-10T05:17:38Z Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study Santos, J.L. (José Luis) Ruiz-Canela, M. (Miguel) Razquin, C. (Cristina) Clish, C.B. (Clary B.) Guasch-Ferre, M. (Marta) Babio, N. (Nancy) Corella, D. (Dolores) Gomez-Gracia, E. (Enrique) Fiol, M. (Miquel) Estruch, R. (Ramón) Lapetra, J. (José) Fito, M. (Montserrat) Aros, F. (Fernando) Serra-Majem, L. (Luis) Liang, L. (Liming) Martínez, M.A. (María Ángeles) Toledo, E. (Estefanía) Salas-Salvado, J. (Jordi) Hu, F.B. (Frank B.) Martinez-Gonzalez, M.A. (Miguel Ángel) Citric acid cycle Tricarboxylic cycle Metabolomics Cardiovascular disease Stroke Background and aim Plasma citric acid cycle (CAC) metabolites might be likely related to cardiovascular disease (CVD). However, studies assessing the longitudinal associations between circulating CAC-related metabolites and CVD risk are lacking. The aim of this study was to evaluate the association of baseline and 1-year levels of plasma CAC-related metabolites with CVD incidence (a composite of myocardial infarction, stroke or cardiovascular death), and their interaction with Mediterranean diet interventions. Methods and results Case-cohort study from the PREDIMED trial involving participants aged 55–80 years at high cardiovascular risk, allocated to MedDiets or control diet. A subcohort of 791 participants was selected at baseline, and a total of 231 cases were identified after a median follow-up of 4.8 years. Nine plasma CAC-related metabolites (pyruvate, lactate, citrate, aconitate, isocitrate, 2-hydroxyglutarate, fumarate, malate and succinate) were measured using liquid chromatography-tandem mass spectrometry. Weighted Cox multiple regression was used to calculate hazard ratios (HRs). Baseline fasting plasma levels of 3 metabolites were associated with higher CVD risk, with HRs (for each standard deviation, 1-SD) of 1.46 (95%CI:1.20–1.78) for 2-hydroxyglutarate, 1.33 (95%CI:1.12–1.58) for fumarate and 1.47 (95%CI:1.21–1.78) for malate (p of linear trend <0.001 for all). A higher risk of CVD was also found for a 1-SD increment of a combined score of these 3 metabolites (HR = 1.60; 95%CI: 1.32–1.94, p trend <0.001). This result was replicated using plasma measurements after one-year. No interactions were detected with the nutritional intervention. Conclusion Plasma 2-hydroxyglutarate, fumarate and malate levels were prospectively associated with increased cardiovascular risk. 2023-07-04T11:10:44Z 2023-07-04T11:10:44Z 2023 info:eu-repo/semantics/article https://hdl.handle.net/10171/66786 eng info:eu-repo/semantics/openAccess application/pdf Elsevier |
| spellingShingle | Citric acid cycle Tricarboxylic cycle Metabolomics Cardiovascular disease Stroke Santos, J.L. (José Luis) Ruiz-Canela, M. (Miguel) Razquin, C. (Cristina) Clish, C.B. (Clary B.) Guasch-Ferre, M. (Marta) Babio, N. (Nancy) Corella, D. (Dolores) Gomez-Gracia, E. (Enrique) Fiol, M. (Miquel) Estruch, R. (Ramón) Lapetra, J. (José) Fito, M. (Montserrat) Aros, F. (Fernando) Serra-Majem, L. (Luis) Liang, L. (Liming) Martínez, M.A. (María Ángeles) Toledo, E. (Estefanía) Salas-Salvado, J. (Jordi) Hu, F.B. (Frank B.) Martinez-Gonzalez, M.A. (Miguel Ángel) Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study |
| title | Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study |
| title_full | Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study |
| title_fullStr | Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study |
| title_full_unstemmed | Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study |
| title_short | Circulating citric acid cycle metabolites and risk of cardiovascular disease in the PREDIMED study |
| title_sort | circulating citric acid cycle metabolites and risk of cardiovascular disease in the predimed study |
| topic | Citric acid cycle Tricarboxylic cycle Metabolomics Cardiovascular disease Stroke |
| url | https://hdl.handle.net/10171/66786 |
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