Leticia Goni1,2,3, Cristina Razquin1,2,3, Estefanía Toledo1,2,3, Marta Guasch-Ferré4,5, Clary B Clish6, Nancy Babio3,7,8, Clemens Wittenbecher4,9,10, Alessandro Atzeni3,7,8, Jun Li4, Liming Liang11,12, Courtney Dennis6, Ángel Alonso-Gómez3,13,14, Montserrat Fitó3,15, Dolores Corella3,16, Enrique Gómez-Gracia17, Ramón Estruch3,18, Miquel Fiol3,19, Jose Lapetra3,20, Lluis Serra-Majem3,21, Emilio Ros3,22, Fernando Arós3,13,14, Jordi Salas-Salvadó3,7,8, Frank B Hu4,5, Miguel A Martínez-González1,2,3,4, Miguel Ruiz-Canela1,2,3. 1. Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain. 2. IdiSNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain. 3. Centro de Investigacion Biomédica en Red Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. 4. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 5. Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, USA. 6. Broad Institute of MIT and Harvard, Cambridge, MA, USA. 7. Universitat Rovira i Virgili, Departament de Bioquímica i Biotecnologia, Unitat de Nutrició Humana, Reus, Spain. 8. Institut d'Investigació Sanitària Pere i Virgili, Hospital Universitari Sant Joan de Reus, Reus, Spain. 9. Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany. 10. German Center for Diabetes Research (DZD), Neuherberg, Germany. 11. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 12. Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 13. Bioaraba Health Research Institute, Osakidetza Basque Health Service, Araba University Hospital, Vitoria-Gasteiz, Spain. 14. University of the Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain. 15. Unit of Cardiovascular Risk and Nutrition, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain. 16. Department of Preventive Medicine, University of Valencia, Valencia, Spain. 17. Department of Preventive Medicine, University of Malaga, Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain. 18. Department of Internal Medicine, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain. 19. Plataforma de Ensayos Clínicos, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Palma de Mallorca, Spain. 20. Department of Family Medicine, Research Unit, Distrito Sanitario Atención Primaria Sevilla, Sevilla, Spain. 21. Nutrition Research Group, Research Institute of Biomedical and Health Sciences (IUIBS), University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 22. Lipid Clinic, Department of Endocrinology and Nutrition, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain.
Abstract
BACKGROUND: Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks. OBJECTIVES: We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications of these associations through Mediterranean diet (MedDiet) interventions in a large, primary-prevention trial. METHODS: Two nested, matched, case-control studies were designed within the Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 incident cases and 547 matched controls for the AF case-control study and 326 cases and 402 matched controls for the HF case-control study using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups compared with control group) were analyzed with the likelihood ratio test. RESULTS: Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73-0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13-2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69-0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68-0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02-1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12-1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 1.02-1.41). In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (P-interaction = 0.044). CONCLUSIONS: Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF. This trial was registered at controlled-trials.com as ISRCTN35739639.
BACKGROUND: Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks. OBJECTIVES: We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications of these associations through Mediterranean diet (MedDiet) interventions in a large, primary-prevention trial. METHODS: Two nested, matched, case-control studies were designed within the Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 incident cases and 547 matched controls for the AF case-control study and 326 cases and 402 matched controls for the HF case-control study using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups compared with control group) were analyzed with the likelihood ratio test. RESULTS: Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73-0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13-2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69-0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68-0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02-1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12-1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 1.02-1.41). In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (P-interaction = 0.044). CONCLUSIONS: Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF. This trial was registered at controlled-trials.com as ISRCTN35739639.
Authors: John D Horowitz; Raffaele De Caterina; Tamila Heresztyn; John H Alexander; Ulrika Andersson; Renato D Lopes; Philippe Gabriel Steg; Elaine M Hylek; Puneet Mohan; Michael Hanna; Petr Jansky; Christopher B Granger; Lars Wallentin Journal: J Am Coll Cardiol Date: 2018-08-14 Impact factor: 24.094
Authors: R H Böger; S M Bode-Böger; A Szuba; P S Tsao; J R Chan; O Tangphao; T F Blaschke; J P Cooke Journal: Circulation Date: 1998-11-03 Impact factor: 29.690
Authors: Oliver M Shannon; Blossom C M Stephan; Anne-Marie Minihane; John C Mathers; Mario Siervo Journal: J Gerontol A Biol Sci Med Sci Date: 2018-06-14 Impact factor: 6.053
Authors: Usman A Tahir; Daniel H Katz; Tianyi Zhao; Debby Ngo; Daniel E Cruz; Jeremy M Robbins; Zsu-Zsu Chen; Bennet Peterson; Mark D Benson; Xu Shi; Lucas Dailey; Charlotte Andersson; Ramachandran S Vasan; Yan Gao; Changyu Shen; Adolfo Correa; Michael E Hall; Thomas J Wang; Clary B Clish; James G Wilson; Robert E Gerszten Journal: Circ Heart Fail Date: 2021-01-19 Impact factor: 10.447