Miguel Ruiz-Canela1, Marta Guasch-Ferré2, Cristina Razquin3, Estefanía Toledo3, Pablo Hernández-Alonso4, Clary B Clish5, Jun Li6, Clemens Wittenbecher7, Courtney Dennis5, Ángel Alonso-Gómez8, Enrique Almanza-Aguilera9, Liming Liang10, Dolores Corella11, Enrique Gómez-Gracia12, Ramón Estruch13, Miguel Fiol14, José Lapetra15, Lluis Serra-Majem16, Emilio Ros17, Fernando Arós8, Jordi Salas-Salvadó4, Frank B Hu2, Miguel Ángel Martínez-González18. 1. Departamento de Medicina Preventiva y Salud Pública, Universidad de Navarra, Pamplona, Navarra, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. Electronic address: mcanela@unav.es. 2. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, United States. 3. Departamento de Medicina Preventiva y Salud Pública, Universidad de Navarra, Pamplona, Navarra, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain. 4. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Unitat de Nutrició Humana, Departament de Bioquímica i Biotecnologia, Universitat Rovira i Virgili, Reus, Tarragona, Spain; Institut d'Investigació Sanitària Pere iVirgili, Hospital Universitari Sant Joan de Reus, Reus, Tarragona, Spain. 5. Broad 13Broad Institute and MIT, Harvard University, Cambridge, MA, United States. 6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States. 7. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany. 8. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Instituto Sanitario de Investigación de Bioaraba, Servicio Vasco de Salud-Osakidetza, Hospital Universitario de Araba; Universidad del País Vasco UPV/EHU; Vitoria-Gasteiz, Spain. 9. Unidad de Riesgo Cardiovascular y Nutrición, Institut Hospital del Mar d'Investigacions Mèdiques (IMIM), Barcelona, Spain; Centro de Investigación Biomédica en Red Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, Madrid, Spain; Instituto de Nutrición y Seguridad Alimentaria (INSA-UB), Universidad de Barcelona, Santa Coloma de Gramanet, Barcelona, Spain. 10. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States. 11. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina Preventiva, Universidad de Valencia, Valencia, Spain. 12. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina Preventiva, Universidad de Málaga, Málaga, Spain. 13. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina Interna, Institut d'Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Universidad de Barcelona, Barcelona, Spain. 14. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Plataforma de Ensayos Clínicos, Instituto de Investigación Sanitaria Illes Balears (IdISBa), Hospital Universitario Son Espases, Palma de Mallorca, Balearic Islands, Spain. 15. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Departamento de Medicina de familia, Unidad de Investigación, Distrito Sanitario Atención Primaria Sevilla, Seville, Spain. 16. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Grupo de Investigación de Nutrición, Instituto de Investigación Biomédica y Ciencias de la Salud (IUIBS), Universidad de Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain. 17. CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Unidad Clínica de Lípidos, Departamento de Nutrición y Endocrinología, Institut d'Investigacions Biomèdiques Agust Pi i Sunyer (IDIBAPS), Hospital Clínic, Universidad de Barcelona, Barcelona, Spain. 18. Departamento de Medicina Preventiva y Salud Pública, Universidad de Navarra, Pamplona, Navarra, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, Navarra, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III, Madrid, Spain; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States.
Abstract
INTRODUCTION AND OBJECTIVES: Fatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. METHODS: Two case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. RESULTS: Elevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. CONCLUSIONS: Among individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines. This trial was registered at controlled-trials.com (Identifier: ISRCTN35739639).
INTRODUCTION AND OBJECTIVES: Fatty acid metabolic dysregulation in mitochondria is a common mechanism involved in the development of heart failure (HF) and atrial fibrillation (AF). We evaluated the association between plasma acylcarnitine levels and the incidence of HF or AF, and whether the mediterranean diet (MedDiet) may attenuate the association between acylcarnitines and HF or AF risk. METHODS: Two case-control studies nested within the Prevención con dieta mediterránea (PREDIMED) trial. High cardiovascular risk participants were recruited in Spain: 326 incident HF and 509 AF cases individually matched to 1 to 3 controls. Plasma acylcarnitines were measured with high-throughput liquid chromatography-tandem mass spectrometry. Conditional logistic regression models were fitted to estimate multivariable OR and 95%CI. Additive and multiplicative interactions were assessed by intervention group, obesity (body mass index ≥ 30 kg/m2), and type 2 diabetes. RESULTS: Elevated levels of medium- and long-chain acylcarnitines were associated with increased HF risk (adjusted ORperDE, 1.28; 95%CI, 1.09-1.51 and adjusted ORperDE, 1.21; 95%CI, 1.04-1.42, respectively). A significant association was observed for AF risk with long-chain acylcarnitines: 1.20 (1.06-1.36). Additive interaction of the association between long-chain acylcarnitines and AF by the MediDiet supplemented with extra virgin olive oil (P for additive interaction=.036) and by obesity (P=.022) was observed in an inverse and direct manner, respectively. CONCLUSIONS: Among individuals at high cardiovascular risk, elevated long-chain acylcarnitines were associated with a higher risk of incident HF and AF. An intervention with MedDiet+extra-virgin olive oil may reduce AF risk associated with long-chain acylcarnitines. This trial was registered at controlled-trials.com (Identifier: ISRCTN35739639).
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