Miguel Ruiz-Canela1, Estefania Toledo1, Clary B Clish2, Adela Hruby3, Liming Liang4, Jordi Salas-Salvadó5, Cristina Razquin1, Dolores Corella6, Ramón Estruch7, Emilio Ros8, Montserrat Fitó9, Enrique Gómez-Gracia10, Fernando Arós11, Miquel Fiol12, José Lapetra13, Lluis Serra-Majem14, Miguel A Martínez-González1, Frank B Hu15. 1. Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; 2. Broad Institute of MIT and Harvard University, Cambridge, MA; 3. Departments of Nutrition. 4. Biostatistics, and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; 5. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Human Nutrition Department, IISPV, Universitat Rovira i Virgili, Reus, Spain; 6. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine, University of Valencia, Valencia, Spain; 7. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Internal Medicine and. 8. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDIBAPS), Hospital Clinic, University of Barcelona, Barcelona, Spain; 9. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain; 10. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Preventive Medicine, University of Malaga, Malaga, Spain; 11. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Cardiology, University Hospital of Alava, Vitoria, Spain; 12. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Institute of Health Sciences IUNICS, University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain; 13. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain; 14. CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Clinical Sciences and Research Institute of Biomedical & Health Sciences, University of Las Palmas de Gran Canaria, Las Palmas, Spain; 15. Departments of Nutrition, Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA; Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Cambridge, MA. nhbfh@channing.harvard.edu.
Abstract
BACKGROUND: The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS: We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS: After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05-2.76) and 2.09 (1.27-3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS: Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.
BACKGROUND: The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS: We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS: After adjustment for potential confounders, baseline leucine and isoleucine concentrations were associated with higher CVD risk: the hazard ratios (HRs) for the highest vs lowest quartile were 1.70 (95% CI, 1.05-2.76) and 2.09 (1.27-3.44), respectively. Stronger associations were found for stroke. For both CVD and stroke, we found higher HRs across successive quartiles of BCAAs in the control group than in the MedDiet groups. With stroke as the outcome, a significant interaction (P = 0.009) between baseline BCAA score and intervention with MedDiet was observed. No significant effect of the intervention on 1-year changes in BCAAs or any association between 1-year changes in BCAAs and CVD were observed. CONCLUSIONS: Higher concentrations of baseline BCAAs were associated with increased risk of CVD, especially stroke, in a high cardiovascular risk population. A Mediterranean-style diet had a negligible effect on 1-year changes in BCAAs, but it may counteract the harmful effects of BCAAs on stroke.
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