title: Plasma Branched-Chain Amino Acids and Incident Cardiovascular Disease in the PREDIMED Trial.
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.
authors.affiliation: 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;
authors.forename: Miguel
authors.initials: M
authors.lastname: Ruiz-Canela
authors.affiliation: 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;
authors.forename: Estefania
authors.initials: E
authors.lastname: Toledo
authors.affiliation: Broad Institute of MIT and Harvard University, Cambridge, MA;
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: Departments of Nutrition.
authors.forename: Adela
authors.initials: A
authors.lastname: Hruby
authors.affiliation: Biostatistics, and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA;
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: 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;
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.affiliation: 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;
authors.forename: Cristina
authors.initials: C
authors.lastname: Razquin
authors.affiliation: 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;
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.affiliation: CIBER Fisiopatología de la Obesidad y Nutrición (CIBER Obn), Instituto de Salud Carlos III, Madrid, Spain; Department of Internal Medicine and.
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.affiliation: 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;
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.affiliation: 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;
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fitó
authors.affiliation: 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;
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez-Gracia
authors.affiliation: 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;
authors.forename: Fernando
authors.initials: F
authors.lastname: Arós
authors.affiliation: 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;
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.affiliation: 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;
authors.forename: José
authors.initials: J
authors.lastname: Lapetra
authors.affiliation: 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;
authors.forename: Lluis
authors.initials: L
authors.lastname: Serra-Majem
authors.affiliation: 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;
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
authors.affiliation: 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.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000178:diet therapy / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D038441:Diet, Mediterranean / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D015999:Multivariate Analysis; D012306:Risk
chemical_list: D000597:Amino Acids, Branched-Chain