title: Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial (Prevención con Dieta Mediterránea).
abstract: BACKGROUND
  Although in vitro studies and investigations in animal models and small clinical populations have suggested that ceramides may represent an intermediate link between overnutrition and certain pathological mechanisms underlying cardiovascular disease (CVD), no prospective studies have investigated the association between plasma ceramides and risk of CVD.
  
  
  METHODS
  The study population consisted of 980 participants from the PREDIMED trial (Prevención con Dieta Mediterránea), including 230 incident cases of CVD and 787 randomly selected participants at baseline (including 37 overlapping cases) followed for ≤7.4 years. Participants were randomized to a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet. Plasma ceramide concentrations were measured on a liquid chromatography tandem mass spectrometry metabolomics platform. The primary outcome was a composite of nonfatal acute myocardial infarction, nonfatal stroke, or cardiovascular death. Hazard ratios were estimated with weighted Cox regression models using Barlow weights to account for the case-cohort design.
  
  
  RESULTS
  The multivariable hazard ratios (HR) and 95% confidence intervals (CIs) comparing the extreme quartiles of plasma concentrations of C16:0, C22:0, C24:0, and C24:1 ceramides were 2.39 (1.49-3.83,Ptrend<0.001), 1.91 (1.21-3.01,Ptrend=0.003), 1.97 (1.21-3.20,Ptrend=0.004), and 1.73 (1.09-2.74,Ptrend=0.011), respectively. The ceramide score, calculated as a weighted sum of concentrations of four ceramides, was associated with a 2.18-fold higher risk of CVD across extreme quartiles (HR, 2.18; 95% CI, 1.36-3.49;Ptrend<0.001). The association between baseline ceramide score and incident CVD varied significantly by treatment groups (Pinteraction=0.010). Participants with a higher ceramide score and assigned to either of the 2 active intervention arms of the trial showed similar CVD risk to those with a lower ceramide score, whereas participants with a higher ceramide score and assigned to the control arm presented significantly higher CVD risk. Changes in ceramide concentration were not significantly different between Mediterranean diet and control groups during the first year of follow-up.
  
  
  CONCLUSIONS
  Our study documented a novel positive association between baseline plasma ceramide concentrations and incident CVD. In addition, a Mediterranean dietary intervention may mitigate potential deleterious effects of elevated plasma ceramide concentrations on CVD.
  
  
  BACKGROUND
  URL: http://www.isrctn.com. Unique identifier: ISRCTN35739639.
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Dong D
authors.initials: DD
authors.lastname: Wang
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Estefanía
authors.initials: E
authors.lastname: Toledo
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Adela
authors.initials: A
authors.lastname: Hruby
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Cristina
authors.initials: C
authors.lastname: Razquin
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Miguel
authors.initials: M
authors.lastname: Ruiz-Canela
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Marta
authors.initials: M
authors.lastname: Guasch-Ferré
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Dolores
authors.initials: D
authors.lastname: Corella
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Enrique
authors.initials: E
authors.lastname: Gómez-Gracia
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Miquel
authors.initials: M
authors.lastname: Fiol
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Ramón
authors.initials: R
authors.lastname: Estruch
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Emilio
authors.initials: E
authors.lastname: Ros
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: José
authors.initials: J
authors.lastname: Lapetra
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Montserrat
authors.initials: M
authors.lastname: Fito
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Fernando
authors.initials: F
authors.lastname: Aros
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Luis
authors.initials: L
authors.lastname: Serra-Majem
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Lee
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Clary B
authors.initials: CB
authors.lastname: Clish
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Jordi
authors.initials: J
authors.lastname: Salas-Salvadó
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.).
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Martínez-González
authors.affiliation: From Department of Nutrition (D.D.W., W.C.W., Q.S., Y.Z., M.G.-F., C.-H.L., F.B.H.); Department of Epidemiology (D.D.W., W.C.W., L.L., F.B.H.), Department of Biostatistics (B.A.R., L.L.), Department of Genetics and Complex Diseases (C.-H.L.), Harvard T.H. Chan School of Public Health, Boston, MA; Department of Nutrition (M.A.M.-G.), Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); Instituto de Investigación Sanitaria de Navarra, Pamplona, Spain (E.T., C.R., M.R.-C., M.A.M.-G.); CIBER Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain (E.T., C.R., M.R.-C., D.C., M.F., R.E., E.R., J.L., M.F., F.A., L.S.-M., J.S.-S., M.A.M.-G.); Jean Mayer US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University and Tufts University Friedman School of Nutrition Science and Policy, Boston, MA (A.H.); Channing Division for Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA (B.A.R., W.C.W., Q.S., F.B.H.); Human Nutrition Unit, Faculty of Medicine and Health Sciences, Institut d'Investigació Sanitària Pere Virgili, Rovira i Virgili University, Reus, Spain (M.G.-F., J.S.-S.); Department of Preventive Medicine, University of Valencia, Spain (D.C.); Department of Preventive Medicine, University of Málaga, Spain (E.G.-G.); University Institute of Health Sciences (IUNICS), University of Balearic Islands and Hospital Son Espases, Palma de Mallorca, Spain (M.F.); Department of Internal Medicine (R.E.), Lipid Clinic, Department of Endocrinology and Nutrition Institut d'Investigacions Biomediques August Pi Sunyer (IDI- BAPS), Hospital Clinic, University of Barcelona, Spain (E.R.); Department of Family Medicine, Primary Care Division of Sevilla, San Pablo Health Center, Sevilla, Spain (J.L.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (M.F.); Department of Cardiology, University Hospital of Alava, Vitoria, Spain (F.A.); Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Spain (L.S.-M.); and Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA (C.B.C.). nhbfh@channing.harvard.edu.
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology* / Q000517:prevention & control*; D002518:Ceramides / Q000097:blood*; D002853:Chromatography, Liquid; D038441:Diet, Mediterranean; D005260:Female; D006801:Humans; D015994:Incidence; D016014:Linear Models; D008297:Male; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D015999:Multivariate Analysis; D009754:Nuts; D000069463:Olive Oil; D016016:Proportional Hazards Models; D011446:Prospective Studies; D065840:Protective Factors; D018570:Risk Assessment; D012307:Risk Factors; D040242:Risk Reduction Behavior; D013030:Spain / Q000453:epidemiology; D053719:Tandem Mass Spectrometry; D013997:Time Factors
chemical_list: D015415:Biomarkers; D002518:Ceramides; D000069463:Olive Oil
keywords: Mediterranean diet; cardiovascular disease; ceramide; coronary heart disease; stroke