Martinez-Gonzalez, Miguel ABuil-Cosiales, PilarCorella, DoloresBullo, MonicaFito, MontserratVioque, JesusRomaguera, DoraMartinez, J AlfredoWärnberg, JuliaLopez-Miranda, JoseEstruch, RamonBueno-Cavanillas, AuroraAros, FernandoTur, Josep ATinahones, FranciscoSerra-Majem, LluisMartin, VicenteLapetra, JoseVazquez, ClotildePinto, XavierVidal, JosepDaimiel, LidiaDelgado-Rodriguez, MiguelMatia, PilarRos, EmilioFernandez-Aranda, FernandoBotella, CristinaPuy-Portillo, MariaLamuela-Raventos, Rosa MMarcos, AscensionSaez, GuillermoGomez-Gracia, EnriqueRuiz-Canela, MiguelToledo, EstefaniaAlvarez-Alvarez, IsmaelDiez-Espino, JavierSorli, Jose VBasora, JosepCastañer, OlgaSchröder, HelmutNavarrete-Muñoz, Eva MariaZulet, Maria AngelesGarcia-Rios, AntonioSalas-Salvado, Jordi2025-01-072025-01-072019-04-02Martínez-González MA, Buil-Cosiales P, Corella D, Bulló M, Fitó M, Vioque J, et al. Cohort Profile: Design and methods of the PREDIMED-Plus randomized trial. Int J Epidemiol. 2019 Apr 1;48(2):387-388o.https://hdl.handle.net/10668/24502The PREDIMED (in Spanish: PREvención con DIeta MEDiterránea ) primary prevention trial1–3 reported in 2013 that long-term adherence to an energy-unrestricted Mediterranean diet (MedDiet), supplemented with either extra-virgin olive oil (EVOO) or nuts , reduced cardiovascular disease (CVD). PREDIMED showed a 30% relative reduction in the composite cardiovascular primary endpoint ( stroke , myocardial infarction or cardiovascular death ).2,,3 However, the PREDIMED trial tested only the composition of the diet , but did not test other lifestyle interventions (i.e. energy reduction, increased physical activity (PA) and behavioural modification) frequently applied in the context of the current unprecedented obesity pandemic .4,,5 With the exception of the null results of the Look-AHEAD trial,6 and the successful results of the EXERDIET-HTA study that found improvements in blood pressure , cardio-respiratory fitness and body composition (though they encouraged adherence to an hypocaloric DASH diet , instead of a Mediterranean diet ),7 lifestyle interventions including such components have never been tested in long-term randomized trials using hard cardiovascular events as endpoints.enCardiovascular DiseasesEvidence-Based MedicineHumansMulticenter Studies as TopicRisk AssessmentSample SizeTime FactorsAgedDietDiet, MediterraneanFemaleHealth StatusMaleMiddle AgedRandomized Controlled Trials as TopicResearch DesignRisk FactorsRisk Reduction BehaviorSurveys and Questionnairesresearch article30476123Restricted AccessDieta MediterráneaEjercicio físicoObesidadAceite de olivaEnfermedades cardiovascularesInfarto del MiocardioMuerteDietaPrevención PrimariaPresión sanguínea10.1093/ije/dyy2251464-3685https://academic.oup.com/ije/article-pdf/48/2/387/28479565/dyy225.pdf