1. Feb 25, 2013 (Epub ahead of print

3. Food industry: only food items Provision of Olive oil ~2 000 l/wk Provision of nuts 30 kg/wk walnuts 15 kg/wk almonds

4.  Men: 55-80 yr  Women: 60-80 yr  High CV risk w ithout CVD type 2 diabetics 3+ risk factors PREDIMED TRIAL: DESIGN Random 1.Smoking 2.Hypertension 3.  LDL 4.  HDL 5.Overweight/obes 6.Family history

5. Recruitment: primary care N= 7,447

7. Random

8. Primary end-point: either – cardiovascular death – myocardial infarction – stroke

9. PREDIMED: intervention Introduce changes in the overall food pattern – Mediterranean diet: 2 groups Total Fat: ad libitum High in – MUFA (virgin olive oil) – Fish – Fruits, vegetables, legumes Low in meats & dairy alcohol permitted: wine – Low-fat diet - Control Reduce every fat Increase CHO – No Energy restriction – No specific recommendation on Physical Activity tocopherols polyphenols flavonoids phytosterols

10. What is the Mediterranean diet?

11. 1.Olive oil main culinary fat 2.Olive oil >=4 tablespoons/d 3.Vegetables>=2 serv./d 4.Fruits>=3 serv./d 5.Red meats<1/d 6.Butter, marg, cream<1/d 7.Soda drinks<1/d 8. Wine >=7 glasses/wk 9. Legumes >=3/wk 10. Fish & seafood >=3/wk 11. Cakes, sweets <3/wk 12. Nuts >=3/wk 13. Poultry > red meats 14. Sofrito >=2/wk14-itemscreener

12. Martínez-Gonzalez et al. Int J Epidemiol 2012;41:377 Sofrito 3

13. August 2012 Volume 7 Isue 8 e43134

14. Strategies for behavior change Repeated personal contacts: every 3-mo Group sessions: every 3-mo Holistic approach Written information Self-monitoring Individualized goal-setting Quick feedback Individual motivational interviews (every 3-mo) – adapted to the patient’s features » clinical condition » preferences » beliefs – expressed in servings/d to improve understanding

15. Additional strategies – Seasonal buying lists – Menus and recipes Only in the 2 MeDiet groups Provision of key food items for free Negotiated goal setting Contracted agreement Understandable: units=servings Options for the negotiation Serving size Frequency of consumption Way of cooking

17. 3-yr attainments (%) for each of the 14 items MeDiet + Virgin olive oil MeDiet + mixed nuts Control group

18. Energy x 1000 Kcal Prot (%E) CHO (%E) Fiber (g/d) Fat (%E) SFA (%E) MUFA (%E) PUFA (%E) Nuts (%E) Olive O. (%E) FFQ: Changes in Energy, Nutrient and Supplemental Food Intake by Study Arm p<.001 except fiber (p=0.10) & SFA (p=0.004) p<.001 except SFA (p=0.30) MeDiet + Virgin olive oil MeDiet + mixed nuts Control group

19. Urinary hydroxytyrosol concentrations (95% confidence intervals) at baseline and at 1, 3 and 5 years of follow-up (N = 750).

20. Plasma alpha-linolenic acid (%) in the three arms of the trial (95% confidence intervals) at baseline and at 1, 3 and 5 years of follow-up (N = 375).

21. N Engl J Med 2013 Suppl. Appendix

22. Primary end-point (MI, stroke or death from CV causes) Crude rates / 1000 person-years N Engl J Med 2013

23. (1). Stratified according to recruiting center and adjusted for sex, age, family history of premature coronary heart disease, and smoking status. (2) Additionallly adjusted for body-mass index, waist-to-height ratio, hypertension at baseline, dyslipidemia at baseline, and diabetes at baseline. N Engl J Med 2013

24. Primary end-point (MI, stroke or death from CV causes)

26. Stratified according to recruiting center and adjusted for sex, age, family history of premature coronary heart disease, and smoking status, body-mass index, waist-to-height ratio, hypertension at baseline, dyslipidemia at baseline, and diabetes at baseline. N Engl J Med 2013

27. Total mortality