www.unav.es/preventiva
The PREDIMED trial
www.unav.es/preventiva
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
www.unav.es/preventiva
Evolution of designs
Evolution of exposure in nutritional epidemiology
evidence
of evidence
Quality of
Quality
High
High
Low
Low
Randomized Trial
Cohort
Nested case-control
Case-control
Ecological (cross-cultural, international comparisons)
Food patterns
Food grouping & indexes
Food items: olive oil, tomato, garlic, etc.
Micronutrients: antioxidants, vitamins, etc.
Single macronutrient: CHO, Types of Fat, Protein
DOG
www.unav.es/preventiva
Mediterranean Food pattern
 Rapidly increasing evidence
 Increased Longevity
 Prevention of







CV mortality
Cancer mortality
CVD incidence
Metabolic syndrome
Diabetes
Dementia
Depression
 Highly palatable!
 Scarcity of large randomized trials
DOG
www.unav.es/preventiva
Mediterranean Food pattern
 Rapidly increasing evidence
 Increased Longevity
 Prevention of







CV mortality
Cancer mortality
CVD incidence
Metabolic syndrome
Diabetes
Dementia
Depression
 Highly palatable!
 Scarcity of large randomized trials
DOG
www.unav.es/preventiva
de Lorgeril M, Salen P, Martin JL, et al. Final Report of
the Lyon Diet Heart Study. Circulation 1999;99:779-785.
DOG
www.unav.es/preventiva
Eur J Epidemiol
2004;19:9-13.
• What is the MeDiet?
•
•
•
•
Olive oil as the main added lipid
Unrestricted Total Fat
MUFA-rich diet in the intervention group
Low consumption of meat / meat products
• and what it is NOT the MeDiet
• Margarine, soybean oil, mustard oil...
DOG
de Lorgeril et al. Lyon trial. Circulation 1999;99:779-785.
Diet assessed in
~30% of control
~50% of experimental
No biochemical
confirmation of
adherence.
Trial stopped
after 27 months.
Low number of
observed endpoints
(14 vs. 44).
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
www.unav.es/preventiva
Funding agency
DOG
www.unav.es/preventiva
Funding History
2003 2004 2005 2006 2007 2008 2009
17
15
15
Initial Network
DOG
14
adhoc
grant
17
18
19
Network RD 06/0045
Consortium ciberobn
www.unav.es/preventiva
Centers
11 RECRUITMENT GROUPS
DOG
8 ONLY-LAB GROUPS
•
•
Navarra- MA Martinez-Gonzalez
Valencia- D Corella
•
•
Barcelona-1- E Ros
Sevilla- V Ruiz-Gutierrez
•
•
•
•
Reus- J Salas-Salvado
Mallorca- M Fiol
Sevilla- J Lapetra
Málaga- E Gomez-Gracia
•
•
•
•
•
Barcelona-1- R Estruch
Vitoria- F Aros
Barcelona-2- MI Covas
Las Palmas- L Serra-Majem
Barcelona-3- X Pinto
•
•
•
•
•
•
Barcelona-2- RM Lamuela-Raventos
Navarra- JA Martinez
Valencia- G Saez
Barcelona-3- MT Mitjavila
Mallorca- JA Tur
Vitoria- MP Portillo
www.unav.es/preventiva
Funded by network (RD 06/0045)
6 RECRUITMENT GROUPS
DOG
7 LAB-ONLY GROUPS
•
•
Navarra- MA Martinez-Gonzalez
Valencia- D Corella
•
•
Barcelona-1- E Ros
Sevilla- V Ruiz-Gutierrez
•
•
•
•
Reus- J Salas-Salvado
Mallorca- M Fiol
Sevilla- J Lapetra
Málaga- E Gomez-Gracia
•
•
•
•
•
Barcelona-1- R Estruch
Vitoria- F Aros
Barcelona-2- MI Covas
Las Palmas- L Serra-Majem
Barcelona-3- X Pinto
•
•
•
•
•
•
Barcelona-2- RM Lamuela-Raventos
Navarra- JA Martinez
Valencia- G Saez
Barcelona-3- MT Mitjavila
Mallorca- JA Tur
Vitoria- MP Portillo
www.unav.es/preventiva
Funded by consortium (ciberobn)
5 RECRUITMENT GROUPS
DOG
1 LAB-ONLY GROUP
•
•
Navarra- MA Martinez-Gonzalez
Valencia- D Corella
•
•
Barcelona-1- E Ros
Sevilla- V Ruiz-Gutierrez
•
•
•
•
Reus- J Salas-Salvado
Mallorca- M Fiol
Sevilla- J Lapetra
Málaga- E Gomez-Gracia
•
•
•
•
•
Barcelona-1- R Estruch
Vitoria- F Aros
Barcelona-2- MI Covas
Las Palmas- L Serra-Majem
Barcelona-3- X Pinto
•
•
•
•
•
•
Barcelona-2- RM Lamuela-Raventos
Navarra- JA Martinez
Valencia- G Saez
Barcelona-3- MT Mitjavila
Mallorca- JA Tur
Vitoria- MP Portillo
www.unav.es/preventiva
Food industry: only food items
DOG
Provision of Olive oil
Provision of nuts
~2 000 l/wk
30 kg/wk walnuts
15 kg/wk almonds
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
PREDIMED TRIAL: DESIGN
 Men: 55-80 yr
 Women: 60-80 yr
 High CV risk without CVD
type 2 diabetics
3+ risk factors
Random
1. Smoking
2. Hypertension
3.  LDL
4.  HDL
5. Overweight/obes
6. Family history
www.unav.es/preventiva
PREDIMED Participants
11 RECRUITMENT GROUPS
•
Navarra- MA Martinez-Gonzalez
•
Valencia- D Corella
•
Reus- J Salas-Salvado
•
Mallorca- M Fiol
•
Málaga- E Gomez-Gracia
•
Barcelona-1- R Estruch
•
Sevilla- J Lapetra
•
Vitoria- F Aros
•
Barcelona-2- MI Covas
•
Las Palmas- L Serra-Majem
•
Barcelona-3- X Pinto
Navarra
Valencia
Reus
Mallorca
Málaga
Barcelona 1
Sevilla
Vitoria
Barcelona 2
Las Palmas
Barcelona 3
Total
DOG
n
~P-Y
1048
1049
870
594
540
667
659
641
570
356
238
5470
3830
3680
2460
2400
2400
2220
2210
2060
690
490
7232 27,910
www.unav.es/preventiva
Project Leader: Dr. Ramón Estruch
DOG
www.unav.es/preventiva
PREDIMED Participants
Mediet + VOO
(n= 2487)
MeDiet + Nuts
(n=2396)
Control
(n=2349)
67 (6)
67 (6)
67 (6)
Women (%)
57
54
58
Diabetes (%)
50
47
48
Hypertension (%)
82
82
84
Current smokers (%)
14
15
14
High cholest. (%)
72
73
72
30 (4)
30 (4)
30 (4)
100 (10)
100 (10)
101 (11)
8.7 (2)
8.7 (2)
8.3 (2)
Age (SD)
BMI (SD)
Waist (SD)
MeDiet 0-14 p (SD)
DOG
www.unav.es/preventiva
PREDIMED: primary end-point
Either:
 cardiovascular death
 myocardial infarction
 stroke
DOG
www.unav.es/preventiva
PREDIMED: Secondary end-points
 total mortality
 heart failure
 major cancers
 diabetes
 dementia
DOG
We will also ascertain
intermediate outcomes:
•blood pressure (BP)
•fasting blood glucose
•lipid profile
•markers of inflammation
•other markers of CVD
www.unav.es/preventiva
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 limitation
DOG
tocopherols
polyphenols
flavonoids
phytosterols
www.unav.es/preventiva
Ann Intern Med 2006;145:1-11
Appendix, table 1 (on-line)
1.
2.
3.
4.
5.
6.
7.
DOG
Olive oil main culinary fat
Olive oil >=4 tablespoons/d
Vegs>=2 serv./d
Fruits>=3 serv./d
Red meats<1/d
Butter, marg, cream<1/d
Soda drinks<1/d
14-point score
8. Wine >=3 glasses/wk
9. Legumes >=3/wk
10. Fish & seafood >=3/wk
11. Cakes, sweets <3/wk
12. Nuts >=1/wk
13. Poultry > red meats
14. Sofrito
www.unav.es/preventiva
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)

DOG

adapted to the patient’s features
 clinical condition
 preferences
 beliefs
expressed in servings/d to improve understanding
www.unav.es/preventiva
Strategies for behavior change-2
 Additional strategies
 Seasonal buying lists
 Menus and recipes
 Only in the 2 MeDiet groups
 Provision of key food items for free
DOG
www.unav.es/preventiva
Special emphasis
 Negotiated goal setting
 Contracted agreement
 Understandable: units=servings
 Options for the negotiation
 Serving size
 Frequency of consumption
 Way of cooking
DOG
www.unav.es/preventiva
Group sessions
DOG
www.unav.es/preventiva
Projected follow-up = 6 years (median)
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013
Recruitm.
% of
1Year
yr
recruitment
22003
yr
9
32004
yr
21
42005
yr
28
52006
yr
11
6 yr
Cum. %
9
30
58
69
2007
13
82
2008
17
99
2009
1
100
Total
DOG
100
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
www.unav.es/preventiva
3-mo changes
Ann Intern Med 2006;145:1-11
DOG
www.unav.es/preventiva
3-mo changes in RF
•772 participants (55-80 yr)
•Randomization:
•257 to a MeDiet + (free provision of olive oil)
•258 to a MeDiet + (free provision of nuts)
•257 to a LFD (control group)
•Follow-up: 3 months
•Nutrient profile and food items consumption
•Mediterranean score (14-point score)
•Classical risk factors
•Novel risk factors (CRP, IL6, VCAM, ICAM)
DOG
www.unav.es/preventiva
3-mo changes in RF
DOG
www.unav.es/preventiva
3-mo changes in diet
DOG
www.unav.es/preventiva
3-mo changes in Risk Factors
3
2
1
0
-1
-2
-3
-4
-5
-6
-7
MeDiet (+VOO)
p<0.001
p=0.048
p<0.001
p=0.001
CONTROL
p<0.001
p=0.006
SBP change
(mmHg)
DOG
MeDiet (+Nuts)
DBP change
(mm Hg)
LDL change
(mg/dl)
HDL change
(mg/dl)
www.unav.es/preventiva
3-mo changes in Risk Factors
8
6
4
2
0
-2
-4
-6
-8
-10
-12
MeDiet (+VOO)
p=0.022
TG change (mg/dl)
DOG
MeDiet (+Nuts)
CONTROL
p=0.017
p<0.001
p=0.039
p<0.001
Glucose change (mg/dl)
Insulin change (pmol/L)
www.unav.es/preventiva
3-mo changes in Risk Factors
0,4
0,2
0
MeDiet (+VOO)
MeDiet (+Nuts)
CONTROL
p<0.001
p<0.001
p=0.37
p=0.002
p<0.001
p=0.84
TC/HDL ratio (change)
HOMA index (change)
-0,2
-0,4
-0,6
-0,8
-1
DOG
Waist change (cm)
www.unav.es/preventiva
3-mo changes in Risk Factors
DOG
www.unav.es/preventiva
3-mo changes in Risk Factors
DOG
www.unav.es/preventiva
3-mo changes in Risk Factors
DOG
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
www.unav.es/preventiva
Salas-Salvado et al, Eur J Clin Nutr 2008;62:651-9
DOG
www.unav.es/preventiva
Salas-Salvado et al, Eur J Clin Nutr 2008;62:651-9
•339 men and 433 women (55-80 yr)
•Exposure:
•Food groups (137-item FFQ)
•MeDiet adherence (14-point score)
•Outcomes:
•hs-C Reactive protein
•interleukin-6 (IL-6)
•intracellular adhesion molecule-1 (ICAM-1)
•vascular cell adhesion molecule-1 (VCAM-1)
DOG
www.unav.es/preventiva
Salas-Salvado et al, Eur J Clin Nutr 2008;62:651-9
Change
(p value*)
CRP
IL6
Cereals
 (0.005)
Fruits
 (0.008)
VCAM1
 (0.003)
Nuts
 (0.02)
Virgin Olive Oil
MeDiet**
ICAM1
 (0.14)  (0.49)
 (0.09)
 (0.09)
*Adjusted for age, gender, diabetes, smoking, BMI, educational level, use of statins,
NSAID, and aspirin.
**Test for linear trend (multivariate adjusted)
DOG
www.unav.es/preventiva
Salas-Salvado et al, Eur J Clin Nutr 2008;62:651-9
1400
8
1200
VCAM-1
ICAM-1 7
IL-6 (pg/ml)
CRP (mg/l)
6
1000
ng/ml
5
800
4
3.59
600
3
400
3.51
2
200
1
0
0
<7
DOG
3.18
7 to 10
MeDiet score (0-14)
>10
<7
7 to 10
MeDiet score (0-14)
>10
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o
•
•
•
•
DOG
MeDiet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
Sánchez-Tainta, et al. Eur J Cardiovasc Prev Rehabil. 2008;15:589-93.
•3204 participants
•Exposure: MeDiet (14-point score)
•Adherence: Above Median (9) in the score
•Ordered categories (5) in the score
•Outcomes:
•Diabetes
•Hypertension
•Obesity
•Hypercholesterolemia
All of them
together
www.unav.es/preventiva
Adj. Prevalence OR (95% CI)
MeDiet (>Median) and prevalence of Risk Factors
1,2
Sánchez-Tainta, et al. Eur J Cardiovasc Prev Rehabil. 2008;15:589-93.
1
0,8
0,6
0,4
0,2
0
Hypertension
Diabetes
Obesity
Hypercholesterolemia
Adjusted for age, gender, leisure-time physical activity (tertiles), smoking (5 categories), marital status (4
categories), educational level (4 categories), and BMI (3 categories, except when using obesity as outcome).
DOG
www.unav.es/preventiva
Adherence to MeDiet and prevalence of diabetes
adj. OR (95% CI)
1,4
1,2
1
1 (ref.)
0.99
1.00
0,8
0.69
0,6
0.67
0,4
0,2
0
<=7 (n=802)
8 (n=547)
9 (n=570)
10 (n=507)
>=11 (n=778)
Mediterranean diet score (14 points)
Adjusted for age, gender, leisure-time physical activity (tertiles), smoking (5 categories), marital status (4
categories), educational level (4 categories), and BMI (3 categories).
DOG
www.unav.es/preventiva
Adherence to MeDiet & prevalence of all 4 RF
p<0.001 for linear trend
1,4
adj. OR (95% CI)
1,2
1
1 (ref.)
1.03
0,8
0.78
0.68
0,6
0,4
0,2
0
0.38
Sánchez-Tainta, et al. Eur J Cardiovasc Prev Rehabil. 2008;15:589-93.
<=7 (n=802)
8 (n=547)
9 (n=570)
10 (n=507)
>=11 (n=778)
Mediterranean diet score (14 points)
Adjusted for age, gender, leisure-time physical activity (tertiles), smoking (5 categories), marital status (4
categories), and educational level (4 categories).
DOG
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
Fitó for the PREDIMED group. Arch Inter Med 2007;167:1195-1203.
Mediet+VOO=123
n = 372
Mediet+nuts=128
control=121
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
www.unav.es/preventiva
1-yr changes in diet
Zazpe et al for the PREDIMED group,
J Am Diet Assoc 2008;108:1134-44
DOG
www.unav.es/preventiva
1-yr changes in diet
n= 1551 in 3 groups:
• MeDiet +VOO: 533
• MeDiet +Nuts: 533
• Control: 485
Assessment of changes from baseline
DOG
Baseline characteristics of the 3 randomized groups
Baseline characteristics of the 3 randomized groups
www.unav.es/preventiva
1-yr within-group changes
in VIRGIN OLIVE OIL (VOO) consumption
3,5
*
3
Servings/d
2,5
2
1,5
1
*
0,5
0
VOO
DOG
Nuts
Control
www.unav.es/preventiva
1-yr within-group changes
in REFINED OLIVE OIL consumption
0,5
0
Servings/d
VOO
-1
-1,5
-2
DOG
Control
*
-0,5
-2,5
Nuts
*
www.unav.es/preventiva
1-yr within-group changes
TOTAL NUTS
1
*
Servings/d
0,8
0,6
0,4
0,2
*
0
VOO
-0,2
DOG
Nuts
Control
www.unav.es/preventiva
1-yr within-group changes
VEGETABLES
0,5
Servings/d
0,4
0,3
*
*
0,2
0,1
0
VOO
DOG
Nuts
Control
www.unav.es/preventiva
1-yr within-group changes
FRUITS
0,6
*
*
Servings/d
0,5
0,4
0,3
*
0,2
0,1
0
VOO
DOG
Nuts
Control
www.unav.es/preventiva
Servings/d
1-yr within-group changes
CEREALS
0,5
0,4
0,3
0,2
0,1
0
-0,1
-0,2
-0,3
-0,4
-0,5
DOG
VOO
*
Nuts
Control
*
Between-group: non-significant
www.unav.es/preventiva
Servings/d
1-yr within-group changes
LEGUMES
0,5
0,4
0,3
0,2
0,1
0
-0,1
-0,2
-0,3
-0,4
-0,5
DOG
*
*
VOO
Nuts
Control
www.unav.es/preventiva
1-yr within-group changes
FISH / SEAFOOD
0,5
0,4
0,3
Servings/d
0,2
0,1
0
-0,1
VOO
Nuts
Control
-0,2
-0,3
-0,4
-0,5
DOG
Between-group: non-significant
www.unav.es/preventiva
1-yr within-group changes
MEAT / MEAT PRODUCTS
0,5
0,4
0,3
Servings/d
0,2
0,1
0
-0,1
-0,2
VOO
Nuts
Control
*
*
*
-0,3
-0,4
-0,5
DOG
Between-group: non-significant
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1-yr within-group changes
DAIRY
0,5
0,4
0,3
Servings/d
0,2
0,1
0
-0,1
VOO
Nuts
Control
-0,2
-0,3
-0,4
-0,5
DOG
Between-group: non-significant
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1-yr within-group changes
ALCOHOL
0
VOO
-2
*
Nuts
*
Control
*
g/d
-4
-6
-8
Between-group: non-significant
-10
DOG
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Baseline vs. 1-yr 14-unit Score
14
12
Units
10
11,2
10,8
9,0
8,9
Baseline
1-y follow-up
8,9
8,4
8
6
4
2
0
DOG
MeDiet+VOO
MeDiet+Nuts
Control
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% Energy
1-yr within-group changes
Nutrient profile
DOG
3
2,5
2
1,5
1
0,5
0
-0,5
-1
-1,5
-2
-2,5
-3
*
*
*
VOO
Nuts
Control
*
*
*
Fat
CHO
Prot.
% Energy
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DOG
15
12,5
10
7,5
5
2,5
0
-2,5
-5
-7,5
-10
-12,5
-15
Fat
CHO
Prot.
Intervention
Control
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% Energy
1-yr within-group changes
Types of Fat
DOG
3
2,5
2
1,5
1
0,5
0
-0,5
-1
-1,5
-2
-2,5
-3
*
*
*
Nuts
VOO
*
*
Control
*
Between-group: non-significant for SFA
*
SFA
MUFA
PUFA
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Urine tyrosol (μg/L): baseline vs. 1-yr
70
60
Baseline
1-y follow-up
55,4
50
41,7
40,3
40
30
20
10
0
VOO (n=127)
DOG
Nuts (n=115)
Control (n=102)
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Plasma alpha-linolenic acid (%): baseline vs. 1-yr
70
61
60
50
Baseline
1-y follow-up
42
41
40
30
20
10
0
VOO (n=112)
DOG
Nuts (n=101)
Control (n=101)
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Intervention vs. control


DOG
Significant between-group changes in food groups

VOO & nuts (+)

Vegetables (+)

Fruits (+)

Legumes (+)

14-unit MeDiet score (+)
Significant between-group changes in nutrient intake

Energy (+)

Carbohydrates (-)

Fiber (+)

Total fat (+)

MUFA, MUFA/SFA (+)

PUFA (+)

alpha-Linolenic acid (+)

Marine n-3 fatty acids (+)
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PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
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
1224 participants




409 VOO
411 Nuts
404 Control
Changes in the prevalence of MetS

ATP-III: 3 out of five





DOG
Waist
TG
HDL
Glucose
BP
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DOG
www.unav.es/preventiva
PREDIMED TRIAL
•
•
•
•
•
•
•
•
•
DOG
Rationale
Funding sources
Methods and intervention protocol
Pilot study: Risk Factors at 3-mo (Ann Intern Med 2006)
Cross-sectional assessments:
o Diet & inflammatory markers (Eur J Clin Nutr 2007)
o MeDiet & risk factors (Eur J CV Prev 2008)
3-mo changes in oxLDL (Arch Intern Med 2008)
1-yr changes in diet (J Am Diet Assoc 2008)
1-yr changes in MetS (Arch Intern Med 2008)
Other nested sub-studies
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Nested substudies
Main trial
DOG
1
2
3
4
5
6
7
...
n
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DOG
www.unav.es/preventiva
www.predimed.es
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Thank you
very much
DOG
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DOG
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de reserva
DOG
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http://www.controlled-trials.com/ISRCTN35739639
Effects of Mediterranean diet on the primary
prevention of cardiovascular disease
DOG
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http://www.controlled-trials.com/ISRCTN35739639
Effects of Mediterranean diet on the primary
prevention of cardiovascular disease
DOG
www.unav.es/preventiva
http://www.controlled-trials.com/ISRCTN35739639
Effects of Mediterranean diet on the primary
prevention of cardiovascular disease
DOG
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Dietary changes at 1-yr & 2-yr follow-up
DOG
Nutrient
MD+VOO
MD+nuts
Control
Prot 1yr
2 yr
CHO 1yr
2 yr
Fat 1yr
2 yr
SFA 1yr
2 yr
-0.1
-0.6*
-1.3*
-1.4*
+1.8*
+2,6*
-0.6*
-0,6*
-0.3*
-0.5*
-2.1*
-0.7*
+2.7*
+1,5*
-0.7*
-0,8*
+0.1
+0.3
+1.0*
+2.5*
-1.0*
-2,5*
-0.4*
-1,0*
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Dietary changes at 1-yr & 2-yr follow-up
DOG
Nutrient
MD+VOO
MD+nuts
Control
MUFA 1yr
2 yr
PUFA 1yr
2 yr
Fibre 1yr
2 yr
MD 1yr
14p 2 yr
+2.1*
+2.5*
+0.2
+0.7*
+2.2*
+2.9*
+1.9*
+2.4*
+1.6*
+1.8*
+1.8
+0.7*
+3.1*
+3.3*
+2.3*
+2.2*
-0.3
-1.0*
-0.3*
-0.4*
-0.5
-0.5
+0.5*
+0.8*
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DOG
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DOG
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DOG
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DOG
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DOG
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Power (asumming RR = 0,75)
1
0,9
0,8
0,7
0,6
0,5
0,4
0,3
0,2
0,1
0
600 580 560 540 520 500 480 460 440 420 400 380 360 340 320 300
DOG
Total # of events
(3 groups together)
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 The data from the
PREDIMED trial will be
analyzed at 5 intervals (4
interim analyses and the
final analysis).
 The 4 interim analyses to
decide on the continuation
of the PREDIMED trial will
be conducted after 2, 3, 4
and 5 years of median
follow-up.
 The 2-sided p-values for
stopping the trial at each
interim analysis are
DOG
Yr
Benefit Harm
2 08 5*10-6 9*10-5
Apr
3 09 0.001
Jun
0.005
4 10
Jul
0.02
0.009
5 11 0.02
Jun
0.05