2. PUBLISHED ON 25 FEB, 2013 IN NEJM

3. MEDITERRANEAN DIET
 The Mediterranean diet is a modern nutritional
recommendation inspired by the traditional dietary
patterns of southern ITALY, GREECE, and SPAIN .
 On November 17, 2010, UNESCO recognized this diet
pattern as an Intangible Cultural Heritage
of Italy, Greece, Spain and Morocco

4. THESE COUNTRIES HAVE A VERY LOW INCIDENCE OF
CARDIOVASCULAR DISEASE .
THE MEDITERRANEAN FOOD PATTERN HAS BEEN THE FACTOR
MOST FREQUENTLY INVOKED TO EXPLAIN THIS HEALTH
ADVANTAGE

5. MEDITERRANEAN DIET
 Its major characteristics are:
 a high consumption of non-refined
grains, legumes, nuts, fruits and vegetables;
 a relatively HIGH FAT INTAKE(>40% greater than
A RELATIVELY high-fat consumption (even OF TOTAL 40
percent of total energy intake) mostly from MUFA, which
CALORIE INTAKE) IN FORM OF OLIVE OIL AND NUTS
accounts for 20 percent or more of the total energy intake;
( MUFA ) IS THE HALLMARK OF MEDITERRANEAN
 olive oil used to cook and for dressing salads is the
DIET ,
principal source of fat;
 fish consumption is moderate to high;
 poultry and dairy products (usually as yogurt or cheese) are
consumed in moderate to small amounts;
 a low consumption of red meats, processed meats or meat
products;
 a moderate alcohol intake, usually in the form of red wine
consumed with meals

6. MEDITERRANEAN DIET
 Trials have shown that increasing adherence to the
Mediterranean diet has been consistently beneficial
with respect to the cardiovascular risk.
 A systematic review ranked the Mediterranean diet as
the most likely dietary model to provide protection
against coronary heart disease.
With this background, a randomized trial was
designed to test the efficacy of Mediterranean diet
on primary cardiovascular prevention.

7. STUDY DESIGN

8. STUDY DESIGN…
 The PREDIMED study (Prevención con Dieta
Mediterránea) was a parallel-group, multicenter,
randomized trial examining the potential benefits of a
Mediterranean-style diet for primary prevention of
cardiovascular disease (CVD).
 A total of 7,447 subjects aged 55 to 80 years were
enrolled.
 57% were female.

9. STUDY DESIGN…inclusion criteria
 Patient should not have any cardiovascular disease at
baseline.
 Patient should either have type 2 diabetes or
 three or more of the following major CVD risk factors:
 smoking,
 hypertension,
 elevated LDL-C,
 low HDL-C,
 overweight or obesity, or
 family history of premature coronary heart disease.

10. Subjects were randomized in a 1:1:1 fashion to 3 groups:
1) Mediterranean diet + extra-virgin olive oil
(≥4 tbsp/day; n=2,543)
2) Mediterranean diet + nuts (30 g mixed nuts/day,
including walnuts, almonds, and hazelnuts;
n=2,454)
3) Low-fat diet (control; n=2,450)
No total calorie restriction was advised and no physical
activity was promoted.

12.  The primary endpoint = composite of myocardial
infarction (MI), stroke, or CV mortality.
 Secondary endpoints included stroke, MI, CV
mortality, and all-cause mortality.
 The trial was stopped after a median of 4.8 years based
on an interim analysis showing benefits seen with
Mediterranean diets.

13. BASELINE CHARACTERISTICS OF
THE STUDY GROUPS

15. BASELINE CHARACTERISTICS CONT…

16. RESULTS

17. PRIMARY ENDPOINT EVENTS
The primary endpoint, a composite of MI, stroke, or CV mortality,
occurred as follows:
 Mediterranean diet + extra-virgin olive oil:
96 events (3.8%)
hazard ratio (HR), 0.70
P=0.009 vs the control diet
 Mediterranean diet + nuts:
83 events (3.4%)
HR, 0.70
P=0.02 vs the control diet
 Control group: 109 events (4.4%)

20. PRIMARY ENDPOINT PER 1000 PERSON YEARS
The rate of the primary endpoint per 1,000 person-years
was as follows:
Mediterranean diet + extra-virgin olive oil:
8.1 (95% CI, 6.6-9.9);
P=0.009 vs the control diet
Mediterranean diet + nuts: 8.0 (95% CI, 6.4-
9.9);
P=0.02 vs the control diet
Control group: 11.2 (95% CI, 9.2-13.5)

22. SECONDARY END POINTS
Stroke
 Mediterranean diet + extra-virgin olive oil: 49 events;
HR vs control, 0.67
P=0.04 vs the control diet
 Mediterranean diet + nuts: 32 events
HR vs control, 0.54
P=0.006 vs the control diet
 Control group: 58 events

23. SECONDARY END POINTS
MYOCARDIAL INFARCTION
 Mediterranean diet + extra-virgin olive oil: 37 events;
HR vs control, 0.80
P=0.34 vs the control diet
 Mediterranean diet + nuts: 31 events;
HR vs control, 0.74
P=0.22 vs the control diet
 Control group: 38 events

24. SECONDARY END POINTS
CV MORTALITY
 Mediterranean diet + extra-virgin olive oil: 26 events;
HR vs control, 0.69
P=0.17 vs the control diet
 Mediterranean diet + nuts: 31 events;
HR vs control, 1.01
P=0.98 vs the control diet
 Control group: 30 events

25. SECONDARY END POINTS
ALL-CAUSE MORTALITY
 Mediterranean diet + extra-virgin olive oil: 118 events;
HR vs control, 0.82 (95% CI, 0.64-1.07);
P=0.15 vs the control diet
 Mediterranean diet + nuts: 116 events; HR vs control,
0.97 (95% CI, 0.74-1.26);
P=0.82 vs the control diet
 Control group: 114 events

27. Groups assigned to Mediterranean diets did
better than the low fat diet group in terms of
both primary and secondary end-points

28.  In this trial, an energy-unrestricted Mediterranean diet
supplemented with either extra-virgin olive oil or nuts
resulted in risk reduction of major cardiovascular events
among high-risk persons who were initially free of
cardiovascular disease.
 These results support the benefits of the Mediterranean
diet for cardiovascular risk reduction.
 The results of our trial might explain, in part, the lower
cardiovascular mortality in Mediterranean countries than
in northern European countries or the United States.

29. PAST STUDIES
Multiple trials in the past have demonstrated beneficial
effects of mediterranian diet in
 Metabolic syndrome
 Diabetes mellitus
 Reducing markers of oxidation/inflammation and
endothelial dysfunction
Thus a causal role of mediterranian diet in
cardiovascular prevention has high biological
plausibility

30. ARCH INTERN MEDICINE 2009 Apr 13;169(7):659-69.
In applying a predefined algorithm, we identified strong evidence of a causal
relationship for protective factors, including intake of vegetables, nuts,
and monounsaturated fatty acids and Mediterranean, prudent, and highquality
dietary patterns, and harmful factors, including intake of trans– fatty acids and
foods with a high glycemic index or load and a western dietary pattern. Among
these dietary exposures, however, only a Mediterranean dietary
pattern has been studied in RCTs and significantly
associated with CHD.

31. lyon diet heart study (2001)showed a large
reduction in
rates of coronary heart disease events with a
modified mediterranean diet enriched with alpha-
linolenic acid (a key constituent of walnuts).

32. CONCLUSION: The adherence to
the Mediterranean Diet seems to reduce
the incidence of metabolic syndrome

33. HOW DOES MEDITERRANEAN DIET HELP?
 IMPROVES THE LIPID PROFILE
Replacing saturated fat with MUFA from
olive oil produces a decline in total and LDL
cholesterol, and maintains HDL cholesterol at
higher levels, thus obtaining a net advantage on
the overall lipid profile.

34. HOW DOES MEDITERRANEAN DIET HELP?
 DECREASES THE OXIDATIVE STRESS
olive oil is resistant to oxidative
modification, thus it does not lead to
formation of oxidation products like
peroxides, hydroxyperoxides etc , which
have a causal implication in heart diseases.

35. HOW DOES MEDITERRANEAN DIET HELP?
NEGATIVE EFFECT ON THROMBOGENECITY AND
ATHEROMA PLAQUE FORMATION
 incorporation of oleic acid into cultured endothelial cells
has shown to decrease the expression of endothelial
leukocyte adhesion molecules with reductions in VCAM-
1 and inhibition of nuclear factor-kappa B activation.
 Postprandial factor VII is significantly lower after a
MUFA-rich diet.
 Olive oil is also associated with a reduced DNA synthesis
in human coronary smooth muscle cells.

36. EFFECTS OF HIGH MUFA CONTENT
IN MEDITERRANEAN DIET

37. CONCLUSION
 This primary prevention trial showed that an energy-
unrestricted Mediterranean diet, supplemented with
extra-virgin olive oil or nuts, resulted in a substantial
reduction in the risk of major cardiovascular events
among high-risk persons. The results support the
benefits of the Mediterranean diet for the
primary prevention of cardiovascular disease

38. THANKYOU
FOR A
HEALTHY
HEART

40. Salient components of the Mediterranean diet reportedly
associated with better survival include
 moderate consumption of ethanol (mostly from wine),
 low consumption of meat and meat products, and
 high consumption of vegetables, fruits, nuts,
 legumes, fish, and olive oil
Perhaps there is a synergy among the nutrient-rich foods
included in the Mediterranean diet that fosters favourable
changes in intermediate pathways of cardio-metabolic risk,
such as blood lipids, insulin sensitivity, resistance to
oxidation, inflammation, and vaso-reactivity.

41. MEDITERRANEAN DIET
 The principal aspects of this diet include
proportionally high consumption of OLIVE OIL,
LEGUMES, UNREFINED CEREALS, FRUITS,
and VEGETABLES, moderate to high consumption of
fish, moderate consumption of dairy products (mostly
as cheese and yogurt), moderate wine consumption,
and low consumption of meat and meat products.
 there are discrepancies among nutrition experts
because of the high-fat content of Mediterranean Diets
(up to >40% of total energy intake), which is in
conflict with the usual recommendation to follow a
low-fat diet in order to avoid overweight/obesity and to
prevent coronary heart disease (CHD)

43.  In its simplest form the hazard ratio can be interpreted
as the chance of an event occurring in the treatment
arm divided by the chance of the event occurring in
the control arm, or vice versa, of a study.

44. Our results compare favourably with those of
the Women’s Health Initiative Dietary
Modification Trial, wherein a low-fat dietary
approach resulted in no cardiovascular benefit.

48. Participants with hypertension, dyslipidemia and
higher BMI responded better to Mediterranean Diets

49. Exclusion criteria
 Documented history of previous cardiovascular disease, including CHD
(angina, myocardial infarction, coronary revascularization procedures or
existence of abnormal Q waves in the electrocardiogram (EKG)), stroke
(either ischemic or hemorrhagic, including transient ischemic attacks), and
clinical peripheral artery disease with symptoms of intermittent
claudication.
 Severe medical condition that may impair the ability of the person to
participate in a nutrition intervention study (e.g. digestive disease with fat
intolerance, advanced malignancy, or major neurological, psychiatric or
endocrine disease)
 Any other medical condition thought to limit survival to less than 1 year.
 Immunodeficiency or HIV-positive status.
 Illegal drug use or chronic alcoholism or total daily alcohol intake >80 g/d.
 Body mass index > 40 kg/m2.
 Difficulties or major inconvenience to change dietary habits

50. Exclusion criteria
 Impossibility to follow a Mediterranean-type diet, for
religious reasons or due to the presence of disorders of
chewing or swallowing (e.g., difficulties to consume nuts)
 History of food allergy with hypersensitivity to any of the
components of olive oil or nuts.
 Participation in any drug trial or use of any
investigational drug within the last year.
 Institutionalized patients for chronic care, those who lack
autonomy, are unable to walk, lack a stable address, or are
unable to attend visits in the PCC every 3 months.
 Illiteracy.
 Patients with an acute infection or inflammation (e.g.,
pneumonia) are allowed to participate in the study 3
months after the resolution of their condition.