Predimed study

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

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Estruch J et al. NEJM February 25, 2013 DOI: 10.1056/NEJMoa1200303

Introduction• Systematic reviews of prospective cohort studies suggest that

Mediterranean Diet pattern (Med Diet) is linked to better cardiovascular (Mente et al. 2009), cognitive (Daviglus et al. 2011), weight management outcomes (Esposito et al. 2011) & cancer outcomes (Sofi et al 2010)

• Lyon Diet Heart Study is so far the only randomized trial with morbidity and mortality outcomes on Med Diet. The study delivered robust results favouring Med Diet vs usual French Diet (de Lorgeril et al 1994).

• It may be argued that Oslo Diet Heart (1966) study was also Med Diet study. It also delivered clear benefits in favor of Med Diet

• The effects of Med Diet as primary prevention strategy are not known

2 www.pronutritionistblog.com

Methods 1/4

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Note! Processed and red meat was restricted in both groups and fish encouraged in both groups.

Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI: 10.1056/NEJMoa1200303

Methods 2/4

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• High risk patients in primary care setting (Spain)– A) Type 2 Diabetes OR

– B) Minimum 3 out of the following: Smoking, LDL>4,1 (or statin in use), low HDL, hypertension, BMI>25 and CHD heritage

– Exclusion criteria: Not ready to the dietary change (Prochaska & DiClemente Scale), MI, peripheral artery disease & allergy to nuts

• N=7447• Diets

– A) American Heart Association diet (version from year 2000) without any free delivery of food items

– B) Mediterranean Diet (Med Diet) with free extra virgin olive oil (minimum use per day is 4 teaspoons)

– C) Mediterranean Diet with free nut mix , 30 g/day (walnuts 15 g, almonds 7,5 g & hazelnuts 7.5 g)

– Diet were constructed and patients informed by study dietitians

– Adherence to diets is evaluated by Med Diet scores and AHA scores

Marttinez-González et al. Cohort Profile: design and methods of the PREDIMED study. International Journal of Epidemiology 2010;1–9

Methods 3/4

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• Primary endpoints – Composite endpoint of myocardial infarction, strokes and

cardiovascular deaths

• Secondary endpoints– Deaths (any reason)

– Myocardial infarctions

– Strokes

– Dementia and other neurodegenerative diseases

– Cancers

– Surrogate markers like LDL, HDL, inflammation markers, glucose, insulin …

Marttinez-González et al. Cohort Profile: design and methods of the PREDIMED study. International Journal of Epidemiology 2010;1–9

Methods 4/4

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Randomization of patients (High risk patients in primary care, Spanish n = 7447)

A) Mediterranean diet including free extra virgin olive oil daily

C) Low fat diet (AHA diet early 2000), no free delivery of any food items

Year 2003 →

B) Mediterranean diet including free nut mix daily

Mean follow up 4,8 years∼

Drop out rates were very low. 11,4 % of participants were lost in control group and 5,4 % in Med Diet groups

Year 2012

Results /primary end point

Risk of composite cardiovascular end point was reduced by 30 % in both Med Diet groups vs controls.

Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI: 10.1056/NEJMoa1200303

Results /myocardial infarctions

Incidence of myocardial infarctions was not significantly different between groups (trend favouring Med Diet)

Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI: 10.1056/NEJMoa1200303 (SUPPLEMENT MATERIAL)

Results /strokes

Strokes were reduced by nut enriched Med Diet by 49 % and by extra virgin olive oil based 36 %

Estruch J et al. Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. NEJM February 25, 2013 DOI: 10.1056/NEJMoa1200303 (SUPPLEMENT MATERIAL)

Results / mortality end points

•Incidence of fatal cardiovascular events was not significantly different between groups

•Total mortality was not significantly different between groups

Results / Diets

• There was no difference is the use of red and prosessed meat bwetween the groups (disencouraged also in the control group)

• Control group used also a diet high in fish, fruits and vegetables– More than 60 % of participants in control group used

veggies and fruits at least five servings per day – 66 % of participants in control group used lean fish at least

three servings per week– Intake of fiber was at the same level in between the groups

• Intake of saturated fat did not differ between the groups. Intake of ALA (plant based PUFA) was higher in nut enriched Med Diet group

• It seems that the biggest changes in diet happened in nut, olive oil, sofrito and wine intake

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Similarities & differences vs other Med Diet trials

• Outcomes on dementia, cancer, strokes and myocardial infarctions and deaths will be published soon

PredimedACTIVE GROUPSN=7447 (at start)

Lyon Heart Study ACTIVE GROUPN=584 (at end)

Oslo Diet HeartACTIVE GROUPN=412 (at start)

Fat used (provides for free in all 3 trials)

Extra virgin olive (Active Group A only)

Canola spread, canola oil & olive oil

Soy oil

Nuts Provided for free (Active Group B only)

Encouraged Encouraged

Fish (oily) Encouraged Encouraged Canned sardines in oil for free

Red & Processed meat

To be restricted To be restricted To be restricted

Whole grains Not stated (neutral) Encouraged Encouraged

Fruit/berries Encouraged Encouraged Encouraged

Vegetables Encouraged Encouraged Encouraged

Butter & milk fat Butter resticted, dairy neutral

To be restricted To be restricted

Alcohol Wine encouraged Wine encouraged Alcohol “allowed”

My discussion

• Thisis the largest randomized study ever on Mediterranean diet. Thus, the results will have strong and lasting impact

• Done in modern era (vs fat replacement RCT during 1960’s)

• The results are in line with surrogate marker trials (short RCTs), prospective cohort studies and ecological correlations. Thus, mediterranean diet pattern has the most robust evidence supporting its effect on cardiovascular health

• This is the first randomized trial on diet demonstrating a clear benefit in terms of strokes

• Mechanism of action is not clear as the data on lipid ,inflammation, blood pressure, sugar and other parameters was not disclosed at his stage

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Please read the whole paper

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Estruch J et al. NEJM February 25, 2013 DOI: 10.1056/NEJMoa1200303

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Reijo Laatikainen, M Sc, MBA,Registered Dietitian

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