Primary prevention of cardiovascular disease with a Mediterranean diet

Estruch R, Ros E, Salas-Salvadó, et al; for the PREDIMED study investigators. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279-1290.

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. Subjects had no CVD at baseline and all had either 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. An average of 40% of subjects enrolled in the trial were using statins at baseline. 

Subjects were randomized in a 1:1:1 fashion to:

  • Mediterranean diet + extra-virgin olive oil (≥4 tbsp/day; n=2,543)
  • Mediterranean diet + nuts (30 g mixed nuts/day, including walnuts, almonds, and hazelnuts; n=2,454)
  • Low-fat diet (control; n=2,450) 

No total calorie restriction was advised and no physical activity was promoted. The primary endpoint was a 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. (Click here for slide) 

Dietary recommendations in PREDIMED were as follows: (Click here for slide) 

Mediterranean Diet (n=4,997)*  Low-fat Diet (control) (n=2,450) 
Recommended (Goal)
  • Olive oil (≥4 tbsp/d)
  • Tree nuts and peanuts (≥3 servings/wk)
  • Fresh fruits (≥3 servings/d)
  • Vegetables (≥2 servings/d)
  • Fish (esp fatty fish), seafood (≥3 servings/wk)
  • Legumes (≥3 servings/wk)
  • Sofrito† (≥2 servings/wk)
  • White meat (instead of red meat)
  • Wine with meals‡ (≥7 glasses/wk)
Discouraged (Goal)
  • Soda (<1 drink/d)
  • Commercial bakery goods, sweets, pastries (<3 servings/wk)
  • Spread fats (<1 serving/d)
  • Red and processed meats (<1 serving/d)
 
Recommended (Goal)
  • Low-fat dairy products (≥3 servings/d)
  • Bread, potatoes, pasta, rice (≥3 servings/d)
  • Fresh fruits (≥3 servings/d)
  • Vegetables (≥2 servings/wk)
  • Lean fish and seafood (≥3 servings/wk)
Discouraged (Goal)
  • Vegetable oils (including olive oil) (≤2 tbsp/d)
  • Commercial bakery goods, sweets, pastries (≤1 serving/wk)
  • Nuts and fried snacks (≤1 serving/wk)
  • Red and processed fatty meats (≤1 serving/wk)
  • Visible fat in meats and soups (always remove)
  • Fatty fish, seafood canned in oil (≤1 serving/wk)
  • Spread fats (≤1 serving/wk)
  • Sofrito† (≤2 servings/wk)
 

*Two treatment groups: Mediterranean diet + extra-virgin olive oil and Mediterranean diet + nuts
†Sauce made with olive oil, tomato, garlic, onion, herbs
‡Optional–only for habitual drinkers

 

Results  

The primary endpoint, a composite of MI, stroke, or CV mortality, occurred as follows: (Click here for slide) 

  • Mediterranean diet + extra-virgin olive oil: 96 events (3.8%); hazard ratio (HR), 0.70; 95% confidence interval (CI), 0.53-0.91; P=0.009 vs the control diet
  • Mediterranean diet + nuts: 83 events (3.4%); HR, 0.70; 95% CI, 0.53-0.94; P=0.02 vs the control diet
  • Control group: 109 events (4.4%)

The rate of the primary endpoint per 1,000 person-years was as follows: (Click here for slide) 

  • 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)
A Mediterranean diet supplemented with extra-virgin olive oil or nuts resulted in an absolute risk reduction of 3 major CV events per 1,000 person-years and a relative risk reduction of approximately 30% in high-risk subjects who were free from CVD at baseline.
 
For secondary endpoints: (Click here for slide) 
Stroke
  • Mediterranean diet + extra-virgin olive oil: 49 events; HR vs control, 0.67 (95% CI, 0.46-0.98); P=0.04 vs the control diet
  • Mediterranean diet + nuts: 32 events; HR vs control, 0.54 (95% CI, 0.35-0.84); P=0.006 vs the control diet
  • Control group: 58 events 
MI
  • Mediterranean diet + extra-virgin olive oil: 37 events; HR vs control, 0.80 (95% CI, 0.51-1.26); P=0.34 vs the control diet
  • Mediterranean diet + nuts: 31 events; HR vs control, 0.74 (95% CI, 0.46-1.19); P=0.22 vs the control diet
  • Control group: 38 events 
 
CV mortality
  • Mediterranean diet + extra-virgin olive oil: 26 events; HR vs control, 0.69 (95% CI, 0.41-1.16); P=0.17 vs the control diet
  • Mediterranean diet + nuts: 31 events; HR vs control, 1.01 (95% CI, 0.61-1.66); P=0.98 vs the control diet
  • Control group: 30 events 
 
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 

 

February 2013 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Last Modified: 3/23/2015