Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

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

Background

A traditional Mediterranean diet consists of high intake of vegetables, fruit, cereals, nuts and olive oil, moderate  intake of fish and poultry, and low consumption of dairy products, red meat, processed meat and sweets, and moderate intake of wine, consumed with a meal.
Previous observational studies already showed a positive effect of such a diet on the risk of developing cardiovascular disease [1-3]. Biological mechanisms that may explain this effect have been described [2-5].
A randomized multicenter PREDIMED trial (Prevención con Dieta Mediterránea [8,9]) now compared the effect of two Mediterranean diets (one supplemented with extra virgin olive oil and one supplemented with nuts) with a control diet (where participants were advised to limit fat intake) on cardiovascular endpoints: myocardial infarction, stroke or death from cardiovascular causes.
7477 participants (55-80 years old) without cardiovascular disease at the time of enrollment, had type 2 diabetes mellitus or at least two of the following risk factors: smoking, hypertension, high LDL-cholesterol, low HDL-cholesterol, overweight or obesitas, or a family history of premature coronary heart disease.
Participants received regular dietary training. Questionnaires were filled out on a yearly basis, on medical information, food intake and physical activity. Biomarkers were measured in randomly picked participants of the Mediterranean diet groups, to monitor adherence to the diet.
A total of 288 cardiovasculair endpoints (myocardial infaction, stroke or death) were observed in the 7-year trial period (median follow-up: 4.8 years). Participants adhered well to dietary assignments  and physical activity was comparable in all diet groups.

Main findings

• The risk of composite primary endpoint of myocardial infarction, stroke or death from cardiovascular cause was reduced by 30% through following a Mediterranean diet supplemented with extra virgin olive oil (Hazard Ratio (HR) 95%CI: 0.53-0.91), or when supplemented with nuts (HR 95%CI: 0.53-0.94), as compared to a control diet.
• Analysis of the separate endpoints showed a statistically significant protective effect only for the risk of stroke (HR: 0.61, 95%CI: 0.44-0.86).

Conclusion

Following a Mediterranean diet protects agains myocardial infarction, stroke or death from cardiovascular cause, in individuals at high cardiovascular risk, without introducing any adverse effects. The protective effect is strongest for the risk of stroke.

References

1. Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr 2010;92:1189-96.
2. Serra-Majem L, Roman B, Estruch R. Scientific evidence of interventions using the Mediterranean diet: a systematic review.Nutr Rev 2006;64:S27-S47.
3. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report
of the Lyon Diet Heart Study. Circulation 1999;99:779-85
4. Esposito K, Marfella R, Ciotola M, et al. Effect of a Mediterranean-style diet on endothelialdysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004; 292:1440-6.
5. Vincent-Baudry S, Defoort C, Gerber M, et al. The Medi-RIVAGE study: reduction of cardiovascular disease risk factors after a 3-mo intervention with a Mediterranean-type diet or a low-fat diet. Am J Clin Nutr 2005;82:964-71.
6. Estruch R, Martínez-González MA, Corella D, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1-11.
7. Shai I, Schwarzfuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean,
or low-fat diet. N Engl J Med 2008;359:229-41. [Erratum, N Engl J Med 2009;361:2681.
8. Martínez-González MA, Corella D,Salas-Salvadó J, et al. Cohort profile: design and methods of the PREDIMED
study. Int J Epidemiol 2012;41:377-85.
9. The PREDIMED Study (http://www.predimed.org).Background:
Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events.

Methods:
In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years.

Results:
A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70
(95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported.

Conclusions:
Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish government’s Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.)