Miguel Ángel Martinez-Gonzalez, MD, PhD, MPH
Professor & Chair, Preventive Medicine
Department of Preventive Medicine and Public Health, University of Navarra, Instituto de Investigación Sanitaria de Navarra (IdiSNA)
Harvard TH Chan School of Public Health
The PREDIMED (“PREvención con DIeta MEDiterránea”) primary prevention trial assessed during 2003-2010 the long-term effects of the Mediterranean diet (MedDiet) on clinical events of cardiovascular disease (CVD). This trial was planned for 6 years, but it stopped early after intervention for 4.8 years, as recommended by the Data and Safety Monitoring Board following stopping rules established a priori in the protocol. PREDIMED randomized 7447 men and women at high CVD risk into three diets: MedDiet supplemented with extra-virgin olive oil (EVOO), MedDiet supplemented with nuts, and control diet (advice on a low-fat diet). During the trial 288 CVD events (a composite of myocardial infarction, stroke or CVD death) were observed. In the initial publication (N Engl J Med 2013) the hazard ratios (HR) were 0.70 (95% CI, 0.53-0.91) for the MedDiet+EVOO and 0.70 (CI, 0.53-0.94) for the MedDiet+nuts compared to the control group. After accounting for small departures from individual randomization in 1 of the 11 centers (affecting 6.2% of total participants) and the clustering effect of allocating partners of a previous participant to the same intervention group as their relatives (5.7% of the trial), the HRs only very slightly changed to 0.69 for the MedDiet+EVOO and 0.72 for the MedDiet+nuts with similar confidence intervals (N Engl J Med 2018). A wide array of sensitivity analyses, including the removal of these participants not individually randomized, demonstrated the robustness of results. Multivariable-adjusted HR for incident diabetes (273 cases) among 3541 non-diabetic participants was 0.70 (0.54-0.92) for both MedDiet groups versus control. Significant improvements in classical and emerging CVD risk factors also supported a favorable effect of both MedDiets rich in olive oil on blood pressure, insulin sensitivity, lipid profiles, lipoprotein particles, inflammation, oxidative stress, and carotid atherosclerosis.
The PREDIMED-Plus is a new trial, started in 2013, designed to evaluate the long-term effectiveness of an intensive weight-loss lifestyle intervention on primary cardiovascular prevention including 6874 participants randomly allocated 1:1 to intervention or control. Extra-virgin olive oil was provided for free to all participants. After 12-month intervention, a 17-item score assessing adherence to an energy-reduced Mediterranean diet exhibited an average increase of 4.3 points in the intervention group (>50% relative improvement) versus 2.0 in control (23% relative improvement). The intervention group showed greater attainments than the control group in other scores reflecting high-quality dietary patterns. A higher proportion of participants improved their 1-year levels of cardiovascular risk factors in the intervention than in the control group.