By Jeffrey T. Jensen, MD, MPH
Synopsis: A Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events in a large, multicenter, randomized study of high-risk women and men conducted in Spain.
Source: Estruch R, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med 2013;368:1279-1290.
With the background of several observational cohort studies and a secondary prevention trial that demonstrate a reduction of adverse cardiovascular outcomes among adults adherent to a Mediterranean diet, the authors designed the PREDIMED (Prevención con Dieta Mediterránea) trial, a parallel-group, multicenter, randomized study conducted in Spain. Beginning in 2003, they recruited and enrolled men and women with no cardiovascular disease (CVD) at enrollment, but who were identified to be at high risk for developing CVD on the basis of having either type 2 diabetes mellitus or at least three of the following major risk factors: smoking, hypertension, elevated low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels, overweight or obesity, or a family history of premature coronary heart disease. Subjects were randomly assigned to one of three dietary intervention groups: a Mediterranean diet supplemented with extra-virgin olive oil (approximately 1 liter per week), a Mediterranean diet supplemented with nuts (30 g of mixed nuts per day [15 g of walnuts, 7.5 g of hazelnuts, and 7.5 g of almonds]), or a control diet (advice to reduce dietary fat).
Participants received baseline dietary counseling and quarterly individual and group educational sessions. Depending on group assignment, subjects also received either free provision of extra-virgin olive oil, the mixed nuts, or small nonfood gifts (control diet group). Biomarkers of compliance, including urinary hydroxytyrosol levels (to confirm compliance in the group receiving extra-virgin olive oil) and plasma alpha-linolenic acid levels (to confirm compliance in the group receiving mixed nuts), were measured in random subsamples of participants at 1, 3, and 5 years.
The primary endpoint 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 after a total of 7447 persons were enrolled (age range, 55-80 years). More than half (57%) of the subjects were women. A reduction in the risk of CVD was seen with both Mediterranean diet groups; the multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54-0.92) for the group assigned to a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54-0.96) for the group assigned to a Mediterranean diet with nuts. No diet-related adverse effects were reported. The two Mediterranean diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses.
The authors concluded that the evidence from this randomized, controlled trial demonstrates that a Mediterranean diet supplemented with extra-virgin olive oil or nuts can reduce the incidence of major cardiovascular events in high-risk adults.
Although this elegant study received only limited press, the implications for our patients are profound. While there has been much written about obesity, lack of exercise, and other factors associated with cardiovascular risk, we have had little to offer high-risk women for risk reduction other than general advice about diet and exercise and statins. In too many primary care practices, the typical approach is to abandon dietary change early, and proceed directly to statin therapy. Many patients seem to like this approach, as it requires no major lifestyle modification.
While substantial evidence1 supports the use of statins to reduce the risk of CVD, the results of the PREDIMED trial should reinforce our counseling of diet changes as the cornerstone of prevention. About 40% of subjects in each of the diet cohorts in this study were statin users; the supplemented Mediterranean diet groups still enjoyed a 30% reduction in CVD. While this study enrolled both men and women, more than half were women, and a subgroup analysis showed no differences in outcomes.
But can we study a Mediterranean diet in Spain? Contrary to cultural expectation, fewer than 9% of subjects were eating a Mediterranean diet, according to results of the baseline dietary screening (perhaps those who did were healthy and not part of the screening population). This was a high-risk group, with almost 50% using ACE inhibitors and almost one-third on oral hypoglycemic agents.
Importantly, subjects in this study overall were compliant with the dietary intervention. By 3 years, they significantly increased weekly servings of fish (by 0.3 servings) and legumes (by 0.4 servings) in comparison with those in the control group. They also increased their consumption of either extra virgin olive oil (to 50 g and 32 g per day, respectively) or nuts (to 0.9 and 6 servings per week) according to their assigned groups. These main nutrient changes were associated with reductions of other fats. For this reason, the incorporation of olive oil or nuts is the key. Notably, there were no significant differences in physical activity between the three groups.
Talking about weight loss and exercise can be difficult, and vague recommendations are not helpful. Evidence from the PREDIMED trial should be presented to encourage women to eat better, not less. There are a number of heart-healthy Mediterranean style cookbooks available. The recipe options are delicious, and go well with an Oregon pinot noir!
1. Taylor F, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev 2013;1:CD004816.