Mediterranean Diet Reduces Atherosclerosis Progression in Coronary Heart Disease

An Analysis of the CORDIOPREV Randomized Controlled Trial

Jose Jimenez-Torres, MD; Juan F. Alcalá-Diaz, MD, PhD; Jose D. Torres-Peña, MD, PhD; Francisco M. Gutierrez-Mariscal, PhD; Ana Leon-Acuña, MD, PhD; Purificación Gómez-Luna, PhD; Carolina Fernández-Gandara, BS; Gracia M. Quintana-Navarro, BS; Jose C. Fernandez-Garcia, MD, PhD; Pablo Perez-Martinez, MD, PhD; Jose M. Ordovas, PhD; Javier Delgado-Lista MD, PhD; Elena M. Yubero-Serrano, PhD; Jose Lopez-Miranda, MD, PhD


Stroke. 2021;52(11):3440-3449. 

In This Article

Abstract and Introduction


Background and Purpose: Lifestyle and diet affect cardiovascular risk, although there is currently no consensus about the best dietary model for the secondary prevention of cardiovascular disease. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention) is an ongoing prospective, randomized, single-blind, controlled trial in 1002 coronary heart disease patients, whose primary objective is to compare the effect of 2 healthy dietary patterns (low-fat rich in complex carbohydrates versus Mediterranean diet rich in extra virgin olive oil) on the incidence of cardiovascular events. Here, we report the results of one secondary outcome of the CORDIOPREV study. Thus, to evaluate the efficacy of these diets in reducing cardiovascular disease risk. Intima-media thickness of both common carotid arteries (IMT-CC) was ultrasonically assessed bilaterally. IMT-CC is a validated surrogate for the status and future cardiovascular disease risk.

Methods: From the total participants, 939 completed IMT-CC evaluation at baseline and were randomized to follow a Mediterranean diet (35% fat, 22% monounsaturated fatty acids, <50% carbohydrates) or a low-fat diet (28% fat, 12% monounsaturated fatty acids, >55% carbohydrates) with IMT-CC measurements at 5 and 7 years. We also analyzed the carotid plaque number and height.

Results: The Mediterranean diet decreased IMT-CC at 5 years (−0.027±0.008 mm; P<0.001), maintained at 7 years (−0.031±0.008 mm; P<0.001), compared to baseline. The low-fat diet did not modify IMT-CC. IMT-CC and carotid plaquemax height were higher decreased after the Mediterranean diet, compared to the low-fat diet, throughout follow-up. Baseline IMT-CC had the strongest association with the changes in IMT-CC after the dietary intervention.

Conclusions: Long-term consumption of a Mediterranean diet rich in extravirgin olive oil, if compared to a low-fat diet, was associated with decreased atherosclerosis progression, as shown by reduced IMT-CC and carotid plaque height. These findings reinforce the clinical benefits of the Mediterranean diet in the context of secondary cardiovascular prevention.

Registration: URL:; Unique identifier: NCT00924937.

Graphic Abstract: An online graphic abstract is available for this article.


Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in developed countries and imposes a significant economic burden on both the health-care system and society.[1,2] Lifestyle and dietary habits have been demonstrated to affect cardiovascular risk.[3] Evidence supports that certain individual nutrients and foods exert cardiovascular benefits. However, the study of overall dietary patterns may provide a more powerful tool for assessing dietary habits by the evaluation of the synergistic and cumulative effects of specific nutrients on cardiovascular health.

The Mediterranean diet is an increasingly popular dietary pattern, recognized for its health benefits such as CVD prevention.[4,5] The effectiveness of the Mediterranean diet in reducing cardiovascular risk has been seen in primary prevention. In this context, the PREDIMED study (Prevención con Dieta Mediterránea) has shown that the Mediterranean diet would provide long-term high benefits on CVD compared with a reduced-fat diet.[6] However, no scientific evidence is currently available to indicate which dietary pattern is more effective in secondary cardiovascular prevention. The CORDIOPREV study (Coronary Diet Intervention With Olive Oil and Cardiovascular Prevention), an ongoing dietary intervention trial, compares the rate of cardiovascular events of 2 healthy dietary patterns for secondary cardiovascular prevention.[7] One of these diets is low in fat and rich in complex carbohydrates, as recommended by the National Cholesterol Education Program for these type of patients.[8] The other diet in this study is a Mediterranean diet, rich in extravirgin olive oil (EVOO), fruit and vegetables, whole grains, fish, and nuts, and low in saturated fats.[9]

Evaluation of the intima-media thickness of both common carotid arteries (IMT-CC) using B mode ultrasound is a noninvasive, well-validated clinical method. IMT-CC is considered a surrogate marker of subclinical atherosclerosis and a strong predictor of new myocardial infarction and stroke.[10,11] A large body of evidence supports the beneficial effect of dietary strategies in decreasing IMT-CC. In a 15-year prospective cohort study in older women, the consumption of a range of vegetables was inversely associated with IMT-CC.[12] Similarly, in a cross-sectional analysis, Maugeri et al[13] found an inverse relationship between the intake of dietary antioxidants and IMT-CC in adults. The PREDIMED study did not show changes in IMT-CC but found a decrease in internal carotid-IMT and plaque height after consumption of a Mediterranean diet supplemented with nuts (but not with EVOO), compared to a reduced-fat diet.[14]

Based on these previous evidence, in this secondary prevention study, we evaluated the efficacy of 2 healthy dietary patterns (a Mediterranean diet rich in EVOO compared to a low-fat diet and rich in complex carbohydrates) in decreasing IMT-CC in patients with coronary heart disease (CHD). The secondary objective was to investigate the effect of these dietary patterns on other parameters related to atherosclerosis progression, as carotid plaque number and height.