Favourable changes in carotid artery intima media thickness with Mediterranean diet plus nuts

Changes in Ultrasound-Assessed Carotid Intima-Media Thickness and Plaque With a Mediterranean Diet: A Substudy of the PREDIMED Trial

Literature - Sala-Vila A et al., ATVB 2013 - Arterioscler Thromb Vasc Biol. 2013 Nov 27

Sala-Vila A, Romero-Mamani ES, Gilabert R, et al.,
Arterioscler Thromb Vasc Biol. 2013 Nov 27. [Epub ahead of print]


The Prevención con Dieta Mediterránea (PREDIMED) trial has previously shown that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil (EVOO) or 30 g/d of mixed nuts reduced incident cardiovascular (CV) events with 30%, as compared to a control (low fat) diet. In the PREDIMED study, 7447 participants at high CV risk but without CV disease at enrolment, were followed for a mean of 4.8 years, in which the incidence of a composite end point of CV death, myocardial infarction and stroke was documented [1].
The underlying biological mechanisms via which EVOO and nuts protect against CVD remains to be uncovered. Their favourable fatty acid profile and richness in bioactive phytochemicals with antioxidant and anti-inflammatory properties suggests that they exert an antiatherogenic effect [2-4].
Artery vessel wall enlargement is an early feature of atherosclerosis that can be evaluated by ultrasound determination of carotid artery intima-media thickness (IMT)[5]. In a previous PREDIMED substudy, participants with a high carotid atherosclerotic burden who followed the MedDiets supplemented with EVOO or nuts showed regression of mean common carotid artery (CCA)-IMT after 1 year, as compared to the control diet [6]. Evidence now exists that IMT of the internal carotid artery (ICA) is  more representative of atherosclerosis and better predict CVD than CCA-IMT [7,8]. Thus, this study analyses maximum ICA-IMT and plaque height in subjects at high vascular risk who were randomised to a MedDiet supplemented with EVOO (n=55) or nuts (n=42) or a control diet (n=58), and who were followed for over 2 years.

Main results

  • Participants in the control group showed a significant progression of ICA-IMT(max) (0.188 mm 95%CI: 0.077-0.299) and plaque (max) (0.106 mm, 95%CI: 0.001-0.210).
    Participants allocated to MedDiet with nuts showed a significant regression in ICA-IMT(mean) (-0.084 mm, 95%CI: -0.158 to -0.010) or arrested progression (ICA-IMT(Max)[ -0.030, 95%CI: -0.153 to 0.093] and plaque(max)[ -0.091 mm, 95%CI: -0.206 to 0.023].
    No significant changes were seen in participants who followed the MedDiet with EVOO.
  • Change in plaque (max) was only significantly determined by allocation into the MedDiet+nuts group as compared to the control diet group (B= -0.0198, 95%CI: -0.343 to -0.054, P=0.008), use of anti-hypertensive drugs at baseline (B=0.132, 95%CI: 0.001 to 0.263, P=0.048) and baseline plaque(max) (B= -0.137, 95%CI: -0.217 to – 0.057, P=0.001).
  • Changes in objective biomarkers were mean increases from baseline to end of the trial of 0.10% for plasma α-linolenic acid in the MedDiet with nuts group and of 337 μg/L in urinary hydroxytyrosol in the MedDiet with EVOO group (P=0.003 versus control diet group for both), respectively, indicating good compliance with the supplemental foods.

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This randomised study shows that an intervention with a MedDiet supplemented with 30 g/day of mixed nuts for a mean of 2.4 years induced regression of ICA-IMT (mean) and delayed the progression of both ICA-IMT(max) and plaque(max). No changes were seen in participants who followed the MedDiet supplemented with EVOO, but progression of ICA-IMT(max) and plaque(max) was observed in the control group.
Delayed IMT and plaque progression may in part explain the reduction of CVD events, in particular stroke, previously observed in the nut-supplemented arm of the PREDIMED trial. Diets rich in polyunsaturated fats and bioactive molecules from plant sources may delay atherosclerosis progression, thereby likely reducing plaque vulnerability.

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1. Estruch R, Ros E, Salas-Salvadó J, et al. Primary prevention of cardiovascular disease with Mediterranean diets. N Engl J Med. 2013;368:1279–1290.
2. López-Miranda J, Pérez-Jiménez F, Ros E, et al. Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008. Nutr Metab Cardiovasc Dis. 2010;20:284–294.
3. Ros E, Mataix J. Fatty acid composition of nuts–implications for cardiovascular health. Br J Nutr. 2006;96(suppl 2):S29–S35.
4. Urpi-Sarda M, Casas R, Chiva-Blanch G, et al. Virgin olive oil and nuts as key foods of the Mediterranean diet effects on inflammatory biomarkers related to atherosclerosis. Pharmacol Res. 2012;65:577–583.
5. de Groot E, van Leuven SI, Duivenvoorden R, et al. Measurement of carotid intima-media thickness
to assess progression and regression of atherosclerosis. Nat Clin Pract Cardiovasc Med. 2008;5:280–288.
6. Murie-Fernandez M, Irimia P, Toledo E, et al; PREDIMED Investigators. Carotid intima-media thickness changes with Mediterranean diet: a randomized trial (PREDIMED Navarra). Atherosclerosis. 2011;219:158–162.
7. Polak JF, Pencina MJ, Pencina KM, et al. Carotid-wall intima-media thickness and cardiovascular events. N Engl J Med. 2011;365:213–221.
8. Inaba Y, Chen JA, Bergmann SR. Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis. 2012;220:128–133.

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