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Peripheral Arterial Disease and Cardiovascular Risk: The Role of Mediterranean Diet Christina Chrysohoou, Katherine Esposito, Dario Giugliano and Demosthenes B. Panagiotakos ANGIOLOGY published online 28 October 2014 DOI: 10.1177/0003319714556651 The online version of this article can be found at: http://ang.sagepub.com/content/early/2014/10/28/0003319714556651

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Editorial

Peripheral Arterial Disease and Cardiovascular Risk: The Role of Mediterranean Diet

Angiology 1-3 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319714556651 ang.sagepub.com

Christina Chrysohoou, MD, PhD1, Katherine Esposito, MD, PhD2, Dario Giugliano, MD, PhD3, and Demosthenes B. Panagiotakos, DrMedSci4

Peripheral arterial disease (PAD) refers to the obstruction of large arteries of the body. The prevalence of PAD in the general population is estimated to be around 12% to 14% and increases up to 20% of those over 70 years old.1 It is of interest that 70% to 80% of affected individuals are asymptomatic and only a minority requires revascularization or amputation.1 Major risk factors for PAD are smoking, physical inactivity, dyslipidemias, hypertension, diabetes, and, consequently, the metabolic syndrome (MetS); PAD affects approximately 30% of people with diabetes mellitus.2-4 Since the early 1990s, studies revealed the association between PAD and mortality from cardiovascular disease (CVD). For example, Criqui et al evaluated the association of large-vessel PAD with mortality rates from CVD and reported that the relative risk of dying among patients with large-vessel PAD when compared to those with no largevessel disease was 3.1-fold higher (95% confidence interval [CI] 1.9-4.9) for all-cause mortality and 5.9-fold higher (95% CI 3.0-11.4) for CVD mortality.5 Diet has long been investigated in relation to CVD risk and its major risk factors, like dyslipidemia, hypertension, diabetes, and the MetS. A recent systematic search of the literature based on 15 relevant observational studies that evaluated the direct effect of diet on CVD risk reported that the attributable risk of an unhealthy dietary pattern varies from 9% to 37%6; moreover, the authors observed that the inclusion of diet component in CVD risk scores may increase the accuracy of the models and better identify people at high risk. The Mediterranean diet is one of the most known and studied dietary patterns in relation to human health. It was described in the late 1960s by Ancel Keys in the Seven Countries Study.7 This traditional dietary pattern is characterized by daily consumption of olive oil, fruits and vegetables, nonrefined grains and dairy products as well as weekly consumption of fish and poultry, potatoes, olives, nuts and legumes, and monthly consumption of red meat. Another major characteristic of this dietary pattern is the moderate consumption of alcohol, mainly wine (1-2 glasses/d), usually with meals.8-10 However, it should be acknowledged that although the dietary patterns that prevail in the wider Mediterranean region share many common characteristics, the

macronutrient distribution varies from area to area. Nevertheless, studies from the Mediterranean region as well as from other parts of the world strongly support the cardioprotective role of this dietary pattern, mainly through its beneficial role on cardiometabolic markers.11-14 At this point it is important to mention that the Mediterranean diet may exert its positive influence on human health and CVD particularly due to its antioxidant and anti-inflammatory effects.15,16 Despite the large body of evidence regarding Mediterranean diet and CVD mortality and morbidity, the role of this traditional dietary pattern on risk of PAD has been rarely studied. Very recently, Ruiz-Canela et al, in a randomized trial conducted from October 2003 and December 2010 in Spain, assessed the association between Mediterranean diet and the occurrence of symptomatic PAD in 7477 participants with type 2 diabetes mellitus or at least 3 cardiovascular risk factors, aged 55 to 80 years and without clinical PAD or baseline CVD. Participants were randomized to the following groups: a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, or counseling on a low-fat diet (control group). All participants received a comprehensive dietary educational program on a quarterly basis. Both Mediterranean diet intervention groups were associated with lower risk of PAD compared to the control group.17 A mechanistic hypothesis of the beneficial effect of Mediterranean

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First Cardiology Clinic, School of Medicine, University of Athens, Athens, Greece 2 Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy 3 Department of Medical, Surgical, Neurological, Metabolic Sciences and Aging, Second University of Naples, Naples, Italy 4 Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece Corresponding Author: Demosthenes B. Panagiotakos, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 46 Paleon Polemiston St Glyfada, Attica, Athens 166 74, Greece. Email: [email protected]

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diet on PAD may be due its pleiotropic beneficial effects on endothelial function, arterial blood pressure, lipids, and glucose levels. For example, Ciccarone et al reported that greater adherence to the Mediterranean diet had a strong, protective role against PAD in patients with type 2 diabetes mellitus, whereas the use of saturated fat increased the risk of PAD even in those patients who were regularly consuming olive oil.18 Recently, Klonizakis et al observed that long-term effects of an exercise and Mediterranean diet intervention may benefit vascular function, even in older (55 + 4 years) healthy people.19 In a review, Marı´n et al reported the relationship between oxidative stress, aging, and the nutritional mechanisms that are involved in longevity.20 In another study, Rallidis et al reported that the Mediterranean diet reduced endothelial damage and improved its regenerative capacity in individuals with abdominal obesity,21 both factors that may promote the development of PAD. Diabetes is a major factor for PAD development; there are findings supporting that Mediterranean diet has beneficial effects against the development of diabetes, mainly due to the overall antioxidant profile of the diet that may suspend oxidative stress accumulation, which mediates the development of insulin resistance and b-cell dysfunction, as well as the moderate alcohol consumption, that characterizes this dietary pattern, and has been associated with enhanced insulin sensitivity, possibly through changes in adiponectin or high-density lipoprotein cholesterol levels.22-24 At this point, it should be mentioned that in 2010, this dietary pattern has been recognized as an Intangible Cultural Heritage of Humanity by United Nations Educational, Scientific and Cultural Organization, giving emphasis not only on the food consumption aspects of the Mediterranean diet but also on the cultural dimension, that is, conviviality, socialization, biodiversity and seasonality, culinary activities, and adequate rest.25 Taking into account that the management of PAD should not be restricted only to the peripheral circulation, but should include measures to manage and decrease the systemic atherosclerotic burden of the people,26 factors that promote healthy living, like adherence to the Mediterranean diet, should accompany general recommendations for prevention of PAD. However, and despite the findings from numerous studies, there is no doubt that the Mediterranean diet is being progressively lost, especially in the younger generations. To prevent the diet of our ancestors, immediate actions are needed by everyone, but especially from public health policy makers, in order to preserve the wisdom hidden in this traditional dietary pattern. Authors’ Note All authors were equally contributed in writing and critically revising the editorial article.

Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.

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Peripheral Arterial Disease and Cardiovascular Risk: The Role of Mediterranean Diet.

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