Nutrition in the primary and secondary prevention of stroke

Maturitas 72 (2012) 29–34

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Review

Nutrition in the primary and secondary prevention of stroke Martha Apostolopoulou a , Konstantinos Michalakis b , Alexander Miras c , Apostolos Hatzitolios d,e , Christos Savopoulos d,e,∗ a

Internal Medicine Department, Agios Pavlos Hospital, Thessaloniki, Greece Barts & The London School of Medicine & Dentistry, Queen Mary University of London, United Kingdom Molecular and Metabolic Imaging Group, Institute of Clinical Sciences, Hammersmith Hospital, London W12 0NN, United Kingdom d Medical Propedeutic Department, Medical School, AHEPA Hospital, Aristotles University of Thessaloniki, Greece e International Centre for Circulatory Health, National Heart & Lung Institute, Imperial College, 59-61 North Wharf Road, London W2 1NY, United Kingdom b c

a r t i c l e

i n f o

Article history: Received 21 January 2012 Received in revised form 6 February 2012 Accepted 7 February 2012

Keywords: Nutrition Diet Stroke Prevention

a b s t r a c t Stroke is a worldwide major health issue. As some of the risk factors are modifiable, it is of high importance to understand how we can minimize the risk for stroke. Multifactorial interventions should be provided to patients in the frame of primary and secondary prevention. Obesity is a well-established modifiable factor as well as the dietary pattern that mostly depends on the social environment, the lifestyle and the habits of each individual. So, dietary changes should be part of the holistic approach which includes improvements in the regulation of hypertension, hyperlipidaemia and hyperglycaemia. In the present review, we try to provide a global approach on how diet can influence the risk of stroke and especially the nutritional influence on lipid profile and vessel disease and the role of dietary modification in the secondary stroke prevention. The importance of salt restriction, DASH and Mediterranean diet low in saturated and high in polyunsaturated fats, and the management of obesity seem to be the most important dietary priorities. © 2012 Elsevier Ireland Ltd. All rights reserved.

Contents 1. 2. 3. 4. 5.

6. 7. 8.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Risk factors for stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nutritional influence on lipid profile and vessel disease: low-calorie and low-cholesterol diets . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Body weight and stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Primary prevention: dietary habits and stroke . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1. Fruits, fibres, whole grain, vegetables and the DASH diet . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2. Electrolytes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3. Lifestyle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4. Multivitamins and antioxidant pills . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5. Macronutrients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6. Drinks: alcohol and caffeine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Secondary stroke prevention: the role of dietary modification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Adherence to the guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Competing interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Provenance and peer review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

∗ Corresponding author at: Medical Propedeutic Department, Medical School, AHEPA Hospital, Aristotles University of Thessaloniki, Stilponos Kyriakidi 1, PC 54636, Thessaloniki, Greece. Tel.: +30 2310994783; fax: +30 2310994918. E-mail address: [email protected] (C. Savopoulos). 0378-5122/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2012.02.006

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1. Introduction Stroke is a major health issue in terms of both morbidity and mortality. It represents a leading cause of functional impairment, with 20% of survivors requiring institutional care after 3 months and 15–30% being permanently disabled [1]. Even though the annual death rate from stroke decreased by 34.8% between 1998 and 2008 and the actual number of deaths from stroke declined by 19.4%, stroke still ranks third among all causes of death [2]. There has been a 42% decrease in the incidence of stroke in high-income countries but a greater than 100% increase in its incidence in lowand middle-income countries; for the first time, between 2000 and 2008, the overall stroke incidence rates in low- and middle-income countries exceeded those in high-income countries, by around 20% [3]. 2. Risk factors for stroke The risk factors for stroke can be classified as modifiable or nonmodifiable. The non-modifiable include age, race, sex, low birth weight and family history [4]. Among the modifiable are obesity per se [4] as well as dietary factors and alcohol excess [4]. In the present review we explore the ways in which diet influences the risk of stroke and examine how modifications to diet can be used as a preventive measure. 3. Nutritional influence on lipid profile and vessel disease: low-calorie and low-cholesterol diets Ischaemic stroke is strongly related to the condition of the blood vessels, which to a significant extent is modified by the consumption of cholesterol and fatty products. However, as dyslipidaemia is considered the major risk factor for coronary heart disease, the majority of studies have focused on the effect of diet and lipid parameters on the vessel endothelium in that context, rather than stroke. According to the National Cholesterol Educational Program (NCEP)-USA, dietary intake of cholesterol should be restricted to a maximum of 300 mg/dl for patients at low risk of vascular disease and to <200 mg/dl for those at high risk [5]. Given that one egg yolk typically contains 275 mg of cholesterol [6], it is evident that clinicians and nutritionists need to address the dietary behaviour of high-risk patients very carefully. Although one egg per day raises the level of low-density lipoproteins (LDL) by only 10%, its degree of oxidation is increased by 34% [7]. People who have relatively low-cholesterol diets (less than 100 mg per day) and low-fat diets have low plasma LDL-cholesterol levels and virtually no coronary artery disease [8,9]. In contrast, the typical ‘American diet’ induces monocyte adhesion and chemotaxis by LDL. A healthy ‘Mediterranean’ diet (discussed further below), which is rich in oleic acid [10], does not appear to have any such effects [11]. Consumption of polyunsaturated fatty acids instead of saturated fats can reduce blood cholesterol levels and atherosclerosis, while the consumption of trans fatty acids increases blood cholesterol as much or even more than does consumption of saturated fats [12]. Trans fatty acids have also been shown to decrease high density lipoproteins (HDL). As a result, the LDL/HDL cholesterol ratio is higher when trans fatty acids are consumed instead of saturated fats [12], further increasing the progression to coronary heart disease, a fact that forced the American Heart Association to strictly recommend lower consumption of trans fatty acids [13]. Fasting levels of lipids alone do not reflect the general lipid content of a person’s diet and there is good evidence that postprandial levels of fats and oxidative stress are as important as fasting lipid levels [14,15]. Endothelial dysfunction caused by a high-fat meal

can be partly counteracted by vitamins C and E [6]. Free radicals that impair endothelial function via oxidation of LDL particles are reduced when probucol and other antioxidants are part of the diet [16]. Overall, natural antioxidant nutrients have been shown to be more effective than antioxidants in the form of a supplementary vitamin [6]. Higher plasma concentrations and greater dietary intake of folate are associated with a reduced risk of haemorrhagic stroke but not ischaemic stroke, independently from hypertension; homocysteine status is likely to be an important component of the putative role for folate in the prevention of haemorrhagic stroke [17]. Despite the protective role of low cholesterol levels, epidemiological studies indicate a higher incidence of intracerebral (but not subarachnoid) haemorrhagic stroke in patients with low total serum cholesterol levels. Indeed, a serum total cholesterol level below the sex-specific 10th percentile (<4.62 mmol/L [178 mg/dL] in men) was associated with a significantly increased risk of intracerebral haemorrhage in men aged 65 years or more (relative risk, 2.7; 95% confidence interval, 1.4–5.0). An excess risk was also observed among elderly women at the lowest end of the cholesterol range, although no relationship was seen among men or women aged 40–64 [18]. In an attempt to develop recommendations for a healthy cardiovascular system and for the prevention of vascular events – stroke in particular – clinical researchers have evaluated the effects of a Mediterranean diet. This diet is high in beneficial oils (olive oil, canola oil and omega-3 rich fish oil), fruits, balsamic vinegar, vitamins and antioxidants; at the same time it is low in trans fat, unhealthy animal fat and cholesterol. Thus, although not necessarily low in caloric intake, the Mediterranean diet is characterised by the substitution of various harmful products with nutritionally healthy alternatives, such as canola margarine instead of butter, alpha-linoleic acid instead of animal fat, and whole grains, fibre and phytoestrogens instead of other derivatives. Several studies have shown that, via the consumption of antioxidant foods and consequent reduced lipid peroxidation [19,20], this diet results in a much lower risk of cardiovascular events, as well as in less insulin resistance and improved endothelial function [21]. Furthermore, beyond the cardiovascular benefits, data from a meta-analysis suggest that changing to a Mediterranean diet reduces cancer mortality by 6% [22]. Finally, returning to the point that fasting lipids are not representative of the whole-day lipid status, the well known 4S Study (Scandinavian Simvastatin Survival Study) [23] showed that the Mediterranean diet (the Cretan diet in particular) resulted in similar levels of fasting lipids to those of people on other diets but also in significantly lower post-prandial lipid levels.

4. Body weight and stroke Body weight is both a modifiable and a non-modifiable risk factor for stroke. Low birth weight is a non-modifiable risk factor. The risk of stroke in later life for a person with a birth weight under 2500 g is more than twice that of a person weighing over 4000 g at birth [4]. This phenomenon can be observed into childhood, with those children not gaining weight being at a higher risk of stroke later in life [24,25]. Body mass index (BMI) has an important place among the modifiable risk factors in adults, as both a low BMI and a high BMI increase the risk of stroke [26]. In a recent Indian study, high rates of premorbid under-nutrition were found in stroke patients [27]. Obesity, on the other hand, confers a relative risk of 1.75–2.37 for stroke and a meta-analysis has shown that overweight and obesity are associated with a progressively increasing risk of 22% and 64% respectively for stroke [4,28].

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5. Primary prevention: dietary habits and stroke 5.1. Fruits, fibres, whole grain, vegetables and the DASH diet The guidelines on the primary prevention of stroke recommend increasing the consumption of fruit and vegetables, as this is associated with a reduced risk of stroke in a dose–response fashion: for each increment of one serving per day of fruit and vegetables, the risk of stroke is reduced by 6% [4]. The same guidelines endorse the Dietary Approaches to Stop Hypertension (DASH), which promotes a diet rich in fruit, vegetables, and low-fat dairy products, and low in saturated and total fat [4]. A meta-analysis of nine studies, with a total of 257,551 participants (among whom 4917 stroke events were seen), over an average follow-up of 13 years, showed that the consumption of more than five servings of fruit and vegetables per day could lead to a reduction in the incidence of stroke [29]. Moreover, cruciferous and green leafy vegetables (e.g. cabbages, turnips, broccoli), together with citrus fruit and juice, protected against stroke [30]. Whole-grain intake was associated with a trend towards a reduction in the incidence of stroke in a recent meta-analysis [4,31] and fibre intake has been shown to have an inverse association with the risk of both haemorrhagic and ischaemic stroke [32]. 5.2. Electrolytes A higher sodium intake is associated with an increased risk of stroke; in contrast, a higher level of potassium intake has been associated with a reduced risk of stroke in prospective studies [33–35]. The recommended sodium intake is <2.3 g/d (100 mmol/d) and the recommended potassium intake >4.7 g/d (120 mmol/d). Magnesium and calcium have been studied for their effect on stroke largely because they are widely taken as dietary supplements. A meta-analysis has shown that magnesium intake is, like potassium intake, inversely associated with the risk of stroke, ischaemic stroke in particular [36]. The effect of calcium is more uncertain, although the data appear to be more against calcium supplementation than in favour [24], with an increase in cardiovascular risk in most studies and a neutral effect when calcium supplementation is added to bisphosphonates [37,38]. 5.3. Lifestyle Studies have shown a beneficial effect of a healthy lifestyle – including ‘prudent’ versus ‘Western’ dietary patterns [39]. For instance, one study found a reduction in total and ischaemic stroke but not of haemorrhagic stroke in women adopting a healthy lifestyle [40]. A prospective cohort study among 43,685 men from the Health Professionals Follow-up Study and 71,243 women from the Nurses’ Health Study showed that the adoption of a healthy lifestyle could prevent 47% of total and 54% of ischaemic stroke in women and 35% of total and 52% of ischaemic stroke in men [41]. Finally, the Mediterranean diet in women is associated with a lower risk of stroke [23]. 5.4. Multivitamins and antioxidant pills Multivitamins and antioxidant pills are widely available. However, a meta-analysis of 68 randomised trials with a total of 232,606 participants concluded that beta carotene, vitamin A and vitamin E supplements, singly or combined, may increase mortality and that the potential roles of vitamin C and selenium on mortality need further study [42]. Regarding vitamin E in particular, two further meta-analyses have suggested that its role is at best ambiguous in the prevention of stroke [43,44]. One of these found that it increased the risk for haemorrhagic stroke by 22% and reduced the

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risk of ischaemic stroke by 10% [44]. Vitamin C, vitamin B and folic acid supplements have not been shown to have a protective effect against stroke in randomised trials [45–49]. Nonetheless, there is a positive correlation between homocysteine levels and stroke [4]. For this reason, guidelines on the primary prevention of stroke recommend the use of folic acid and B vitamins in patients with known elevated homocysteine levels, given their safety and low cost [4]. Moreover, given that vitamin B12 levels in the elderly are often below the ‘normal’ reference range [6], it seem prudent to boost these levels before any additional intervention is undertaken. Low levels of vitamin D have been found in a number of studies to be associated with hypertension, atherosclerosis and cardiovascular disease. These results were supported by the Nurses’ Health Study and the Health Professionals Follow-Up Study [50], where it was found that, over a total of 2,280,324 person-years, a higher intake of vitamin D (≥600 IU/d) was associated with a lower incidence of coronary heart disease and stroke, in men but not in women. Contrary to this, a recent meta-analysis found that vitamin D supplements had no benefit in terms of cardiovascular outcomes [51].

5.5. Macronutrients The effects of the various macronutrients within the diet are not yet clear. There is no association between a low-fat intake and stroke [24,52,53]. However, a recent Dutch study of 20,069 men and women [54] showed that low intakes of alpha-linolenic acid may be a risk factor for stroke. Food with a high glycaemic index has been shown to increase the risk of mortality from stroke (ischaemic and haemorrhagic) in Japanese women [55] and a higher dietary glycaemic load (GL) was associated with a greater risk of haemorrhagic stroke in Swedish middle-aged and older men [56], as well as an increased risk of total stroke, but not haemorrhagic stroke, in overweight women [32]. Rice consumption has been associated with an increased risk of stroke in Chinese adults [57] and a reduced risk of cardiovascular disease in Japanese men [58]. The origin of proteins appears to be important. For instance, the consumption of fish has been shown to have a protective effect against stroke [59]. A recent meta-analysis of 15 studies concluded that an increment of three servings per week in fish consumption was associated with a 6% reduction in the total risk of stroke [60] and a recently published study found a 17% risk reduction from a single serving of fish per day [61]. When the effect of the consumption of red meat was evaluated in a recent meta-analysis of 20 studies, the pooled risk estimate demonstrated a 24% higher risk of stroke per daily serving [62]. Using data from 84,010 women from the Nurses’ Health Study and from 43,150 men from the Health Professionals Follow-Up Study, a study showed that a higher intake of red meat (1 serving/day) was associated with an elevated risk of stroke, whereas a higher intake of poultry (1 serving/day) was associated with a risk reduction of 27%; further, the consumption of low-fat dairy products was associated with an 11% lower risk of stroke, the consumption of whole-fat dairy products with a 10% lower risk, and the consumption of nuts – another common protein source – with a 17% lower risk. Finally, no significant effects were found when red meat was exchanged for legumes or eggs [61].

5.6. Drinks: alcohol and caffeine The guidelines for the prevention of stroke recommend the consumption of a maximum of 2 alcoholic drinks per day for men and 1 alcoholic drink per day for non-pregnant women [4]. Finally, the consumption of coffee (3–4 cups) and tea (>3 cups) has been associated with a reduction in the risk of stroke (of 17% and 21%,

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respectively), as has the consumption of chocolate (29% reduction) [24,63–65].

6. Secondary stroke prevention: the role of dietary modification Multifactorial interventions should be provided for patients after a first stroke in order to prevent a future event. Dietary changes should be part of a holistic approach to reducing hypertension, hyperlipidaemia and hyperglycaemia. Unfortunately, there are no reported studies of the effect of dietary changes on the secondary prevention of stroke as the primary endpoint. All published studies and trials have focused on coronary or cardiovascular events in patients with a history of cardiac atheromatous disease. The incidence of recurrent stroke was too low to allow these studies to detect significant differences between dietary interventions. In the Oslo Diet Heart Study, 412 men were randomised to a lipid-lowering or a control diet 1–2 years after a first myocardial infarction and followed for 5 years [66]. The experimental diet was low in animal saturated fats and high in vegetable polyunsaturated fats. A dietician assessed the concordance of a selected subgroup through direct supervision. At the end of the study, total cholesterol was reduced by 13% in the experimental group. Two patients had a stroke event in the experimental group and one in the control group. Singh et al. randomized 406 patients with suspected acute myocardial infarction to two groups, both consuming a diet low in animal fat, but group A were also asked to eat fruit, vegetable, pulses, nuts and fish [67]. Concordance was assessed during hospital admissions and clinic visits. At 1 year, total cholesterol was reduced significantly more in group A (7.3% reduction). One patient had a fatal stroke in group A compared with two in the control group. The Dietary Intervention Randomized Controlled Trial-Carotid (DIRECT-Carotid) study offered some more insights into how diet may affect the risk of stroke [68]. In this 2-year study, 322 patients with obesity were randomised to a low-fat calorie-restricted diet, a Mediterranean-calorie restricted diet or a low-carbohydrate calorie-unrestricted diet [69]. The adherence rates were surprisingly high, at 84.6% at 2 years. The Mediterranean and low-carbohydrate diets were superior to the low-fat diet in terms of weight loss. The Mediterranean diet had superior metabolic effects, by reducing fasting glucose and insulin levels, whereas the predominant effect of the low-carbohydrate diet was to reduce the total cholesterol/HDL ratio by 20%. Follow-up of a subset of 175 participants who had carotid vessel wall volumes quantified by ultrasonography showed that the three diets were equally effective in achieving intima-media thickness, possibly via a reduction in blood pressure. No ‘hard’ endpoints in terms of cardiovascular outcomes were recorded. The Lyon Diet Heart Study has received much attention. In this trial, 605 patients who survived a first myocardial infarction were randomised to either a control or a Mediterranean diet [70,71]. The latter was designed to supply less than 35% of its energy as fat and less than 10% as saturated fat; it was low in linoleic acid and high in alpha-linolenic acid. The control group was advised to follow step 1 of the American Heart Association ‘prudent diet’ [72]. Concordance was assessed through dietary surveys and measurement of plasma fatty acids. The trial was discontinued early due to the significant superiority of the Mediterranean diet in an interim analysis. Following publication of the initial results, the two groups were followed up further for a mean of 4 years. The composite outcome – which factored in myocardial infarction, cardiovascular death, episodes of unstable angina, overt heart failure, stroke and pulmonary or peripheral embolism–was reduced by 70% in the

group on the Mediterranean diet relative to the control group (27 events versus 90 events). Four patients had a stroke in the control group and none in the experimental group. According to the authors, 93.4% of the control group and 92.4% of the experimental group attended the final visit, but the daily nutrient intake was recorded for only 40.7% of the control group and 65.7% of the experimental group. It is unclear whether the rest of the participants were still concordant with their diets. Interestingly, traditional risk factors, including BMI, blood pressure, total cholesterol, HDL, LDL and glycated haemoglobin (HbA1c) levels did not differ between the two groups at the end of the study. The authors suggest that the favourable profile of high omega-3 fatty acids and low omega6 fatty acids and their anti-inflammatory and plaque-stabilising effects may be the protective mediators of the Mediterranean diet. As far as dietary recommendations are concerned, the Stroke Council of the American Heart Association [73] suggests the American Heart Association Step II diet, which consists of 30% of calories derived from fat (and less than 7% from saturated fat) and with less than 200 mg cholesterol a day [74]. According to the American Stroke Association’s guidelines and recommendations [75], patients who have had a first stroke should: • limit saturated and trans fatty acids to a minimum, avoid fried foods, fatty meats, butter and margarine and creamed or wholemilk products (instead they should choose lean meats, poultry and fish or substitute legumes and soy products for meats); • choose tub margarines containing plant stanol or sterol esters, which help to lower cholesterol, and minimise their use of highly processed, canned and frozen prepared foods; • limit salt to 2300 mg per day and substitute other seasonings and flavourings; • limit alcohol to two drinks per day for most men and one drink per day for women and low-weight people (1 drink = 12 oz beer, 5 oz wine or 1.5 oz 80-proof liquor); • choose low-fat or fat-free dairy products in place of higher-fat versions; • read food labels carefully and select foods for which ‘whole grain’ appears as one of the first ingredients, and substitute whole-grain breads, pastas and flours for their traditional white versions; • eat a variety of nuts (if their swallowing is normal). 7. Adherence to the guidelines The above dietary guidelines for people who have had a first stroke (secondary prevention) do not differ from those for primary prevention. It is not surprising that multimodal approaches offer the best results. In a literature review of relevant meta-analyses, it was shown that the combination of dietary modification, exercise, aspirin, antihypertensives and statins may offer a relative risk reduction of 80% for vascular events after a stroke [76]. Unfortunately, no specific dietary modification is detailed in that review. Patient adherence to dietary advice and modification is obviously crucial, as reflected in the substantial decrease in the occurrence of a second stroke among those who do adhere to a new diet. Gillham and Endacott reported that although all the patients in their sample of people who had had a stroke declared the same readiness and willingness to adjust to a healthier lifestyle, only those receiving enhanced secondary prevention (motivation and surveillance) were capable of following a ‘strict’ diet. As a result, patients in the supervised group were able to consume 10 portions of fruit and vegetables per week, compared with 1 or 2 portions a week for the control group (P = 0.033) [77]. Similarly, Kastorini et al. found differences between sufferers of a first and a second stroke in terms of adherence to a

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Mediterranean diet. After various adjustments, it was observed that for each 1-point increase in the MedDietScore (on a scale of 1–55, with increasing scores indicating greater adherence to the Mediterranean diet), the corresponding odds ratio for having an acute coronary syndrome (ACS) was 0.91 (95% CI 0.87–0.96), whereas the odds ratio for stroke was 0.88 (95% CI 0.82–0.94) [78]. Strict adherence to Mediterranean diet significantly reduces the risk of mortality from cardiovascular diseases as well as the occurrence of and mortality from neoplasm [22,79]. Also, it seems that the adoption of a healthier lifestyle resulting in a reduction in BMI subsequently lowers the risk of several kinds of cancer, including breast cancer, by 40% [80]. Da Luz et al. highlighted the importance of multidisciplinary care, including medical, nutritional and psychological counselling [81]. They showed that all the measures patients are advised to take face the obstacle of personal habit. They believed that only national awareness campaigns would provide sufficient support for all patients to persuade them to modify their lifestyle during their rehabilitation. 8. Conclusion Genetic and environmental factors are implicated in the pathogenesis of stroke; these risk factors may be classified as modifiable or non-modifiable. Body weight is a risk factor that belongs to both groups, while nutrition mostly depends on the social environment, the lifestyle and the habits of each individual. High caloric intake increases BMI but it does not reflect exactly the degree of abdominal obesity and consequent risk of stroke. In recent studies, high as well as low BMI has been implicated in the pathogenesis of stroke. It seems that the whole balance between caloric intake and expenditure and a healthy diet are more important parameters in the determination of the risk of stroke. There is, though, a lack of nutritional studies determining the risk of first or recurrent stroke as the primary endpoint and well designed studies distinguishing the primary and secondary prevention of stroke are needed. Nonetheless, the importance of salt restriction, DASH and a Mediterranean diet low in saturated and high in polyunsaturated fats, and the management of obesity would seem to be the most important dietary priorities of a holistic national intervention. Contributors M. Apostolopoulou performed literature review, participated in the writing and the editing of the review. K. Michalakis assisted in designing, performed literature review, participated in the writing. A. Miras performed literature review, participated in the writing and critiqued the review. A. Hatzitolios designed, edited and critically revised the review. C. Savopoulos designed, supervised all the literature research and participated in the writing, critiqued and edited the review. Competing interest The authors have no competing interests. Provenance and peer review Commissioned and externally peer reviewed.

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