Adherence to the Mediterranean diet and risk of metabolic syndrome and its components

Adherence to the Mediterranean diet and risk of metabolic syndrome and its components

Nutrition, Metabolism & Cardiovascular Diseases (2009) 19, 563e570 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/nmcd...

149KB Sizes 0 Downloads 39 Views

Nutrition, Metabolism & Cardiovascular Diseases (2009) 19, 563e570

available at www.sciencedirect.com

journal homepage: www.elsevier.com/locate/nmcd

Adherence to the Mediterranean diet and risk of metabolic syndrome and its components ´ a,b, J. Basora a,b,c, M.A. Martı´nez-Gonza ´lez b,d, N. Babio a, M. Bullo ´ndez-Ballart b,e, F. Ma ´rquez-Sandoval a, C. Molina a,b, J. Ferna ´ a,b,*, on behalf of the Nureta-PREDIMED investigators J. Salas-Salvado a

Human Nutrition Unit, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences, Rovira i Virgili University, Spain b CIBER Fisiopatologı´a de la Obesidad y Nutricio´n CB06/03. Instituto de Salud Carlos III, Madrid, Spain c Direccio´ d’Atencio´ Prima`ria Tarragona-Reus. Institut Catala` de la Salut, Reus, Spain d Department of Preventive Medicine and Public Health, Medical School-Clı´nica Universitaria, University of Navarra, Pamplona, Spain e Preventive Medicine and Public Health Unit, Faculty of Medicine and Health Sciences, Rovira i Virgili University, Spain Received 28 July 2008; received in revised form 24 October 2008; accepted 29 October 2008

KEYWORDS Metabolic syndrome; Mediterranean diet; PREDIMED study; Olive oil; Legumes; Red wine

Abstract Background and aims: The role of diet in the aetiology of metabolic syndrome (MetS) is not well understood. The aim of the present study was to evaluate the relationship between adherence to the Mediterranean diet (MedDiet) and MetS. Methods and results: A cross-sectional study was conducted with 808 high cardiovascular risk participants of the Reus PREDIMED Centre. MetS was defined by the updated National Cholesterol and Education Program Adult Treatment Panel III criteria. An inverse association between quartiles of adherence to the MedDiet (14-point score) and the prevalence of MetS (P for trend < 0.001) was observed. After adjusting for age, sex, total energy intake, smoking status and physical activity, participants with the highest score of adherence to the MedDiet (9 points) had the lowest odds ratio of having MetS (OR [95% CI] of 0.44 [0.27e0.70]) compared to those in the lowest quartile. Participants with the highest MedDiet adherence had 47 and 54% lower odds of having low HDL-c and hypertriglyceridemia MetS criteria, respectively, than those in the lowest quartile. Some components of the MedDiet, such as olive oil, legumes and red wine were associated with lower prevalence of MetS. Conclusion: Higher adherence to a Mediterranean diet is associated with a significantly lower odds ratio of having MetS in a population with a high risk of cardiovascular disease. ª 2008 Elsevier B.V. All rights reserved.

* Corresponding author. Human Nutrition Unit, Department of Biochemistry and Biotechnology, Faculty of Medicine and Health Sciences, Rovira i Virgili University, C/Sant Llorenc ¸ 21, 43201 Reus, Spain. E-mail address: [email protected] (J. Salas-Salvado ´). 0939-4753/$ - see front matter ª 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2008.10.007

564

N. Babio et al.

Introduction

Methods

The MetS is a cluster of common cardiovascular risk factors, including central obesity, hyperglycaemia, low HDLcholesterol concentrations, hypertension and hypertriglyceridemia. The association of MetS with the risk of developing diabetes and cardiovascular disease (CVD) is well documented, implying a greater risk of mortality [1,2]. In developed countries the MetS seems to affect around 25% of the population [3,4], and there is evidence that MetS has become more prevalent over the last decade [4] probably influenced in part by increases in obesity. The aetiology of MetS, although largely unknown, is considered to reside in a complex interaction between genetic, metabolic, and environmental factors [5e7]. Weight loss or gain can be considered to be one of the main environmental determinants of the MetS [8]. Physical activity and diet have also been reported to be important factors related to the MetS [9]. Adherence to a healthy dietary pattern has been shown to be inversely associated with MetS [10,11], some of its components [12] and type-2 diabetes[13]. In contrast, prospective finding have suggested that a Western dietary pattern is directly associated with the risk of MetS [14]. Clinical trials have also shown that behavioural programs can be used to implement healthy dietary patterns and decrease the prevalence of MetS [15e17]. In recent decades the Mediterranean Diet (MedDiet) has emerged as a healthy dietary pattern that protects against CVD and other chronic conditions [18]. The MedDiet is characterized by a high consumption of legumes, fruit and vegetables, grains and olive oil, a moderate consumption of wine and dairy products and a low consumption of red and processed meat, cream and pastries. Few studies have analysed the relationship between MedDiet adherence and the prevalence or incidence of MetS and its components [15,19e21]. With the exception of the cross-sectional study of Alvarez-Leo ´n and co-workers [19] who did not find any relationship between the adherence to the MedDiet and MetS prevalence, other studies, conducted in samples of healthy participants do support the beneficial effect of the MedDiet pattern on MetS [15,20,21]. Recent data from the SUN prospective study also show an inverse relationship between MedDiet adherence and the incidence of MetS [21]. Finally, Esposito et al. by means of a feeding trial showed a decrease in the prevalence of MetS in patients losing weight by adhering to a low-fat MedDiet [15]. To the best of our knowledge, the association between MedDiet or its components and MetS has never been explored in an elderly population with a high risk of CVD. Likewise, no studies have analysed which of the components of the MedDiet are most associated with MetS. So, the aim of the present study was to assess the relationship between adherence to the MedDiet and the prevalence of the MetS in participants of the PREDIMED study, and to identify specific components of the MedDiet associated with this syndrome that might support the beneficial effects attributed to this overall healthy dietary pattern.

Patients A cross-sectional analysis on baseline data from the PREDIMED trial centre in Reus was conducted. The PREDIMED is a 5-year clinical trial and constitutes a randomized, parallel-group multicentre that aims to assess the effects of the MedDiet on the primary prevention of CVD [22]. Participants were men and women, without prior CVD and who fulfilled at least one of the following two criteria: (1) type-2 diabetes or (2) 3 major cardiovascular risk factors (current smoking, hypertension [blood pressure  140/ 90 mmHg or treatment with antihypertensive drugs], LDLcholesterol level  160 mg/dL [or treatment with hypolipidemic drugs], HDL-cholesterol level  40 mg/dL, body mass index [BMI]  25 kg/m2, or a family history of premature CVD). Other details have been reported elsewhere [22]. Of the first 847 participants recruited in the Reus node, 39 were excluded because some of the MetS variables were missing. Our centre’s institutional review boards approved the study protocol, and all the participants signed an informed consent form.

Measurements The baseline examination included assessment of cardiovascular risk factors, medical conditions and medication use. Height and weight were measured with light clothing and no shoes. Waist circumference was measured midway between the lowest rib and the iliac crest. Blood pressure was measured (using a validated oscillometer [Omron HEM705CP, Hoofddorp, Netherlands]) in triplicate with a 5-min interval between each measurement, and the mean of these values was recorded. The validated Spanish version of the Minnesota Leisure-Time Physical Activity Questionnaire [23] was used to estimate energy expenditure.

Nutritional assessment A previously validated 136-item food frequency questionnaire [24] was used to appraise dietary habits. Spanish food composition tables were used to derive nutrient intake. A 14-point food-items questionnaire, an extension of a previously validated questionnaire [25], was used to assess adherence to the traditional MedDiet (see Appendix 1). Previously applied scores [26,27] were also used to assess adherence to the MedDiet in secondary analyses. In the Trichopoulou score, [26] subjects whose consumption was at or above the sex-specific median (monounsaturatedto-saturated fat ratio, legumes, cereals, vegetables, fruits and fish) or below the median (meat and dairy products) were assigned 1 point. Moderate alcohol consumption was also assigned 1 point. Therefore, the total Trichopoulou score [26] had a potential range from 0 to 9 points.

Laboratory determinations Centralized laboratory analyses were performed on frozen serum samples obtained in fasting conditions. Serum

Mediterranean diet and metabolic syndrome

565

glucose, cholesterol, and triglyceride levels were measured using standard enzymatic automated methods. HDLcholesterol was measured by enzymatic procedure after precipitation.

abnormal waist circumference and low level of HDLcholesterol features were significantly higher in women. No significant differences between women and men were observed in relation to the MedDiet scores.

Metabolic syndrome

Association between Mediterranean diet and metabolic syndrome

The updated criteria from the National Cholesterol Education Program’s Adult Treatment Panel III [28] were used to define MetS. That is to say, subjects had to have 3 of the following: (1) waist circumference > 102 cm in men and >88 cm in women; (2) serum triglyceride  150 mg/dL; (3) HDL-cholesterol < 40 mg/dL in men and <50 mg/dL in women; (4) blood pressure  130/85 mmHg; and (5) fasting plasma glucose level  100 mg/dL. Participants who were being treated with antidiabetic, antihypertensive or triglyceride-lowering medications were considered as diabetic, hypertensive or hypertriglyceridemic, respectively.

Statistical analyses We built categories (approximately quartiles) of the 14-point food-item MedDiet or Trichopoulou score. A multiple logistic regression model was used to evaluate the odds ratio for each of the three upper quartiles of adherence to the MedDiet (compared with the lowest quartile) and the prevalence of MetS or its components. Multiple logistic regression models with polynomial contrast were used to generate the P for trend. After the univariate model, we built first a sex- and age-adjusted model (model 1) and another model additionally adjusted for energy intake, smoking and physical activity (model 2). Further adjustments were made for BMI (model 3). We conducted the analyses first for the whole sample and then separately for men and women. In addition, a multiple logistic regression model was fitted to evaluate which of the 14-point food items in the MedDiet were most strongly associated with the prevalence of the MetS, having previously adjusted for the above-mentioned potential confounders and mutually adjusted for the rest of the items of the score. Also, a multiple logistic regression model was fitted to evaluate which of the 14-point food MedDiet items were most strongly associated with the risk of having MetS, forcing the adjustment for non-dietary variables (sex, age, energy intake, smoking [current smoker or not] and physical activity), but using the stepwise algorithm (forward method) to allow the additional inclusion of each of the 14 items included in the MedDiet adherence score according to their P values. The level of significance for all statistical tests was P < 0.05 for bilateral contrasts.

Multiple logistic regression models with polynomial contrast (Table 2) showed an inverse association between adherence to the MedDiet (14-point food-item score) and the prevalence of the MetS (P for trend < 0.001). This association persisted after adjusting for age, sex, energy intake, smoking status and physical activity, and even after adjusting for BMI (P for trend Z 0.002). The category with the highest score of adherence to the MedDiet exhibited the lowest odds ratio of having MetS, (OR (95% CI) 0.44 (0.27e0.70) for subjects on quartile 4 compared to those in quartile 1). No interaction between gender or age category (<65 and 65e80 years old) and the MedDiet score was observed (P Z 0.537 for gender and P Z 0.321 for age category). Significant inverse associations between adherence to MedDiet and MetS were observed only in men, even when adjusted for all potential confounders. This association was not statistically significant among women (P for trend Z 0.056). Men at the top quartile of adherence to the MedDiet had a statistically significant lower odds ratio of having MetS in comparison with the lowest quartile. Higher adherence to the MedDiet in men between 65 and 80 years old was significantly associated to a lower prevalence of MetS (P Z 0.019). An inverse association between adherence to the Trichopoulou score and MetS was observed in the unadjusted model (Appendix 2). However, when we adjusted for potential confounders the models were not statistically significant. No significant association between MedDiet score and MetS prevalence was observed when the Panagiotakos MedDiet score was used (Appendix 3). Table 3 shows the results of the multiple logistic regression analysis evaluating which of the 14 elements used to define the MedDiet score were more strongly associated with the prevalence of MetS. Even when mutually adjusted, no item in the score was significantly associated to MetS. When we used the forward method, the items ‘olive oil as culinary fat’, ‘legumes consumption’ and ‘wine consumption’ were selected in this order into an overall model as the highest odds ratio of having MetS. There was no evidence of multicolinearity when the items were simultaneously adjusted for each other. No colinearity between the food item included in the score was observed (VIF < 2). In separated models stratified by sex, we found that ‘legumes consumption’ and ‘red meat consumption’, were significantly associated with the MetS risk only among men.

Results Metabolic syndrome and its components

Mediterranean diet adherence and metabolic syndrome components

MetS was significantly more prevalent in women than in men (Table 1). The prevalence of each ATP III component of the MetS is summarized in Table 1. The prevalence of

The associations between the adherence to the MedDiet and each of the MetS criteria were considered separately (Table 4) using multiple logistic regression models with

566 Table 1

N. Babio et al. General characteristics of the subjects studied.

Age in years, mean  SD Weight in kg, mean  SD BMI in kg/m2, mean  SD Type 2 diabetes prevalence, % (n) Subjects treated with antihypertensive drugs, % (n) Subjects treated with hypotriglyceridemic drugs, % (n) Subjects treated with oral antidiabetic drugs, % (n) Subjects treated with insulin, % (n) Metabolic syndromea and Metabolic syndrome Abnormal waist circumference Low level of HDL cholesterol High triglycerides levels or lowering treatment High fasting serum glucose level or drug diabetes treatment High blood pressure or antihypertensive treatment Lifestyle variables Energy intake in kcal/ day  SD Current smokers, % (n) 14-point food-item Mediterranean diet score, mean  SD Trichopoulou Mediterranean Diet score, mean  SD Daily expenditure for physical activity in the last week in kcal/day, mean  SD

Women (n Z 446)

Men (n Z 362)

67.8  5.6 73.1  10.0 30.2  3.3 46.6 (208)

66.9  6.3 79.8  10.1 29.0  3.1 53.6 (194)

76.2 (340)

71.8 (260)

2.7 (12)

3.3 (12)

6.7 (30)

5.5 (20)

31.2 (139)

35.9 (130)

its components, % (n) 69.5 (310) 53.9 (195) 91.9 (410) 57.7 (209) 24.2 (108)

17.9 (65)

32.9 (147)

30.6 (111)

60.1 (268)

66.0 (239)

96.9 (432)

95.0 (344)

2171.1  564.8

2496.4  644.6

3.6 (16) 8.2  1.8

22.9 (83) 8.3  2.0

4.0  1.71

179.3  146.1

4.4 (1.6)

345.0  325.5

a The metabolic syndrome was defined by using the updated National Cholesterol Education program’s Adult Treatment Panel III criteria.

polynomial contrast and all the MetS components as dependent variables. A higher adherence to the MedDiet (quartile 4) was associated with a lower prevalence of the low HDL-cholesterol and high triglycerides criteria (47.0 and 54%; P for trend Z 0.034 and 0.006 respectively) in relation to the first quartile. After adjusting for BMI (data not shown), only higher adherence to the MedDiet (quartile

4) was associated with a lower prevalence of hypertriglyceridemia criteria (P for trend Z 0.011). When we stratified by sex, marginally significant differences across successively increasing quartiles of the score were found for the high triglyceride criterion both among women (P for trend Z 0.055) and men (P for trend Z 0.059). This was also observed in men for the central obesity criteria (P for trend Z 0.062).

Discussion Although there is some evidence that the Mediterranean dietary pattern protects against CVD [26], few epidemiologic studies have assessed the relationship between adherence to the MedDiet and MetS. The present study is unique in assessing this relationship in an elderly population with a high risk of CVD and also a high baseline level of MetS risk factors (including diet). Our main finding is that the highest adherence to MedDiet is associated with a lower prevalence of MetS defined by the ATP III criteria. It is important to note that this association remained significant when the MetS criteria given by the International Diabetes Federation (IDF) were used (data not shown) and adjustments had been made for BMI. To the best of our knowledge, only one longitudinal study [21], two cross-sectional studies [19,20] and one clinical trial[15] have been conducted to assess the association between MedDiet and MetS. The longitudinal study, including only university graduates at low cardiovascular risk, reported an inverse association with the MetS (defined by the IDF criteria) but only weak associations with most of its defining criteria [21,29]. The two cross-sectional studies found contradictory results. In both studies, in contrast to our high risk participants, this association was analysed in population samples with low cardiovascular risk. In a sample of the general Greek population, individuals with higher adherence to a MedDiet had a 20% lower odds ratio of having MetS [20]. In contrast, in a cross-sectional study performed on subjects from the general population of the Canary Islands no significant relationship between MedDiet adherence and MetS was found [19]. In a Spanish cohort [21], after 6 years follow-up, participants with the highest Trichopoulou score at baseline presented the lowest cumulative incidence of MetS. In our study we observed a better relationship between MedDiet adherence and MetS when we used the 14-point food-item score compared with the Trichopoulou score. For this reason, the 14-item MetDiet score should be evaluated in the future as a possible tool for analysing the relationship between MedDiet adherence and chronic diseases. The advantage of the 14-item tool is that it is assessed using only a short questionnaire and, therefore, the application of a full-length food frequency questionnaire may not be needed to assess adherence to the MedDiet. However, no significant relationship between MedDiet adherence and MetS prevalence was observed when the Panagiotakos MedDiet score was used [27]. The cross-sectional design of our study and the space limits of the manuscript precluded any analysis of specificity and sensitivity estimates such as that done by Panagiotakos in previous papers [30].

Mediterranean diet and metabolic syndrome

567

Table 2 Metabolic syndrome risk (odds ratio and their 95% confidence intervals) across quartiles of adherence to the Mediterranean diet. n (women/men)

Q1a <7 points

Q2 7 points

Q3 8 points

Q4 9 points

81/66

171/117

86/86

108/93

P for trend

Unadjusted model

All subjects Women Men

1 1 1

0.88 (0.57e1.36) 1.15 (0.63e2.07) 0.63 (0.33e1.18)

0.69 (0.43e1.10) 0.82 (0.42e1.59) 0.59 (0.30e1.15)

0.42 (0.27e0.65) 0.60 (0.32e1.11) 0.27 (0.14e0.53)

< 0.001 0.059 < 0.001

Model 1

All subjectsb Womenc Menc

1 1 1

0.89 (0.57e1.37) 1.15 (0.63e2.07) 0.70 (0.37e1.34)

0.73 (0.46e1.18) 0.82 (0.42e1.59) 0.65 (0.33e1.29)

0.42 (0.27e0.66) 0.60 (0.32e1.11) 0.30 (0.15e0.59)

< 0.001 0.059 0.001

Model 2

All subjectsd Womene Mene

1 1 1

0.92 (0.58e1.45) 1.13 (0.65e2.30) 0.75 (0.38e1.46)

0.69 (0.42e1.13) 0.72 (0.36e1.44) 0.67 (0.03e1.37)

0.44 (0.27e0.70) 0.61 (0.32e1.17) 0.36 (0.18e0.73)

< 0.001 0.056 0.005

Model 3

All subjectsf Womeng Meng

1 1 1

0.99 (0.62e1.58) 1.19 (0.62e2.27) 0.89 (0.44e1.80)

0.81 (0.48e1.35) 0.78 (0.38e1.59) 0.86 (0.40e1.84)

0.48 (0.29e0.78) 1.01 (0.97e1.05) 0.41 (0.20e0.87)

0.002 0.093 0.024

Multiple logistic regression was used to assess the association between MedDiet quartiles (dependent variables) and MetS (dependent variable), and multiple logistic regression with polynominal contrast was used to generate the P for trend. a Quartiles of Mediterranean diet score (0e14). b Adjusted for sex and age. c Adjusted for age. d Adjusted for sex, age, energy intake, smoking and physical activity. e Adjusted for age, energy intake, smoking and physical activity. f Adjusted for sex, age, energy intake, smoking, physical activity and body mass index. g Adjusted for age, energy intake, smoking, physical activity and body mass index.

Only one clinical trial has analysed the effect of the traditional MedDiet on the MetS. Esposito et al. [15] showed that an intervention using a Mediterranean-style diet seems effective in reducing the prevalence of the MetS. Although Alvarez-Leon et al. [19] found no relationship between adherence to the MedDiet and lower MetS prevalence, they did observe that some components of the traditional MedDiet (wine, fruit, vegetables and cereals) showed an inverse association with MetS and its components. In fact, it has been suggested that not all the components of the MedDiet are likely to provide the same level of protection [18]. In this sense, in our study, the use of olive oil as culinary fat, the high consumption of legumes and the moderate consumption of wine were the principal components of the MedDiet associated with lower risk of MetS. The inverse relationship observed between those typical foods present in the MedDiet and MetS prevalence could be explained by many of the constituents of these foods. For example olive oil is very rich in oxidation-resistant MUFA [31], especially if the olive oil consumed is as the virgin variety retaining all its polyphenol content [32]. Replacing SFA by MUFA beneficially affects the plasma lipid profile and improves insulin sensitivity [33]. Olive oil consumption was reported to be associated with lower risk of developing hypertension, but only among men [34]. Virgin olive oil [35] or a diet rich in MUFA has been shown to reduce blood pressure more than an SFA-rich diet [36] and, unlike a lowfat, carbohydrate-rich diet, has no deleterious effect on blood pressure in normotensive subjects [37]. Some polyphenols present in red wine have beneficial endothelial and anti-inflammatory properties. An inverse association between red wine consumption and blood

pressure has been reported [38]. A clinical trial [39] did not show any blood pressure effect after consumption of red wine or de-alcoholized red wine. Moderate alcohol consumption raises HDL-cholesterol levels [40] and decreases plasma concentrations of some inflammatory molecules. A metaanalysis indicated that the consumption of 30 g/day of alcohol increased HDL-cholesterol levels by a mean of 4 mg/dL, irrespective of the alcoholic beverage consumed [41]. High legume and low red meat consumption were inversely associated in our study with MetS, but only among men. Red meat is rich in saturated fat, which increases inflammation, LDL and TG-levels. Individuals adopting a Western dietary pattern (characterized mainly by high red or processed meat consumption) have an increased risk of developing diabetes [13], whereas a MedDiet, low in meat or meat products but rich in legumes was associated with a substantially lower diabetes risk [42]. Red meat intake was also positively associated with the risk of hypertension in middle-aged and older men [43]. Furthermore, dietary pattern analyses have shown that a dietary pattern characterized by high red meat consumption is associated with a higher risk of the MetS [14]. Legumes are rich in fibre, magnesium and other components that are associated with a better lipid profile, and with improved glucose and inflammatory responses [44]. Subjects consuming legumes four or more times per week registered a lower risk of CVD [44]. Whole grain products and legumes protect against the development of diabetes [45]. The viscous fibre content of legumes tends to slow down carbohydrate digestion, decreasing the glycaemic index of the diet, thus contributing to an increase in the HDL-c levels and insulin sensitivity [46].

Table 3 itemsa.

Metabolic syndrome risk (odds ratio and their 95% confidence intervals) in all subjects and Mediterranean diet food

Using olive oil as main culinary fat Consumption  4 spoons/day of olive oil Consumption  2 servings/day of vegetables Consumption  3 fruit units/day (including natural fruit juices) Consumption < 1 serving/day of red meat, hamburger or meat products Consumption < 1 serving/day of butter, margarine or cream Consumption < 1 serving/day of sweetened or carbonated beverages Consumption  3 glasses/week of wine Consumption  3 servings/week of legumes Consumption  3 servings/week of fish or shellfish Consumption < 3 times/week of commercial sweets or pastries (not homemade) Consumption  1 servings/week of nuts (including peanuts) Consumption preferentially of chicken, turkey, or rabbit meat instead of veal, pork, hamburger or sausages Consumption  2 servings/week of vegetables, pasta, rice or other dishes seasoned with sofrito (sauce made with tomato and onion, leek, or garlic and simmered with olive oil)

Adjusted by all the other food items (n Z 737)

Forward method (n Z 737)

0.63 0.99 0.80 0.93 0.69 0.83 0.99 0.77 0.68 0.82 1.04

0.61 (0.38e0.97) e e e e e e 0.68 (0.48e0.95) 0.62 (0.35e0.99) e e

(0.37e1.06) (0.61e1.62) (0.54e1.17) (0.67e1.29) (0.46e1.03) (0.46e1.50) (0.59e1.64) (0.54e1.11) (0.43e1.08) (0.59e1.14) (0.74e1.44)

0.82 (0.58e1.13) 1.17 (0.81e1.69)

e e

0.86 (0.62e1.20)

e

Multiple logistic regression models (enter method or forward method) including the presence or not of metabolic syndrome (dependent variable) and the diet food items (independent variables), adjusted for sex, age, energy intake, smoking status and physical activity. a Specific questions about these items are shown in Supplementary Appendix 1.

Table 4 Metabolic syndrome components risk (odds ratio 95% confidence intervals) by quartiles of adherence to Mediterranean diet in women (n Z 446) and men (n Z 362). Q1a

Q2

Q3

Q4

81/66

171/117

86/86

108/93

Waist circumference (>102 cm in men, >88 cm in women) All subjects 1 0.73 (0.43e1.23) Women 1 0.99 (0.38e2.55) Men 1 0.63 (0.32e1.24)

0.71 (0.40e1.26) 1.04 (0.34e3.17) 0.63 (0.30e1.30)

0.67 (0.38e1.17) 1.23 (0.42e3.62) 0.49 (0.24e1.00)

0.168 0.691 0.062

HDL-cholesterol (<40 mg/dL in men, <50 mg/dL in women) All subjects 1 0.71 (0.44e1.14) Women 1 0.61 (0.33e1.12) Men 1 0.94 (0.44e2.02)

0.78 (0.46e1.33) 0.89 (0.45e1.77) 0.70 (0.29e1.66)

0.53 (0.31e0.90) 0.46 (0.22e0.92) 0.74 (0.31e1.73)

0.034 0.081 0.375

Triglycerides (150 mg/dL or hypotriglyceridemic treatment) All subjects 1 0.70 (0.45e1.08) Women 1 0.68 (0.38e1.20) Men 1 0.76 (0.40e1.47)

0.83 (0.51e1.33) 0.82 (0.42e1.59) 0.85 (0.42e1.71)

0.46 (0.28e0.76) 0.48 (0.25e0.92) 0.46 (0.22e0.96)

0.006 0.055 0.059

Glucose (>100 mg/dL or antidiabetic All subjects 1 Women 1 Men 1

medication) 1.37 (0.89e2.1) 1.64 (0.92e2.92) 1.10 (0.55e2.13)

0.93 (0.58e1.50) 1.00 (0.53e1.92) 0.83 (0.41e1.68)

0.88 (0.56e1.39) 1.00 (0.54e1.85) 0.86 (0.42e1.73)

0.293 0.618 0.505

Blood pressure (systolic 130 mmHg, All subjects 1 Women 1 Men 1

diastolic 85 or antihypertensive medication) 0.56 (0.15e2.12) 0.22 (0.06e0.80) 0.47 (0.05e4.45) 0.13 (0.02e1.17) 0.60 (0.11e3.28) 0.28 (0.05e1.44)

0.46 (0.12e1.79) 0.33 (0.35e3.08) 0.60 (0.10e3.28)

0.125 0.185 0.410

n (women/men)

P for trend

Metabolic syndrome criteria

The multivariable logistic regression was adjusted for age, energy intake, smoking and physical activity. Multiple logistic regression was used to assess the association between MedDiet quartiles (dependent variables) and each of the MetS components (dependent variable). Multiple logistic regression with polynominal contrast was used to generate the P for trend. a Quartiles of Mediterranean diet score (0e14).

Mediterranean diet and metabolic syndrome Finally, consistent with previous evidence regarding outcomes other than MetS [26], a beneficial association of the overall MedDiet pattern contrasts with the lack of evidence of an important association of each of its individual components. We highlight that the associations we found for the individual components of the MedDiet with MetS were mostly nonsignificant. This may be because individual components are associated only when they are integrated into an overall score. The main limitation of the present analysis is its crosssectional nature, which does not allow any causal relationship between MedDiet and MetS to be established. Moreover, since the sample was composed of older participants from Spain with a high risk of CVD, our findings cannot be extrapolated to younger lower risk populations from other Mediterranean countries. Furthermore, studying high cardiovascular risk individuals is a limitation rather than an advantage for testing our hypothesis. These individuals may have additional confounders because of their dietary recommendations or medication, which probably makes it more difficult to detect associations. In summary, a higher adherence to a MedDiet was found to be associated with significantly lower odds of having MetS in a population with a high risk of CVD. Subjects in the fourth quartile of the MedDiet adherence have a 56, 47, and 54% lower odds ratios of having MetS, low HDL-c and hypertriglyceridemia MetS criteria respectively than those in the lowest quartile. Some components of the MedDiet, such as olive oil, legumes and red wine were associated with lower odds of MetS. Further longitudinal study designs, including trials, are needed in order to clarify these relationships.

Acknowledgements The authors thank the participants for their enthusiastic collaboration, the PREDIMED personnel for excellent assistance and the personnel of all primary care centres affiliated and to Carles Munne ´-Cuevas (Human Nutrition Unit, URV) for the administrative and technical support provided. We gratefully acknowledge the Spanish Ministry of Health (Instituto de Salud Carlos III, Thematic Network G03/140 and RTIC RD06/0045, Fondo de Investigaciones Sanitarias, PI04/1828 and PI05/1839, PI07/0240), CYCYT AGL20050365, the Public Health Division of the Department of Health of the Autonomous Government of Catalonia, and the Centre Catala ` de la Nutricio ´ de l’Institut d’Estudis Catalans. None of the funding sources played a role in the design, collection, analysis or interpretation of the data or in the decision to submit the manuscript for publication. None of the authors have any conflict of interest. CIBER is an initiative of the Instituto Carlos III, Spain. Nureta-PREDIMED Investigators not listed as authors: Garcı´a-Rosello ´ J, Isach-Subirana A, Tort Vernet R, Marti E, Castro-Guardiola P, Mas Escoda R, Gonza ´lez-Pe ´rez R, Martı´n-Lujan F, Sagarra Alomo R, Cabre ´ Vila JJ.

Appendix Supplementary material Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.numecd. 2008.10.007.

569

References [1] Gami AS, Witt BJ, Howard DE, Erwin PJ, Gami LA, Somers VK, et al. Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. J Am Coll Cardiol 2007;49:403e14. doi: 10.1016/j.jacc.2006.09.032. [2] Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709e16. [3] Athyros VG, Ganotakis ES, Elisaf M, Mikhailidis DP. The prevalence of the metabolic syndrome using the National Cholesterol Educational Program and International Diabetes Federation definitions. Curr Med Res Opin 2005;21:1157e9. [4] Ford ES, Giles WH, Mokdad AH. Increasing prevalence of the metabolic syndrome among US adults. Diabetes Care 2004;27: 2444e9. [5] Park YW, Zhu S, Palaniappan L, Heshka S, Carnethon MR, Heymsfield SB. The metabolic syndrome: prevalence and associated risk factor findings in the US population from the Third National Health and Nutrition Examination Survey, 1988e1994. Arch Intern Med 2003;163:427e36. [6] Mirmiran P, Noori N, Azizi F. A prospective study of determinants of the metabolic syndrome in adults. Nutr Metab Cardiovasc Dis 2008;18:567e73. [7] Branth S, Ronquist G, Stridsberg M, Hambraeus L, Kindgren E, Olsson R, et al. Development of abdominal fat and incipient metabolic syndrome in young healthy men exposed to longterm stress. Nutr Metab Cardiovasc Dis 2007;7:427e35. [8] Phelan S, Wadden TA, Berkowitz RI, Sarwer DB, Womble LG, Cato RK, et al. Impact of weight loss on the metabolic syndrome. Int J Obes (Lond) 2007;31:1442e8. [9] Buckland G, Salas-Salvado ´ J, Roure E, Bullo ´ M, Serra-Majem L. Sociodemographic risk factors associated with metabolic syndrome in a Mediterranean population. Public Health Nutr 2008;11:1372e815. [10] Williams DE, Prevost AT, Whichelow MJ, Cox BD, Day NE, Wareham NJ. A cross-sectional study of dietary patterns with glucose intolerance and other features of the metabolic syndrome. Br J Nutr 2000;83:257e66. [11] Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC. Dietary patterns and markers of systemic inflammation among Iranian women. J Nutr 2007;137:992e8. [12] Newby PK, Muller D, Tucker KL. Associations of empirically derived eating patterns with plasma lipid biomarkers: a comparison of factor and cluster analysis methods. Am J Clin Nutr 2004;80:759e67. [13] van Dam RM, Rimm EB, Willett WC, Stampfer MJ, Hu FB. Dietary patterns and risk for type 2 diabetes mellitus in U.S. men. Ann Intern Med 2002;136:201e9. [14] Lutsey PL, Steffen LM, Stevens J. Dietary intake and the development of the metabolic syndrome: the atherosclerosis risk in communities study. Circulation 2008;117:754e61. [15] Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004; 292:1440e6. [16] Azadbakht L, Mirmiran P, Esmaillzadeh A, Azizi T, Azizi F. Beneficial effects of a Dietary Approaches to Stop Hypertension eating plan on features of the metabolic syndrome. Diabetes Care 2005;28:2823e31. [17] Orchard TJ, Temprosa M, Goldberg R, Haffner S, Ratner R, Marcovina S, et al. Diabetes Prevention Program Research Group. The effect of metformin and intensive lifestyle intervention on the metabolic syndrome: the Diabetes

570

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

N. Babio et al. Prevention Program randomized trial. Ann Intern Med 2005; 142:611e9. Martı´nez-Gonza ´lez MA, Sa ´nchez-Villegas A. The emerging role of Mediterranean diets in cardiovascular epidemiology: monounsaturated fats, olive oil, red wine or the whole pattern? Eur J Epidemiol 2004;19:9e13. Alvarez-Leo ´n EE, Henrı´quez P, Serra-Majem L. Mediterranean diet and metabolic syndrome: a cross-sectional study in the Canary Islands. Public Health Nutr 2006;9:1089e98. Panagiotakos DB, Pitsavos C, Chrysohoou C, Skoumas J, Tousoulis D, Toutouza M, et al. Impact of lifestyle habits on the prevalence of the metabolic syndrome among Greek adults from the ATTICA study. Am Heart J 2004;147:106e12. doi:10.1016/j.jada.2007.03.006. Tortosa A, Bes-Rastrollo M, Sanchez-Villegas A, BasterraGortari FJ, Nun ˜ez-Cordoba JM, Martinez-Gonzalez MA. Mediterranean diet inversely associated with the incidence of metabolic syndrome: the SUN prospective cohort. Diabetes Care 2007;30:2957e9. Estruch R, Martı´nez-Gonza ´lez MA, Corella D, Salas-Salvado ´ J, Ruiz-Gutie ´rrez V, Covas MI, et al. Effects of a Mediterraneanstyle diet on cardiovascular risk factors: a randomized trial. Ann Intern Med 2006;145:1e11. Elosua R, Garcia M, Aguilar A, Molina L, Covas MI, Marrugat J. Validation of the Minnesota leisure time physical activity questionnaire in Spanish women. Investigators of the MARATDON group. Med Sci Sports Exerc 2000;32:1431e7. Martin-Moreno JM, Boyle P, Gorgojo L, Maisonneuve P, Fernandez-Rodriguez JC, Salvini S, et al. Development and validation of a food frequency questionnaire in Spain. Int J Epidemiol 1993;22:512e9. Martı´nez-Gonza ´lez MA, Ferna ´ndez-Jarne E, SerranoMartı´nez M, Wright M, Gomez-Gracia E. Development of a short dietary intake questionnaire for the quantitative estimation of adherence to a cardioprotective Mediterranean diet. Eur J Clin Nutr 2004;58:1550e2. Trichopoulou A, Costacou T, Bamia C, Trichopoulos D. Adherence to a Mediterranean diet and survival in a Greek population. N Engl J Med 2003;348:2599e608. Panagiotakos DB, Pitsavos C, Stefanadis C. Dietary patterns: a Mediterranean diet score and its relation to clinical and biological markers of cardiovascular risk. Nutr Metab Cardiovasc Dis 2006;16:559e68. Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome. An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112:2735e52. Martı´nez-Gonza ´lez MA, Tortosa A, Basterra-Gortari FJ, BesRastrollo M. Mediterranean diet inversely associated with the incidence of metabolic syndrome: the SUN prospective cohort: response to Giugliano, Ceriello, and Esposito. Diabetes Care 2008;31:e37. Panagiotakos DB, Pitsavos C, Das UN, Skoumas Y, Stefanadis C. The implications of anthropometric, inflammatory and glycaemic control indices in the epidemiology of the metabolic syndrome given by different definitions: a classification analysis. Diabetes Obes Metab 2007;9:660e8.

[31] Aparicio R, Roda L, Albi MS, Gutierrez F. Effect of various compounds on virgin olive oil stability measured by rancimat. J Agric Food Chem 1999;47:4150e5. [32] Kecely T, Gordon MH. The antioxidant activity and stability of the phenolic fraction of green olives and extra virgin olive oil. J Agric Food Chem 2001;81:1391e6. [33] Vessby B, Uusitupa M, Hermansen K, Riccardi G, Rivellese AA, Tapsell LC, et al. Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU Study. Diabetologia 2001;44:312e9. [34] Alonso A, Martı´nez-Gonza ´lez MA. Olive oil consumption and reduced incidence of hypertension: the SUN study. Lipids 2004;39:1233e8. [35] Ferrara LA, Raimondi AS. d’Episcopo L, Guida L, Dello Russo A, Marotta T. Olive oil and reduced need for antihypertensive medications. Arch Intern Med 2000;160:837e42. [36] Rasmussen BM, Vessby B, Uusitupa M, Berglund L, Pedersen E, Riccardi G, et al. Effects of dietary saturated, monounsaturated, and n-3 fatty acids on blood pressure in healthy subjects. Am J Clin Nutr 2006;83:221e6. [37] Mensink RP, Janssen MC, Katan MB. Effect on blood pressure of two diets differing in total fat but not in saturated and polyunsaturated fatty acids in healthy volunteers. Am J Clin Nutr 1988;47:976e80. [38] Brenn T. The Tromsø heart study: alcoholic beverages and coronary risk factors. J Epidemiol Community Health 1986;40:249e56. [39] Zilkens RR, Burke V, Hodgson JM, Barden A, Beilin LJ, Puddey IB. Red wine and beer elevate blood pressure in normotensive men. Hypertension 2005;45:874e87. [40] Ellison RC, Zhang Y, Qureshi MM, Knox S, Arnett DK, Province MA, et al. Lifestyle determinants of high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study. Am Heart J 2004;147:529e35. doi:10.1016/j.ahj.2003.10.033. [41] Rimm EB, Williams P, Fosher K, Criqui M, Stampfer MJ. Moderate alcohol intake and lower risk of coronary heart disease: meta-analysis of effects on lipids and haemostatic factors. BMJ 1999;319:1523e8. [42] Martı´nez-Gonza ´lez MA, de la Fuente-Arrillaga C, NunezCordoba JM, Basterra-Gortari FJ, Beunza JJ, Vazquez Z, et al. Adherence to Mediterranean diet and risk of developing diabetes: prospective cohort study. BMJ 2008;336: 1348e51. [43] Wang L, Manson JE, Buring JE, Sesso HD. Meat intake and the risk of hypertension in middle-aged and older women. J Hypertens 2008;26:215e22. [44] Bazzano LA, He J, Ogden LG, Loria C, Vupputuri S, Myers L, et al. Legume consumption and risk of coronary heart disease in US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med 2001;161:2573e8. [45] Mellen PB, Walsh TF, Herrington DM. Whole grain intake and cardiovascular disease: a meta-analysis. Nutr Metab Cardiovasc Dis 2008;18:283e90. doi:10.1016/j.numecd.2006.12.008. [46] Frost G, Leeds AA, Dore CJ, Madeiros S, Brading S, Dornhorst A. Glycaemic index as a determinant of serum HDLcholesterol concentration. Lancet 1999;353:1045e8. doi: 10.1016/S0140-6736(98)07164-5.