Curr Cardiol Rep (2014) 16:491 DOI 10.1007/s11886-014-0491-6
ISCHEMIC HEART DISEASE (D MUKHERJEE, SECTION EDITOR)
Ischemic Heart Disease and the Mediterranean Diet Thomas F. Whayne Jr.
Published online: 18 April 2014 # Springer Science+Business Media New York 2014
Abstract Lifestyle modification is primary in cardiovascular (CV) disease prevention. A major contribution is the Mediterranean diet (MedDiet), defined by two of seven components. Italian investigators determined a significant decrease in peripheral arterial disease of 56 % for a high score. Multiple specific CV risk factors are also favorably modified by the MedDiet. This includes beneficial effect on inflammation, vascular endothelium, and insulin resistance. There is also evidence that coronary heart disease, diabetes mellitus, and metabolic syndrome are decreased. Benefit appears to extend to new migrants in France. The economics of dietary adherence are favorable with decreased total lifetime health costs. Although mixed nuts appear to be a major factor in the MedDiet, special emphasis goes to extra virgin olive oil. Benefit also extends to other noncommunicable diseases with a decrease in cancer, Parkinson’s disease, and Alzheimer’s disease. Further quantitation of benefit and understanding of mechanisms involved in dietary benefit is essential. Keywords Cardiovascular risk . Coronary heart disease . Ischemic heart disease . Lipoproteins . Mediterranean diet . Metabolic syndrome . Myocardial infarction . Peripheral arterial disease Abbreviations apoB apolipoprotein B CHD Coronary heart disease CI Confidence interval CV Cardiovascular This article is part of the Topical Collection on Ischemic Heart Disease T. F. Whayne Jr. (*) Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, 326 Wethington Building, 900 South Limestone Street, Lexington, KY 40536-0200, USA e-mail: [email protected]
DM HbA1c HDL-C HOMA-IR HR LDL-C MedDiet MI MetSyn PAD PREDIMED RR VLDL-C
Diabetes mellitus Glycated hemoglobin High-density lipoprotein cholesterol Homeostatic model assessment-insulin resistance Hazard ratio Low-density lipoprotein cholesterol Mediterranean diet Myocardial infarction Metabolic syndrome Peripheral arterial disease Prevención con Dieta Mediterránea Relative risk Very low-density lipoprotein cholesterol
Introduction Diet should always be first-line in any effort to reduce cardiovascular (CV) risk. However, many published diets are limited in scope, emphasize one concept as a fad, or are so excessively involved in extreme restrictions, that adherence by any significant number of individuals is highly improbable. On the other hand, the Mediterranean diet (MedDiet) involves many delightful and tasty choices and there is accumulating evidence of its value and practicality. The relationship of the MedDiet to ischemic heart disease and results with CV risk are considered in this article.
Definition of Mediterranean Diet Rees et al. defined the MedDiet as follows after including 11 clinical trials involving 15 articles and made up of 52,044 randomized participants [1•]. The definition involves seven
491, Page 2 of 7
components to be considered with the presence of at least two of these components to qualify as a MedDiet (Table 1). The seven possible components are: a high ratio of monounsaturated to saturated fat, some red wine consumption defined as low to moderate, high legume consumption, significant grain and cereal consumption, consumption of fruits and vegetables in significant quantities, low consumption of meats and meat products with increased consumption of fish, and moderate consumption of milk and dairy products. Therefore, individuals consistently consuming two of the seven components would qualify as following a Mediterranean diet. Rees et al. interpreted their analysis as showing limited evidence to suggest a favorable effect on CV risk factors [1•]. They commented that more comprehensive interventions involving a description as MedDiet might have a more beneficial effect on plasma lipid levels than a dietary intervention with minimal components. Dietary interventions should be considered firstline therapy for CV disease prevention and there is increasing evidence that the traditional MedDiet may decrease the risk of CV disease [2]. The extent of coronary heart disease (CHD) is major and any nutritional approach that can contribute to decreasing CHD and improving CV health is essential.
Prevención Con Dieta Mediterránea (PREDIMED) Study The Prevención con Dieta Mediterránea (PREDIMED) study was a primary prevention dietary trial in Spain that was randomized and involved multiple centers [3, 4•, 5•]. The trial was carried out from October 2003 until December 2010 [3] with a median follow up of 4.8 years [5•]. There was a blinded assessment of end points. The participants were men from ages 55 to 80 years and women from ages 60 to 80 years [3] and the female participants were 57 % of the total [5•]. The primary end point was the rate of major CV events consisting of myocardial infarction (MI), stroke, or death from a CV etiology). The overall study showed that among persons at increased CV risk, both the MedDiet supplemented with extra-virgin olive oil and MedDiet supplemented with 30 g/
Table 1 Definition of the Mediterranean diet involves presence of at least two of the following seven components [1•] High ratio of monounsaturated to saturated fat Some red wine consumption defined as low to moderate High legume consumption Significant grain and cereal consumption Significant consumption of fruits and vegetables Low consumption of meats and meat products with increased fish consumption Moderate consumption of milk and dairy products
Curr Cardiol Rep (2014) 16:491
day of mixed nuts decreased the incidence of major CV events [5•]. A primary end-point event occurred in 288 of 7447 individuals enrolled. The multivariable-adjusted hazard ratio (HR) was 0.70 (95 % confidence interval [CI], 0.54 to 0.92) and 0.72 (95 % CI, 0.54 to 0.96) for the group assigned to the MedDiet/extra-virgin olive oil (96 events) and the group assigned to the MedDiet/with nuts (83 events), respectively. Each of these two groups was compared to the control group which had an occurrence of 109 events. Also with PREDIMED, Ruiz-Canela et al. looked specifically at individuals where the requirement was that the participants have no clinical evidence of peripheral arterial disease (PAD) or CV disease at baseline [3]. However, the participants had to have either type 2 diabetes mellitus (DM) or otherwise, at least three CV risk factors. There were a total of three groups: a MedDiet with extra-virgin olive oil (2539 patients); a MedDiet with mixed nuts; and the control group which was counseled on a low-fat diet. There was an extensive program of dietary education for all participants on a quarterly basis. Each of the two MedDiet groups had a lower risk of PAD in comparison to the control group: 18 cases out of 2539 participants for MedDiet/extra-virgin olive oil group; 26 cases out of 2452 participants for the MedDiet/mixed nuts group; and 45 cases out of 2444 participants in the controsl group. After adjusting for classic CV risk factors, the HR was 0.34 (95 % CI, 0.20-0.58) for the MedDiet/extra-virgin olive oil group and HR 0.50 (95 % CI, 0.30-0.81) for the MedDiet/mixed nuts group; both were compared to the control group. The KaplanMeier curves diverged early in the PREDIMED trial; there was not a significant difference between the two diet intervention groups. The authors commented on this being the first randomized primary prevention trial that showed benefit from a specific diet in reducing PAD although they could not separate true primary prevention from a decreased development of symptomatic PAD from an early stage of PAD [3]. In a fairly small substudy of PREDIMED, Estruch et al. assessed 772 asymptomatic subjects, ages 55-80 years who were at high CV risk [6]. After following one of the following for 3 months: MedDiet/extra-virgin olive oil (n=257), MedDiet/ mixed nuts (n=258), or a control low fat diet (n=257), the outcomes were evaluated. Compared to the control, the following results were obtained for MedDiet/extra-virgin olive oil, MedDiet/mixed nuts respectively: plasma glucose -7.02 mg/ dL (95 % CI, -12.6 to -1.26 mg/dL) and -5.4 mg/dL (95 % CI, -01.44 to -0.18 mg/dL); systolic blood pressure -5.9 mmHg (95 % CI, -8.7 to -3.1 mmHg) and -7.1 mmHg (95 % CI, -10.0 to -4.1 mmHg); and total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio -.38 (95 % CI, -0.55 to -0.22) and -0.26 (CI, -0.422 to -0.10). In addition, compared to the control, MedDiet/extra-virgin olive oil decreased C-reactive protein by 0.54 mg/L (95 % CI, 1.04 to 0.03 mg/L). The study shows that even a short-term MedDiet can favorably affect significant CV risk factors [6].
Curr Cardiol Rep (2014) 16:491
From PREDIMED, Sala-Vila et al. studied changes in carotid intima-media thickness (CIMT) in 175 subjects, 164 with complete data [7]. They found that compared to a control low fat diet where CIMT progressed, MedDiet/mixed nuts resulted in regression of CIMT after a mean intervention of 2.4 years. There were no changes of CIMT in association with MedDiet/extra-virgin olive oil.
Dietary Scores and Indexes Methodology to assess adherence to a MedDiet is essential in epidemiological studies. Diet indexes are used in an attempt to do a global evaluation of diet quality [8]. An index is supposed to be general and qualitative and in the case of the MedDiet, it is supposed to be based on a traditional MedDiet reference pattern. Therefore, MedDiet indices summarize the diet with a single score that is the result of the contribution of different components such as food, food groups, food combinations, and nutrients. The methods can involve positive or negative scoring of components, subtraction or addition of standardized components, and a ratio between components. For example, an Italian cohort study looked at the risk of developing PAD in type 2 DM patients and the postulate was that a higher score was better. A point was added according to food intake with evidence of benefit in CHD prevention and a 0 was given for foods with potential harm [9]. These Italian investigators found that a score of 11 or more resulted in a 56 % decreased incidence of PAD. Dietary scores can be employed to assess multiple associations between the Med Diet and observations such as life expectancy, incidence of obesity, CV disease presence, and association with some cancers [8]. However, better quantitation than such indices is essential to improve the accuracy of measuring adherence.
Dietary Percent Benefit The traditional MedDiet has been analyzed by Willett to show percent benefit [10]. A half century ago, Keys and colleagues described very low rates of CHD in the Mediterranean region, an area with relatively high fat intake but principally from olive oil. It has been noted that trans fat from partially hydrogenated vegetable oils is strongly related to CHD risk and such oils are absent in the traditional MedDiet. Epidemiologic evidence also supports a CHD benefit from increased intake of fruits, vegetables, whole grains, and fish, as well as daily consumption of moderate amounts of alcohol. In the analysis of Willett, it was noted that associated with regular physical activity in nonsmokers, health food choices consistent with a traditional MedDiet can result in the avoidance of 80 % of CHD, 70 % of stroke, and 90 % of type 2 diabetes [10].
Page 3 of 7, 491
Mediterranean Diet Effects on CV Risk Factors Multiple analyses have assessed the value of the MedDiet in modifying CV risk. Nordmann et al. searched multiple data bases from their onset, including MEDLINE and Cochrane Central Register of Controlled Trials, until January 2011 and, in addition, contacted various experts to identify randomized controlled trials that had compared the MedDiet to low-fat diets in overweight or obese subjects [11]. Their analysis was limited to a minimum 6 month follow-up and intention-to-treat data and its effect on CV risk factors. The inclusion criteria of the authors was met by 2650 subjects that consisted of 50 % women. After 2 years of follow-up, the subjects following the MedDiet (as compared to a low-fat diet) had more favorable changes in weighted mean differences of body weight (-2.2 kg; 95 % CI, -3.9 to -0.6), body mass index (-0.6 kg/m2; 95 % CI, -1 to -0.1), systolic blood pressure (-1.7 mmHg; 95 % CI, -3.3 to -.05), diastolic blood pressure (-1.5 mmHg; 95 % CI, -2.1 to -0.8), fasting plasma glucose (-3.8 mg/dL, 95 % CI, -7 to -0.6), total cholesterol (-7.4 mg/dL; 95 % CI, -10.3 to -4.4), and high-sensitivity C-reactive protein (hsCRP) (-1.0 mg/L; 95 % CI, -1.5 to-0.5). Therefore, Nordmann et al. concluded the MedDiet appeared to be more effective than a low-fat diet in effecting long-term change in CV risk factors and inflammatory markers [11]. Much other data supports the advantage of the MedDiet. Martínez-González et al. performed a systematic review of prospective studies that evaluated the relationship of fruit and/ or vegetable consumption with occurrence of chronic disease [12]. They also evaluated 18,457 university graduates enrolled in a dynamic cohort with baseline data collected between 1999 and 2010. This systematic review found that increased fruit and vegetable consumption was inversely associated with CV disease incidence and mortality. However, even dealing with health-conscious university graduates, it was found that low fruit and vegetable consumption was relatively prevalent, emphasizing the need for improvement strategies [12]. Sofi reviewed the effectiveness of the MedDiet in primary or secondary prevention and focused on the effect of a complete dietary approach rather than focusing on single nutrients [13]. The significant health benefit to a general population from the MedDiet in decreasing overall mortality and in decreasing the incidence of CV disease was emphasized. Estruch et al. studied 772 subjects (age 69± 5 years) with high CV risk and assigned them to either a low-fat diet or to one of two styles of the MedDiet [14]. They found that body weight, waist circumference, and mean systolic/diastolic blood pressure decreased (P
ISCHEMIC HEART DISEASE (D MUKHERJEE, SECTION EDITOR)
Ischemic Heart Disease and the Mediterranean Diet Thomas F. Whayne Jr.
Published online: 18 April 2014 # Springer Science+Business Media New York 2014
Abstract Lifestyle modification is primary in cardiovascular (CV) disease prevention. A major contribution is the Mediterranean diet (MedDiet), defined by two of seven components. Italian investigators determined a significant decrease in peripheral arterial disease of 56 % for a high score. Multiple specific CV risk factors are also favorably modified by the MedDiet. This includes beneficial effect on inflammation, vascular endothelium, and insulin resistance. There is also evidence that coronary heart disease, diabetes mellitus, and metabolic syndrome are decreased. Benefit appears to extend to new migrants in France. The economics of dietary adherence are favorable with decreased total lifetime health costs. Although mixed nuts appear to be a major factor in the MedDiet, special emphasis goes to extra virgin olive oil. Benefit also extends to other noncommunicable diseases with a decrease in cancer, Parkinson’s disease, and Alzheimer’s disease. Further quantitation of benefit and understanding of mechanisms involved in dietary benefit is essential. Keywords Cardiovascular risk . Coronary heart disease . Ischemic heart disease . Lipoproteins . Mediterranean diet . Metabolic syndrome . Myocardial infarction . Peripheral arterial disease Abbreviations apoB apolipoprotein B CHD Coronary heart disease CI Confidence interval CV Cardiovascular This article is part of the Topical Collection on Ischemic Heart Disease T. F. Whayne Jr. (*) Division of Cardiovascular Medicine, Gill Heart Institute, University of Kentucky, 326 Wethington Building, 900 South Limestone Street, Lexington, KY 40536-0200, USA e-mail: [email protected]
DM HbA1c HDL-C HOMA-IR HR LDL-C MedDiet MI MetSyn PAD PREDIMED RR VLDL-C
Diabetes mellitus Glycated hemoglobin High-density lipoprotein cholesterol Homeostatic model assessment-insulin resistance Hazard ratio Low-density lipoprotein cholesterol Mediterranean diet Myocardial infarction Metabolic syndrome Peripheral arterial disease Prevención con Dieta Mediterránea Relative risk Very low-density lipoprotein cholesterol
Introduction Diet should always be first-line in any effort to reduce cardiovascular (CV) risk. However, many published diets are limited in scope, emphasize one concept as a fad, or are so excessively involved in extreme restrictions, that adherence by any significant number of individuals is highly improbable. On the other hand, the Mediterranean diet (MedDiet) involves many delightful and tasty choices and there is accumulating evidence of its value and practicality. The relationship of the MedDiet to ischemic heart disease and results with CV risk are considered in this article.
Definition of Mediterranean Diet Rees et al. defined the MedDiet as follows after including 11 clinical trials involving 15 articles and made up of 52,044 randomized participants [1•]. The definition involves seven
491, Page 2 of 7
components to be considered with the presence of at least two of these components to qualify as a MedDiet (Table 1). The seven possible components are: a high ratio of monounsaturated to saturated fat, some red wine consumption defined as low to moderate, high legume consumption, significant grain and cereal consumption, consumption of fruits and vegetables in significant quantities, low consumption of meats and meat products with increased consumption of fish, and moderate consumption of milk and dairy products. Therefore, individuals consistently consuming two of the seven components would qualify as following a Mediterranean diet. Rees et al. interpreted their analysis as showing limited evidence to suggest a favorable effect on CV risk factors [1•]. They commented that more comprehensive interventions involving a description as MedDiet might have a more beneficial effect on plasma lipid levels than a dietary intervention with minimal components. Dietary interventions should be considered firstline therapy for CV disease prevention and there is increasing evidence that the traditional MedDiet may decrease the risk of CV disease [2]. The extent of coronary heart disease (CHD) is major and any nutritional approach that can contribute to decreasing CHD and improving CV health is essential.
Prevención Con Dieta Mediterránea (PREDIMED) Study The Prevención con Dieta Mediterránea (PREDIMED) study was a primary prevention dietary trial in Spain that was randomized and involved multiple centers [3, 4•, 5•]. The trial was carried out from October 2003 until December 2010 [3] with a median follow up of 4.8 years [5•]. There was a blinded assessment of end points. The participants were men from ages 55 to 80 years and women from ages 60 to 80 years [3] and the female participants were 57 % of the total [5•]. The primary end point was the rate of major CV events consisting of myocardial infarction (MI), stroke, or death from a CV etiology). The overall study showed that among persons at increased CV risk, both the MedDiet supplemented with extra-virgin olive oil and MedDiet supplemented with 30 g/
Table 1 Definition of the Mediterranean diet involves presence of at least two of the following seven components [1•] High ratio of monounsaturated to saturated fat Some red wine consumption defined as low to moderate High legume consumption Significant grain and cereal consumption Significant consumption of fruits and vegetables Low consumption of meats and meat products with increased fish consumption Moderate consumption of milk and dairy products
Curr Cardiol Rep (2014) 16:491
day of mixed nuts decreased the incidence of major CV events [5•]. A primary end-point event occurred in 288 of 7447 individuals enrolled. The multivariable-adjusted hazard ratio (HR) was 0.70 (95 % confidence interval [CI], 0.54 to 0.92) and 0.72 (95 % CI, 0.54 to 0.96) for the group assigned to the MedDiet/extra-virgin olive oil (96 events) and the group assigned to the MedDiet/with nuts (83 events), respectively. Each of these two groups was compared to the control group which had an occurrence of 109 events. Also with PREDIMED, Ruiz-Canela et al. looked specifically at individuals where the requirement was that the participants have no clinical evidence of peripheral arterial disease (PAD) or CV disease at baseline [3]. However, the participants had to have either type 2 diabetes mellitus (DM) or otherwise, at least three CV risk factors. There were a total of three groups: a MedDiet with extra-virgin olive oil (2539 patients); a MedDiet with mixed nuts; and the control group which was counseled on a low-fat diet. There was an extensive program of dietary education for all participants on a quarterly basis. Each of the two MedDiet groups had a lower risk of PAD in comparison to the control group: 18 cases out of 2539 participants for MedDiet/extra-virgin olive oil group; 26 cases out of 2452 participants for the MedDiet/mixed nuts group; and 45 cases out of 2444 participants in the controsl group. After adjusting for classic CV risk factors, the HR was 0.34 (95 % CI, 0.20-0.58) for the MedDiet/extra-virgin olive oil group and HR 0.50 (95 % CI, 0.30-0.81) for the MedDiet/mixed nuts group; both were compared to the control group. The KaplanMeier curves diverged early in the PREDIMED trial; there was not a significant difference between the two diet intervention groups. The authors commented on this being the first randomized primary prevention trial that showed benefit from a specific diet in reducing PAD although they could not separate true primary prevention from a decreased development of symptomatic PAD from an early stage of PAD [3]. In a fairly small substudy of PREDIMED, Estruch et al. assessed 772 asymptomatic subjects, ages 55-80 years who were at high CV risk [6]. After following one of the following for 3 months: MedDiet/extra-virgin olive oil (n=257), MedDiet/ mixed nuts (n=258), or a control low fat diet (n=257), the outcomes were evaluated. Compared to the control, the following results were obtained for MedDiet/extra-virgin olive oil, MedDiet/mixed nuts respectively: plasma glucose -7.02 mg/ dL (95 % CI, -12.6 to -1.26 mg/dL) and -5.4 mg/dL (95 % CI, -01.44 to -0.18 mg/dL); systolic blood pressure -5.9 mmHg (95 % CI, -8.7 to -3.1 mmHg) and -7.1 mmHg (95 % CI, -10.0 to -4.1 mmHg); and total cholesterol to high-density lipoprotein cholesterol (HDL-C) ratio -.38 (95 % CI, -0.55 to -0.22) and -0.26 (CI, -0.422 to -0.10). In addition, compared to the control, MedDiet/extra-virgin olive oil decreased C-reactive protein by 0.54 mg/L (95 % CI, 1.04 to 0.03 mg/L). The study shows that even a short-term MedDiet can favorably affect significant CV risk factors [6].
Curr Cardiol Rep (2014) 16:491
From PREDIMED, Sala-Vila et al. studied changes in carotid intima-media thickness (CIMT) in 175 subjects, 164 with complete data [7]. They found that compared to a control low fat diet where CIMT progressed, MedDiet/mixed nuts resulted in regression of CIMT after a mean intervention of 2.4 years. There were no changes of CIMT in association with MedDiet/extra-virgin olive oil.
Dietary Scores and Indexes Methodology to assess adherence to a MedDiet is essential in epidemiological studies. Diet indexes are used in an attempt to do a global evaluation of diet quality [8]. An index is supposed to be general and qualitative and in the case of the MedDiet, it is supposed to be based on a traditional MedDiet reference pattern. Therefore, MedDiet indices summarize the diet with a single score that is the result of the contribution of different components such as food, food groups, food combinations, and nutrients. The methods can involve positive or negative scoring of components, subtraction or addition of standardized components, and a ratio between components. For example, an Italian cohort study looked at the risk of developing PAD in type 2 DM patients and the postulate was that a higher score was better. A point was added according to food intake with evidence of benefit in CHD prevention and a 0 was given for foods with potential harm [9]. These Italian investigators found that a score of 11 or more resulted in a 56 % decreased incidence of PAD. Dietary scores can be employed to assess multiple associations between the Med Diet and observations such as life expectancy, incidence of obesity, CV disease presence, and association with some cancers [8]. However, better quantitation than such indices is essential to improve the accuracy of measuring adherence.
Dietary Percent Benefit The traditional MedDiet has been analyzed by Willett to show percent benefit [10]. A half century ago, Keys and colleagues described very low rates of CHD in the Mediterranean region, an area with relatively high fat intake but principally from olive oil. It has been noted that trans fat from partially hydrogenated vegetable oils is strongly related to CHD risk and such oils are absent in the traditional MedDiet. Epidemiologic evidence also supports a CHD benefit from increased intake of fruits, vegetables, whole grains, and fish, as well as daily consumption of moderate amounts of alcohol. In the analysis of Willett, it was noted that associated with regular physical activity in nonsmokers, health food choices consistent with a traditional MedDiet can result in the avoidance of 80 % of CHD, 70 % of stroke, and 90 % of type 2 diabetes [10].
Page 3 of 7, 491
Mediterranean Diet Effects on CV Risk Factors Multiple analyses have assessed the value of the MedDiet in modifying CV risk. Nordmann et al. searched multiple data bases from their onset, including MEDLINE and Cochrane Central Register of Controlled Trials, until January 2011 and, in addition, contacted various experts to identify randomized controlled trials that had compared the MedDiet to low-fat diets in overweight or obese subjects [11]. Their analysis was limited to a minimum 6 month follow-up and intention-to-treat data and its effect on CV risk factors. The inclusion criteria of the authors was met by 2650 subjects that consisted of 50 % women. After 2 years of follow-up, the subjects following the MedDiet (as compared to a low-fat diet) had more favorable changes in weighted mean differences of body weight (-2.2 kg; 95 % CI, -3.9 to -0.6), body mass index (-0.6 kg/m2; 95 % CI, -1 to -0.1), systolic blood pressure (-1.7 mmHg; 95 % CI, -3.3 to -.05), diastolic blood pressure (-1.5 mmHg; 95 % CI, -2.1 to -0.8), fasting plasma glucose (-3.8 mg/dL, 95 % CI, -7 to -0.6), total cholesterol (-7.4 mg/dL; 95 % CI, -10.3 to -4.4), and high-sensitivity C-reactive protein (hsCRP) (-1.0 mg/L; 95 % CI, -1.5 to-0.5). Therefore, Nordmann et al. concluded the MedDiet appeared to be more effective than a low-fat diet in effecting long-term change in CV risk factors and inflammatory markers [11]. Much other data supports the advantage of the MedDiet. Martínez-González et al. performed a systematic review of prospective studies that evaluated the relationship of fruit and/ or vegetable consumption with occurrence of chronic disease [12]. They also evaluated 18,457 university graduates enrolled in a dynamic cohort with baseline data collected between 1999 and 2010. This systematic review found that increased fruit and vegetable consumption was inversely associated with CV disease incidence and mortality. However, even dealing with health-conscious university graduates, it was found that low fruit and vegetable consumption was relatively prevalent, emphasizing the need for improvement strategies [12]. Sofi reviewed the effectiveness of the MedDiet in primary or secondary prevention and focused on the effect of a complete dietary approach rather than focusing on single nutrients [13]. The significant health benefit to a general population from the MedDiet in decreasing overall mortality and in decreasing the incidence of CV disease was emphasized. Estruch et al. studied 772 subjects (age 69± 5 years) with high CV risk and assigned them to either a low-fat diet or to one of two styles of the MedDiet [14]. They found that body weight, waist circumference, and mean systolic/diastolic blood pressure decreased (P
