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Olive oil, the Mediterranean diet, and arterial blood pressure: the Greek European Prospective Investigation into Cancer and Nutrition (EPIC) study^1,2,3

¹ From the Department of Hygiene and Epidemiology, University of Athens Medical School, Athens, Greece (TP, AN, PO, DT, and AT); the Department of Epidemiology, Harvard School of Public Health, Boston (DT); and the Hypertension Center, Third University Department of Medicine, Sotiria Hospital, Athens, Greece (TM).

² Supported by the Europe Against Cancer Program of the European Commission, the Greek Ministry of Health, and the Greek Ministry of Education.

³ Address reprint requests to A Trichopoulou, Department of Hygiene and Epidemiology, School of Medicine, University of Athens, 75 Mikras Asias Street, GR-115 27 Athens, Greece. E-mail: antonia{at}nut.uoa.gr.

	ABSTRACT

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
Background: Diet has been reported to influence arterial blood pressure, and evidence indicates that the Mediterranean diet reduces cardiovascular mortality.

Objective: The objective was to examine whether the Mediterranean diet, as an entity, and olive oil, in particular, reduce arterial blood pressure.

Design: Arterial blood pressure and several sociodemographic, anthropometric, dietary, physical activity, and clinical variables were recorded at enrollment among participants in the Greek arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Of these participants, 20 343 had never received a diagnosis of hypertension and were included in an analysis in which systolic and diastolic blood pressure were regressed on the indicated possible predictors, including a 10-point score that reflects adherence to the Mediterranean diet and, alternatively, the score’s individual components and olive oil.

Results: The Mediterranean diet score was significantly inversely associated with both systolic and diastolic blood pressure. Intakes of olive oil, vegetables, and fruit were significantly inversely associated with both systolic and diastolic blood pressure, whereas cereals, meat and meat products, and ethanol intake were positively associated with arterial blood pressure. Mutual adjustment between olive oil and vegetables, which are frequently consumed together, indicated that olive oil has the dominant beneficial effect on arterial blood pressure in this population.

Conclusions: Adherence to the Mediterranean diet is inversely associated with arterial blood pressure, even though a beneficial component of the Mediterranean diet score—cereal intake—is positively associated with arterial blood pressure. Olive oil intake, per se, is inversely associated with both systolic and diastolic blood pressure.

Key Words: Olive oil • Mediterranean diet • arterial blood pressure • European Prospective Investigation into Cancer and Nutrition study • EPIC study • Greece

	INTRODUCTION

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Hypertension can result in stroke, myocardial infarction, congestive heart failure, sudden cardiac death, peripheral vascular disease, and renal insufficiency, and yet it is clearly modifiable (1). Guidelines for the management of hypertension emphasize dietary factors (2, 3). Adoption of the low-saturated fat, plant-based DASH (Dietary Approaches to Stop Hypertension) diet has been advocated together with weight reduction, dietary sodium reduction, enhancement of physical activity, and moderation in alcohol consumption (2). An increase in fruit, vegetable, and fish intakes and a reduction in saturated fat and cholesterol intakes has also been advocated by the European Society of Hypertension (3).

The Mediterranean diet has been considered to be a healthy eating pattern ever since Ancel Keys initiated the Seven Countries Study in the 1950s (4, 5). Several studies have indicated that adherence to a Mediterranean diet is associated with a reduction in total and cardiovascular mortality (6-9). High intakes of olive oil are considered a hallmark of the traditional Mediterranean diet, resulting in high intakes of monounsaturated fatty acids and lower intakes of saturated fatty acids. Replacement of saturated with monounsaturated lipids is associated with a considerable reduction in coronary heart disease risk, through a mechanism involving reduction of LDL cholesterol, without a reduction of HDL cholesterol or an increase in triacylglycerols (10). Less is known about the relation of arterial blood pressure with Mediterranean diet or its dominant components. In a cross-sectional study of 2282 residents of the Attica area in Greece (which surrounds and includes the capital city of Athens), it was reported that adherence to a Mediterranean diet increases the likelihood of having the arterial blood pressure controlled (11).

To further evaluate the association between a Mediterranean diet and its components and systolic and diastolic blood pressure, we conducted a general population study in a large sample that covers most of the geographic regions of Greece. To avoid problems generated by diet modification subsequent to the diagnosis of hypertension, we excluded all persons who reported a diagnosis of hypertension at any time in the past. We ascertained diet through a validated, extensive food-frequency questionnaire and we controlled in the analysis for several factors with confounding potential, including total energy intake and physical activity.

	SUBJECTS AND METHODS

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Subjects
The study sample consisted of volunteers aged 20–86 y, who were recruited during a 5-y period (1994–1999) from around Greece to participate in the Greek component of the EPIC study (European Prospective Investigation into Cancer and Nutrition). EPIC is a multicountry, prospective study conducted in 22 research centers in 10 European countries and coordinated by the International Agency for Research on Cancer (IARC) to examine the role of dietary, biological, lifestyle, and environmental factors in the etiology of cancer and other chronic diseases. Details on the design and methods of the EPIC study and the Greek cohort were previously described in detail (9, 12, 13). All participants signed an informed consent form before enrollment. The study protocol was approved by the ethics committees of IARC and the University of Athens Medical School. A total of 28572 volunteers were enrolled in the Greek EPIC cohort, but 1750 of them (6.1%) were excluded because of missing values for one or more variables used in the present analysis. Of the remaining 26 822 participants, 6479 (24.2%) of them had already received a diagnosis of hypertension and were also excluded because they may have changed their diet in response to that diagnosis. Thus, 20 343 persons were included in the current study.

Methods
Standard interviewing procedures were used to assess sociodemographic characteristics, such as age, place of residence, and years of schooling. Anthropometric measurements also followed standard procedures and were taken with subjects wearing light clothing and no shoes. Body weight was measured to the nearest 100 g and height to the nearest 0.1 cm. Body mass index (BMI) was calculated as weight (in kg) over height squared (in m²). Waist and hip circumferences were measured with an inelastic tape and were recorded to the nearest 0.1 cm.

Usual dietary intake over the past year was assessed through a validated, semiquantitative, interviewer-administered food-frequency questionnaire (14, 15). The questionnaire included 150 food items and beverages as well as questions on habitual cooking methods and type of lipids used in cooking. Standard portion sizes were used for the estimation of consumed quantities (14, 15). A gradient of adherence to the traditional Greek-Mediterranean diet was constructed on the basis of 9 nutritional components (6, 9). Values of 0 to 1 were assigned to each of the 9 indicated components by using the respective sex-specific medians as cutoffs (9). Specifically, persons with a below the median consumption of components with a presumably beneficial effect on overall mortality (vegetables, legumes, fruit, cereals, and fish) were assigned a value of 0, whereas persons with consumption above the median were given a value of 1. In contrast, persons with a below the median consumption of components with a presumably detrimental effect on overall mortality (meat, meat products, and dairy products, which are rarely non- or low-fat in Greece) were assigned a value of 1, whereas persons whose consumption of these components was above the corresponding median were given a value of 0. For ethanol, a value of 1 was given to men whose consumption of ethanol was from 10 to <50 g/d, whereas for women the corresponding cutoffs were 5 and 25 g/d (9). Finally, for lipid intake, the ratio of monounsaturated to saturated lipids instead of the ratio of polyunsaturated to saturated lipids was used, because monounsaturated lipids are consumed in much higher quantities in Greece. Thus, a 10-point Mediterranean diet scale was constructed, which could take a value from 0 (minimal adherence to the traditional Mediterranean diet) to 9 (maximal adherence to the traditional Mediterranean diet).

Professional and leisure time physical activity were assessed by a special section of the lifestyle EPIC questionnaire (13, 16). Briefly, the average time per day spent on household, professional, sporting, and other activities was calculated. A metabolic equivalent index was computed by assigning a multiple of resting metabolic rate (17) to each activity (MET value). Time spent on each of the activities was multiplied by the MET value of the activity, and all MET-hour products were summed to give a total daily MET score, which represented the amount of energy per kilogram body weight expended during an average day.

Years of schooling was used as a proxy to socioeconomic status. Type of residence was determined according to the population of the area the person was living in. Urban areas were classified as those having >10000 inhabitants and, rural areas (including semiurban) with 9999 inhabitants (18).

Arterial blood pressure measurements were conducted by specially trained physicians with the use of a mercury sphygmomanometer (Baumanometer; WABaum Co. Inc, New York). Participants were seated on a chair with their backs supported and their right arm bared at the level of the heart. After 5 min of rest, systolic and diastolic blood pressures were measured twice, with at least a 2-min interval between the 2 measurements. The averages of the 2 readings for both systolic and diastolic blood pressure were used. As indicated, persons who reported a diagnosis of hypertension at any time in the past or who were using antihypertensive drugs were excluded from the analysis.

Statistical analysis
Systolic and diastolic blood pressure were alternatively regressed on age (continuously, expressed per 10-y increment); sex; place of residence; interaction terms of the former 3 variables, 2 at a time; years of schooling (continuously, expressed per 3-y increment); BMI (continuously, per SD); waist-to-hip ratio (continuously, per SD); energy intake (continuously, per SD); physical activity (continuously, per SD); and Mediterranean diet score (continuously, expressed per 3 unit increment). In additional models, the components of the Mediterranean diet score, as well as olive oil, were alternatively substituted for the Mediterranean diet score (all of them continuously per SD increment, except for ethanol intake). In all instances, SDs were sex-specific. The STATA statistical package was used for the analysis (Intercooled Stata 7.0 for WINDOWS 98/95/NT; STATA Corporation, College Station, TX).

	RESULTS

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The distribution of 8685 men and 11 658 women without a prior diagnosis of hypertension, by systolic and diastolic blood pressure in the Greek EPIC study, is shown in Table 1; 2666 (30.7%) men and 2758 (23.7%) women had a systolic or diastolic blood pressure that would classify them as probable hypertensives, notwithstanding the absence of a relevant diagnosis. In Table 2, representative values of the participants’ age, Mediterranean diet score, and variables considered to be predictive of hypertension (ie, years of schooling, BMI, waist-to-hip ratio, energy intake, and physical activity expenditure) are shown. The latter variables are potential confounders in the association between qualitative aspects of diet and arterial blood pressure.

Table 3

Tables 4

5

We repeated our analyses by substituting waist circumference for waist-to-hip ratio, by adding tobacco smoking among the core variables, and by controlling for dieting for any reason at the time the subjects were examined. When waist circumference was controlled for, instead of waist-to-hip ratio, the only regression coefficients that were substantially affected were, as expected, those for BMI, whereas no noticeable changes were evident with respect to the regression coefficients for Mediterranean diet score, its components, or olive oil. Both tobacco smoking and dieting for any reason were significantly inversely associated with both systolic and diastolic blood pressure, but, again, none of these variables were found to confound the association between Mediterranean diet score, its components, or olive oil on the one hand and systolic or diastolic blood pressure on the other hand.

We examined the association between arterial blood pressure and a variant of the Mediterranean diet score, in which a high intake of cereals was considered to be detrimental (value = 0) and a low intake of cereals as beneficial (value = 1). As expected, the regression coefficient of systolic blood pressure per 3 units of Mediterranean diet score changed from –0.8 (Table 4) to –1.0, and the regression coefficient of diastolic blood pressure for the same increment changed from –0.2 (Table 5) to –0.4 (P for both < 0.001).

	DISCUSSION

TOP ABSTRACT INTRODUCTION SUBJECTS AND METHODS RESULTS DISCUSSION REFERENCES

 
In a large, general, population-based study, we found evidence that adherence to a Mediterranean diet, as operationalized through the Mediterranean diet score, is inversely associated with both systolic and diastolic blood pressure. The values of the regression coefficients, which describe the average change in the systolic and diastolic blood pressure per specified increment in the Mediterranean diet score, are small. Because, however, arterial blood pressure is characteristic of all persons, small individual changes are translated into substantial changes in morbidity from hypertension-related diseases, including coronary heart disease and stroke, at the population level (19, 20). Of the components of the Mediterranean diet, vegetables, fruit, and olive oil (as reflected in the high ratio of monounsaturated to saturated lipids), are mainly responsible for the apparent protection against hypertension conveyed by the Mediterranean diet. The high content of plant foods in minerals, which tend to reduce arterial blood pressure (including potassium, magnesium, and calcium), may represent mediating mechanisms of the apparent protective effects of these foods, whereas the high content of plant foods and olive oil in antioxidants may also contribute to the health of the vascular system (21-24). Compatible with the apparent effect of the Mediterranean diet score is the detrimental effect associated with the intake of meat and meat products (significant with respect to diastolic blood pressure), the beneficial effect associated with the intake of fish and seafood (significant with respect to systolic blood pressure), and the detrimental effect associated with a high intake of ethanol. A high intake of alcoholic beverages has been consistently associated with high arterial blood pressure (25, 26), whereas meat intake has been reported to increase and fish intake to decrease arterial blood pressure (27, 28). Note, however, that one of the beneficial components of the Mediterranean diet, cereal consumption, is actually positively associated with both systolic and diastolic blood pressure, possibly because carbohydrate intake has been linked to several cardiovascular disease risk factors and clinical entities (29, 30) and because salt is frequently added to cereal products, particularly bread, which is a widely consumed staple food in Greece. Indeed, it may be worth examining in future studies the data-derived evidence that cereal intake is positively associated with arterial blood pressure.

The Mediterranean diet shares many of the characteristics of the DASH diet, which is widely recommended in the United States. The main difference between the 2 diets is that the Mediterranean diet is high in olive oil (2, 31, 32). Simply put, it could be argued that the DASH diet, which is enriched in olive oil rather than in other fatty acids and perhaps in some grain products, could represent an improvement over the classic DASH diet, provided that the balance between total energy intake and expenditure is preserved and the dietary pattern is culinary acceptable. On the basis of the Greek EPIC data, it is difficult to argue whether olive oil or monounsaturated lipids in general have differential effects on arterial blood pressure.

There is considerable evidence that the consumption of fruit and vegetables is inversely associated and the consumption of cereals and meat and meat products is positively associated with arterial blood pressure (20, 33, 34). Evidence suggests, but does not conclude, that fish intake is inversely associated with arterial blood pressure (27, 35). The results of the few comprehensive studies that have been conducted to evaluate the association between arterial blood pressure and intake of dairy products suggest an inverse association (36). In contrast, there is wide agreement that a high consumption of alcoholic beverages is positively associated with arterial blood pressure (25, 26).

A Mediterranean diet is widely regarded as a health-promoting diet, in terms of both general and cardiovascular mortality (4, 6, 9, 37, 38). The search for mediating processes has mainly focused on the blood lipid profile and mechanisms of thrombogenesis (29, 39). Few studies have examined the relation of olive oil or a Mediterranean diet with arterial blood pressure. The fatty acids in olive oil are protected by natural antioxidants (40), including carotenes, tocopherols, and phenolic compounds. Antioxidants tend to inactivate the effects of free radicals and lipid peroxidation, which could affect arterial stiffness (41-44). In animal experiments, olive oil has been compared with sunflower oil, which is more susceptible to oxidation (45). It has been shown that olive oil decreased arterial blood pressure more than did sunflower oil, an effect that was attributed, at least in part, to olive oil’s polyphenolic content (21). In a recent publication, Alemany et al reported that intraperitoneal or oral administration to animals of 2-hydroxyoleic acid, a synthetic derivative of oleic acid, which is the primary monounsaturated fatty acid found in olive oil, induced substantial decreases in arterial blood pressure, mainly systolic blood pressure (46).

In humans, olive oil was again compared with sunflower oil and was found to reduce the need for daily pharmaceutical antihypertensive treatment. According to Ferrara et al (47), daily doses of blood pressure medication were reduced by 48% during the olive oil diet and by 4% during the sunflower oil diet; this finding could be attributed to polyphenols, which enhance nitric oxide concentrations and may help dilate arteries, which reduces blood pressure. Polyphenols are completely absent in sunflower oil. In an epidemiologic study undertaken in Greece, a Mediterranean diet—operationalized in line with the recommendations of Trichopoulou et al (6, 48, 49)—was found to be inversely associated with arterial blood pressure (11). The current study, however, is considerably larger, and its design allowed both the control for a large set of potential confounders and a separate examination of the specific effects of the various components of the Mediterranean diet.

The strengths of this study were its large sample size, reliance on a validated food-frequency questionnaire, coverage of a large set of potential confounders, and exclusion of persons with a diagnosis of hypertension, the latter of which prevents bias that could be introduced from changes in habitual diet in response to the diagnosis of hypertension. The cross-sectional nature of the study was a drawback; however, the results of our evaluation of the association of arterial blood pressure with socioeconomic status, BMI, and waist-to-hip ratio indicate that overt biases were not operating in the study.

Salt intake is one of the principal dietary components involved in increases in arterial blood pressure, but it is difficult to ascertain (50). Thus, a conceivable relation between salt intake and Mediterranean diet could not be evaluated in our study. Dietary recommendations to manage hypertension, such as the DASH diet, are, however, considered independently of advice to reduce salt intake (2).

In conclusion, we found evidence that a Mediterranean diet, which shares many of the characteristics of the DASH diet, is inversely associated with both systolic and diastolic blood pressure. Olive oil intake per se may be as important as fruit and vegetable intakes in the apparent beneficial effect of the Mediterranean diet in the context of arterial blood pressure control.

	ACKNOWLEDGMENTS

 
TP took the lead in the development of several aspects of the manuscript. PO coordinated the data analysis. AN contributed to the data collection and processing. TM was the clinical consultant for hypertension. DT was the epidemiology consultant. AT was the principal investigator of the Greek EPIC project and supervised all aspects of this project. All authors contributed to the writing of the manuscript. None of the authors declared a conflict of interest.

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