The Mediterranean diet and incidence of hypertension: the Seguimiento Universidad de Navarra (SUN) Study.
ABSTRACT The Mediterranean diet is receiving increasing attention in cardiovascular epidemiology. The association of adherence to the Mediterranean diet with the incidence of hypertension was evaluated among 9,408 men and women enrolled in a dynamic Spanish prospective cohort study during 1999-2005. Dietary intake was assessed at baseline with a validated semiquantitative food frequency questionnaire, and a 9-point Mediterranean diet score was constructed. During a median follow-up period of 4.2 years (range, 1.9-7.9), 501 incident cases of hypertension were identified. After adjustment for major hypertension risk factors and nutritional covariates, adherence to the Mediterranean diet was not associated with hypertension (the hazard ratio was 1.10 (95% confidence interval (CI): 0.81, 1.41) for moderate adherence and 1.12 (95% CI: 0.79, 1.60) for high adherence). However, it was associated with reduced changes in mean levels of systolic blood pressure (moderate adherence, -2.4 mm Hg (95% CI: -4.0, -0.8); high adherence, -3.1 mm Hg (95% CI: -5.4, -0.8)) and diastolic blood pressure (moderate adherence, -1.3 mm Hg (95% CI: -2.5, -0.1); high adherence, -1.9 mm Hg (95% CI: -3.6, -0.1)) after 6 years of follow-up. These results suggest that adhering to a Mediterranean-type diet could contribute to the prevention of age-related changes in blood pressure.
- Journal of the American Academy of Nutrition and Dietetics 11/2014; 114(11):1723–1729. · 2.44 Impact Factor
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ABSTRACT: Little evidence exists on the effect of an energy-unrestricted healthy diet on metabolic syndrome. We evaluated the long-term effect of Mediterranean diets ad libitum on the incidence or reversion of metabolic syndrome.Canadian Medical Association Journal 10/2014; 186(17). · 5.81 Impact Factor
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ABSTRACT: The aim of this work was to evaluate factors associated with arterial blood pressure in a sample of older Mediterranean people without known cardiovascular disease. During 2005 to 2011, 2813 older (aged 65–100 years) individuals from 22 Mediterranean islands and the rural Mani region (Peloponnesus) voluntarily enrolled. Standard procedures were used to determine arterial BP and pulse pressure and for the evaluation of dietary habits (including tea and alcoholic beverages consumption), lifestyle, and anthropometric and clinical characteristics of the participants. Participants who reported low alcohol consumption (ie, 0–1 glasses per day) were less likely to have hypertension (odds ratio, 0.34; 95% confidence interval, 0.14–0.84) as compared with those who reported high alcohol consumption (ie, 5+ glasses per day). Adherence to the Mediterranean diet was inversely associated with mean arterial pressure (β coefficient, −0.18; 95% confidence interval, −0.33 to −0.16). Alcohol drinking remains an important modifiable risk factor for hypertension. Adherence to the Mediterranean diet was associated with decreased arterial peripheral resistance.Journal of Clinical Hypertension 07/2014; · 2.36 Impact Factor
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The Mediterranean Diet and Incidence of Hypertension
The Seguimiento Universidad de Navarra (SUN) Study
Jorge M. Nu ´n ˜ez-Co ´rdoba, Fe ´lix Valencia-Serrano, Estefanı ´a Toledo, Alvaro Alonso, and Miguel
5 A. Martı ´nez-Gonza ´lez
Initially submitted July 8, 2008; accepted for publication September 18, 2008.
The Mediterranean diet is receiving increasing attention in cardiovascular epidemiology. The association of
adherence to the Mediterranean diet with the incidence of hypertension was evaluated among 9,408 men and
women enrolled in a dynamic Spanish prospective cohort study during 1999–2005. Dietary intake was assessed at
baseline with a validated food frequency questionnaire, and a 9-point Mediterranean diet score was constructed.
During a median follow-up period of 4.2 years (range, 1.9–7.9), 501 incident cases of hypertension were identified.
After adjustment for major hypertension risk factors and nutritional covariates, adherence to the Mediterranean diet
was not associated with hypertension (the hazard ratio was 1.10 (95% confidence interval (CI): 0.81, 1.41) for
moderate adherence and 1.12 (95% CI: 0.79, 1.60) for high adherence). However, it was associated with reduced
changes in mean levels of systolic blood pressure (moderate adherence, ?2.4 mm Hg (95% CI: ?4.0, ?0.8); high
adherence, ?3.1 mm Hg (95% CI: ?5.4, ?0.8)) and diastolic blood pressure (moderate adherence, ?1.3 mm Hg
(95% CI: ?2.5, ?0.1); high adherence, ?1.9 mm Hg (95% CI: ?3.6, ?0.1)) after 6 years of follow-up. These results
suggest that adhering to a Mediterranean-type diet could contribute to the prevention of age-related changes in
blood pressure; dairy products; diet; diet, Mediterranean; food; hypertension; longitudinal studies
Abbreviations: CI, confidence interval; DASH, Dietary Approaches to Stop Hypertension; MUFA, monounsaturated fatty acid(s);
PREDIMED, Prevencio ´n con Dieta Mediterra ´nea; PUFA, polyunsaturated fatty acid(s); SFA, saturated fatty acid(s); SUN,
Seguimiento Universidad de Navarra.
Hypertension is an important cause of disability and mor-
25 tality throughout the world. Worldwide, approximately 7.6
adjusted life years (6.0% of all disability-adjusted life
years) are attributable to high blood pressure (1). One of
the basic strategies for addressing this public health problem
30 involves a population-wide approach to prevent the rise in
blood pressure with age and to achieve primary prevention
by improving dietary and lifestyle habits (2). Therefore, it is
crucial to identify dietary patterns that have a preventive
effect on the development of hypertension.
Greater adherence to a Mediterranean food pattern has
been shown to be associated with substantial reductions in
total mortality and cancer and cardiovascular disease mor-
tality (3, 4). The Mediterranean diet has been described by
the following characteristics: an abundance of plant foods
(fruits, vegetables, breads, other forms of cereals, potatoes,
beans, nuts, and seeds); minimally processed, seasonally
fresh, and locally grown foods; fresh fruit as the typical
daily dessert, with sweets containing concentrated sugars
or honey consumed only a few times per week; olive oil
as the main source of fat; dairy products (principally cheese
and yogurt) only in low-to-moderate amounts; red meat
in low amounts; and wine, usually red wine, in low-to-
moderate amounts, normally with meals (5). The beneficial
effects of this food pattern or some of its constituents on
Correspondence to Prof. Miguel A. Martinez-Gonzalez, Department of Preventive Medicine and Public Health, Medical School–Clinica
Universitaria, University of Navarra, c/Irunlarrea, 1 Ed. Investigacion, 31008 Pamplona (Navarra), Spain (e-mail: firstname.lastname@example.org).
50 cardiovascular disease risk factors and on the incidence of
high blood pressure have been previously reported using
operational definitions (6–8). Additionally, links between
adherence to the Mediterranean diet and reduced incidence
of the metabolic syndrome (9) and diabetes mellitus (10)
55 have recently been observed. However, to our knowledge,
there is no evidence from either large prospective cohort
studies or long-term clinical trials regarding the overall
effect of the Mediterranean food pattern on the risk of
The Seguimiento Universidad de Navarra (SUN) Study, a
prospective Mediterranean cohort study conducted in Spain,
provides an excellent opportunity to evaluate the role of the
Mediterranean food pattern in the development of hyperten-
sion. Therefore, we prospectively examined the association
65 between adherence to a Mediterranean food pattern and the
incidence of hypertension using a 9-point Mediterranean
diet score (3, 9, 10) in the SUN Study cohort.
MATERIALS AND METHODS
The SUN Study is a dynamic Spanish prospective cohort
study with permanently open recruitment. Participants are
all university graduates, nurses, and other educated adults
who are contacted and followed up using mailed question-
naires. The study methods have been described in detail
75 previously (10, 11). In brief, beginning in December 1999,
all graduates of the University of Navarra, other university
graduates and educated professionals, and registered nurses
in several Spanish provinces received a mailed question-
naire and a letter of invitation to participate in the SUN
80 Study. Response to the initial questionnaire was considered
informed consent to participate in the study. The project
protocol was approved by the institutional review board of
the University of Navarra.
After the baseline assessment, participants received bi-
85 ennial mailed follow-up questionnaires collecting a wide
variety of information about diet, lifestyle, risk factors,
and medical conditions. Up to 5 additional mailings were
sent to nonrespondents.
As of February 2008, the SUN Study had enrolled 19,057
90 participants aged 20–90 years at baseline. Among them,
15,552 persons were recruited before May 2005 and there-
fore were able to receive and answer the first follow-up
questionnaire. There were 9,190 participants who com-
pleted the 2-year follow-up questionnaire, 6,428 who com-
95 pleted the 4-year follow-up questionnaire, and 3,509 who
completed the 6-year follow-up questionnaire.
We excluded 1,733 participants who had hypertension at
baseline; 1,536 who reported a baseline history of cardio-
vascular disease, cancer, or diabetes; and 1,349 who had
100 missing values for a covariate. We also excluded female
participants whose total energy intakes were less than 500
kcal/day or more than 3,500 kcal/day and male participants
whose total energy intakes were less than 800 kcal/day or
more than 4,000 kcal/day (1,563 persons excluded). After
105 application of the exclusion criteria, 10,629 participants
were available for follow-up; among them, 9,408 (89%)
responded to at least 1 follow-up questionnaire and were
included in the final analysis.
Baseline data collection
titative food frequency questionnaire with 136 items, pre-
viously validated in Spain (12). The questionnaire was
based on typical portion sizes and had 9 options for the
frequency of intake of each food item (ranging from never
or almost never to 6 or more times per day) during the pre-
vious year. Trained dieticians updated the nutrient database
using the latest available information included in the food
composition tables for Spain (13, 14).
The baseline questionnaire requested information about
a large array of sociodemographic factors (sex, age, univer-
sity degree, marital status, and employment status), anthro-
pometric measures (weight, height), health-related habits
(smoking status, physical activity), and clinical variables
(use of medication, personal and family history of hyperten-
sion, coronary heart disease, cancer, and other diseases).
Body mass index was defined as weight in kilograms di-
vided by the square of height in meters. The questionnaire
assessed involvement in 17 different activities and amounts
of time spent in them. We assigned a multiple of the resting
metabolic rate (metabolic equivalent score) to each of these
activities using previously published guidelines (15) in or-
der to quantify the average intensity of physical activity. The
validity of data on self-reported weight, body mass index,
and self-reported leisure-time physical activity in the SUN
cohort has been previously reported (16, 17).
Mediterranean diet scale
We used the score proposed by Trichopoulou et al. (3) to
estimate the degree of adherence to the traditional Mediter-
ranean dietary pattern. This score includes 9 components:
vegetables, legumes, fruits and nuts, cereals, fish, meat and
meat products, dairy products, alcohol, and the ratio of
monounsaturated fatty acids (MUFA) to saturated fatty
acids (SFA). Values of 0 or 1 were assigned to each of the
9 components, using as cutoffs the sex-specific median val-
ues for the cohort participants for all components except
alcohol. Thus, for 5 beneficial components (vegetables, le-
gumes, fruits and nuts, cereals, and fish), subjects whose
consumption was at or above the sex-specific median were
assigned a value of 1, while those whose consumption was
below the median were assigned a value of 0. For compo-
nents presumed to be detrimental (meats or meat products
and dairy products), participants whose consumption was
below the sex-specific median were assigned a value of 1
and participants whose consumption was at or above the
median were assigned a value of 0. For alcohol intake,
a value of 1 was assigned to men who consumed 10–50
g/day and women who consumed 5–25 g/day. Finally, the
ratio of MUFA to SFA was used to assess the quality of fat
intake, giving a value of 0 to participants whose MUFA:SFA
ratio was below the sex-specific median and a value of 1
to participants whose ratio was at or above the median.
2 Nu ´n ˜ez-Co ´rdoba et al.
If participants had all of the characteristics of the Mediter-
ranean diet, their score was the highest possible (9 points),
reflecting maximum adherence. If they had none of the
165 characteristics, their score was the minimum possible (0
points), reflecting no adherence at all. Adherence to the
Mediterranean diet was categorized as low (score 0–2),
moderate (score 3–6), or high (score 7–9) (10).
Ascertainment of hypertension
The study endpoint was incident hypertension diagnosed
between the dates of completion of the baseline question-
naire and the last follow-up questionnaire. Participants were
asked about receipt of a medical diagnosis of hypertension
in the baseline and follow-up questionnaires, as well as the
175 date of diagnosis. The baseline questionnaire and the third
(6-year) follow-up questionnaire also asked for information
regarding participants’ most recent systolic and diastolic
blood pressure values. Finally, the follow-up question-
naires inquired as to whether participants had had their
180 blood pressure measured in the time elapsed since the pre-
Participants were considered to have hypertension at
baseline if they reported a medical diagnosis of hyperten-
sion, a systolic blood pressure greater than or equal to 140
185 mm Hg, a diastolic blood pressure greater than or equal to
90 mm Hg, or use of antihypertensive medication (18). In-
cident cases of hypertension were defined as participant-
reported receipt of a physician’s diagnosis of hypertension
on the follow-up questionnaire and no hypertension at base-
190 line. The diagnosis of hypertension in this cohort has been
validated in a previous study (19). Among participants re-
porting a diagnosis of hypertension, 82.3% (95% confidence
interval (CI): 72.8, 92.8) of cases were confirmed in a domi-
ciliary visit at which the participant’s blood pressure
195 was measured twice (using a standardized protocol) by a
tion (19). Among participants who did not report a diagnosis
of hypertension, 85.4%(95% CI:72.4, 89.1)wereconfirmed
to be nonhypertensive during the domiciliary visit (19).
200 Statistical analysis
For each participant, person-time of follow-up was calcu-
lated from the date of completion of the baseline question-
naire to the date of diagnosis of hypertension or the date of
completion of the last follow-up questionnaire, whichever
205 occurred first. We estimated hazard ratios for hypertension
and their 95% confidence intervals across increasing cate-
gories of adherence to the Mediterranean diet using Cox
proportional hazards models, controlling for the following
variables: age, sex, baseline body mass index, family his-
210 tory of hypertension, hypercholesterolemia, caffeine intake,
sodium intake, total energy intake, physical activity, and
smoking. In all analyses, the lowest adherence category
(Mediterranean diet adherence score of 0–2) was considered
the reference category. Statistical interaction was assessed
215 by means of likelihood ratio tests in which full models, in-
cluding interaction terms, were compared with reduced
models without interaction terms.
We also quantified the relation of Mediterranean diet ad-
herence to relative average change in blood pressure among
participants without hypertension who had completed the
6-year follow-up assessment, using multiple linear regres-
sion models with adjustment for age, sex, body mass index,
family history of hypertension, hypercholesterolemia, basal
blood pressure, caffeine intake, total energy intake, physical
activity, and smoking. The reference category was the low-
est level of adherence to the Mediterranean diet, and we
estimated differences in blood pressure changes with respect
to that category.
We conducted linear trend tests across increasing cat-
egories of Mediterranean diet adherence by treating the
All P values are 2-tailed, and statistical significance was
set a priori at P < 0.05. For all analyses, we used SPSS,
version 15.0 (SPSS, Inc., Chicago, Illinois).
The median duration of follow-up was 4.2 years (range,
1.9–7.9). During 41,126 person-years of follow-up, 501 in-
cident cases of hypertension were identified. Baseline char-
acteristics of the study population according to sex and
category of adherence to the Mediterranean diet are pre-
sented in Table 1.
Men had a higher mean age, a higher body mass index,
a greater level of physical activity, and a higher alcohol
intake. Mean fruit consumption, mean vegetable consump-
tion, intake of low-fat dairy products, and intake of olive oil
were higher among women. Participants with better adher-
ence to the Mediterranean diet were older, more physically
active, and less likely to be current smokers.
Mediterranean diet adherence and risk of hypertension
We evaluated the association between baseline adherence
to the Mediterranean diet and risk of incident hypertension
(Table 2). In the multivariate-adjusted analysis, increased
adherence to the traditional Mediterranean diet was not as-
sociated with the development of hypertension. Compared
with those with the lowest adherence to the Mediterranean
food pattern (score 0–2), the hazard ratio for hyperten-
sion among participants with moderate adherence to the
Mediterranean food pattern (score 3–6) was 1.10 (95% CI:
0.81, 1.41). The hazard ratio for those with the highest ad-
herence (score 7–9) was 1.12 (95% CI: 0.79, 1.60). We
conducted this analysis after excluding participants with
very low or very high total energy intakes, using the criteria
suggested by Willett (total energy intakes of <500 kcal/day
or >3,500 kcal/day for women and <800 kcal/day or
>4,000 kcal/day for men) (20). When we repeated this
analysis without excluding any participants because of high
or low values for total energy intake, no appreciable change
was observed, and the estimates were attenuated only
slightly (data not shown).
When we specifically assessed the association with
hypertension risk for each of the 9 components of the
Mediterranean Diet and Hypertension3
Mediterranean food pattern score, we found a direct associ-
ation with intermediate alcohol intake (hazard ratio ¼ 1.25,
275 95% CI: 1.03, 1.51) but an inverse association for consump-
tion of legumes above the sex-specific median level (hazard
ratio ¼ 0.84, 95% CI: 0.70, 1.00) after adjusting for age,
sex, body mass index, family history of hypertension,
Mediterranean Diet, Seguimiento Universidad de Navarra (SUN) Study, Spain, 1999–2005a
Baseline Characteristics of the Study Population (n ¼ 9,408), by Sex and Level of Adherence to the
(n 5 5,825)
(n 5 3,583)
Adherence to the Mediterranean Diet
(n 5 1,535)
(n 5 6,730)
(n 5 1,143)
Sociodemographic and lifestyle factors
Body mass indexb
34.0 (9.7) 39.4 (11.2)32 (9)36 (10)41 (12)
22 (3)25 (3)23 (3)23 (3)24 (3)
Physical activity, metabolic
22 (18) 29 (26)21 (19)25 (22)28 (24)
Hypercholesterolemia, % 11 199 13 24
Family history of hypertension, %49 474648 51
Alcohol intake, g/day 4 (6)10 (12) 4 (7) 6 (10)9 (9)
Current smoker, %25 21 2424 20
Sodium, g/day 3.1 (1.9)3.7 (2.4) 3.6 (2.4)3.3 (2.1) 3.2 (1.9)
Potassium, g/day4.8 (1.5)4.6 (1.5) 3.8 (1.0) 4.7 (1.5)5.8 (1.6)
Calcium, g/day1.3 (0.5) 1.2 (0.4)1.2 (0.4)1.2 (0.4) 1.3 (0.4)
Magnesium, mg/day 411 (118)409 (118)338 (84) 412 (113) 501 (121)
Dietary consumption, servings/day
Fruits2.5 (2.0) 2.0 (1.8) 1.2 (0.9)2.3 (1.9)3.5 (2.3)
Vegetables 2.4 (1.4) 1.9 (1.3)1.4 (0.8)2.2 (1.4) 3.1 (1.5)
Legumes 0.4 (0.3) 0.4 (0.3)0.3 (0.3) 0.4 (0.3)0.5 (0.3)
Nuts and dried fruits0.2 (0.3)0.2 (0.3)0.1 (0.1) 0.2 (0.3) 0.3 (0.4)
Cereals1.8 (1.2) 2.1 (1.4)1.4 (1.1) 1.9 (1.3)2.5 (1.4)
Meat 1.8 (0.8)2.0 (0.9)2.2 (0.9) 1.9 (0.9)1.5 (0.7)
Fish0.7 (0.4)0.7 (0.4) 0.5 (0.3) 0.7 (0.4) 1.0 (0.4)
Eggs0.4 (0.2) 0.4 (0.3)0.4 (0.3) 0.4 (0.3)0.4 (0.2)
Dairy products3.2 (1.7) 2.8 (1.6)2.4 (1.4)1.7 (1.3) 1.0 (0.8)
Low-fat dairy products 1.5 (1.5)0.9 (1.2)0.8 (1.2)1.3 (1.4)1.7 (1.5)
Intake of other dietary constituents
Olive oil, g/day 20 (16)17 (14) 13 (12) 19 (15)24 (16)
Fiber, g/day 27 (12)26 (11)18 (6)27 (11) 37 (13)
Fiber from cereal, g/day 3.3 (2.9)3.4 (2.9) 2.4 (1.9)3.3 (2.8)5.0 (3.9)
Caffeine, mg/day45 (39) 46 (41)43 (40) 46 (40)45 (37)
Total energy intake, kcal/day2,319 (567) 2,488 (652) 2,261 (580)2,387 (615)2,528 (548)
Percentage of energy intake
Carbohydrates43 (7) 43 (7)41 (7)43 (7) 47 (7)
Protein18 (3)18 (3)18 (3) 18 (3) 18 (3)
Vegetable protein5.3 (1.2)5.2 (1.2) 4.4 (0.9) 5.3 (1.1)6.4 (1.2)
Lipids 37 (7)36 (6) 40 (6)37 (6) 33 (6)
Saturated fatty acids 13 (3)13 (3) 15 (3)13 (3) 10 (2)
Monounsaturated fatty acids16 (4) 15 (3)16 (3) 16 (4)15 (4)
Polyunsaturated fatty acids5.3 (1.7)5.3 (1.5) 5.5 (1.7)5.3 (1.6)5.1 (1.5)
aValues are expressed as mean (standard deviation) unless otherwise stated.
4Nu ´n ˜ez-Co ´rdoba et al.
hypercholesterolemia, caffeine intake, total energy intake,
280 physical activity, smoking, and the other components of the
Mediterranean diet score. No significant association was
apparent for any of the other 7 components.
When we assessed the role of intake of MUFA or poly-
unsaturated fatty acids (PUFA), we found that persons with
285 higher levels of MUFA intake had a lower risk of hyperten-
sion; however, the results were not statistically significant
(for the fifth quintile vs. the first quintile, multivariate-
adjusted hazard ratio ¼ 0.81, 95% CI: 0.59, 1.11; P for
trend ¼ 0.10). We did not observe any significant associa-
290 tion between PUFA intake and the risk of hypertension (data
We did not observe any significant interaction between
Mediterranean diet adherence and age, sex, or body mass
Mediterranean diet adherence and blood pressure
We also assessed the association between average differ-
ence in the change in blood pressure from baseline to 6-year
follow-up and Mediterranean diet adherence score among
participants without hypertension who had completed the
6-year follow-up assessment. Of 2,990 participants who an-
swered the 6-year questionnaire and did not have incident
cases of hypertension, 1,513 provided blood pressure values
at baseline and 6 years later. A significant inverse associa-
tion between adherence to the Mediterranean diet and blood
pressure change was apparent (Table 3). All categories of
adherence to the Mediterranean diet showed lower levels of
systolic and diastolic blood pressure change than the cate-
gory with low adherence. Adjusted relative differences in
Universidad de Navarra (SUN) Study, Spain, 1999–2008
Hazard Ratios for Hypertension According to Level of Adherence to the Mediterranean Diet, Seguimiento
HR95% CI HR95% CI
Low (score 0–2)b
1,535 62 7,041 1.001.00
Moderate (score 3–6) 6,730 35929,436 1.110.85, 1.46 1.100.81, 1.41
High (score 7–9)1,143804,649 1.17 0.83, 1.641.12 0.79, 1.60
P for trend0.46 0.41
Abbreviations: CI, confidence interval; HR, hazard ratio.
aAdjusted for age, sex, body mass index, family history of hypertension, hypercholesterolemia, caffeine intake,
sodium intake, total energy intake, physical activity, and smoking.
Changea(mm Hg) Among Nonhypertensive Participants Who Completed the 6-Year Follow-up Assessment
(n ¼ 1,513), Seguimiento Universidad de Navarra (SUN) Study, Spain, 1999–2008
Association Between Adherence to the Mediterranean Diet and Average Difference in Blood Pressure
Adherence to the Mediterranean Diet
Low (Score 0–2)b
(n 5 229)
Moderate (Score 3–6)
(n 5 1,109)
High (Score 7–9)
(n 5 175)
Change95% CI Change 95% CIChange 95% CI
Systolic blood pressure, mm Hg
Age- and sex-adjusted
Diastolic blood pressure, mm Hg
Absolute change 00.1 0.2
Age- and sex-adjusted
Abbreviation: CI, confidence interval.
aBlood pressure after 6 years of follow-up minus blood pressure at baseline.
cAdjusted for age, sex, body mass index, family history of hypertension, hypercholesterolemia, basal blood
pressure, caffeine intake, total energy intake, physical activity, and smoking.
Mediterranean Diet and Hypertension 5
310 systolic blood pressure were ?2.4 mm Hg (95% CI: ?4.0,
?0.8) for persons with intermediate adherence (score 3–6)
and ?3.1 mm Hg (95% CI: ?5.4, ?0.8) for persons with
high adherence (score 7–9) (P for trend ¼ 0.01). The
relative differences for diastolic blood pressure change
315 were ?1.3 mm Hg (95% CI: ?2.5, ?0.1) for moderate
adherence and ?1.9 mm Hg (95% CI: ?3.6, ?0.1) for high
adherence (P for trend ¼ 0.05). When we did not exclude
persons with more than 6 years of follow-up who had de-
veloped hypertension during the follow-up period (n ¼
significant inverse trend of blood pressure change with in-
creasing adherence to the Mediterranean diet (test for trend:
P ¼ 0.04 and P ¼ 0.02 for systolic and diastolic blood
pressure, respectively) (data not shown).
In this prospective Spanish cohort study, which included
more than 41,000 person-years of follow-up, adherence to
the traditional Mediterranean diet was not associated with
the risk of hypertension. Adherence to this food pattern,
330 however, appeared to be inversely associated with changes
in average systolic and diastolic blood pressure levels over
up assessment and were not hypertensive at baseline.
Our study had certain limitations. First, dietary exposures
335 can be misclassified despite the good correlation between
food frequency questionnaires and usual diet (21). Even
though the validation study of our dietary questionnaire
demonstrated fair validity and reliability (12), misclassifi-
cation of dietary exposures could have occurred. Another
340 important limitation is the fact that hypertension status was
self-reported. However, the validity of a self-reported med-
ical diagnosis of hypertension in this highly educated cohort
has been sufficiently demonstrated elsewhere (19).
Among participants with 6 years of follow-up (n ¼
345 3,509), the proportion who provided their blood pressure
levels (n ¼ 2,685) was only 77%. However, no significant
differences in mean baseline levels of physical activity or
alcohol consumption were observed between persons who
provided data on their blood pressure and thosewith missing
350 data. Women, older participants, and those with a higher
body mass index were more likely to provide data about
their blood pressure after the 6-year follow-up, but we ad-
justed all of the estimates for these variables.
Substantial evidence has accrued linking adherence to the
355 Mediterranean food pattern to a reduced risk of total mor-
tality and the incidence of cardiovascular disease (3, 4, 22).
Thus, we considered the possibility that the reduction in the
risk of hypertension could be one of the main pathways that
might explain this beneficial effect of the Mediterranean diet
360 on cardiovascular clinical outcomes.
The Dietary Approaches to Stop Hypertension (DASH)
Trial, which included 459 adults aged 22 years or older,
tested 3 diets for 8 weeks. DASH investigators found pre-
ventive effects for a diet rich in fruits and vegetables—
365 especially a combination diet rich in fruits, vegetables, and
low-fat dairy products—and for reduced intakes of saturated
fat and total fat. Among the 326 participants without hyper-
tension in the DASH Trial, the combination diet reduced
systolic and diastolic blood pressures by 3.5 mm Hg and
2.1 mm Hg more, respectively, than the control diet. How-
ever, the DASH Trial and other trials that assessed the
effects of dietary interventions on blood pressure (23–26)
were not designed to evaluate the long-term effect of diet
on blood pressure (27).
In the Prevencio ´n con Dieta Mediterra ´nea (PREDIMED)
Study, Estruch et al. (7) evaluated the effect of the Mediter-
ranean diet on the risk of cardiovascular disease in 772 men
and women aged 55–80 years at high risk of cardiovascular
disease and reported decreased systolic and diastolic blood
pressures after 3 months offollow-up in the 2 Mediterranean
diet groups compared with participants assigned to a low-fat
diet group. Our results agreed with those of the PREDIMED
Study when we examined the association between Mediter-
ranean diet adherence and average difference in blood pres-
sure change among participants without hypertension who
had completed the 6-year follow-up questionnaire. Never-
theless, the short-term nature of the PREDIMED trial is
a limitation that could weaken the conclusions.
We did not repeat the full-length food frequency ques-
tionnaire to assess dietary changes during the follow-up of
participants, and we used only baseline food habits as the
relevant exposure. Therefore, we do not know whether di-
etary changes that may have occurred during the course of
the study may have concealed some potentially protective
effect afforded by a Mediterranean food pattern.
In addition, there could be other reasons for the lack of
association between greater adherence to the Mediterranean
diet and the development of hypertension found inourstudy.
On the one hand, observed absolute differences in food
habits between low- and high-adherence subjects in our co-
hort were not very large. Therefore, this between-subject
homogeneity in exposure could partly explain our null find-
ings. On the other hand, by using the Mediterranean diet
score proposed by Trichopoulou et al. (3), we were indi-
rectly assuming that intermediate levels of total alcohol
consumption (5–25 g/day among women or 10–50 g/day
among men) might be protective against hypertension.
Nevertheless, a direct association between total alcohol con-
sumption and hypertension is very likely, because interven-
tions aimed at reducing total alcohol consumption have
obtained clinically significant reductions in blood pressure
levels (28). Some specific beverages (e.g., red wine) may
behave differently, but the evidence on this issue is scarce,
and the score we used does not rank participants specifically
on their red wine consumption (29).
Another explanation related to the Mediterranean diet
score is that overall consumption of dairy products was in-
directly assumed to be detrimental for blood pressure. How-
ever, consumption of low-fat dairy foods was part of the
successful DASH combination diet (27), and other studies
have suggested beneficial effects of consumption of low-fat
dairy products (but not whole-fat dairy products) (30–33).
Perhaps a more sensible approach to defining a score for
hypertension prevention would be to use a score similar to
the one proposed by Trichopoulou et al. (3) but exclude low-
fat dairy products from the dairy products group. In any
6 Nu ´n ˜ez-Co ´rdoba et al.
case, we acknowledge that the specific intake of low-fat
dairy products (not intake of total dairy products) was in
fact slightly higher among those of our participants who
430 scored highest on the Mediterranean food pattern. Another
modification could consist of weighting red wine con-
sumption positively but not consumption of other alcoholic
beverages, since red wine could be more likely to confer
cardiovascular benefits than white wine or other alcoholic
435 beverages (29, 34–36). Nevertheless, we decided not to
modify the well-known and widely used score proposed
by Trichopoulou et al. (3), to improve consistency with pre-
vious assessments. Besides, this score preserves well the
classical concept of the Mediterranean diet as it was origi-
440 nally defined by Keys and Grande (37)—as the traditional
dietary pattern found in olive-growing areas of Crete,
Greece, and southern Italy in the late 1950s and early 1960s.
Consumption of MUFA and PUFA in our cohort partic-
ipants did not increase across categories of adherence to the
445 Mediterranean diet. The Mediterranean diet index devel-
oped by Trichopoulou et al. (3) does not include total MUFA
SFA ratio could be explained by decreased SFA intake,
not only by increased MUFA intake. The main determinant
450 of an increased MUFA:SFA ratio across levels of Mediterra-
nean diet adherence in our cohort was decreased SFA intake.
MUFA and PUFA consumption are believed to have car-
dioprotective effects, and the fact that their consumption did
not increase across levels of adherence to the Mediterranean
455 diet might partly explain our null findings. However, addi-
tional analyses showed no important relation between
MUFA or PUFA intake and hypertension, although a certain
(not statistically significant) trend suggesting an inverse as-
sociation between MUFA and incident hypertension was
In summary, our results do not support an association
between the classical Mediterranean dietary pattern and
the risk of hypertension. The observation of lower age-
related changes in systolic and diastolic blood pressure
465 among participants with higher adherence to the Mediterra-
nean diet deserves further attention.
Author affiliations: Department of Preventive Medicine
and Public Health, Medical School–Clı ´nica Universitaria,
University of Navarra, Pamplona, Spain (Jorge M. Nu ´n ˜ez-
Co ´rdoba, Fe ´lix Valencia-Serrano, Estefanı ´a Toledo, Alvaro
Alonso, Juan J. Beunza, Miguel A. Martı ´nez-Gonza ´lez) and
475 Division of Epidemiology and Community Health, School
of Public Health, University of Minnesota, Minneapolis,
Minnesota (Alvaro Alonso).
Financial support was provided by the Spanish govern-
ment (grant RD 06/0045 from the Instituto de Salud Carlos
480 III and projects PI030678, PI040233, PI042241, PI050514,
PI050976, and PI070240 from the Instituto de Salud Carlos
III–Fondo de Investigaciones Sanitarias) and the Navarra
regional government (grant PI41/2005 from the Department
The authors thank the members of the Seguimiento
Universidad de Navarra (SUN) study group, including C.
de la Fuente, Z. Vazquez, S. Benito, Dr. F. J. Basterra-
Gortari, Dr. E. H. Martinez-Piscina, Dr. M. Segui-Gomez,
Dr. J. de Irala, Dr. J. A. Martinez, Dr. A. Marti, Dr. F.
Guillen-Grima, and Dr. M. Serrano-Martinez (University
of Navarra); Dr. M. Delgado-Rodriguez (University of Jaen);
Dr. J. Llorca (University of Cantabria); Dr. A. Sanchez-
Villegas (University of Las Palmas); and A. Marc xal-Pimenta
(Federal University of Minas Gerais). The authors thank the
faculty of the Department of Nutrition at Harvard School of
Public Health (Drs. A. Ascherio, F. B. Hu, W. C. Willett) for
helping them design the SUN Study.
Conflict of interest: none declared.
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