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Originally Published 5 May 2014
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Mediterranean Diet Reduces 24-Hour Ambulatory Blood Pressure, Blood Glucose, and Lipids: One-Year Randomized, Clinical Trial

Mónica Doménech, Pilar Roman, José Lapetra, Francisco J. García de la Corte, Aleix Sala-Vila, Rafael de la Torre, Dolores Corella, … Show All … , Jordi Salas-Salvadó, Valentina Ruiz-Gutiérrez, Rosa-María Lamuela-Raventós, Estefania Toledo, Ramón Estruch, Antonio Coca, and Emilio RosAuthor Info & Affiliations
Hypertension
Volume 64, Number 1
https://doi.org/10.1161/HYPERTENSIONAHA.113.03353
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Abstract

The PREvención con DIeta MEDiterránea (PREDIMED) trial showed that Mediterranean diets (MedDiets) supplemented with either extravirgin olive oil or nuts reduced cardiovascular events, particularly stroke, compared with a control, lower fat diet. The mechanisms of cardiovascular protection remain unclear. We evaluated the 1-year effects of supplemented MedDiets on 24-hour ambulatory blood pressure (BP), blood glucose, and lipids. Randomized, parallel-design, controlled trial was conducted in 2 PREDIMED sites. Diets were ad libitum, and no advice on increasing physical activity or reducing sodium intake was given. Participants were 235 subjects (56.5% women; mean age, 66.5 years) at high cardiovascular risk (85.4% with hypertension). Adjusted changes from baseline in mean systolic BP were −2.3 (95% confidence interval [CI], −4.0 to −0.5) mm Hg and −2.6 (95% CI, −4.3 to −0.9) mm Hg in the MedDiets with olive oil and the MedDiets with nuts, respectively, and 1.7 (95% CI, −0.1 to 3.5) mm Hg in the control group (P<0.001). Respective changes in mean diastolic BP were −1.2 (95% CI, −2.2 to −0.2), −1.2 (95% CI, −2.2 to −0.2), and 0.7 (95% CI, −0.4 to 1.7) mm Hg (P=0.017). Daytime and nighttime BP followed similar patterns. Mean changes from baseline in fasting blood glucose were −6.1, −4.6, and 3.5 mg/dL (P=0.016) in the MedDiets with olive oil, MedDiets with nuts, and control diet, respectively; those of total cholesterol were −11.3, −13.6, and −4.4 mg/dL (P=0.043), respectively. In high-risk individuals, most with treated hypertension, MedDiets supplemented with extravirgin olive oil or nuts reduced 24-hour ambulatory BP, total cholesterol, and fasting glucose.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: ISRCTN35739639.

Introduction

See Editorial Commentary, pp 26–27
High blood pressure (BP) is a major risk factor for coronary heart disease, congestive heart failure, stroke, and renal disease1 and as such is the leading cause of preventable deaths worldwide.2 In 2000, 26.4% of the adult world population (972 million) had hypertension, defined as BP ≥140/90 mm Hg or current use of antihypertensive medication, and 29.2% were projected to be hypertensive by 2025.3 The prevalence of hypertension increases with age, with the estimated lifetime risk for elderly subjects reaching 90%.4 The magnitude of this burden underscores the need for increased awareness, treatment, control, and, primarily, prevention.
A healthful lifestyle is a critical component of hypertension reduction strategies,5 and diet is the lifestyle factor with the strongest effects on BP.6,7 Established dietary modifications that effectively lower BP are weight loss, reduced sodium and increased potassium intake, reduction in excessive alcohol consumption, and vegetarian and dietary approaches to stop hypertension (DASH)–type dietary patterns.6,7 The original DASH diet combined increased intake of fruits, vegetables, and low-fat dairy products with a relatively low intake of total and saturated fat,8 and a subsequent version incorporated sodium restriction to further enhance BP reduction.9 Two reduced carbohydrate DASH diet modalities were tested in the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OmniHeart), which showed a beneficial effect on BP of increasing vegetable protein or total fat to 37% of energy, with monounsaturated fatty acids (MUFA) as the predominant fat component.10
The traditional Mediterranean diet (MedDiet), a plant-based dietary pattern high in MUFA because of the customary use of olive oil,11 shares many constituents with DASH-type diets, especially with the high-MUFA OmniHeart diet,10 but information about its effects on BP is scarce. Two prospective studies have examined this issue. Increased adherence to the MedDiet was associated with reduced BP in the Greek-European Prospective Investigation into Cancer and Nutrition (EPIC) study12 and with lower increases of BP over time in the Seguimiento Universidad de Navarra (SUN) cohort.13 In addition, 2 randomized clinical trials have shown a BP-lowering effect of either an energy-restricted MedDiet with attendant weight loss14 or ad libitum MedDiets without weight changes.15
Prior studies of the effects of the MedDiet on BP have relied on clinic (office) BP measurements, an approach that is limited by poor reproducibility, the white-coat effect, and observer and patient variability.16 At present, 24-hour ambulatory BP (ABP) monitoring is considered the gold standard to assess the effects of interventions on BP because repeated measurements more accurately reflect usual BP than isolated office measurements.17,18 Within the framework of the PREvención con DIeta MEDiterránea (PREDIMED) trial of nutritional intervention for the primary prevention of cardiovascular disease (CVD),19 we assessed the effects of MedDiets and a control diet on 24-hour ABP, blood glucose, and lipids in elderly subjects at high cardiovascular risk.

Methods

The PREDIMED study is a nutritional intervention trial with a randomized, 3-arm, parallel design (ISRCTN35739639). The protocol has been reported in detail elsewhere.19 Two PREDIMED recruiting centers in Barcelona and Seville conducted the present trial. The study protocol complied with the Declaration of Helsinki, institutional review boards at each center approved the study, and all participants provided written informed consent.

Participants

We enrolled 284 consecutive subjects randomized to the PREDIMED study between July 2008 and June 2010 in 2 recruitment sites: the Hospital Clinic of Barcelona (n=185) and the Primary Care Division of Seville (n=99). Study participants were men aged 55 to 80 years and women aged 60 to 80 years at high cardiovascular risk but with no CVD at enrollment. Criteria for eligibility were either type 2 diabetes mellitus or ≥3 cardiovascular risk factors: current smoking, hypertension, dyslipidemia, overweight or obesity, and family history of early-onset coronary heart disease.19 Any severe chronic illness, substance abuse, and a history of intolerance to olive oil or nuts (supplemental foods given in 2 arms of the study) were exclusion criteria. At baseline and after 1 year we collected data on the medical history, drug treatments and lifestyle, including dietary habits, performed anthropometric and 24-hour ABP measurements, and collected fasting blood and spot urine for biochemical analyses.

Assessment of Risk Factors

Diabetes mellitus, hyperlipidemia, and hypertension were diagnosed by the clinical history. Smoking status was categorized as never, current, or past smoker. Physical activity was determined using the Minnesota Leisure-Time Physical Activity questionnaire. Height, weight, and waist circumference were measured with standard methods. Office BP was measured according to the current guidelines17 with a validated semiautomatic oscillometer (Omron HEM-705CP; Hoofddorp, The Netherlands).

Diets

Full details of the dietary intervention of the PREDIMED trial have been published.19 Please see online-only Data Supplement.

Biochemical Determinations

Fasting blood samples were collected and subsequently centrifuged. Standard enzymatic assays were used to measure glucose, total cholesterol, total triglycerides, and high-density lipoprotein cholesterol. Low-density lipoprotein cholesterol was estimated using the Friedewald equation for samples with triglycerides <400 mg/dL (10.4 mmol/L).
Objective biomarkers of compliance were determined in random subsamples of participants at baseline and 1 year in central laboratories.15,19 Urinary hydroxytyrosol was measured by gas chromatography–mass spectrometry and used to assess compliance in the MedDiet+extravirgin olive oil (EVOO) group. The plasma proportion of α-linolenic acid was measured by gas chromatography and used to assess compliance in the MedDiet+Nuts group.

ABP Measurements

Patients attended the research facility of each institution on a weekday between 8:00 am and 10:00 am. ABP monitoring was performed using Spacelabs 90207/90217 devices (SpacelabsW Inc, Richmond, WA), with readings scheduled every 20 minutes during the 24-hour period. Periods of activity and rest were determined on an individual basis according to hours of sleep and waking. The duration of the procedure in hours, the percentage of valid readings, and mean systolic BP and diastolic BP during periods of activity and rest, and for the whole 24-hour period, were measured. To assess circadian BP patterns, we included 4 categories based on night/day BP ratios: rising or absence of dipping (ratio, ≥1.0), mild dipping (ratio, 0.9≤1.0), dipping (ratio, 0.8≤0.9), and extreme dipping (ratio, ≤0.8).18 We included all ABP recordings lasting 24 hours±30 minutes and having >70% measurements, including ≥1 valid measurement per hour. Average 24-hour ABP was defined as normal when values were <130/80 mm Hg.18

Statistical Analyses

The primary interest of our trial was the contrast between the 2 MedDiets and the control diet. A target sample size of 75 per group provided >80% power to detect a mean between-diet difference of 4 mm Hg (SD, 8.3) in 24-hour systolic BP.16 We used descriptive statistics with mean (SD) for quantitative variables and absolute numbers (percentages) for qualitative variables. Baseline between-group differences in cardiovascular risk factors were assessed using the χ2 test and ANOVA with Bonferroni post hoc tests, as appropriate. The effect of the interventions on changes in food and nutrient consumption, anthropometric variables, biomarkers of adherence, blood glucose and lipids, and ABP was assessed using ANOVA with Bonferroni post hoc tests. In addition to between-diet differences, we report mean (95% confidence interval) changes from baseline to the end of the intervention. There were no between-group differences in baseline demographic and anthropometric characteristics or cardiovascular risk factors, including office BP and treatment regimens for dyslipidemia, diabetes mellitus, or hypertension, and therefore we did not adjust for these factors. Given that baseline ABP values were slightly imbalanced between groups and there were different in-trial changes in antihypertensive medication, we adjusted for these factors using ANCOVA. Statistical significance was established as P<0.05 (2-tailed). Analyses were performed using SPSS software, version 18.0 (SPSS Inc, Chicago, IL).

Results

Of 284 eligible participants, 4 rejected 24-hour ABP monitoring. A further 45 participants randomized into the study dropped out for various reasons (Figure 1). The characteristics of dropouts were similar to those of participants completing the trial, but voluntary withdrawals were higher in the control group than in the MedDiet groups. No adverse effects from the dietary interventions were reported.
Figure 1. Flow chart of participants throughout the trial. ABP indicates ambulatory blood pressure; EVOO, extravirgin olive oil; and MedDiet, Mediterranean diet.
The baseline characteristics of the 235 participants who completed the study were well balanced between the 3 diet groups (Table 1). The mean age was 66.5 years, 56.5% were women, and 85.4% had hypertension, with most receiving drug treatment, although office BP control was suboptimal. Drug-treatment regimens were similar in the 3 groups. Our population was similar to that of the whole PREDIMED cohort with respect to sex, age, adiposity measurements, and risk factors, except for a lower proportion of participants with diabetes mellitus (35.7% versus 48.5%, respectively; P<0.001) and a higher proportion of dyslipidemia (76.6% versus 72.3%, respectively; P=0.006).
Table 1. Baseline Characteristics of Participants Completing Intervention for 1 Year by Study Group
VariableMedDiet+EVOO (n=78)MedDiet+Nuts (n=82)Control Diet (n=75)P Value*
Age, y66.2 (5.8)67.2 (5.2)66.2 (6.2)0.443
Men, n (%)33 (42.3)38 (46.3)32 (42.7)0.850
Current smokers, n (%)10 (12.8)8 (9.8)13 (17.3)0.372
Weight, kg76.1 (13.7)78.5 (11.4)77.4 (11.1)0.442
Body mass index, kg/m229.5 (3.9)30.3 (3.7)30.4 (3.5)0.300
Waist circumference, cm100.4 (10.0)101.6 (9.1)100.9 (8.6)0.495
Energy expenditure in physical activity, MET-min/d431 (306)415 (275)416 (276)0.925
Hypertension, n (%)65 (83.3)72 (87.8)64 (85.3)0.723
Office systolic BP, mm Hg146.2 (21.1)149.1 (21.1)143.8 (18.8)0.302
Office diastolic BP, mm Hg80.4 (10.7)81.0 (10.6)83.0 (9.5)0.312
Dyslipidemia, n (%)62 (79.5)60 (73.2)58 (77.3)0.630
Type 2 diabetes mellitus, n (%)30 (38.5)29 (35.4)25 (33.3)0.800
Educational level, n (%)   0.757
 Illiterate/primary education54 (72.0)57 (69.5)50 (66.7)…
 Secondary education13 (17.3)19 (23.2)19 (25.3)…
 Academic/graduate8 (10.7)6 (7.3)6 (8.0)…
Medication use, n (%)
 Antihypertensive agents60 (76.9)70 (85.4)61 (81.3)0.392
  ACE inhibitors/ARB45 (71.3)45 (67.1)41 (65)…
  Diuretics32 (61.1)35 (52.1)29 (57.9)…
  Calcium channel blockers13 (20.9)14 (23.9)11 (21.1)…
  Other antihypertensive drugs4 (5.1)4 (4.8)4 (5.3)…
 Antidiabetic agents23 (29.5)21 (25.6)19 (25.3)0.807
  Oral hypoglycemic agents16 (73.9)17 (80)17 (73.7)…
  Insulin1 (4.3)2 (8.1)1 (5.6)…
 Hypolipidemic agents40 (54.3)45 (54.9)40 (53.3)0.901
  Statins36 (90)40 (90.9)38 (94.3)…
  Other lipid-lowering drugs4 (10)4 (9.1)2 (5.7)…
 Antiplatelet therapy15 (19.5)20 (24.4)18 (24.7)0.784
Values are mean (SD) except for quantitative variables, expressed as n (%). ACE indicates angiotensin-converting enzyme; ARB, aldosterone receptor blockers; BP, blood pressure; EVOO, extravirgin olive oil; MedDiet, Mediterranean diet; and MET-min, minutes at a given metabolic equivalent level (units of energy expenditure in physical activity; 1 MET-min is roughly equivalent to 1 kcal).
*
P value for comparisons among groups with Pearson χ2 test for categorical variables or 1-way ANOVA for continuous variables.
Participants in the 3 groups reported good baseline adherence to the MedDiet and similar intake of key foods (Table S1 in the online-only Data Supplement). Intake of cereals, vegetables, legumes, fruit, nuts, fish, and olive oil was high, but intake of meat and meat products and dairy products was also high and clearly deviated from the traditional MedDiet. After the intervention, participants assigned to the 2 MedDiets significantly (P<0.001) increased adherence to the 14-item MedDiet score, whereas there were no changes in the control group. The main dietary changes were large increases in EVOO and nut consumption in the corresponding MedDiet groups, whereas intake of common olive oil was reciprocally reduced in the MedDiet+EVOO group. All groups reduced intake of cereals (mostly refined-flour bread) and meat and meat products, whereas changes in intake of vegetables, fruit, fish, dairy products, and alcohol were negligible.
Compliance with supplemental foods was good, as shown by objective biomarker measurements in ≈50% of participants (Table S2). Urinary hydroxytyrosol levels increased from baseline by 50% in MedDiet+EVOO participants and by 33% in MedDiet+nuts participants, whereas plasma α-linolenic acid increased (by 34%) only in the latter group. Increased urinary hydroxytyrosol in the MedDiet+nuts group reflects increased EVOO intake in compliance with MedDiet recommendations. No changes occurred in the control group.
Baseline levels of energy and nutrient intake were similar in the 3 study groups (Table S3). After the intervention, all groups significantly reduced energy intake, whereas marginally increasing protein consumption. Other changes partly reflect the dietary recommendations given to each group. Total fat intake increased in the 2 MedDiet groups and decreased in the control group, with reciprocal changes in carbohydrate intake. Saturated fat intake was reduced in all groups, whereas MUFA intake increased in the 2 MedDiet groups and polyunsaturated fatty acid intake increased substantially in the MedDiet+nuts group. Although no specific recommendations on the use of salt were given, sodium intake decreased in all diet groups by 10 to 15 mmol/d (0.6–0.9 g of salt) from a moderate baseline intake of 92 to 98 mmol/d (5–6 g of salt). There were minor changes in intake of other minerals.

Changes in Medication

There were few antihypertensive medication changes during the study, but they differed between diet groups, with 8, 1, and 4 participants (P=0.044) having add-on medication prescribed by primary care physicians in the MedDiet+EVOO, MedDiet+nuts, and control groups, respectively. Respective changes in hypolipidemic and antidiabetic medication occurred in 4, 2, and 2 and 8, 4, and 5 participants.

Energy Expenditure, Adiposity, Blood Glucose, and Lipids

Estimated changes in energy expenditure in physical activity were similar between the 3 groups (Table 2). There were no between-group differences in changes in body weight or body mass index. Compared with the control group, blood glucose decreased significantly in the MedDiet+EVOO group, whereas total cholesterol decreased significantly in the MedDiet+nuts group. Low-density lipoprotein cholesterol decreased to a similar extent in all groups. There were no changes in high-density lipoprotein cholesterol.
Table 2. Baseline Levels and Changes in Energy Expenditure, Adiposity, Blood Glucose, and Lipids by Group Assignment
VariableMedDiet+EVOO (n=78)MedDiet+Nuts (n=82)Control Diet (n=75)P Value*
Energy expenditure in physical activity, MET-min/d
 Baseline431 (362 to 500)415 (354 to 475)416 (352 to 479)0.925
 Change−4 (−64 to 57)−11 (−64 to 43)−71 (−111 to −31)0.147
Waist circumference, cm
 Baseline100.4 (98.2 to 102.7)101.6 (99.6 to 103.6)99.9 (97.9 to 101.8)0.495
 Change−0.07 (−0.96 to 0.83)−0.29 (−1.19 to 0.61)−0.09 (−1.18 to 0.99)0.935
Body weight, kg
 Baseline76.1 (73.0 to 79.2)78.5 (76.0 to 81.0)77.4 (74.8 to 79.9)0.442
 Change0.10 (−0.58 to 0.77)0.09 (−0.56 to 0.73)−0.83 (−1.46 to −0.20)0.078
Body mass index, kg/m2
 Baseline29.5 (28.7 to 30.4)30.3 (29.5 to 31.1)30.4 (29.4 to 31.2)0.300
 Change0.04 (−0.24 to 0.31)0.04 (−0.21 to 0.29)−0.30 (−0.56 to −0.03)0.128
Glucose, mg/dL
 Baseline123.1 (114.6 to 131.6)119.6 (111.8 to 127.4)113.8 (106.2 to 121.5)0.265
 Change−6.13 (−11.62 to −0.64)†−4.61 (−9.82 to 0.60)3.51 (−0.51 to 7.54)0.016
Total cholesterol, mg/dL
 Baseline223.4 (212.2 to 234.6)214.7 (206.4 to 223.0)208.1 (199.6 to 216.6)0.078
 Change−11.3 (−16.8 to −5.7)−13.6 (−18.3 to −9.0)†−4.6 (−9.9 to 0.6)0.043
Triglycerides, mg/dL
 Baseline160.8 (126.8 to 194.8)132.6 (112.6 to 152.6)123.6 (110.0 to 137.2)0.083
 Change−10.3 (−22.9 to 2.3)−6.7 (−15.7 to 2.3)−4.7 (−16.4 to 7.1)0.774
LDL cholesterol, mg/dL (n=206)
 Baseline138.2 (130.2 to 146.1)135.7 (128.5 to 142.9)129.9 (122.6 to 137.3)0.295
 Change−6.5 (−11.5 to −1.6)−11.3 (−15.9 to −6.6)−5.8 (−10.5 to −1.2)0.211
HDL cholesterol, mg/dL
 Baseline52.2 (49.5 to 54.9)53.7 (51.0 to 56.4)53.4 (50.4 to 56.4)0.727
 Change0.48 (−0.68 to 1.64)0.36 (−0.53 to 1.25)0.40 (−0.56 to 1.36)0.986
Data are expressed as mean (95% CI). Changes for which the 95% CI does not include zero are significantly different from the baseline. CI indicates confidence interval; EVOO, extravirgin olive oil; HDL, high-density lipoprotein; LDL, high-density lipoprotein; MedDiet, Mediterranean diet; and MET-min, minutes at a given metabolic equivalent level (units of energy expenditure in physical activity; 1 MET-min is roughly equivalent to 1 kcal).
*
P value for comparisons among groups with 1-way ANOVA.
†
Significant differences compared with control group (Bonferroni multiple comparisons).

Ambulatory BP

Baseline 24-hour ABP values were similar between the 3 groups, although there were borderline differences (P<0.1) in mean systolic BP. Table 3 shows that all BP values decreased from baseline in the MedDiet groups and increased in the control group. Given the between-group imbalances in baseline BP and on-trial medication changes, we performed a covariate analysis adjusting for these factors. Figure 2 shows mean (95% confidence interval) adjusted 24-hour ABP differences from baseline for each diet group. For the main outcome, mean systolic BP changes from baseline were reductions of −2.3 (−4.0 to −0.5) mm Hg and −2.6 (−4.3 to – 0.9) mm Hg in the MedDiet+EVOO and the MedDiet+nuts, respectively, and an increase of 1.7 (−0.1 to 3.5) mm Hg in the control group (P=0.001). Respective changes in mean diastolic BP were −1.2 (−2.2 to – 0.2), −1.2 (−2.2 to −0.2), and 0.7 (−0.4 to 1.7) mm Hg (P=0.017). At the end of the study, adjusted 24-hour BP differences between the MedDiet+EVOO and MedDiet+nuts and the control diet were −4.0 and −4.3 mm Hg for average systolic BP and −1.9 and −1.9 mm Hg for average diastolic BP, respectively. Circadian BP patterns were similar between the 3 diet groups both at baseline and after the intervention (Table S4).
Table 3. Ambulatory Blood Pressure Values at Baseline and Changes at 1 Year by Study Group
Blood Pressure, mm HgMedDiet+EVOO (n=78)MedDiet+Nuts (n=82)Control Diet (n=75)P Value*
Systolic
24 hours
 Baseline127.3 (124.0 to 130.6)125.3 (122.3 to 128.2)122.5 (119.5 to 125.5)0.098
 Change−3.14 (−5.30 to −0.98)†−2.35 (−4.16 to −0.55)†2.73 (0.57 to 4.18)<0.001
Daytime
 Baseline130.5 (127.3 to 133.7)128.9 (126.0 to 131.9)126.4 (123.4 to 129.4)0.173
 Change−2.94 (−5.29 to −0.58)†−3.12 (−5.14 to −1.10)†2.36 (0.53 to 4.19)<0.001
Nighttime
 Baseline118.0 (114.3 to 121.8)117.0 (113.8 to 120.2)114.0 (110.5 to 117.4)0.244
 Change−2.84 (−5.35 to −0.34)†−1.61 (−3.42 to 0.20)1.57 (−1.11 to 4.25)0.027
Diastolic
24 hours
 Baseline71.8 (70.3 to 73.4)71.2 (69.5 to 73.0)70.4 (68.6 to 72.1)0.466
 Change−1.68 (−3.11 to −0.24)†−1.00 (−2.03 to 0.04)0.96 (−0.07 to 1.99)0.006
Daytime
 Baseline74.9 (73.3 to 76.4)74.2 (72.5 to 75.9)73.6 (71.8 to 75.4)0.591
 Change−1.63 (−3.13 to −0.12)†−1.51 (−2.71 to −0.32)†0.73 (−0.42 to 1.88)0.018
Nighttime
 Baseline64.5 (62.6 to 66.4)64.6 (62.8 to 66.3)63.1 (61.1 to 65.1)0.493
 Change−1.71 (−3.28 to −0.15)†−0.78 (−1.81 to 0.25)1.43 (−0.15 to 3.01)0.007
Data are expressed as mean (95% CI). Changes for which the 95% CI does not include zero are significantly different from the baseline. CI indicates confidence interval; EVOO, extravirgin olive oil; and MedDiet, Mediterranean diet.
*
P value for comparisons among groups with 1-way ANOVA.
†
Significant differences compared with control group (Bonferroni multiple comparisons).
Figure 2. Adjusted changes in ambulatory systolic (A) and diastolic (B) 24-hour blood pressure (BP) after 1 year of diet intervention. Error bars are mean (95% confidence interval). Statistical analysis by ANCOVA with baseline ambulatory BP values and on-trial antihypertensive medication changes as covariates: P=0.001 for mean systolic BP, P=0.001 for daytime systolic BP, and P=0.107 for nighttime systolic BP; P=0.017, P=0.021, and P=0.019 for mean, daytime, and nighttime diastolic BP, respectively. *Significant differences compared with control group (Bonferroni multiple comparisons). EVOO indicates extravirgin olive oil; and MedDiet, Mediterranean diet.
Control rates of hypertension, defined by standard cutoffs, were dissimilar between the 3 intervention groups according to both office BP and 24-hour ABP measurements (Table S5). In all groups, office BP control was similar at baseline and after the intervention. However, 24-hour and daytime ABP control improved variably from baseline in the MedDiet groups, whereas nighttime ABP control worsened in the control group. BP control was always better with ABP monitoring compared with office BP, with the differences ranging between 16% and 42%.
As shown in Figure S1, the effects of the diets in different subgroups defined by sex, age, and cardiovascular risk factors were comparable with those of the whole group for systolic BP except for diabetic participants, in whom greater reductions with the MedDiets versus the control diet were observed compared with participants without diabetes mellitus (P for interaction, 0.031). Subgroup analyses showed no significant interactions for diastolic BP.

Discussion

In this substudy of the PREDIMED trial, MedDiets supplemented with either EVOO or nuts resulted in significant reductions in 24-hour ABP compared with a control diet in individuals at high risk of CVD, most of whom had treated hypertension. Our primary interest was in the between-diet contrasts, because no recommendations to restrict energy, increase physical activity, lose weight, or limit sodium intake were given. However, as usual in a nutrition intervention trial focusing on BP, participants reduced energy and sodium intake, albeit to a similar degree in the 3 study arms and without significant changes in body weight. The results of this 1-year study build on the findings of our earlier PREDIMED report documenting the BP-lowering effect of the MedDiets versus the control diet after a 3-month intervention.15
The results on BP control in the total PREDIMED cohort have been published recently.20 The reported differences in BP between the MedDiets and the control diet at the end of the study were small and significant between-group differences were observed only in mean diastolic BP: −1.53 mm Hg in the MedDiet+EVOO and −0.65 mm Hg in the MedDiet+nuts. The known limitations of office BP measurements versus 24-hour ABP, with repeated measurements during usual living conditions,17,18 apply to the results of the total PREDIMED sample. We think our ABP results more accurately reflect the true effects of the diets on usual BP, because BP control defined by standard thresholds was always better with ABP monitoring compared with office BP (Table S5), and there were sizeable differences in BP control between office BP and ABP, which can be equated to white-coat hypertension in the office setting. Noticeably, the proportion of participants with good office BP control at both the baseline and the end of the intervention was similar in our study and in the full PREDIMED cohort,19 further supporting the differential added value of the ABP results.
As shown in an earlier report on a larger PREDIMED cohort,15 blood glucose and total cholesterol decreased variably in the 2 MedDiet groups. Interestingly, diabetic participants on the MedDiets achieved a greater systolic ABP reduction than those without diabetes mellitus, suggesting an added beneficial effect in diabetes mellitus. These findings need to be confirmed in larger series. Our results provide first-level evidence that energy-unrestricted, high-fat, high-unsaturated fat MedDiets impart a substantial benefit on BP, akin to that demonstrated for the original low-fat DASH diet8 and the unsaturated fat-rich version tested in OmniHeart,10 both of which share many characteristics with the MedDiet.6,7
In our study, the net differences between the MedDiets supplemented with EVOO and nuts and the control diet for mean systolic ABP were −4.0 and −4.3 mm Hg, respectively, and for mean diastolic ABP, −1.9 mm Hg for both MedDiets, after adjusting for between-diet imbalances in baseline BP and on-trial changes in antihypertensive medication. The impact of such BP changes, even if their magnitude seems small, could be remarkable at the population level. It has been estimated that a reduction of 3 mm Hg in office systolic BP will be associated with an 8% reduction in stroke mortality and a 5% reduction in coronary heart disease mortality.21
Evidence from our study and other reports that increasing adherence to the MedDiet is associated with lower BP12–15 and beneficial changes in glycemic control and the lipid profile15 might partly explain why CVD mortality rates in Spain and other Southern European countries are low compared with those of Northern Europe22,23 and the United States.23 One reason for such a North-to-South gradient in CVD risk could be local dietary habits, such as adherence to the MedDiet. This hypothesis is supported strongly by the findings from the full PREDIMED trial, in which each MedDiet reduced the incidence of major CVD events by 30% compared with the control diet after treatment for ≈5 years.19 Incident stroke was substantially reduced by the PREDIMED MedDiets. As hypertension is a powerful determinant of stroke risks,17–23 our data showing a BP-lowering effect of the MedDiets provide a plausible mechanism to partly explain protection against stroke. Recent epidemiological evidence suggesting that adherence to the MedDiet24,25 and olive oil use26 are associated with reduced stroke rates is also supportive.
The 3 diets tested in our study were plant-based and generally complied with current dietary recommendations for CVD prevention and BP reduction.5,6 The main macronutrient differences between the MedDiets and the control diet were the higher unsaturated fat content of the former, which was attributable to the supplemental foods. Both EVOO and nuts have a favorable fatty acid profile, with abundant oleic acid, the main MUFA, in EVOO and both MUFA and polyunsaturated fatty acid in nuts; they are also particularly rich in bioactive phytochemicals with antioxidant and anti-inflammatory properties.27 However, until now, evidence on the effects of these foods on BP has been scarce, probably because BP was usually a secondary outcome in nutritional studies.28
Our study has limitations, including the assessment of sodium intake by dietary records rather than the more robust measurement of urinary sodium excretion. In addition, there were losses to follow-up, predominantly in the control group, probably because participants did not receive food incentives. The generalization of our findings to younger and healthier individuals from other geographical locations is uncertain. The study also had strengths, including the relatively long duration of the intervention, the evaluation of diet adherence by objective biomarkers, and, primarily, the use of 24-hour ABP monitoring as the best available tool to determine BP changes in intervention studies.
In conclusion, this PREDIMED substudy conducted in subjects at high cardiovascular risk, most of them with treated hypertension, showed that adherence to MedDiets supplemented with EVOO or nuts for 1 year reduced 24-hour ABP and improved blood glucose and total cholesterol levels in comparison with a control diet. These results were obtained with dietary intervention alone in subjects under stable antihypertensive, antidiabetic, and hypolipidemic treatment regimens who followed a moderately sodium-restricted diet and without the confounding effects of weight loss or changes in physical activity, sodium intake, or alcohol consumption. The magnitude of BP reduction has both clinical and public health implications for the dietary management of hypertension and CVD prevention.

Perspectives

In a randomized controlled clinical trial conducted in older individuals at high cardiovascular risk, most of them with treated hypertension, we showed that an energy-unrestricted MedDiet enhanced with extra virgin olive oil or mixed nuts during 1 year reduced ambulatory systolic and diastolic BP compared with a control diet. These results could have public health implications because the MedDiet, a vegetable-based and high-unsaturated fat dietary pattern, seems to be a useful adjunct to established dietary and pharmacological approaches for improving hypertension control while incurring no expense for the health system. Our findings should be tested in prehypertensive individuals and in non-Mediterranean cohorts.

Acknowledgments

We thank the participants and staff of the PREvención con DIeta MEDiterránea (PREDIMED) trial for their invaluable contributions to this study. We also thank Emili Corbella for expert assistance with statistical analyses. Supplemental foods were donated, including extravirgin olive oil (by Hojiblanca and Patrimonio Comunal Olivarero, both in Spain), walnuts (by the California Walnut Commission), almonds (by Borges, in Spain), and hazelnuts (by La Morella Nuts, in Spain). None of the sponsors had any role in the trial design, data analysis, or reporting of the results. CIBERobn is an initiative of Instituto de Salud Carlos III, Spain.

Novelty and Significance

What Is New?

•
To our knowledge this is the first study showing that energy-unrestricted Mediterranean diet enhanced with extra virgin olive oil or mixed nuts during 1 year reduced ambulatory systolic and diastolic blood pressure compared with a control diet in older subjects at high cardiovascular risk.

What Is Relevant?

•
Mediterranean diet, a vegetable-based and high-unsaturated fat dietary pattern, improves blood pressure in treated hypertensive subjects.

Summary

In subjects at high cardiovascular risk, most of them with treated hypertension, adherence to Mediterranean diet for 1 year reduced 24-hour ambulatory blood pressure and improved blood glucose and total cholesterol levels in comparison with a control diet. This has both clinical and public health implications for the dietary management of hypertension and cardiovascular disease prevention.

Supplemental Material

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Published In

Go to Hypertension
Go to Hypertension
Hypertension
Volume 64 • Number 1 • July 2014
Pages: 69 - 76
PubMed: 24799608

Copyright

© 2014 American Heart Association, Inc.

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History

Received: 25 February 2014
Revision received: 3 March 2014
Accepted: 5 March 2014
Published online: 5 May 2014
Published in print: July 2014

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Keywords

  1. blood pressure
  2. clinical trials, randomized
  3. diet, Mediterranean
  4. olive oil
  5. nuts

Subjects

  1. Hypertension

Authors

Affiliations

Mónica Doménech
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Pilar Roman
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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José Lapetra
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Francisco J. García de la Corte
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Aleix Sala-Vila
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Rafael de la Torre
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Dolores Corella
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Jordi Salas-Salvadó
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Valentina Ruiz-Gutiérrez
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Rosa-María Lamuela-Raventós
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Estefania Toledo
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Ramón Estruch
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Antonio Coca
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Emilio Ros
From the Lipid Clinic, Endocrinology and Nutrition Service (M.D., A.S.-V., E.R.) and Hypertension and Vascular Risk Unit, Department of Internal Medicine (M.D., R.E., A.C.), Institut d’Investigacions Biomèdiques August Pi Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain; Ciber Fisiopatología de la Obesidad y Nutrición (CIBERobn), Instituto de Salud Carlos III (ISCIII), Madrid, Spain (M.D., P.R., J.L., F.J.G.d.l.C., A.S.-V., R.d.l.T., D.C., J.S.-S., V.R.-G., R.-M.L.-R., E.T., R.E., E.R.); Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville, Spain (P.R., J.L., F.J.G.d.l.C.); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona, Spain (R.d.l.T.); Department of Preventive Medicine, University of Valencia, Valencia, Spain (D.C.); Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus, Spain (J.S.-S.); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville, Spain (V.R.-G.); Department of Nutrition and Food Science, School of Pharmacy, XaRTA, INSA, University of Barcelona, Barcelona, Spain (R.-M.L.-R.); and Department of Preventive Medicine and Public Health, Facultad de Medicina-Clínica, Universidad de Navarra, Pamplona, Spain (E.T.).
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Notes

The online-only Data Supplement is available with this article at http://hyper.ahajournals.org/lookup/suppl/doi:10.1161/HYPERTENSIONAHA.113.03353/-/DC1.
Correspondence to Emilio Ros, Lipid Clinic, Endocrinology and Nutrition Service, Hospital Clinic, C. Villarroel 170, 08036 Barcelona, Spain. E-mail [email protected]

Disclosures

Dr Salas-Salvadó has received research funding and is a nonpaid member of the scientific advisory committee of the International Nut Council. Dr Ros has received research funding and is a nonpaid member of the scientific advisory committee of the California Walnut Commission. The other authors report no conflicts.

Sources of Funding

This work was supported by grants from Instituto de Salud Carlos III (ISCIII; PI05/2584, PI07/1138, PI12/01231), Ministry of Science and Innovation (AGL 2010-22319 and AGL 2011-23430), Consejería de Salud de la Junta de Andalucía (PI015/2007), Sociedad Española de Medicina de Familia y Comunitaria, and Sociedad Andaluza de Medicina Familiar y Comunitaria. Dr Mónica Doménech was supported by Fundació per l’Estudi de la Hipertensió Arterial dels Hospitals Comarcals de Catalunya (FEHTACC). Dr Sala-Vila was supported by postdoctoral contract FIS CP12/03299. Dr Toledo was supported by a Rio Hortega postresidency fellowship from the ISCIII, Ministry of Economy and Competitiveness, Spanish Government.

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Mediterranean Diet Reduces 24-Hour Ambulatory Blood Pressure, Blood Glucose, and Lipids
Hypertension
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