HTN: Diet Patterns (2015)


Toledo E, Hu FB, Estruch R, Buil-Cosiales P, Corella D, Salas-Salvado J, Covas MI, Aros F, Gomez-Gracia E, Fiol M, Lapetra J, Serra-Majem L, Pinto X, Lamuela-Raventos RM, Saez G, Bullo M, Ruiz-Gutierrez V, Ros E, Sorli JV, Martinez-Gonzalez MA. Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: Results from a randomized controlled trial. BMC Medicine. 2013; 11: 207.

PubMed ID: 24050803
Study Design:
Randomized Controlled Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
To assess the four-year effect on blood pressure control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern.
Inclusion Criteria:
  • Males aged 55 years to 80 years
  • Females aged 60 to 80 years
  • Free from CVD at baseline
  • Type 2 diabetes or presence of three or more CVD risk factors:
    • Current smoking
    • Hypertension
    • High LDL-C
    • Low HDL-C
    • Overweight or obesity
    • Family history of premature CHD.
Exclusion Criteria:
Described in previous manuscript.
Description of Study Protocol:


Subjects recruited from October 2003 to June 2009, and were selected from databases of Spanish primary healthcare facilities; 89% agreed to participate.


Randomized controlled trial.

Blinding Used

Implied with measurements.


  • Participants were assigned to a control group or one of two Mediterranean diets:
    • Mediterranean diet (MD) supplemented with extra-virgin olive oil (EVOO) ( MD+EVOO): Provided 1L per week
    • MD supplemented with mixed nuts (walnuts, almonds, and hazelnuts) (MD+nuts): Provided 15g walnuts, 7.5g each hazelnuts and almonds per day
    • Control: Low-fat diet.
  • Individual and group sessions for each group separately, with dietary screening questionnaire to check adherence and personalize intervention. Energy restriction and physical activity were not specifically advised, and sodium intake was not targeted.

Statistical Analysis

  • Intention to treat analysis
  • Differences in changes in BP between groups assessed
  • Mean differences in SBP and DBP between MD+EVOO or MD+nuts and control group calculated using generalized estimating equations in crude analysis and adjusting for center, age, sex and baseline T2D and additionally for baseline number of anti-hypertensive drugs and baseline SBP or DBP
  • Percentage of participants with controlled BP (SBP less than 140mm Hg; DBP less than 90mm Hg) during follow-up calculated using generalized estimating equations
  • Number of anti-hypertensive drugs prescribed during follow-up were ascertained using generalized estimating equations.
Data Collection Summary:

Timing of Measurements

Baseline and once annually to four years of follow-up.

Dependent Variables

  • Change in blood pressure was measured in each arm with a validated semi-automatic oscillometer at three time points, separated by two minutes, in seated position and after five minutes of rest
  • Percentage of participants with controlled BP levels during follow-up (SBP less than 140mm Hg; DBP less than 90mm Hg)
  • Number of anti-hypertensive drugs prescribed during follow-up.

Independent Variables

  • Participants randomized to the control diet or one of two Mediterranean diets:
    • MD + EVOO
    • MD + nuts
    • Control low-fat diet
  • Adherence was assessed through dietary screening questionnaire.

Control Variables

  • Center
  • Age
  • Sex
  • Baseline type 2 diabetes
  • Anti-hypertensive drugs
  • Baseline BP.
Description of Actual Data Sample:
  • Initial N: N=7,447 subjects (58.3% female; 41.7% male)
  • Attrition (final N): 7,158 subjects
  • Age: 67 years.

Other Relevant Demographics

Baseline MD score (possible total = 14):

  • EVOO: 8.7±2.0
  • Nuts: 8.8±2.0
  • Control: 8.4±2.0.


All three groups were well balanced in their baseline characteristics, including their dietary and non-dietary traits.

  • BMI (kg/m2) :
    • EVOO: 29.9±3.7
    • Nuts: 29.7±3.8
    • Control: 30.2±4.0.
  • SBP (mm Hg):
    • EVOO: 148±19
    • Nuts: 149±18
    • Control: 149±19.
  • DBP (mm Hg):
    • EVOO: 83±10
    • Nuts: 83±10
    • Control: 82±10.
  • Percent with hypertension:
    • EVOO: 81.9
    • Nuts: 82.4
    • Control: 83.9.




Summary of Results:

Key Findings

  • SBP:
    • Mean differences in changes between EVOO vs. control ranged from 0.42 in crude model to 0.39 after adjustment for age sex, center, diabetes, number of baseline anti-hypertensive drugs and SBP (NS)
    • Mean differences in changes between nuts vs. control ranged from 0.35 in crude model to 0.38 after adjustment (NS).
  • DBP:
    • Mean differences in changes between EVOO vs. control ranged from -1.41 (-1.92 to -0.91) in crude model to -1.53 (-2 .01 to -1.04) after adjustment (all P<0.001)
    • Mean differences in changes between nuts vs. control ranged from -0.61 (-1.12 to -0.09, P<0.02) in crude model to -0.65 (-1.15 to -0.15) after adjustment (P<0.01).

Other Findings

  • Percentage who attained appropriate control of BP levels significantly increased during follow-up time in all three intervention groups (P<0.001); no significant differences between groups
  • Average number of anti-hypertensive drugs prescribed during follow-up significantly increased during follow-up; no significant differences between groups.
Author Conclusion:
Both the traditional Mediterranean diet and a low-fat diet showed beneficial effects on BP. Lower values of DBP were seen in those following a tradition Mediterranean diet supplemented either with EVOO or with nuts, compared to the low-fat diet.
Funding Source:
Government: Official Funding Agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III (ISCIII)
Foods from Patrimonio Comunal Olivarero, Hojiblanca, California Walnut Commission, Borges S.A. and La Morella Nuts
Food Company:
Commodity Group:
Reviewer Comments:
Blood pressure was a secondary outcome of the study, established during study design. Authors note that magnitude of between group differences may have been small due to the fairly high baseline MD scores, and that the control group maintained a MD diet during the trial. Adherence scores to MD intervention diet reported to be relatively high as reported in a previous study.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? Yes
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes