Miquel Fiol

Primary Prevention of Cardiovascular Disease with a Mediterranean Diet

BACKGROUND Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events. (Funded by the Spanish governments Instituto de Salud Carlos III and others; Controlled-Trials.com number, ISRCTN35739639.).

Effect of a Mediterranean Diet Supplemented With Nuts on Metabolic Syndrome Status One-Year Results of the PREDIMED Randomized Trial

BACKGROUND Epidemiological studies suggest that the Mediterranean diet (MedDiet) may reduce the risk of developing the metabolic syndrome (MetS). We compared the 1-year effect of 2 behavioral interventions to implement the MedDiet vs advice on a low-fat diet on MetS status. METHODS A total of 1224 participants were recruited from the PREDIMED (Prevención con Dieta Mediterránea) Study, a multicenter, 3-arm, randomized clinical trial to determine the efficacy of the MedDiet on the primary prevention of cardiovascular disease. Participants were older subjects at high risk for cardiovascular disease. Interventions were quarterly education about the MedDiet plus provision of either 1 L/wk of virgin olive oil (MedDiet + VOO) or 30 g/d of mixed nuts (MedDiet + nuts), and advice on a low-fat diet (control diet). All diets were ad libitum, and there was no increase in physical activity for any of the interventions. Lifestyle variables and MetS features as defined by the National Cholesterol Education Program Adult Treatment Panel III criteria were assessed. RESULTS At baseline, 61.4% of participants met criteria for the MetS. One-year prevalence was reduced by 6.7%, 13.7%, and 2.0% in the MedDiet + VOO, MedDiet + nuts, and control diet groups, respectively (MedDiet + nuts vs control groups, P = .01; MedDiet + VOO vs control group, P = .18). Incident rates of the MetS were not significantly different among groups (22.9%, 17.9%, and 23.4%, respectively). After adjustment for sex, age, baseline obesity status, and weight changes, the odds ratios for reversion of MetS were 1.3 (95% confidence interval, 0.8-2.1) for the MedDiet + VOO group and 1.7 (1.1-2.6) for the MedDiet + nuts group compared with the control diet group. CONCLUSION A traditional MedDiet enriched with nuts could be a useful tool in the management of the MetS.

A Short Screener Is Valid for Assessing Mediterranean Diet Adherence among Older Spanish Men and Women

Ensuring the accuracy of dietary assessment instruments is paramount for interpreting diet-disease relationships. The present study assessed the relative and construct validity of the 14-point Mediterranean Diet Adherence Screener (MEDAS) used in the Prevención con Dieta Mediterránea (PREDIMED) study, a primary prevention nutrition-intervention trial. A validated FFQ and the MEDAS were administered to 7146 participants of the PREDIMED study. The MEDAS-derived PREDIMED score correlated significantly with the corresponding FFQ PREDIMED score (r = 0.52; intraclass correlation coefficient = 0.51) and in the anticipated directions with the dietary intakes reported on the FFQ. Using Bland Altmans analysis, the average MEDAS Mediterranean diet score estimate was 105% of the FFQ PREDIMED score estimate. Limits of agreement ranged between 57 and 153%. Multiple linear regression analyses revealed that a higher PREDIMED score related directly (P < 0.001) to HDL-cholesterol (HDL-C) and inversely (P < 0.038) to BMI, waist circumference, TG, the TG:HDL-C ratio, fasting glucose, and the cholesterol:HDL-C ratio. The 10-y estimated coronary artery disease risk decreased as the PREDIMED score increased (P < 0.001). The MEDAS is a valid instrument for rapid estimation of adherence to the Mediterranean diet and may be useful in clinical practice.

Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial.

BACKGROUND Despite the richness in antioxidants of the Mediterranean diet, to our knowledge, no randomized controlled trials have assessed its effect on in vivo lipoprotein oxidation. METHODS A total of 372 subjects at high cardiovascular risk (210 women and 162 men; age range, 55-80 years), who were recruited into a large, multicenter, randomized, controlled, parallel-group clinical trial (the Prevención con Dieta Mediterránea [PREDIMED] Study) directed at testing the efficacy of the traditional Mediterranean diet (TMD) on the primary prevention of coronary heart disease, were assigned to a low-fat diet (n = 121) or one of 2 TMDs (TMD + virgin olive oil or TMD + nuts). The TMD participants received nutritional education and either free virgin olive oil for all the family (1 L/wk) or free nuts (30 g/d). Diets were ad libitum. Changes in oxidative stress markers were evaluated at 3 months. RESULTS After the 3-month interventions, mean (95% confidence intervals) oxidized low-density lipoprotein (LDL) levels decreased in the TMD + virgin olive oil (-10.6 U/L [-14.2 to -6.1]) and TMD + nuts (-7.3 U/L [-11.2 to -3.3]) groups, without changes in the low-fat diet group (-2.9 U/L [-7.3 to 1.5]). Change in oxidized LDL levels in the TMD + virgin olive oil group reached significance vs that of the low-fat group (P = .02). Malondialdehyde changes in mononuclear cells paralleled those of oxidized LDL. No changes in serum glutathione peroxidase activity were observed. CONCLUSIONS Individuals at high cardiovascular risk who improved their diet toward a TMD pattern showed significant reductions in cellular lipid levels and LDL oxidation. Results provide further evidence to recommend the TMD as a useful tool against risk factors for CHD. Trial Registration isrctn.org Identifier: ISRCTN35739639.

Cohort Profile: Design and methods of the PREDIMED study

The Spanish Ministry of Health—Instituto de Salud Carlos III (ISCIII) funded the project for the period 2003–05 (RTIC G03/140). In 2006 a new funding modality was established by ISCIII through the CIBER (Centros de Investigacion Biomedica En Red). Fisiopatologia de la Obesidad y Nutricion (CIBERobn), which is providing funding for 7 of the original research groups, whereas the other 12 were funded by a new research network (RTIC RD 06/0045). Other official funds from Spanish government agencies have been obtained for subprojects related to intermediate outcomes (lipoproteins, inflammatory markers, vascular imaging, genomic and proteomic studies, etc.). Obviously, the donation by food companies of all the VOO and mixed nuts needed throughout the duration of the study is a substantial contribution.

Components of the mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease

Objective:To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease.Subjects/Methods:A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by immunonephelometry and those of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay.Results:After adjusting for age, gender, body mass index, diabetes, smoking, use of statins, non-steroidal antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals was associated with lower concentrations of IL-6 (P for trend 0.005;both). Subjects with the highest consumption of nuts and virgin olive oil showed the lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants with higher adherence to the Mediterranean-type diet did not show significantly lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1).Conclusions:The consumption of some typical Mediterranean foods (fruits, cereals, virgin olive oil and nuts) was associated with lower serum concentrations of inflammatory markers especially those related to endothelial function, in subjects with high cardiovascular risk living in a Mediterranean country.

A 14-Item Mediterranean Diet Assessment Tool and Obesity Indexes among High-Risk Subjects: The PREDIMED Trial

Objective Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circumference and waist-to-height ratio (WHtR) as outcomes. Design Cross-sectional assessment of all participants in the “PREvención con DIeta MEDiterránea” (PREDIMED) trial. Subjects 7,447 participants (55–80 years, 57% women) free of cardiovascular disease, but with either type 2 diabetes or ≥3 cardiovascular risk factors. Trained dietitians used both a validated 14-item questionnaire and a full-length validated 137-item food frequency questionnaire to assess dietary habits. Trained nurses measured weight, height and waist circumference. Results Strong inverse linear associations between the 14-item tool and all adiposity indexes were found. For a two-point increment in the 14-item score, the multivariable-adjusted differences in WHtR were −0.0066 (95% confidence interval, –0.0088 to −0.0049) for women and –0.0059 (–0.0079 to –0.0038) for men. The multivariable-adjusted odds ratio for a WHtR>0.6 in participants scoring ≥10 points versus ≤7 points was 0.68 (0.57 to 0.80) for women and 0.66 (0.54 to 0.80) for men. High consumption of nuts and low consumption of sweetened/carbonated beverages presented the strongest inverse associations with abdominal obesity. Conclusions A brief 14-item tool was able to capture a strong monotonic inverse association between adherence to a good quality dietary pattern (Mediterranean diet) and obesity indexes in a population of adults at high cardiovascular risk.

A Large Randomized Individual and Group Intervention Conducted by Registered Dietitians Increased Adherence to Mediterranean-Type Diets: The PREDIMED Study

OBJECTIVE To assess the effectiveness of an intervention aimed to increase adherence to a Mediterranean diet. DESIGN A 12-month assessment of a randomized primary prevention trial. SUBJECTS/SETTINGS One thousand five hundred fifty-one asymptomatic persons aged 55 to 80 years, with diabetes or > or =3 cardiovascular risk factors. INTERVENTION Participants were randomly assigned to a control group or two Mediterranean diet groups. Those allocated to the two Mediterranean diet groups received individual motivational interviews every 3 months to negotiate nutrition goals, and group educational sessions on a quarterly basis. One Mediterranean diet group received free virgin olive oil (1 L/week), the other received free mixed nuts (30 g/day). Participants in the control group received verbal instructions and a leaflet recommending the National Cholesterol Education Program Adult Treatment Panel III dietary guidelines. MAIN OUTCOME MEASURES Changes in food and nutrient intake after 12 months. STATISTICAL ANALYSES Paired t tests (for within-group changes) and analysis of variance (for between-group changes) were conducted. RESULTS Participants allocated to both Mediterranean diets increased their intake of virgin olive oil, nuts, vegetables, legumes, and fruits (P<0.05 for all within- and between-group differences). Participants in all three groups decreased their intake of meat and pastries, cakes, and sweets (P<0.05 for all). Fiber, monounsaturated fatty acid, and polyunsaturated fatty acid intake increased in the Mediterranean diet groups (P<0.005 for all). Favorable, although nonsignificant, changes in intake of other nutrients occurred only in the Mediterranean diet groups. CONCLUSIONS A 12-month behavioral intervention promoting the Mediterranean diet can favorably modify an individuals overall food pattern. The individual motivational interventions together with the group sessions and the free provision of high-fat and palatable key foods customary to the Mediterranean diet were effective in improving the dietary habits of participants in this trial.

Effect of the Mediterranean diet on blood pressure in the PREDIMED trial: results from a randomized controlled trial

BackgroundHypertension can be prevented by adopting healthy dietary patterns. Our aim was to assess the 4-year effect on blood pressure (BP) control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern.MethodsThe PREDIMED primary prevention trial is a randomized, single-blinded, controlled trial conducted in Spanish primary healthcare centers. We recruited 7,447 men (aged 55 to 80 years) and women (aged 60 to 80 years) who had high risk for cardiovascular disease. Participants were assigned to a control group or to one of two Mediterranean diets. The control group received education on following a low-fat diet, while the groups on Mediterranean diets received nutritional education and also free foods; either extra virgin olive oil, or nuts. Trained personnel measured participants’ BP at baseline and once yearly during a 4-year follow-up. We used generalized estimating equations to assess the differences between groups during the follow-up.ResultsThe percentage of participants with controlled BP increased in all three intervention groups (P-value for within-group changes: P<0.001). Participants allocated to either of the two Mediterranean diet groups had significantly lower diastolic BP than the participants in the control group (−1.53 mmHg (95% confidence interval (CI) −2.01 to −1.04) for the Mediterranean diet supplemented with extra virgin olive oil, and −0.65 mmHg (95% CI -1.15 to −0.15) mmHg for the Mediterranean diet supplemented with nuts). No between-group differences in changes of systolic BP were seen.ConclusionsBoth the traditional Mediterranean diet and a low-fat diet exerted beneficial effects on BP and could be part of advice to patients for controlling BP. However, we found lower values of diastolic BP in the two groups promoting the Mediterranean diet with extra virgin olive oil or with nuts than in the control group.Trial registrationCurrent Controlled Trials ISRCTN35739639

Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: The PREDIMED study

BACKGROUND AND AIMS Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. METHODS AND RESULTS The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55-80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day⁻¹ (443 ± 218 mg day⁻¹ of flavonoids and 304 ± 156 mg day⁻¹ of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. CONCLUSION In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil.