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Estefanía Toledo Atucha

Most recent scientific publications (since 2010)

Authors: Rodriguez-Garcia, C.; Sanchez-Quesada, C.; Toledo, Estefanía Ainhoa; et al.
Journal: MOLECULES
ISSN 1420-3049  Vol. 24  Nº 5  2019  pp. 917
Dietary guidelines universally advise adherence to plant-based diets. Plant-based foods confer considerable health benefits, partly attributable to their abundant micronutrient (e.g., polyphenol) content. Interest in polyphenols is largely focused on the contribution of their antioxidant activity to the prevention of various disorders, including cardiovascular disease and cancer. Polyphenols are classified into groups, such as stilbenes, flavonoids, phenolic acids, lignans and others. Lignans, which possess a steroid-like chemical structure and are defined as phytoestrogens, are of particular interest to researchers. Traditionally, health benefits attributed to lignans have included a lowered risk of heart disease, menopausal symptoms, osteoporosis and breast cancer. However, the intake of naturally lignan-rich foods varies with the type of diet. Consequently, based on the latest humans' findings and gathered information on lignan-rich foods collected from Phenol Explorer database this review focuses on the potential health benefits attributable to the consumption of different diets containing naturally lignan-rich foods. Current evidence highlight the bioactive properties of lignans as human health-promoting molecules. Thus, dietary intake of lignan-rich foods could be a useful way to bolster the prevention of chronic illness, such as certain types of cancers and cardiovascular disease.
Authors: Munoz-Garcia, M.; Razquin, Cristina; et al.
Journal: GACETA SANITARIA
ISSN 0213-9111  Vol. 33  Nº 5  2019  pp. 415 - 420
Objective: To compare the Spanish version of the modified Telephone Interview of Cognitive Status (STICS-m) with the Mini-Mental State Examination (MMSE) and predict its ability to detect the development of dementia. Method: 106 participants in a dietary intervention trial underwent face-to-face evaluation with the MMSE, and phone interview with the STICS-m. The correlation between STICS-m and MMSE was assessed with the intraclass correlation coefficient (ICC) of consistency. Secondly, 932 participants over 55 years old from the "Seguimiento Universidad de Navarra" cohort were evaluated with the STICS-m and data on dementia diagnosis were gathered (median follow-up time of 6.5 years). A logistic regression model evaluated the association between STICS-m score or 2-year changes in STICS-m score and risk of developing dementia, adjusting for ApoE, age and years of university education. Results: The ICC between the MMSE and the STICS-m was 0.31 (95% confidence interval [95%CI]: 0.13-0.48). The adjusted odds ratio (OR) for the development of dementia for each additional point in the baseline STICS-m score was 0.85 (95%Cl: 0.72-1.02; p =0.084). When considering the 2-year change in the STICS-m score as exposure, the OR for the development of dementia was 0.79 (95%CI: 0.67-0.93; p = 0.006). Conclusions: The weak correlation between the STICS-m and the MMSE reflects moderate-low concurrent validity. Even so, the STICS-m can be regarded as an useful tool in the epidemiological setting since increasing scores appear to be able to predict a lower risk of developing dementia. (C) 2018 SESPAS. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Authors: Ruiz-Canela, Miguel, (Autor de correspondencia); Sánchez-Bayona, Rodrigo; et al.
Journal: CLINICAL NUTRITION
ISSN 0261-5614  Vol. 38  Nº 54  2019  pp. 2259 - 2268
Background & aims: Breast cancer (BC) is the most commonly diagnosed cancer, and diet is suspected to play a role in its development. Dietary factors may mediate this process through modulation of inflammation, though findings from previous studies have not been consistent. We aimed to longitudinally assess the association between the dietary inflammatory index (DII (R)), a frequently used method to assess the inflammatory potential of the diet, and incident BC. Methods: We included 10,713 middle-aged, Spanish female university graduates from the SUN cohort. DII (R) scores were derived from a validated 136-item food-frequency questionnaire, and it was based on scientific evidence on the relationship between diet and inflammatory biomarkers. Diagnosis of BC was reported by the participant or, if deceased, by the next of kin or identified from death certificates. Self-reports of BC were confirmed by revision of medical reports by an experienced oncologist. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between quartiles of DII (R) and incident BC. Results: After 10.3 years of median follow-up, we identified 100 confirmed and 168 probable incident BC cases. The multivariable-adjusted HR for participants in the 4th quartile to the 1st quartile was 1.44 (95% CI 0.76-2.72; p-trend: 0.339) when confirmed cases were analyzed, and 1.20 (95% CI 0.72-1.99; p-trend: 0.757) for the probable cases. We neither observed statistically significant differences in regard to menopausal status. Conclusions: The apparent increase in risk between DII (R) scores and BC in our cohort was not statistically significant, which could be partly explained by the small number of observed cases. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Authors: Abete, Itziar; Konieczna, J.; Zulet, María de los Ángeles, (Autor de correspondencia); et al.
Journal: JOURNAL OF CACHEXIA, SARCOPENIA AND MUSCLE
ISSN 2190-5991  Vol. 10  Nº 5  2019  pp. 974 - 984
Background Sarcopenia is a progressive age-related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to 'sarcopenic obesity'. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity. Methods A cross-sectional analysis based on baseline data from the PREDIMED-Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 +/- 3.3 kg/m(2); age: 65.2 +/- 4.9 years old) and metabolic syndrome were categorized according to sex-specific tertiles (T) of the sarcopenic index (SI) as assessed by dual-energy X-ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables. Results Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P-trend < 0.05), PA (P-trend < 0.0001), and the 30 s chair stand test (P-trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P-trend < 0.05), visceral fat and leucocyte count (all P-trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil-to-lymphocyte ratio, and platelet count (all P-trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance. Conclusions Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age-related sarcopenia.
Authors: Bibiloni, M. D. M.; Julibert, A.; Bouzas, C.; et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 4  2019  pp. 754
BACKGROUND: Nut consumption has been associated with improved nutrient adequacy and diet quality in healthy adult populations but this association has never been explored in individuals at high cardiovascular risk. OBJECTIVE: to assess the associations between consumption of nuts and nutrient adequacy and diet quality in a Mediterranean population at high cardiovascular risk. DESIGN: baseline assessment of nutritional adequacy in participants (n = 6060, men and women, with ages 55¿75 years old, with overweight/obesity and metabolic syndrome) in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. METHODS: nut intake was assessed using a validated food frequency questionnaire. Participants who reported consuming zero quantity of nuts were classified as 'non-nut consumers'. 'Nut consumers' were participants who reported consuming any quantity of nuts. Nineteen micronutrients were examined (vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid; Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine). The proportion of micronutrient inadequacy was estimated using the estimated average requirements (EAR) or adequate intake (AI) cut-points. Diet quality was also assessed using a 17-item Mediterranean dietary questionnaire (Mediterranean diet score, MDS), a carbohydrate quality index (CQI) and a fat quality index (FQI). RESULTS: eighty-two percent of participants were nut consumers (median of nut consumption 12.6 g/day; interquartile range: 6.0¿25.2). Nut consumers were less likely to be below the EAR for vitamins A, B1, B2, B6, C, D, E, folic acid, and Ca, Mg, Se and Zn than non-nut consumers. Nut consumers were also more likely to be above the AI for K and Cr than non-nut consumers. Nut consumers had lower prevalence of inadequate micronutrient intakes, but also higher CQI, higher FQI, and better scores of adherence to the Mediterranean diet (Mediterranean diet score, MDS). CONCLUSIONS: nut consumers had better nutrient adequacy, diet quality, and adherence to the MedDiet than those non-nut consumers.
Authors: Guasch-Ferre, M., (Autor de correspondencia); Ruiz-Canela, Miguel; Li, J. ; et al.
Journal: JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM
ISSN 0021-972X  Vol. 104  Nº 5  2019  pp. 1508 - 1519
Context: The potential associations between acylcarnitine profiles and incidence of type 2 diabetes (T2D) and whether acylcarnitines can be used to improve diabetes prediction remain unclear. Objective: To evaluate the associations between baseline and 1-year changes in acylcarnitines and their diabetes predictive ability beyond traditional risk factors. Design, Setting, and Participants: We designed a case-cohort study within the PREDIMED Study including all incident cases of T2D (n = 251) and 694 randomly selected participants at baseline (follow-up, 3.8 years). Plasma acylcarnitines were measured using a targeted approach by liquid chromatography-tandem mass spectrometry. We tested the associations between baseline and 1-year changes in individual acylcarnitines and T2D risk using weighted Cox regression models. We used elastic net regressions to select acylcarnitines for T2D prediction and compute a weighted score using a cross-validation approach. Results: An acylcarnitine profile, especially including short-and long-chain acylcarnitines, was significantly associated with a higher risk of T2D independent of traditional risk factors. The relative risks of T2D per SD increment of the predictive model scores were 4.03 (95% CI, 3.00 to 5.42; P < 0.001) for the conventional model and 4.85 (95% CI, 3.65 to 6.45; P < 0.001) for the model including acylcarnitines, with a hazard ratio of 1.33 (95% CI, 1.08 to 1.63; P < 0.001) attributed to the acylcarnitines. Including the acylcarnitines into the model did not significantly improve the area under the receiver operator characteristic curve (0.86 to 0.88, P = 0.61). A 1-year increase in C4OH-carnitine was associated with higher risk of T2D [per SD increment, 1.44 (1.03 to 2.01)]. Conclusions: An acylcarnitine profile, mainly including short-and long-chain acylcarnitines, was significantly associated with higher T2D risk in participants at high cardiovascular risk. The inclusion of acylcarnitines into the model did not significantly improve the T2D prediction C-statistics beyond traditional risk factors, including fasting glucose.
Authors: Dominguez, L. J., (Autor de correspondencia); Bes-Rastrollo, Maira; Toledo, Estefanía Ainhoa; et al.
Journal: EUROPEAN JOURNAL OF NUTRITION
ISSN 1436-6207  Vol. 58  Nº 8  2019  pp. 3009 - 3022
PurposeTo prospectively assess the association of dietary fiber intake (from different dietary sources) with all-cause mortality in a Mediterranean cohort.MethodsWe assessed 19,703 participants of the SUN (Seguimiento Universidad de Navarra) cohort (mean follow-up: 10.1 years). A validated 136-item FFQ was administered at baseline. We used Cox proportional hazards models adjusted for multiple socio-demographic, anthropometric, lifestyle factors, and prevalent conditions at baseline.ResultsWe observed 323 deaths during 198,341 person-years of follow-up. A significantly inverse linear trend in Cox models was observed for the association of total dietary fiber intake and all-cause mortality after adjustment for confounders (p for trend 0.017). Each additional intake of 5 g/1000 kcal of dietary fiber was associated with a 9% relative reduction in all-cause mortality risk (HR 0.91, 95% CI 0.84-0.99). Considering separate dietary sources in separate models, a significant inverse trend was apparent for fiber derived from vegetables (p for trend 0.001), but it was non-significant for fiber derived from fruit, legumes, cereals, or other sources. Soluble fiber was significantly inversely associated with all-cause mortality in the fully adjusted model (p for trend 0.007), and insoluble fiber was marginally significant (p for trend 0.08).ConclusionsA higher intake of total dietary fiber, and particularly fiber from vegetables, was related to a reduced all-cause mortality in our Mediterranean cohort. Dietary messages to increase the consumption of dietary patterns rich in fiber-rich foods should be broadly disseminated to decrease the alarming rate of chronic diseases and its derived mortality.
Authors: Camacho-Barcia, L.; Bullo, M., (Autor de correspondencia); Garcia-Gavilan, J. F. ; et al.
Journal: EUROPEAN JOURNAL OF NUTRITION
ISSN 1436-6207  Vol. 58  Nº 2  2019  pp. 619 - 627
ProposalThe aim of this study was to examine the association between the consumption of total and specific types of dairy products and the risk of incident cataracts in an elderly Mediterranean population at high cardiovascular risk.MethodsWe prospectively analyzed 5860 subjects from the PREvencion con DIeta MEDiterranea (PREDIMED) Study. The time to cataract surgery was calculated as the time between recruitment and the date of the surgery, last visit of the follow-up, date of death, or until the end of the study. Dairy products intake was assessed using validated food frequency questionnaires. We used Cox proportional hazard regression to assess the risk of cataract surgery according to average dietary energy-adjusted total dairy products, milk, yogurt and cheese consumption.ResultsWe documented a total of 768 new cataract events after a median of 5.6years of follow-up. Subjects in the second [hazard ratio (HR) 0.62; 95% CI 0.52, 0.74] and third tertile (HR: 0.71; 95% CI 0.60, 0.85) of skimmed yogurt intake had a significantly lower risk of cataracts after adjusting for potential confounders. No significant associations were observed for total dairy products, whole and skimmed milk, whole yogurt and cheese consumption.ConclusionThe intake of skimmed yogurt was associated with a reduced risk of cataracts in an elderly Mediterranean population with high cardiovascular risk. No significant associations were observed for other type of dairy product.Clinical Trial registrationInternational Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.
Authors: Roncal, Carmen; Salicio, Agustina; et al.
Journal: TRANSLATIONAL STROKE RESEARCH
ISSN 1868-4483  Vol. 10  Nº 4  2019  pp. 389 - 401
Diabetes is an important risk factor for ischemic stroke (IS). Tissue-type plasminogen activator (tPA) has been associated with less successful revascularization and poor functional outcome in diabetes. We assessed whether a new thrombolytic strategy based on MMP10 was more effective than tPA in a murine IS model of streptozotocin (STZ)-induced diabetes. Wild-type mice were administered a single dose of streptozotocin (STZ) (180mg/kg) to develop STZ-induced diabetes mellitus. Two weeks later, IS was induced by thrombin injection into the middle cerebral artery and the effect of recombinant MMP10 (6.5 mu g/kg), tPA (10mg/kg) or tPA/MMP10 on brain damage and functional outcome were analysed. Motor activity was assessed using the open field test. Additionally, we studied plasminogen activator inhibitor-1 (PAI-1) and thrombin-antithrombin complex levels (TAT) by ELISA and oxidative stress and blood-brain barrier (BBB) integrity by immunohistochemistry and western blot. MMP10 treatment was more effective at reducing infarct size and neurodegeneration than tPA 24h and 3days after IS in diabetic mice. Locomotor activity was impaired by hyperglycemia and ischemic injury, but not by the thrombolytic treatments. Additionally, TAT, oxidative stress and BBB permeability were reduced by MMP10 treatment, whereas brain bleeding or PAI-1 expression did not differ between treatments. Thrombolytic treatment with MMP10 was more effective than tPA at reducing stroke and neurodegeneration in a diabetic murine model of IS, without increasing haemorrhage. Thus, we propose MMP10 as a potential candidate for the clinical treatment of IS in diabetic patients.
Authors: Martínez, Miguel Ángel; et al.
Journal: BRITISH JOURNAL OF NUTRITION
ISSN 0007-1145  Vol. 122  Nº 5  2019  pp. 542 - 551
Polyphenols are a wide family of phytochemicals present in diverse foods. They might play a role in cancer development and progression. In vivo and in vitro studies have suggested beneficial properties and potential mechanisms. We aimed to evaluate the association between total and main classes of polyphenol intake and breast cancer (BC) risk in the Seguimiento Universidad de Navarra project - a prospective Mediterranean cohort study. We included 10 713 middle-aged, Spanish female university graduates. Polyphenol intake was derived from a semi-quantitative FFQ and matching food consumption data from the Phenol-Explorer database. Women with self-reported BC were asked to return a copy of their medical report for confirmation purposes; death certificates were used for fatal cases. Cox models were fitted to estimate multivariable-adjusted hazard ratios (HR) and 95 % CI for the association between tertiles (T) of polyphenol intake and BC. After 10 center dot 3 years of median follow-up, 168 probable incident BC cases were identified, out of which 100 were confirmed. We found no association between polyphenol intake and the overall BC risk. Nevertheless, we observed a significant inverse association between total polyphenol intake and BC risk for postmenopausal women, either for probable or only for confirmed cases (HRT3 v. T1 0 center dot 31 (95 % CI 0 center dot 13, 0 center dot 77; P-trend=0 center dot 010)). Also, phenolic acid intake was inversely associated with postmenopausal BC. In summary, we observed no significant association between total polyphenol intake and BC risk. Despite a low number of incident BC cases in our cohort, higher total polyphenol intake was associated with a lower risk of postmenopausal BC.
Authors: Navarro, A. M. ; Martínez, Miguel Ángel; Gea, Alfredo; et al.
Journal: CLINICAL NUTRITION
ISSN 0261-5614  Vol. 38  Nº 1  2019  pp. 389 - 397
BACKGROUND & AIMS: Evidence on coffee consumption and its association with the incidence of hypertension is still inconsistent. The aim of this study was to examine the association of regular or decaffeinated coffee consumption with the risk of developing hypertension in a middle-aged Mediterranean cohort. METHODS: The SUN Project is a prospective open cohort with more than 22,500 Spanish university graduates. For the present study, we analyzed data from 13,374 participants initially free of hypertension (mean follow-up 9.1 years). The consumption of regular and decaffeinated coffee was obtained at baseline using a previously validated semi-quantitative food frequency questionnaire. Validated, self-reported medical diagnoses of hypertension were collected biennially. We used Cox regression models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for incident hypertension according to baseline coffee consumption. We assessed the interaction with sex and baseline adherence to the Mediterranean diet. RESULTS: Among 121,397 person-years of follow-up, a total of 1757 participants developed hypertension. Overall, coffee consumption -either caffeinated or decaffeinated- was not significantly associated with the risk of hypertension. Only among women, higher consumption of regular coffee was associated with a 26% lower risk of hypertension (>=2 cups/d vs. never/seldom, 95% CI 9%-39%; p for interaction: 0.0236). Women with a low baseline adherence to the Mediterranean diet showed the strongest risk reduction (HR ¿ 2 cups/d vs. never/seldom 0.58, 95% CI (0.41-0.82) p for interaction = 0.0452). CONCLUSION: In the SUN project we found an inverse association between regular coffee consumption and the risk of hypertension in women, which was strongest among women with a suboptimal food pattern (low adherence to the Mediterranean diet).
Authors: Konieczna, J.; Abete, Itziar; Galmes, A. M. ; et al.
Journal: CLINICAL NUTRITION
ISSN 0261-5614  Vol. 38  Nº 4  2019  pp. 1883 - 1891
Background & aims: Excess adiposity is associated with poor cardiometabolic (CM) health. To date, several techniques and indicators have been developed to determine adiposity. We aimed to compare the ability of traditional anthropometric, as well as standard and novel DXA-derived parameters related to overall and regional adiposity, to evaluate CM risk. Methods: Using the cross-sectional design in the context of the PREDIMED-Plus trial, 1207 Caucasian senior men and women with overweight/obesity and metabolic syndrome (MetS) were assessed. At baseline, anthropometry- and DXA-measured parameters of central, visceral, peripheral and central-to peripheral adiposity together with comprehensive set of CM risk factors were obtained. Partial correlations and areas under the ROC curve (AUC) were estimated to compare each adiposity measure with CM risk parameters, separately for men and women, and in the overall sample. Results: DXA-derived indicators, other than percentage of total body fat, showed stronger correlations (rho 0.172 to 0.206, p < 0.001) with CM risk than anthropometric indicators, after controlling for age, diabetes and medication use. In both sexes, DXA-derived visceral adipose tissue measures (VAT, VAT/Total fat, visceral-to-subcutaneous fat) together with lipodystrophy indicators (Trunk/Legs fat and Android/Gynoid fat) were strongly and positively correlated (p < 0.001) with glycated hemoglobin (HbA1c), the triglyceride and glucose index (TyG), triglycerides (TG), the ratio TG/HDL-cholesterol (TG/HDL-C), and were inversely related to HDL-C levels (p < 0.001). Furthermore, in AUC analyses for both sexes, VAT/Total fat showed the highest predictive ability for abnormal HbAl c levels (AUC = 0.629), VAT for TyG (AUC = 0.626), both lipodystrophy indicators for TG (AUCs = 0.556), and Trunk/Legs fat for HDL-C (AUC = 0.556) and TG/HDL-C (AUC = 0.581). Conclusions: DXA regional adiposity measures offer advantages beyond traditional anthropometric and DXA overall adiposity indicators for CM risk assessment in senior overweight/obese subjects with MetS. In particular, in both sexes, visceral adiposity better stratifies individuals at risk for glucose abnormalities, and indicators of lipodystrophy better predict markers of dyslipidemia. (C) 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Authors: Liu, X. R.; Zheng, Y.; Guasch-Ferre, M.; et al.
Journal: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
ISSN 0939-4753  Vol. 29  Nº 10  2019  pp. 1040 - 1049
Background and aims: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). Methods and results: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95%CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). Conclusion: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at http://www.controlled-trials.com, ISRCTN35739639. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Authors: Yu, E.; Ruiz-Canela, Miguel; Razquin, Cristina; et al.
Journal: DIABETES OBESITY AND METABOLISM
ISSN 1462-8902  Vol. 21  Nº 2  2019  pp. 397 - 401
The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year changes in arginine (adjusted hazard ratio [HR] per SD 0.68, 95% confidence interval [CI] 0.49, 0.95; Q4 vs. Q1 0.46, 95% CI 0.21, 1.04; P trend = 0.02) and arginine/ADMA ratio (adjusted HR per SD 0.73, 95% CI 0.51, 1.04; Q4 vs. Q1 0.52, 95% CI 0.22, 1.25; P trend = 0.04) were associated with a lower risk of T2D. Positive changes of citrulline and ornithine, and negative changes in SDMA and arginine/(ornithine + citrulline) were associated with concurrent 1-year changes in homeostatic model assessment of insulin resistance. Individuals in the low-fat-diet group had a higher risk of T2D for 1-year changes in NMMA than individuals in Mediterranean-diet groups (P interaction = 0.02). We conclude that arginine bioavailability is important in T2D pathophysiology.
Authors: Papandreou, C.; Hernandez-Alonso, P.; Bullo, M., (Autor de correspondencia); et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 5  2019  pp. E1032
Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56-0.64), 0.78 (95% CI 0.75-0.81) and 0.52 (95% CI 0.49-0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.
Authors: Alvarez, Ismael; Martínez, Miguel Ángel, (Autor de correspondencia); Sánchez Tainta, Ana; et al.
Journal: REVISTA ESPAÑOLA DE CARDIOLOGIA
ISSN 0300-8932  Vol. 72  Nº 11  2019  pp. 925 - 934
Introduction and objectives: The cardiovascular benefits of the Mediterranean diet have usually been assessed under assumptions of ad libitum total energy intake (ie, no energy restriction). In the recently launched PREDIMED-Plus, we conducted exploratory analyses to study the baseline associations between adherence to an energy-restricted Mediterranean diet (MedDiet) and the prevalence of cardiovascular risk factors (CVRF). Methods: Cross-sectional assessment of all PREDIMED-Plus participants (6874 older adults with overweight/obesity and metabolic syndrome) at baseline. The participants were assessed by their usual primary care physicians to ascertain the prevalence of 4 CVRF (hypertension, obesity, diabetes, and dyslipidemia). A 17-point PREDIMED-Plus score was used to measure adherence to the MedDiet. Multivariable models were fitted to estimate differences in means and prevalence ratios for individual and clustered CVRF. Results: Better adherence to a MedDiet pattern was significantly associated with lower average triglyceride levels, body mass index, and waist circumference. Compared with low adherence (<= 7 points in the 17-point score), better adherence to the MedDiet (11-17 points) showed inverse associations with hypertension (prevalence ratio = 0.97; 95%CI, 0.94-1.00) and obesity (prevalence ratio = 0.96; 95%CI, 0.92-1.00), but positive associations with diabetes (prevalence ratio = 1.19; 95%CI, 1.07-1.32). Compared with the lowest third of adherence, women in the upper third showed a significantly lower prevalence of the clustering of 3 or more CVRF (prevalence ratio = 0.91; 95%CI, 0.83-0.98). Conclusions: Among participants at high cardiovascular risk, better adherence to a MedDiet showed significant inverse associations with CVRF among women, and improved lipid profiles and adiposity measures. (C) 2018 Sociedad Espanola de Cardiologia. Published by Elsevier Espana, S.L.U. All rights reserved.
Authors: Julibert, A.; Bibiloni, M. D.; Bouzas, C.; et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 11  Nº 7  2019 
Background: The effect of dietary fat intake on the metabolic syndrome (MetS) and in turn on cardiovascular disease (CVD) remains unclear in individuals at high CVD risk. Objective: To assess the association between fat intake and MetS components in an adult Mediterranean population at high CVD risk. Design: Baseline assessment of nutritional adequacy in participants (n = 6560, men and women, 55-75 years old, with overweight/obesity and MetS) in the PREvencion con DIeta MEDiterranea (PREDIMED)-Plus randomized trial. Methods: Assessment of fat intake (total fat, monounsatured fatty acids: MUFA, polyunsaturated fatty acids: PUFA, saturated fatty acids: SFA, trans-fatty acids: trans-FA, linoleic acid, alpha-linolenic acid, and omega-3 FA) using a validated food frequency questionnaire, and diet quality using 17-item Mediterranean dietary questionnaire and fat quality index (FQI). Results: Participants in the highest quintile of total dietary fat intake showed lower intake of energy, carbohydrates, protein and fiber, but higher intake of PUFA, MUFA, SFA, TFA, LA, ALA and omega-3 FA. Differences in MetS components were found according to fat intake. Odds (5th vs. 1st quintile): hyperglycemia: 1.3-1.6 times higher for total fat, MUFA, SFA and omega-3 FA intake; low high-density lipoprotein cholesterol (HDL-c): 1.2 higher for LA; hypertriglyceridemia: 0.7 lower for SFA and omega-3 FA intake. Conclusions: Dietary fats played different role on MetS components of high CVD risk patients. Dietary fat intake was associated with higher risk of hyperglycemia.
Authors: Papandreou, C.; Diaz-Lopez, A.; Babio, N.; et al.
Journal: JOURNAL OF CLINICAL MEDICINE
ISSN 2077-0383  Vol. 8  Nº 7  2019 
Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping >= 90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping >= 30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk.
Authors: Toledo, Estefanía Ainhoa, (Autor de correspondencia); et al.
Journal: EUROPEAN JOURNAL OF NUTRITION
ISSN 1436-6207  Vol. 58  Nº 7  2019  pp. 2875 - 2886
Purpose Breast cancer (BC) incidence is increasing worldwide. Higher insulin resistance may potentially lead to an increased risk of BC. Sugar-sweetened beverages (SSB) are an acknowledged dietary factor that increases insulin resistance. However, the association between SSB and BC has not been widely explored. We evaluated the association between baseline consumption of SSB and the incidence of BC among relatively young women in a cohort of Spanish university graduates. Methods We evaluated 10,713 middle-aged, Spanish female university graduates (median age 33) from the Seguimiento Universidad de Navarra (SUN) cohort, initially free of BC. SSB consumption was collected at baseline using a validated 136-item semi-quantitative food-frequency questionnaire. Incidence of BC was confirmed by a trained oncologist using medical records. We fitted Cox regression models to assess the relationship between baseline categories of SSB consumption and the incidence of BC during follow-up. We stratified the analyses by menopausal status. Results During 106,189 person-years follow-up, 100 incident cases of BC were confirmed. Among postmenopausal women, regular consumption of SSB was associated with a significantly higher incidence of BC (HR 2.12; 95% CI 1.02, 4.41) in the fully adjusted model, compared to women who never or seldom consumed SSB. No association was found among premenopausal women (HR 1.16; 95% CI 0.66, 2.07). Conclusions Even though the number of cases was small, in this Mediterranean cohort, we observed a direct association between SSB consumption and BC risk among postmenopausal women. Nonetheless further larger longitudinal studies are needed to support this association.
Authors: Toledo, Estefanía Ainhoa; Salas-Salvado, J.; et al.
Journal: ANNALS OF NUTRITION AND METABOLISM
ISSN 0250-6807  Vol. 75  Nº Supl, 2  2019  pp. 20 - 21
Authors: Visioli, F. , (Autor de correspondencia); Franco, M.; Toledo, Estefanía Ainhoa; et al.
Journal: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
ISSN 0939-4753  Vol. 28  Nº 7  2018  pp. 649 - 656
Olive oil is the foremost source of fat in the Mediterranean area and, among other features, sets the Mediterranean diet apart from other dietary regimens. In January 2018, the International Olive Council convened several worldwide experts at the Robert Mondavi Institute (Davis, CA), to discuss and summarize the available data on the effects of olive oil consumption on human health. In this paper, we critically provide a synthesis of the main reported findings, which underscore how and why consuming this oil as part of a balanced diet and healthful lifestyle improves prognosis and extends life- and health-spans. (C) 2018 Published by Elsevier B. V.
Authors: Corella, D., (Autor de correspondencia); Ramirez-Sabio, J. B.; Coltell, O. ; et al.
Journal: JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
ISSN 2212-2672  Vol. 118  Nº 4  2018  pp. 589 - 605
Background Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. Objective Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet. Design Secondary analysis in the PREDIMED (Prevencion con Dieta Mediterranea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010. Participants/setting Study participants (n = 7,170) were at high risk for CVD and were aged 55 to 80 years. Intervention Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline. Main outcome measures Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years. Statistical analyses Multivariable-adjusted Cox regression models were fitted. Results Three hundred eighteen deaths were detected (cancer, n = 127; CVD, n = 81; and other, n = 110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P = 0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carrierswas 1.69 (95% CI 1.09 to 2.62; P = 0.018). This association was greater for CVD mortality (P = 0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P = 0.867), but a significant age interaction (P = 0.048) was observed, as Cys326Cys was associated with cancer mortality in participants <66.5 years (P = 0.029). Recessive effects limited our ability to investigate Cys326Cys x diet interactions for cancer mortality. No statistically significant interactions for total or CVD mortality were found for the Mediterranean diet intervention. However, significant protective interactions for CVD mortality were found for vegetable intake (hazard ratio interaction per standard deviation 0.42; 95% CI 0.18 to 0.98; P = 0.046). Conclusions In this population, the Cys326Cys-OGG1 genotype was associated with all-cause mortality, mainly CVD instead of cancer mortality. Additional studies are needed to provide further evidence on its dietary modulation.
Authors: Ruiz-Canela, Miguel, (Autor de correspondencia); Guasch-Ferre, M. ; Toledo, Estefanía Ainhoa; et al.
Journal: DIABETOLOGIA
ISSN 0012-186X  Vol. 61  Nº 7  2018  pp. 1560 - 1571
Aims/hypothesis Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial. Methods We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvencin con DIeta MEDiterranea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n = 273), a MedDiet+nuts (n = 324) or a control diet (n = 295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial. Results Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend = 0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD = 1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p = 0.005 vs the control group). Conclusions/interpretation Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence.
Authors: Sanchez-Quesada, C.; Lopez-Biedma, A. ; Toledo, Estefanía Ainhoa; et al.
Journal: EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE
ISSN 1741-427X  Vol. 2018  2018  pp. 9473094
Anti-inflammatory effects of virgin olive oil (VOO) have been described recently, along with its wound healing effect. One of the main minor compounds found in VOO is squalene (SQ), which also possesses preventive effects against skin damage and anti-inflammatory properties. The inflammatory response is involved in wound healing and manages the whole process by macrophages, among others, as the main innate cells with a critical role in the promotion and resolution of inflammation for tissue repair. Because of that, this work is claimed to describe the role that squalene exerts in the immunomodulation of M1 proinflammatory macrophages, which are the first cells implicate in recent injuries. Pro-and anti-inflammatory cytokines were analysed using TPH1 cell experimental model. SQ induced an increase in the synthesis of anti-inflammatory cytokines, such as IL-10, IL-13, and IL-4, and a decrease in proinflammatory signals, such as TNF-alpha and NF-kappa B in M1 proinflammatory macrophages. Furthermore, SQ enhanced remodelling and repairing signals (TIMP-2) and recruitment signals of eosinophils and neutrophils, responsible for phagocytosis processes. These results suggest that SQ is able to promote wound healing by driving macrophage response in inflammation. Therefore, squalene could be useful at the resolution stage of wound healing.
Authors: Razquin, Cristina; Liang, L. M.; Toledo, Estefanía Ainhoa; et al.
Journal: INTERNATIONAL JOURNAL OF CARDIOLOGY
ISSN 0167-5273  Vol. 253  2018  pp. 126 - 132
Background: The study of the plasma lipidome may help to better characterize molecular mechanisms underlying cardiovascular disease. The identification of new lipid biomarkers could provide future targets for prevention and innovative therapeutic approaches. In the frame of the PREDIMED trial, our aim was to examine the associations of baseline lipidome patterns or their changes with the risk of clinical CVD events. Methods: We included 983 participants in our case-cohort study. The end-point was the incidence of major CVD during 4.8 years of median follow-up. We repeatedly measured 202 plasma known lipid metabolites at baseline and after 1-year of intervention. Principal component analysis was used to identify lipidome factors. Among the 15 identified factors, 7 were significantly associated with CVD. Considering common patterns among factors, lipids were grouped (summed) into scores. Results: After adjustment for traditional CVD risk factors, scores of baseline polyunsaturated phosphatidylcholines (PC)/lysoPC/PC-plasmalogens and polyunsaturated cholesterol esters (CE) showed inverse associations with CVD (p = 0,036 and 0.012, respectively); whereas scores of monoacylglycerols (MAGs)/diacylglycerols (DAGs) and short triacylglycerols (TAGs) showed a direct association with CVD (p = 0,026 and 0.037, respectively). Baseline phosphatidylethanolamines (PEs) and their 1-y changes tended to be associated with higher CVD risk (p = 0.066 and 0.081, respectively). We did not find a significant effect of the intervention with the Mediterranean Diet on these scores. Conclusions: Our study suggests that polyunsaturated PCs and CEs may confer protection against CVD. In contrast, MAGs, DAGs, TAGs and PEs appeared to be associated with higher CVD risk. (c) 2017 Elsevier B.V. All rights reserved.
Authors: Navarro, A. M.; Martínez, Miguel Ángel; Gea, Alfredo; et al.
Journal: AMERICAN JOURNAL OF CLINICAL NUTRITION
ISSN 0002-9165  Vol. 108  Nº 5  2018  pp. 1113 - 1120
Background: The relation of coffee consumption with total mortality is controversial, because the available evidence is still inconsistent. Objective: This study aimed to assess this association in a highly educated, middle-aged Mediterranean cohort. Design: We analyzed data from 201,055 person-years of follow-up arising from 19,888 participants. Coffee consumption was obtained at baseline with the use of a previously validated semi-quantitative food-frequency questionnaire. Information on mortality was ascertained by permanent contact with the "Seguimiento Universidad de Navarra" (SUN) participants and their families, postal authorities, and consultation of the National Death Index. We used Cox regression models to estimate HRs and 95% CIs for mortality according to baseline total coffee consumption adjusted for potential confounders. Sex, age, and baseline adherence to the Mediterranean diet were considered as potential effect modifiers. Results: Among the 19,888 participants, 337 died. Overall, in the multivariable adjusted analysis, we found a 22% lower risk of all-cause mortality for each 2 additional cups of total coffee per day (HR: 0.78; 95% CI: 0.66, 0.93). This association was stronger for participants aged >= 55 y (HR: 0.67; 95% CI: 0.52, 0.86) than for younger participants, who showed no significant association (P-interaction = 0.002). Conclusion: In a Mediterranean cohort, we found an inverse linear association between total coffee consumption and the risk of all-cause mortality that was strongest among participants older than 54 y.
Authors: Schroder, H. , (Autor de correspondencia); Cardenas-Fuentes, G. ; Martínez, Miguel Ángel; et al.
Journal: INTERNATIONAL JOURNAL OF BEHAVIORAL NUTRITION AND PHYSICAL ACTIVITY
ISSN 1479-5868  Vol. 15  2018 
BackgroundThe development and implementation of effective physical activity (PA) intervention programs is challenging, particularly in older adults. After the first year of the intervention program used in the ongoing PREvencion con DIeta MEDiterranea (PREDIMED)-Plus trial, we assessed the initial effectiveness of the PA component.MethodsPREDIMED-Plus is an ongoing randomized clinical trial including 6874 participants randomized to an intensive weight-loss lifestyle intervention based on an energy-restricted Mediterranean diet (MedDiet), physical activity promotion and behavioral support and to a control group using MedDiet recommendations but without calorie restriction or PA advice. Body mass index (BMI) and waist circumference (WC) are measured by standard clinical protocols. Duration and intensity of PA is self-reported using the validated REGICOR Short Physical Activity Questionnaire. The primary endpoint of the PREDIMED-Plus trial is a combined cardiovascular outcome: myocardial infarction (acute coronary syndromes with positive troponin test), stroke, or cardiovascular mortality. The present study involved secondary analysis of PA data (n=6059; mean age 654.9years) with one-year changes in total, light, and moderate-to-vigorous PA within and between intervention groups as the outcome. Generalized estimating equation models were fitted to evaluate time trends of PA, BMI, and WC within groups and differences between intervention and control groups.ResultsAfter 12months, average daily MVPA increased by 27.2 (95%CI 5.7;48.7) METs-min/day and 123.1 (95%CI 109.7-136.6) METs-min/day in the control and intervention groups, respectively. Total-PA, light-PA, and MVPA increased significantly (p<0.01) in both groups. A significant (p<0.001) time*intervention group interaction was found for Total-PA and MVPA, meaning the PA trajectory over time differed between the intervention and control groups. Age, sex, education level, and BMI did not moderate the effectiveness of the PA intervention. BMI and WC decreased significantly with increasing MVPA, compared with participants who reported no changes in MVPA.ConclusionAfter one year of follow-up, the PREDIMED-Plus PA intervention has been effective in increasing daily PA in older adults.Trial registration Retrospectively registered at the International Standard Randomized Controlled Trial (http://www.isrctn.com/ISRCTN89898870), registration date: 24 July 2014.
Authors: Galilea-Zabalza, I. ; Buil-Cosiales, P.; Salas-Salvado, J. ; et al.
Journal: PLOS ONE
ISSN 1932-6203  Vol. 13  Nº 6  2018  pp. Article number e0198974
We assessed if a 17-item score capturing adherence to a traditional Mediterranean diet (MedDiet) was associated with better health-related quality of life among older Spanish men and women with overweight or obesity harboring the metabolic syndrome. We analyzed baseline data from 6430 men and women (age 55-70 years) participating in the PREDIMED-Plus study. PREDIMED-Plus is a multi-centre randomized trial testing an energy-restricted MedDiet combined with promotion of physical activity and behavioral therapy for primary cardiovascular prevention compared to a MedDiet alone. Participants answered a 36-item questionnaire about health-related quality of life (HRQoL) and a 17-item questionnaire that assessed adherence to an MedDiet. We used ANCOVA and multivariable-adjusted linear regression models to compare baseline adjusted means of the quality of life scales according to categories of adherence to the MedDiet. Higher adherence to the MedDiet was independently associated with significantly better scores in the eight dimensions of HRQoL. Adjusted differences of > = 3 points between the highest and the lowest dietary adherence groups to the MedDiet were observed for vitality, emotional role, and mental health and of > = 2 points for the other dimensions. In conclusion, this study shows a positive association between adherence to a MedDiet and several dimensions of quality of life.
Authors: Papandreou, C. ; Bullo, M., (Autor de correspondencia); Zheng, Y. ; et al.
Journal: AMERICAN JOURNAL OF CLINICAL NUTRITION
ISSN 0002-9165  Vol. 108  Nº 1  2018  pp. 163 - 173
Background: The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective: The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design: This is a case-cohort design study within the Prevencion con Dieta Mediterranea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, a-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results: After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and a-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16: 0 LPC, C18: 1 LPC, C18: 0 LPC, C20: 4 LPC, C22: 6 LPC, C18: 1 LPC plasmalogen, and C16: 0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion: Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated.
Authors: Martínez, Miguel Ángel; Toledo, Estefanía Ainhoa; et al.
Journal: ATHEROSCLEROSIS
ISSN 0021-9150  Vol. 275  2018  pp. 133 - 140
Background and aims: The PREDIMED (PREvencion con Dleta MEDiterranea) is a multicentre trial analyzed as a prospective cohort study. A total of 7122 participants (aged 55-80 years) at high risk of cardiovascular disease in the PREDIMED trial were recruited in 11 centres in Spain. The prevalence of subjects with type 2 diabetes was 50%. Our objective was to determine the contribution of lifestyle factors to the development of peripheral artery disease (PAD). Methods: Incident clinical PAD in relation to a healthy lifestyle 5-point score defined as adherence to a Mediterranean diet (MedDiet), moderate alcohol intake, regular physical activity, normal weight (BMI<25) and non-smoking was measured. Results: Eighty-seven incident PAD cases were diagnosed during a median follow-up of 4.8 years. Compared with participants with 0 or 1 healthy lifestyle factor, the multivariable hazard ratio for PAD was 0.65 (95% confidence interval (CI) 0.37 to 1.14) for 2 factors, and 0.40 (0.22-0.72) for 3 or more. Moderate alcohol consumption, non-smoking, physical activity and following a MedDiet were significantly inversely associated with PAD whereas no association was found for normal weight (BMI<25 kg/m(2)). PAD risk monotonically decreased with an increasing number of lifestyle factors, and the greatest reduction was found for a score combining moderate alcohol consumption, MedDiet and physical activity or non-smoking. The multivariable-adjusted population attributable risk percent for the combination of these 4 factors was 80.5% (95% CI: 21.3%-95.1%). Conclusions: Our results demonstrate that a simple healthy lifestyle score is associated with a substantially reduced risk of PAD in a high cardiovascular risk population with a high prevalence (50%) of subjects with type 2 diabetes. (C) 2018 Elsevier B.V. All rights reserved.
Authors: Yu, E.; Papandreou, C.; Ruiz-Canela, Miguel; et al.
Journal: CLINICAL CHEMISTRY
ISSN 0009-9147  Vol. 64  Nº 8  2018  pp. 1211 - 1220
BACKGROUND: Metabolites of the tryptophan-kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case-cohort design nested in the Prevencion con Dieta Mediterranea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS: Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS: Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04-1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09-1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS: Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity. (C) 2018 American Association for Clinical Chemistry
Authors: Barrubes, L.; Babio, N., (Autor de correspondencia); Mena-Sanchez, G. ; et al.
Journal: INTERNATIONAL JOURNAL OF CANCER
ISSN 0020-7136  Vol. 143  Nº 6  2018  pp. 1356 - 1366
Prospective studies have reported an inverse association between the consumption of total dairy products and milk and the risk of colorectal cancer (CRC). Nonetheless, there is little and inconsistent evidence regarding subtypes of dairy product and CRC risk. We assessed the associations between the consumption of total dairy products, their different subtypes and CRC risk in older Mediterranean individuals at high cardiovascular risk. We analyzed data from 7,216 men and women (55-80 years) without CRC at baseline from the PREvencion con DIeta MEDiterranea study. Individuals were recruited between 2003 and 2009 and followed up until December 2012. At baseline and yearly thereafter, consumption of total and specific dairy products was assessed using a validated 137-item food-frequency questionnaire. Cox proportional hazards ratios (HRs) of CRC incidence were estimated for tertiles of mean consumption of dairy products during the follow-up. During a median [interquartile range] follow-up of 6.0 [4.4-7.3] years, we documented 101 incident CRC cases. In the multivariable-adjusted models, HRs and 95% confidence intervals (CIs) of CRC for the comparison of extreme tertiles of total dairy product and low-fat milk consumption were 0.55 (95% CI: 0.31-0.99; p-trend = 0.037) and 0.54 (95% CI: 0.32-0.92; p-trend = 0.022), respectively. No significant associations with other dairy products (whole-fat and low-fat dairy products; total, low-fat and whole-fat yogurt; cheese; total, low-fat and whole-fat milk; concentrated full-fat dairy products, sugar-enriched dairy products and fermented dairy products) were found. A high consumption of total dairy products and low-fat milk was significantly associated with a reduced CRC risk.
Authors: Navarro, A. M.; Abasheva, D.; Martínez, Miguel Ángel; et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 10  Nº 9  2018  pp. E1333
Coffee is one of the most widely consumed drinks around the world, while depression is considered the major contributor to the overall global burden of disease. However, the investigation on coffee consumption and depression is limited and results may be confounded by the overall dietary pattern. We assessed the relationship between coffee intake and the risk of depression, controlling for adherence to the Mediterranean diet. We studied 14,413 university graduates of the Seguimiento Universidad de Navarra' (SUN) cohort, initially free of depression. We evaluated coffee consumption using a validated food-frequency questionnaire (FFQ). Incident depression cases were adjudicated only if the participant met two criteria simultaneously: (a) validated physician-diagnosed depression together with (b) new onset of habitual antidepressant use. Both criteria were needed; participants meeting only one of them were not classified as cases. Participants who drank at least four cups of coffee per day showed a significantly lower risk of depression than participants who drank less than one cup of coffee per day (HR: 0.37 (95% CI 0.15-0.95)). However, overall, we did not observe an inverse linear dose-response association between coffee consumption and the incidence of depression (p for trend = 0.22).
Authors: Sanchez-Villegas, A. , (Autor de correspondencia); Alvarez-Perez, J.; Toledo, Estefanía Ainhoa; et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 10  Nº 12  2018 
Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (-3 PUFA) intake, and depression prevalence. Methods: Cross-sectional analyses of the PREDIMED-Plus trial. Fish and seafood consumption and -3 PUFA intake were assessed through a validated food-frequency questionnaire. Self-reported life-time medical diagnosis of depression or use of antidepressants was considered as outcome. Depressive symptoms were collected by the Beck Depression Inventory-II. Logistic regression models were used to estimate the association between seafood products and -3 PUFA consumption and depression. Multiple linear regression models were fitted to assess the association between fish and long-chain (LC) -3 PUFA intake and depressive symptoms. Results: Out of 6587 participants, there were 1367 cases of depression. Total seafood consumption was not associated with depression. The odds ratios (ORs) (95% confidence intervals (CIs)) for the 2nd, 3rd, and 4th quintiles of consumption of fatty fish were 0.77 (0.63-0.94), 0.71 (0.58-0.87), and 0.78 (0.64-0.96), respectively, and p for trend = 0.759. Moderate intake of total LC -3 PUFA (approximately 0.5-1 g/day) was significantly associated with a lower prevalence of depression. Conclusion: In our study, moderate fish and LC -3 PUFA intake, but not high intake, was associated with lower odds of depression suggesting a U-shaped relationship.
Authors: de la Fuente-Arrillaga, Carmen; Bes-Rastrollo, Maira; et al.
Journal: NUTRICION HOSPITALARIA
ISSN 0212-1611  Vol. 35  Nº 1  2018  pp. 153 - 161
Introduction and objectives: Our aim was to prospectively evaluate the association between egg consumption and dyslipidemia in a Mediterranean cohort. Methods: We followed-up 13,104 Spanish university graduates for a mean period of 8 years. Dietary habits at baseline were assessed using a validated semi-quantitative 136-item food-frequency questionnaire. Self-reported blood concentrations of total cholesterol, high-density lipoproteins cholesterol (HDL-c) and triglycerides were evaluated according to categories of egg consumption after 6 and 8 years of follow-up. We also assessed the association between baseline egg consumption and the incidence of hypercholesterolemia, low HDL-c concentrations and hypertriglyceridemia during follow-up. Results: We observed a significant inverse association for intermediate levels of egg consumption (2 to 4 eggs/week vs. less than 1 egg/week) and hypertriglyceridemia with OR = 0.71 (95% confidence interval [CI]: 0.54 to 0.93, p < 0.05) in the multivariable-adjusted model. Using HDL-c values after 8-year follow-up, we found an association between higher egg consumption and lower HDL-c levels (p for trend = 0.02) with an adjusted difference of -4.01 mg/dl (-7.42 to -0.61) for > 4 vs. < 1 egg/week. Lower means of triglycerides were found in each of the three upper categories of egg consumption compared to the lowest category (< 1 egg/week) with significant results for some of these categories both after 6 and 8 year follow-up. Conclusions: Our data do not support that higher egg consumption was associated with abnormal blood levels of total cholesterol or triglycerides; an inverse association with HDL-c as a quantitative variable was found only in one of our analyses.
Authors: Razquin, Cristina; Toledo, Estefanía Ainhoa; Clish, C. B.; et al.
Journal: DIABETES CARE
ISSN 0149-5992  Vol. 41  Nº 12  2018  pp. 2617 - 2624
OBJECTIVE Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. RESEARCH DESIGN AND METHODS We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. RESULTS Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend <0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs. CONCLUSIONS Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another profile composed of TAGs, DAGs, and PEs was associated with higher T2D risk.
Authors: Sánchez-Bayona, Rodrigo; et al.
Journal: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 29  Nº Supl. 8  2018  pp. 572
Authors: Gea, Alfredo; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl 1  2018  pp. 175 - 176
Authors: Ruiz-Canela, Miguel; Guasch-Ferre, M.; Toledo, Estefanía Ainhoa; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  pp. 173
Authors: Mallorqui-Bague, N. ; Lozano-Madrid, M.; Toledo, Estefanía Ainhoa; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  pp. 68 - 69
Authors: Sánchez-Bayona, Rodrigo; et al.
Journal: ANNALS OF ONCOLOGY
ISSN 0923-7534  Vol. 29  Nº Supl. 8  2018  pp. 572
Background: Obesity is a well-known risk factor for some types of cancer including post-menopausal breast cancer. Nevertheless, the influence of adiposity over life course on cancer risk remains poorly understood. The objective of this study was to assess body shape trajectories in early and middle life in relation to subsequent risk of breast cancer in a Mediterranean cohort. Methods: We used a group-based modelling approach to assess body shape trajectories from age 5 to 40 years, among 10679 women from the SUN cohort study from 1999 to 2014. Four distinct body shape trajectories were identified (lean-heavy increase, medium-stable, medium-heavy increase and heavy-stable). Cox regression models were used to estimate the hazard ratio (HR) for breast cancer according to the assigned body shape trajectory. Results: Among 106,537 women-years of follow-up a total of 133 probable incident cases of breast cancer were identified (70 of these cases were confirmed). When compared to those in the medium-stable category, women who were lean and had a marked increase (lean-heavy increase category) showed a subsequent higher risk of probable breast cancer (HR¿=¿1.55, 95%CI 1.05-2.29). When stratifying according to menopausal status, there was a higher risk of probable postmenopausal breast cancer for women in the lean-heavy increase category (HR¿=¿2.0, 95%CI 1.06- 3.80) compared to the medium-stable group. The statistical power was reduced and significance was lost when we considered only confirmed cases.
Authors: Toledo, Estefanía Ainhoa, (Autor de correspondencia)
Journal: EUROPEAN JOURNAL OF PUBLIC HEALTH
ISSN 1101-1262  Vol. 28  Nº Supl. 4  2018  pp. 261 - 261
Authors: Razquin, Cristina; Toledo, Estefanía Ainhoa; Clish, C.; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  pp. 179
Authors: Konieczna, J. ; Abete, Itziar; Galmes, A. M.; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  pp. 172 - 172
Authors: Papandreou, C.; Bullo, M. ; Zheng, Y. ; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  pp. 176
Authors: Perez, V. P. ; Romaguera, D.; Konieczna, J.; et al.
Journal: EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  pp. 171 - 171
Authors: Toledo, Estefanía Ainhoa, (Autor de correspondencia); Martínez, Miguel Ángel;
Journal: LANCET
ISSN 0140-6736  Vol. 390  Nº 10107  2017  pp. 2017 - 2018
Cardiovascular disease is the leading cause of death worldwide, accounting for a third of all deaths. Three of four cardiovascular deaths and more than 80% of premature deaths attributable to non-communicable diseases occur in low-income and middle-income countries.1 Thus, preventive strategies to tackle premature mortality and, particularly, cardiovascular mortality represent a major public health goal not only for high-income countries, but also for low-income and middle-income countries. The most effective and sustainable preventive strategies should rely on healthy diet and lifestyle.
Authors: Yu, E.; Ruiz-Canela, Miguel; Guasch Ferre, M.; et al.
Journal: JOURNAL OF NUTRITION
ISSN 0022-3166  Vol. 147  Nº 3  2017  pp. 314 - 322
Background: During development of cardiovascular disease (CVD), interferon-gamma-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extravirgin olive oil (EVOO), nuts, fruits, vegetables, and cereals has been demonstrated to lower the risk of CVD. The longitudinal relation between tryptophan and its downstream metabolites and CVD in the context of a MedDiet is unstudied. Objective: We sought to investigate the relation between metabolites in the tryptophan-kynurenine pathway and CVD in the context of a MedDiet pattern. Methods: We used a case-cohort design nested in the Prevencion con DietaMediterranea randomized controlled trial. There were 231 CVD cases (stroke, myocardial infarction, cardiovascular death) among 985 participants over a median of 4.7 y of follow-up [mean +/- SD age: 67.6 +/- 6.1 y; 53.7% women; mean6 SD bodymass index (in kg/m(2)): 29.7 +/- 3.7]. We assessed plasma tryptophan, kynurenine, kynurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid concentrations at baseline and after 1 y of intervention with aMedDiet. We combined thesemetabolites in a kynurenine risk score (KRS) by weighting each metabolite by the adjusted coefficient of its associations with CVD. Cox models were used in the primary analysis. Results: Increases in tryptophan after 1 ywere associatedwith a lower risk of compositeCVD(HR per SD: 0.79; 95% CI: 0.63, 0.98). The baseline kynurenic acid concentration was associated with a higher risk of myocardial infarction and coronary artery disease death but not stroke. A higher KRSwas more strongly associatedwith CVD in the control group than in the 2 intervention groups (P-interaction = 0.003). Adjustment for changes in plasma tryptophan attenuated the inverse association between MedDiet+ EVOO and CVD. Conclusions: An increase in the plasma tryptophan concentrationwas significantly associated with a decreased risk of CVD. A MedDiet may counteract the deleterious effects of a high tryptophan risk score.
Authors: Toledo, Estefanía Ainhoa; Wang, D. D.; Ruiz-Canela, Miguel; et al.
Journal: AMERICAN JOURNAL OF CLINICAL NUTRITION
ISSN 0002-9165  Vol. 106  Nº 4  2017  pp. 973 - 983
Background: Lipid metabolites may partially explain the inverse association between the Mediterranean diet (MedDiet) and cardiovascular disease (CVD). Objective: We evaluated the associations between 1) lipid species and the risk of CVD (myocardial infarction, stroke, or cardiovascular death); 2) a MedDiet intervention [supplemented with extra virgin olive oil (EVOO) or nuts] and 1-y changes in these molecules; and 3) 1-y changes in lipid species and subsequent CVD. Design: With the use of a case-cohort design, we profiled 202 lipid species at baseline and after 1 y of intervention in the PREDIMED (PREvencion con DIeta MEDiterranea) trial in 983 participants [230 cases and a random subcohort of 790 participants (37 overlapping cases)]. Results: Baseline concentrations of cholesterol esters (CEs) were inversely associated with CVD. A shorter chain length and higher saturation of some lipids were directly associated with CVD. After adjusting for multiple testing, direct associations remained significant for 20 lipids, and inverse associations remained significant for 6 lipids. When lipid species were weighted by the number of carbon atoms and double bonds, the strongest inverse association was found for CEs [HR: 0.39 (95% CI: 0.22, 0.68)] between extreme quintiles (P-trend = 0.002). Participants in the MedDiet + EVOO and MedDiet + nut groups experienced significant (P < 0.05) 1-y changes in 20 and 17 lipids, respectively, compared with the control group. Of these changes, only those in CE(20:3) in the MedDiet + nuts group remained significant after correcting for multiple testing. None of the 1-y changes was significantly associated with CVD risk after correcting for multiple comparisons. Conclusions: Although the MedDiet interventions induced some significant 1-y changes in the lipidome, they were not significantly associated with subsequent CVD risk. Lipid metabolites with a longer acyl chain and higher number of double bonds at baseline were significantly and inversely associated with the risk of CVD.
Authors: Wang, D. D.; Toledo, Estefanía Ainhoa; Hruby, A.; et al.
Journal: CIRCULATION
ISSN 0009-7322  Vol. 135  Nº 21  2017  pp. 2028 - 2040
BACKGROUND: Although in vitro studies and investigations in animal models and small clinical populations have suggested that ceramides may represent an intermediate link between overnutrition and certain pathological mechanisms underlying cardiovascular disease (CVD), no prospective studies have investigated the association between plasma ceramides and risk of CVD. METHODS: The study population consisted of 980 participants from the PREDIMED trial (Prevencion con Dieta Mediterranea), including 230 incident cases of CVD and 787 randomly selected participants at baseline ( including 37 overlapping cases) followed for <= 7.4 years. Participants were randomized to a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet. Plasma ceramide concentrations were measured on a liquid chromatography tandem mass spectrometry metabolomics platform. The primary outcome was a composite of nonfatal acute myocardial infarction, nonfatal stroke, or cardiovascular death. Hazard ratios were estimated with weighted Cox regression models using Barlow weights to account for the case-cohort design. RESULTS: The multivariable hazard ratios (HR) and 95% confidence intervals (Cls) comparing the extreme quartiles of plasma concentrations of C16:0, C22:0, C24:0, and C24: 1 ceramides were 2.39 (1.49-3.83, P-trend < 0.001), 1.91 (1.21-3.01, P-trend = 0.003), 1.97 (1.21-3.20, P-trend = 0.004), and 1.73 (1.09-2.74, P-trend = 0.011), respectively. The ceramide score, calculated as a weighted sum of concentrations of four ceramides, was associated with a 2.18-fold higher risk of CVD across extreme quartiles (HR, 2.18; 95% Cl, 1.36-3.49; P-trend < 0.001). The association between baseline ceramide score and incident CVD varied significantly by treatment groups (P-interaction = 0.010). Participants with a higher ceramide score and assigned to either of the 2 active intervention arms of the trial showed similar CVD risk to those with a lower ceramide score, whereas participants with a higher ceramide score and assigned to the control arm presented significantly higher CVD risk. Changes in ceramide concentration were not significantly different between Mediterranean diet and control groups during the first year of follow-up. CONCLUSIONS: Our study documented a novel positive association between baseline plasma ceramide concentrations and incident CVD. In addition, a Mediterranean dietary intervention may mitigate potential deleterious effects of elevated plasma ceramide concentrations on CVD.
Authors: Ramallal, R.; Toledo, Estefanía Ainhoa; Martínez, JA; et al.
Journal: OBESITY
ISSN 1930-7381  Vol. 25  Nº 6  2017  pp. 997 - 1005
Objective: This study prospectively assessed the association of the inflammatory potential of a diet using the dietary inflammatory index (DII) with average yearly weight changes and incident overweight/obesity. Methods: Seven thousand and twenty-seven university graduates with body mass index <25 from the Seguimiento Universidad de Navarra (SUN) cohort were followed up during a median of 8.1 years. The DII, a validated tool based on scientific evidence to appraise the relationship between dietary parameters and inflammatory biomarkers, was used. A validated food-frequency questionnaire was used to assess intake of total energy, food, and nutrients, from which DII scores were calculated at baseline and after 10 years of follow-up. Results: After a median follow-up of 8.1 years, 1,433 incident cases of overweight or obesity were observed. Hazard ratios for overweight/obesity were calculated, including multivariable time-dependent Cox regression models with repeated measures of diet. The hazard ratio for subjects in the highest quartile (most pro-inflammatory diet) was 1.32 (95% confidence interval 1.08-1.60) compared with participants in the lowest quartile (most anti-inflammatory diet), with a significant linear dose-response relationship (P=0.004). Consistently, increases in average yearly weight gains were significantly associated with proinflammatory diets. Conclusions: A proinflammatory diet was significantly associated with a higher annual weight gain and higher risk of developing new-onset overweight or obesity.
Authors: Buil Cosiales, P.; Martínez, Miguel Ángel; Ruiz-Canela, Miguel; et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 9  Nº 3  2017  pp. Article number 295
Fiber and fiber-rich foods have been inversely associated with cardiovascular disease (CVD), but the evidence is scarce in young and Mediterranean cohorts. We used Cox regression models to assess the association between quintiles of total fiber and fiber from different sources, and the risk of CVD adjusted for the principal confounding factors in a Mediterranean cohort of young adults, the SUN (Seguimiento Universidad de Navarra, Follow-up) cohort. After a median follow-up of 10.3 years, we observed 112 cases of CVD among 17,007 participants (61% female, mean age 38 years). We observed an inverse association between fiber intake and CVD events (p for trend = 0.024) and also between the highest quintile of fruit consumption (hazard ratio (HR) 0.51, 95% confidence interval (CI) 0.27-0.95) or whole grains consumption (HR 0.43 95% CI 0.20-0.93) and CVD compared to the lowest quintile, and also a HR of 0.58 (95% CI 0.37-0.90) for the participants who ate at least 175 g/day of fruit. Only the participants in the highest quintile of fruit-derived fiber intake had a significantly lower risk of CVD (HR 0.52, 95% CI 0.28-0.97). The participants who ate at least one serving per week of cruciferous vegetables had a lower risk than those who did not (HR 0.52, 95% CI 0.30-0.89). In conclusion, high fruit consumption, whole grain consumption, or consumption of at least one serving/week of cruciferous vegetables may be protective against CVD in young Mediterranean populations.
Authors: Barba, Joaquín; Guembe, M. J. ; et al.
Journal: REVISTA ESPAÑOLA DE CARDIOLOGIA
ISSN 0300-8932  Vol. 70  Nº 4  2017  pp. 254 - 260
Introduction and objectives: There is currently increasing interest in epicardial adipose tissue (EAT) as a marker of cardiovascular disease. Our purpose was to describe EAT, measured by transthoracic echocardiography, and to assess its association with metabolic syndrome (MS) in the RIVANA population-based study. Methods: Physical examination was performed in 880 participants aged 45 to 74 years (492 of them with MS according to the harmonized definition). Fasting glucose, high-density lipoprotein cholesterol, triglyceride, and C-reactive protein concentrations were determined in a blood sample. In all participants, EAT thickness was measured with transthoracic echocardiography at end-systole. Results: Among participants without MS, the prevalence of EAT >= 5 mm significantly increased with age (OR > 65 years vs 45-54 years = 8.22; 95% CI, 3.90-17.35; P for trend < .001). Increasing EAT quintiles were significantly associated with MS (OR fifth quintile vs first quintile = 3.26; 95% CI, 1.59-6.71; P for trend = .001). Considering the different MS criteria, increasing quintiles of EAT were independently associated with low high-density lipoprotein cholesterol (OR fifth quintile vs first quintile = 2.65; 95% CI, 1.16-6.05; P for trend = .028), high triglycerides (OR fifth quintile vs first quintile = 2.22; 95% CI, 1.26-3.90; P for trend = .003), and elevated waist circumference (OR fifth quintile vs first quintile = 6.85; 95% CI, 2.91-16.11; P for trend < .001). Conclusions: In a subsample of the general population, EAT measured by echocardiography increased significantly and independently with age. Increased EAT thickness was independently associated with MS and with low high-density lipoprotein cholesterol, high triglycerides, and elevated waist circumference as individual criteria. (C) 2016 Published by Elsevier Espana, S.L.U. on behalf of Sociedad Espanola de Cardiologia.
Authors: Barba, Joaquín; Guembe MJ; et al.
Journal: REVISTA ESPAÑOLA DE CARDIOLOGÍA (ENGLISH ED.)
ISSN 1885-5857  Vol. 70  Nº 4  2017  pp. 254-260
In a subsample of the general population, EAT measured by echocardiography increased significantly and independently with age. Increased EAT thickness was independently associated with MS and with low high-density lipoprotein cholesterol, high triglycerides, and elevated waist circumference as individual criteria.
Authors: Pérez-de-Arcelus, M.; Toledo, Estefanía Ainhoa; Martínez, Miguel Ángel; et al.
Journal: MEDICINE (BALTIMORE)
ISSN 0025-7974  Vol. 96  Nº 1  2017  pp. e5761
Smoking is a serious global public health concern that has been related to many chronic diseases. However, the effect of smoking on eye disorders has been less studied. The aim of this cohort study was to assess the association between current tobacco smokers and the risk of developing glaucoma and furthermore to evaluate the relationship between passive or former smokers and glaucoma. In this prospective and dynamic cohort, 16,797 participants initially who were found not to have glaucoma were followed up for a median of 8.5 years. Validated data on lifestyle, including tobacco consumption, were assessed at baseline. Information about new diagnosis of glaucoma was collected by follow-up questionnaires every 2 years. The outcome was the incidence of self-reported glaucoma during the follow-up. A subsample was used to validate the glaucoma diagnosis. During the 8.5 years of follow-up, 184 new glaucoma cases were identified. Current smokers had a significantly higher risk of glaucoma compared to participants who had never smoked after controlling for potential confounders (Hazard ratio [HR] 1.88 [95% coefficient interval (CI): 1.26-2.81]; P=0.002). A nonsignificant increased risk was found among former smokers (HR 1.27 [95% CI: 0.88-1.82]; P=0.198). When we assessed the exposure as per the number of cigarette pack-years, a dose-response relationship between pack-years and the risk of glaucoma was found (HR for the 5th quintile versus the 1st quintile: 1.70 [95% IC: 1.10-2.64], P for trend, 0.009). However, no relationship was found between passive smokers and glaucoma. (HR 0.67 [95% CI: 0.37-1.21]; P=0.189). Our results suggest a direct association between current smokers and the incidence of glaucoma. In particular, this association was related to the number of pack-years, which was not found in the case of former smokers nor in the case of passive smokers.
Authors: Storniolo, C. E.; Casillas, R.; Bullo, M.; et al.
Journal: EUROPEAN JOURNAL OF NUTRITION
ISSN 1436-6207  Vol. 56  Nº 1  2017  pp. 89 - 97
Serum nitric oxide (NO) reduction and increased endothelin-1 (ET-1) play a pivotal role in endothelial dysfunction and hypertension. Considering that traditional Mediterranean diet (TMD) reduces blood pressure (BP), the aim of this study was to analyze whether TMD induced changes on endothelial physiology elements such as NO, ET-1 and ET-1 receptors which are involved in BP control. Non-smoking women with moderate hypertension were submitted for 1 year to interventions promoting adherence to the TMD, one supplemented with extra virgin olive oil (EVOO) and the other with nuts versus a control low-fat diet (30 participants/group). BP, NO, ET-1 and related gene expression as well as oxidative stress biomarkers were measured. Serum NO and systolic BP (SBP) or diastolic BP (DBP) were negatively associated at baseline, as well as between NO and ET-1. Our findings also showed a DBP reduction with both interventions. A negative correlation was observed between changes in NO metabolites concentration and SBP or DBP after the intervention with TMD + EVOO (p = 0.033 and p = 0.044, respectively). SBP reduction was related to an impairment of serum ET-1 concentrations after the intervention with TMD + nuts (p = 0.008). We also observed changes in eNOS, caveolin 2 and ET-1 receptors gene expression which are related to NO metabolites levels and BP. The changes in NO and ET-1 as well as ET-1 receptors gene expression explain, at least partially, the effect of EVOO or nuts on lowering BP among hypertensive women.
Authors: Guasch-Ferre, M., (Autor de correspondencia); Hu, F. B.; Ruiz-Canela, Miguel; et al.
Journal: JOURNAL OF THE AMERICAN HEART ASSOCIATION. CARDIOVASCULAR AND CEREBROVASCULAR DISEASE
ISSN 2047-9980  Vol. 6  Nº 11  2017  pp. e006524
Background-The relationship between plasma concentrations of betaine and choline metabolism and major cardiovascular disease (CVD) end points remains unclear. We have evaluated the association between metabolites from the choline pathway and risk of incident CVD and the potential modifying effect of Mediterranean diet interventions. Methods and Results-We designed a case-cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography-tandem mass spectrometry to measure, at baseline and at 1 year of follow-up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N-oxide, betaine, choline, phosphocholine, and a-glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1-SD increase in choline and alpha-glycerophosphocholine metabolites were 1.24 (1.05-1.46) and 1.24 (1.03-1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21-fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36-3.59; P<0.001 for trend) and a 2.27-fold higher risk of stroke (95% confidence interval, 1.24-4.16; P<0.001 for trend). Participants in the higher quartiles of the score who were randomly assigned to the control group had a higher risk of CVD compared with participants in the lower quartile and assigned to the Mediterranean diet groups (P= 0.05 for interaction). No significant associations were observed for 1-year changes in individual plasma metabolites and CVD. Conclusions-A metabolite score combining plasma metabolites from the choline pathway was associated with an increased risk of CVD in a Mediterranean population at high cardiovascular risk.
Authors: Fitó, M.; Melander, O.; Martínez, JA; et al.
Journal: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
ISSN 1422-0067  Vol. 17  Nº 9  2016  pp. 1469
Intervention with Mediterranean diet (MedDiet) has provided a high level of evidence in primary prevention of cardiovascular events. Besides enhancing protection from classical risk factors, an improvement has also been described in a number of non-classical ones. Benefits have been reported on biomarkers of oxidation, inflammation, cellular adhesion, adipokine production, and pro-thrombotic state. Although the benefits of the MedDiet have been attributed to its richness in antioxidants, the mechanisms by which it exercises its beneficial effects are not well known. It is thought that the integration of omics including genomics, transcriptomics, epigenomics, and metabolomics, into studies analyzing nutrition and cardiovascular diseases will provide new clues regarding these mechanisms. However, omics integration is still in its infancy. Currently, some single-omics analyses have provided valuable data, mostly in the field of genomics. Thus, several gene-diet interactions in determining both intermediate (plasma lipids, etc.) and final cardiovascular phenotypes (stroke, myocardial infarction, etc.) have been reported. However, few studies have analyzed changes in gene expression and, moreover very few have focused on epigenomic or metabolomic biomarkers related to the MedDiet. Nevertheless, these preliminary results can help to better understand the inter-individual differences in cardiovascular risk and dietary response for further applications in personalized nutrition.
Authors: Guruceaga, Elisabet; et al.
Journal: CARDIOVASCULAR RESEARCH
ISSN 0008-6363  Vol. 110  Nº 3  2016  pp. 309 - 318
AIMS: Atrial fibrillation (AF) is a major risk factor for cardio-embolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern. This study sought to identify new targets to develop safer antithrombotic therapies. METHODS AND RESULTS: Here, microarray analysis in peripheral blood cells in eight patients with AF and stroke and eight AF subjects without stroke brought to light a stroke-related gene expression pattern. HSPA1B, which encodes for heat-shock protein 70 kDa (Hsp70), was the most differentially expressed gene. This gene was down-regulated in stroke subjects, a finding confirmed further in an independent AF cohort of 200 individuals. Hsp70 knock-out mice subjected to different thrombotic challenges developed thrombosis significantly earlier than their wild-type (WT) counterparts. Remarkably, the tail bleeding time was unchanged. Accordingly, both TRC051384 and tubastatin A, i.e. two Hsp70 inducers via different pathways, delayed thrombus formation in WT mice, the tail bleeding time still being unaltered. Most interestingly, Hsp70 inducers did not increase the bleeding risk even when aspirin was concomitantly administered. Hsp70 induction was associated with an increased vascular thrombomodulin expression and higher circulating levels of activated protein C upon thrombotic stimulus. CONCLUSIONS: Hsp70 induction is a novel approach to delay thrombus formation with minimal bleeding risk, and is especially promising for treating AF patients and in other situations where there is also a major bleeding hazard.
Authors: Allende, M.; Gonzalez-Porras, J. R. ; et al.
Journal: STROKE
ISSN 0039-2499  Vol. 47  Nº 3  2016  pp. 863 - 865
Background and Purpose- The risk of cardioembolic stroke in patients with atrial fibrillation (AF) cannot be accurately assessed and novel tools are needed to improve prediction. We hypothesize that telomere shortening constitutes a novel risk factor for cardioembolic stroke in patients with AF. Methods- The peripheral blood leukocyte telomere length (LTL) was determined by real-time polymerase chain reaction in 187 patients with AF, 93 of them without stroke history and 94 of them having suffered 1 cardioembolic stroke. Percentiles were calculated according to LTL values in the nonstroke group to estimate the cardioembolic stroke risk associated with LTL using logistic regression models. Results- Short LTL values were independently and dose-dependently associated with an increased risk of cardioembolic stroke, with an odds ratio (95% confidence interval) of 2.93 (1.24-6.94) and 6.26 (2.01-19.52), respectively, for sex, hypertension, diabetes mellitus, heart failure, and age-adjusted models using the LTL 10th and 5th percentile cut-offs, respectively. Conclusions- Telomere shortening is associated with cardioembolic stroke risk in patients with AF. Prospective studies are encouraged to establish the value of LTL to improve prediction tools to categorize cardioembolic stroke risk in AF.
Authors: Eguaras, S.; Toledo, Estefanía Ainhoa; Buil-Cosiales, P.; et al.
Journal: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
ISSN 0939-4753  Vol. 25  Nº 6  2015  pp. 569 - 574
BACKGROUND AND AIM: We tested the hypothesis that an intervention with a Mediterranean diet (MeDiet) could mitigate the well-known harmful effects of abdominal obesity on cardiovascular health. METHODS AND RESULTS: We assessed the relationship between baseline waist-to-height ratio (WHtR) and major cardiovascular events during a median follow-up of 4.8 years in the Prevention with Mediterranean Diet (PREDIMED) randomized primary prevention trial, which tested a MeDiet against a control diet (advice on a low-fat diet). We also examined whether the MeDiet intervention was able to counteract the detrimental cardiovascular effects of an increased WHtR. The trial included 7447 participants (55-80 years old, 57% women) at high cardiovascular risk but free of cardiovascular disease (CVD) at enrollment. An increased risk of CVD events (myocardial infarction, stroke, or cardiovascular death) was apparent for the highest versus the lowest quartile of WHtR (multivariable-adjusted hazard ratio: 1.98) (95% confidence interval: 1.10-3.57; linear trend: p = 0.019) only in the control-diet group, but not in the two groups allocated to intervention with MeDiet (p for interaction = 0.034). This apparent interaction suggesting that the intervention counterbalanced the detrimental cardiovascular effects of adiposity was also significant for body mass index (BMI) (p = 0.01) and waist circumference (p = 0.043). CONCLUSIONS: The MeDiet may counteract the harmful effects of increased adiposity on the risk of CVD.
Authors: Henríquez-Sánchez; Ruiz-Canela, Miguel; et al.
Journal: BMC MEDICINE
ISSN 1741-7015  Vol. 13  Nº 1  2015  pp. 197
Background: Some studies have pointed out that several dietary patterns could be associated with a reduced risk of depression among adults. This association seems to be consistent across countries, cultures and populations. The objective of the study was to compare and to establish the type of relationship between three diet quality scores and depression in the SUN (Seguimiento Universidad de Navarra) Cohort study. Methods: We performed a dynamic cohort study based on Spanish university graduates free of depression at baseline. Dietary intake was repeatedly assessed at baseline and after 10years of follow-up with a validated semi-quantitative food-frequency questionnaire. Three previously described diet quality scores: Mediterranean Diet Score (MDS), Pro-vegetarian Dietary Pattern (PDP) and Alternative Healthy Eating Index-2010 (AHEI-2010) were built. Participants were classified as having depression if they reported a new clinical diagnosis of depression by a physician or initiated the use of an antidepressant drug during follow-up. Time-dependent Cox regression models with cumulative averages of diet and restricted cubic splines were used to estimate hazard ratios of depression according to quintiles of adherence to the MDS, PDP and AHEI-2010. Results: One thousand and fifty one incident cases of depression were observed among 15,093 participants from the SUN Cohort after a median follow-up of 8.5years. Inverse and significant associations were observed between the three diet quality scores and depression risk. The hazard ratios and 95% confidence intervals for extreme quintiles (fifth versus first) of updated adherence to MDS, PDP and AHEI-2010 were 0.84 (0.69-1.02), 0.74 (0.61-0.89) and 0.60 (0.49-0.72), respectively. The dose-response analyses showed non-linear associations, suggesting that suboptimal adherence to these dietary patterns may partially be responsible for increased depression risk. Conclusions: Better adherence to the MDS, PDP and AHEI-2010 was associated with a reduced risk of depression among Spanish adults. However, our data suggested a threshold effect so that although the risk of depression was reduced when comparing moderate versus lower adherence, there was not much extra benefit for the comparison between moderate and high or very high adherence.
Authors: Lopez-del Burgo, C; Gea, Alfredo; de Irala, J; et al.
Journal: NUTRIENTS
ISSN 2072-6643  Vol. 7  Nº 8  2015  pp. 6167 - 6178
The role of alcohol on fertility remains unclear. We aimed to investigate the association between alcohol and specific alcoholic beverages consumption and the risk of difficulty getting pregnant. We used a case-control study nested within the Seguimiento Universidad de Navarra (SUN) cohort, a prospective, dynamic and multipurpose cohort of 21,705 Spanish university graduates, followed biennially with mailed questionnaires. We identified 686 case-control pairs, matched for age and time in the cohort. Cases were women reporting difficulty getting pregnant. Controls did not consult due to difficulty conceiving and had at least one child during follow-up. After adjustment for potential confounders, we found no association between self-reported difficulty getting pregnant and the number of alcoholic beverages consumed per week, (Odds Ratio [OR] > 5 drinks/week vs. none = 1.04, 95% Confidence Interval [CI] = 0.72-1.51). No association between types of alcoholic beverage and difficulty conceiving (OR > 5 drinks of wine/week vs. none = 1.16, 95% CI = 0.72-1.88; OR > 5 drinks of beer/week vs. none = 1.06, 95% CI = 0.82-1.37; OR > 5 drinks of spirits/week vs. none = 1.24, 95% CI = 0.84-1.64) was observed. In conclusion, we found no association between alcohol intake and risk of consulting a physician due to difficulty conceiving. More studies are needed to clearly elucidate the effects of alcohol intake on women's fertility. In the meantime, recommendations about alcohol intake to couples trying to conceive have to be given cautiously.
Authors: Goñi Ruiz, N.; Martínez, Miguel Ángel; Salas Salvadó, J.; et al.
Journal: NUTRICION HOSPITALARIA
ISSN 0212-1611  Vol. 32  2015  pp. 2319-2330
en el marco del estudio PREDIMED (PREvención con Dieta MEDiterránea), se seleccionaron de manera aleatorizada 187 sujetos del centro PREDIMED-NAVARRA. A estos pacientes asintomáticos, pero con alto riesgo cardiovascular, se les realizó una ecografía carotídea basal para determinar su GIMC, y tras un año en el estudio se les repitió la misma medición. Se usó un cuestionario validado de frecuencia de consumo de alimentos (137 ítems) tanto basal como anualmente para obtener el IG y la CG, que fueron categorizados en cuartiles, tras ser ajustados por energía. Mediante modelos multivariables (ANCOVA) se estudió la posible asociación entre el IG o la CG de la dieta y el GIMC o su cambio al año. Resultados: en la población estudiada no se observó una asociación estadísticamente significativa entre el IG o la CG y el GIMC, ni al inicio ni tras un año de seguimiento.
Authors: Buil-Cosiales, P.; Zazpe I; Toledo, Estefanía Ainhoa; et al.
Journal: AMERICAN JOURNAL OF CLINICAL NUTRITION
ISSN 0002-9165  Vol. 100  Nº 6  2014  pp. 1498 - 1507
Few observational studies have examined the effect of dietary fiber intake and fruit and vegetable consumption on total mortality and have reported inconsistent results. All of the studies have been conducted in the general population and typically used only a single assessment of diet. OBJECTIVE: We investigated the association of fiber intake and whole-grain, fruit, and vegetable consumption with all-cause mortality in a Mediterranean cohort of elderly adults at high cardiovascular disease (CVD) risk by using repeated measurements of dietary information and taking into account the effect of a dietary intervention. DESIGN: We followed up 7216 men (55-75 y old) and women (60-75 y old) at high CVD risk in the Prevención con Dieta Mediterránea (PREDIMED) trial for a mean of 5.9 y. Data were analyzed as an observational cohort. Participants were initially free of CVD. A 137-item validated food-frequency questionnaire administered by dietitians was repeated annually to assess dietary exposures (fiber, fruit, vegetable, and whole-grain intakes). Deaths were identified through the continuing medical care of participants and the National Death Index. An independent, blinded Event Adjudication Committee adjudicated causes of death. Cox regression models were used to estimate HRs of death during follow-up according to baseline dietary exposures and their yearly updated changes. RESULTS: In up to 8.7 y of follow-up, 425 participants died. Baseline fiber intake and fruit consumption were significantly associated with lower risk of death [HRs for the fifth compared with the first quintile: 0.63 (95% CI: 0.46, 0.86; P = 0.015) and 0.59 (95% CI: 0.42, 0.82; P = 0.004), respectively]. When the updated dietary information was considered, participants with fruit consumption >210 g/d had 41% lower risk of all-cause mortality (HR: 0.59; 95% CI: 0.44, 0.78). Associations were strongest for CVD mortality than other causes of death. CONCLUSION: Fiber and fruit intakes are associated with a reduction in total mortality. PREDIMED was registered at controlled-trials.com as ISRCTN35739639.
Authors: Toledo, Estefanía Ainhoa; et al.
Journal: INTERNATIONAL JOURNAL OF CARDIOLOGY
ISSN 0167-5273  Vol. 171  Nº 2  2014  pp. 299-301
Authors: Zazpe I; Sánchez Tainta, Ana; Toledo, Estefanía Ainhoa; et al.
Journal: ACADEMY OF NUTRITION AND DIETETICS. JOURNAL
ISSN 2212-2672  Vol. 114  Nº 1  2014  pp. 37 - 47
Background: Different dietary patterns have been associated with several health outcomes, including morbidity and mortality. There is little evidence on the association between empirically derived dietary patterns and all-cause mortality in Southern European populations. Objective: The aim of our study was to prospectively evaluate the association between an empirically derived dietary pattern and all-cause mortality. Design: The Seguimiento Universidad de Navarra (SUN) Project is an ongoing, multipurpose, prospective and dynamic Spanish cohort. Participants/setting: Participants were a prospective cohort of 16,008 middle-aged Spanish adults. All of them were university graduates (alumni) (59.6% women, mean age 38 years). Usual diet was assessed at baseline with a validated semiquantitative food frequency questionnaire. Main Outcome Measures: Deaths were confirmed by review of medical records and of the National Death Index. Statistical Analysis: Dietary patterns were ascertained through a factor (principal component) analysis based on 30 predefined food groups. Participants were classified according to tertiles of adherence to the three main dietary patterns identified with factor analysis. Cox regression models were fitted to estimate multivariable-adjusted hazard ratios and 95% CIs for mortality. Results: Three major dietary patterns were identified. They were labelled Western dietary pattern (rich in red and processed meat, potatoes, and fast food), Mediterranean dietary pattern (rich in vegetables, fish and seafood, fruits, and olive oil), and alcoholic beverages dietary pattern. During follow-up, 148 deaths were reported (mean age at death 54.5 years). After adjustment for potential confounders, the lowest risk of all-cause mortality was found in the tertile of highest adherence to the Mediterranean dietary pattern (adjusted hazard ratio for third vs first tertile 0.53, 95% CI 0.34 to 0.84) (P for trend &lt;0.01). The Western dietary pattern and alcoholic beverages dietary pattern showed no significant association with mortality. Conclusions: Greater adherence to an empirically derived dietary pattern approaching the traditional Mediterranean diet was associated with a reduction in the risk of all-cause mortality among middle-aged Mediterranean adults.
Authors: Martínez, Miguel Ángel; Zazpe I; Razquin, Cristina; et al.
Journal: CLINICAL NUTRITION
ISSN 0261-5614  Vol. 34  Nº 5  2014  pp. 859 - 867
Background& Aims: There is little evidence on post hoc-derived dietary patterns (DP) and all-cause mortality in Southern-European populations. Furthermore, the potential effect modification of a DP by a nutritional intervention has not been sufficiently assessed. We assessed the association between a posteriori defined baseline major DP and total mortality or cardiovascular events within each of the three arms of a large primary prevention trial (PREDIMED) where participants were randomized to two active interventions with Mediterranean-type diets or to a control group (allocated to a low-fat diet). Design: We followed-up 7216 participants for a median of 4.3 years. A validated 137-item food-frequency questionnaire was administered. Baseline DP were ascertained through factor analysis based on 34 predefined groups. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HR) for cardiovascular disease (CVD) or mortality across quartiles of DP within each of the three arms of the trial. Results: We identified two major baseline DP: the first DP was rich in red and processed meats, alcohol, refined grains and whole dairy products and was labeled Western dietary pattern (WDP). The second DP corresponded to a "Mediterranean-type" dietary pattern (MDP). During follow-up, 328 participants died. After controlling for potential confounders, higher baseline adherence to the MDP was associated with lower risk of CVD (adjusted HR for fourth vs. first quartile: 0.52; 95% CI (Confidence Interval): 0.36, 0.74; p-trend <0.001) and all-cause mortality (adjusted HR: 0.53; 95% CI: 0.38, 0.75; p-trend <0.001), regardless of the allocated arm of the trial. An increasing mortality rate was found across increasing quartiles of the WDP in the control group (allocated to a low-fat diet), though the linear trend was not statistically significant (p = 0.098). Conclusions: Higher adherence to an empirically-derived MDP at baseline was associated with a reduced risk of CVD and mortality in the PREDIMED trial regardless of the allocated arm. The WDP was not associated with higher risk of mortality or cardiovascular events.
Authors: Hermida, José; Goñi, M.J.; et al.
Journal: DIABETOLOGIA
ISSN 0012-186X  Vol. 56  Nº 12  2013  pp. 2743-2752
MMP-10 is involved in the development of microvascular complications in type 1 diabetes and emerges as a potential therapeutic target for slowing down the evolution of diabetic nephropathy and retinopathy.
Authors: Toledo, Estefanía Ainhoa; Martínez, Miguel Ángel; et al.
Journal: OBESITY
ISSN 1469-3259  Vol. 21  Nº 7  2013  pp. 1486-1495
The meta-analysis revealed a higher BMI with an overall estimation of +0.065 kg/m(2) (95%CI = 0.026-0.103, P = 0.001) for homo-/heterozygous carriers of the Ala allele of the PPARG2 gene in comparison to non-carriers. The analysis also showed that there was heterogeneity (P for heterogeneity <0.001), but funnel plots did not suggest apparent publication bias. Furthermore, the association between the Pro12Ala polymorphism of the PPARG2 gene and increased BMI was stronger in Caucasian. Thus, carriers of the Ala allele had significantly higher BMI than non-carriers in a subsample of 6,528 Caucasian male subjects (standardized mean difference = 0.090, 95%CI=0.032-0.148, P = 0.002, P for heterogeneity = 0.121). CONCLUSION: This updated meta-analysis showed that carriers of the Ala12 allele of the PPARG2 gene had a higher average BMI.
Authors: Martínez Lapiscina EH; Toledo, Estefanía Ainhoa; et al.
Journal: JOURNAL OF NUTRITION HEALTH AND AGING
ISSN 1279-7707  Vol. 17  Nº 6  2013  pp. 544-552
Objective: To assess the effect on cognition of a controlled intervention testing Mediterranean diets (MedDiet). Design: Randomized trial after 6.5 years of nutritional intervention. Setting: Eight primary care centers affiliated to the University of Navarra. Participants: A random subsample of 285 participants (95 randomly allocated to each of 3 groups) of the PREDIMED-NAVARRA trial. All of them were at high vascular risk (44.8% men, 74.1±5.7 years at cognitive evaluation). Interventions: Nutritional intervention comparing two MedDiets (supplemented with extra-virgin olive oil [EVOO] or mixed nuts) versus a low-fat control diet. Participants received intensive education to increase adherence to the intended intervention. Participants allocated to the MedDiet groups received EVOO (1 l/week) or 30 g/day of mixed nuts. Dietary habits were evaluated using a validated 137-item food frequency questionnaire (FFQ). Additionally, adherence to MedDiet was appraised using a 14-item questionnaire both at baseline and yearly thereafter. Measurements: Cognitive performance as a main outcome and cognitive status (normal, mild cognitive impairment [MCI] or dementia) as a secondary outcome were evaluated by two neurologists blinded to group assignment after 6.5 years of nutritional intervention. Results: Better post-trial cognitive performance versus control in all cognitive domains and significantly better performance across fluency and memory tasks were observed for participants allocated to the MedDiet+EVOO group. After adjustment for sex, age, education, apolipoprotein E genotype, family history of cognitive impairment/dementia, smoking, physical activity, body mass index, hypertension, dyslipidaemia, diabetes, alcohol and total energy intake, this group also showed lower MCI (OR=0.34 95% CI: 0.12-0.97) compared with control group. Participants assigned to MedDiet+Nuts group did not differ from controls. Conclusion: A long-term intervention with an EVOO-rich MedDiet resulted in a better cognitive function in comparison with a control diet. However, non-significant differences were found for most cognitive domains. Participants allocated to an EVOO-rich MedDiet had less MCI than controls.
Authors: Hermida, José; Toledo, Estefanía Ainhoa; et al.
Journal: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 35  Nº 3  2012  pp. 425 - 432
BACKGROUND: Type 1 diabetes is associated with vascular morbidity. The aim of this study was to evaluate the role of polymorphisms rs1410996 CFH and rs10490924 ARMS2 with proliferative diabetic retinopathy and coronary disease in type 1 diabetes patients. MATERIAL AND METHODS: We present a retrospective study that analyses the clinical characteristics and the polymorphisms rs1410996 CFH and rs10490924 ARMS2 of 147 type 1 diabetes patients. RESULTS: The patients who developed proliferative diabetic retinopathy in the first 20 years carried the rs1410996 CFH polymorphism. The overall risk-allele frequency was significantly higher among patients with coronary artery disease than in those without it (75 vs. 53%, p<0.001). CONCLUSIONS: rs1410996 CFH polymorphism could be associated with both proliferative diabetic retinopathy and coronary artery disease in type 1 diabetes patients. However, rs10490924 ARMS2 does not seem to be associated either with retinopathy or coronary artery disease.
Authors: Martínez, Miguel Ángel; Guillén-Grima, F; de Irala, J; et al.
Journal: JOURNAL OF NUTRITION
ISSN 0022-3166  Vol. 142  Nº 9  2012  pp. 1672-8
The available large prospective studies supporting an inverse association between better adherence to the Mediterranean diet and lower mortality have mainly included older adults. It is not clear whether this inverse association is also present among younger individuals at lower mortality risk. Our aim was to assess the association between adherence to the Mediterranean diet and total mortality in middle-aged adults from the Seguimiento Universidad de Navarra (SUN) Project. We followed 15,535 Spanish university graduates for a mean of 6.8 y. Their mean age was 38 ± 12 y, 59.6% were females, and all were initially free of cardiovascular disease, cancer, and diabetes. A validated FFQ was used to assess dietary habits. Adherence to the Mediterranean diet was categorized into 3 groups according to the Mediterranean Diet Score (low, 0-2 points; moderate, 3-5 points; and high, 6-9 points). The outcome variable was total mortality. Cox proportional hazards models were used to estimate HR and 95% CI. We adjusted the estimates for sex, age, years of university education, BMI, smoking, physical activity, television watching, history of depression and baseline hypertension, and hypercholesterolemia. We observed 125 deaths during 105,980 person-years of follow-up. The fully adjusted HR for moderate and high adherence were 0.58 (95% CI: 0.34, 0.99; P = 0.05) and 0.38 (95% CI: 0.21, 0.70; P = 0.002), respectively. For each 2-point increment in the Mediterranean Diet Score, the HR of death
Authors: Sánchez-Villegas, A.; Toledo, Estefanía Ainhoa; de Irala, J; et al.
Journal: PUBLIC HEALTH NUTRITION
ISSN 1368-9800  Vol. 15  Nº 3  2012  pp. 424-432
Fast-food and commercial baked goods consumption may have a detrimental effect on depression risk
Authors: Martínez, Miguel Ángel; García-Arellano, A.; Toledo, Estefanía Ainhoa; et al.
Journal: PLOS ONE
ISSN 1932-6203  Vol. 7  Nº 8  2012  pp. e43134
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 "PREvencion con DIeta MEDiterranea'' (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.
Authors: Gea, Alfredo; Toledo, Estefanía Ainhoa; et al.
Journal: BMC PUBLIC HEALTH
ISSN 1471-2458  Vol. 12  2012  pp. 954
Background: Longitudinal studies assessing the long-term association between alcohol intake and depression are scarce. The type of beverage may also be important. Therefore we aimed to prospectively evaluate the influence of alcohol intake on incident depression in a Mediterranean cohort. Methods: We assessed 13,619 university graduates (mean age: 38 years, 42% men) participating in a Spanish prospective epidemiological cohort (the SUN Project), initially free of depression. They were recruited between 1999-2008 and biennially followed-up during 2001-2010. At baseline, a 136-item validated food-frequency questionnaire was used to assess alcohol intake. Wine was the preferred beverage. Participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and/or initiated the use of antidepressant drugs. Cox regression and restricted cubic splines analyses were performed over 82,926 person-years. Results: Only among women, an U-shaped relationship between total alcohol intake and depression risk was found (P=0.01). Moderate alcohol intake (5-15 g/day) was associated with lower risk (Hazard Ratio: 0.62; 95% Confidence Interval: 0.43-0.89). No association was apparent for higher intakes of alcohol or for any specific type of alcoholic beverage. Conclusions: Moderate alcohol intake might protect against depression among women. Further confirmatory studies are needed.
Authors: Toni, M. ; Hermida, José; Toledo, Estefanía Ainhoa; et al.
Journal: ANALES DEL SISTEMA SANITARIO DE NAVARRA
ISSN 1137-6627  Vol. 35  Nº 3  2012  pp. 425 - 432
Background. Type 1 diabetes is associated with vascular morbidity. The aim of this study was to evaluate the role of polymorphisms rs1410996 CFH and rs10490924 ARMS2 with proliferative diabetic retinopathy and coronary disease in type 1 diabetes patients. Material and methods. We present a retrospective study that analyses the clinical characteristics and the polymorphisms rs1410996 CFH and rs10490924 ARMS2 of 147 type 1 diabetes patients. Results. The patients who developed proliferative diabetic retinopathy in the first 20 years carried the rs1410996 CFH polymorphism. The overall risk-allele frequency was significantly higher among patients with coronary artery disease than in those without it (75 vs. 53%, p<0.001). Conclusions. rs1410996 CFH polymorphism could be associated with both proliferative diabetic retinopathy and coronary artery disease in type 1 diabetes patients. However, rs10490924 ARMS2 does not seem to be associated either with retinopathy or coronary artery disease.
Authors: Martínez, Miguel Ángel; Bes-Rastrollo, Maira; et al.
Journal: NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
ISSN 0939-4753  Vol. 21  Nº 4  2011  pp. 237 - 244
Background and aim: The Mediterranean diet is considered a model for healthy eating. However, prospective evidence in Mediterranean countries evaluating the relationship between this dietary pattern and non-fatal cardiovascular events is scarce. The aim of the present study was to evaluate the association between the adherence to the Mediterranean diet and the incidence of fatal and non-fatal cardiovascular events among initially healthy middle-aged adults from the Mediterranean area. Methods and results: We followed-up 13,609 participants (60 percent women, mean age: 38 years) initially free of cardiovascular disease (CVD) during 4.9 years. Participants were part of a prospective cohort study of university graduates from all regions of Spain. Baseline diet was assessed using a validated 136-item food-frequency questionnaire. A 9-point score was used to appraise adherence to the Mediterranean diet. Incident clinical events were confirmed by a review of medical records. We observed 100 incident cases of CVD. In multivariate analyses, participants with the highest adherence to the Mediterranean diet (score > 6) exhibited a lower cardiovascular risk (hazard ratio = 0.41, 95% confidence interval [CI]: 0.18-0.95) compared to those with the lowest score (<3). For each 2-point increment in the score, the adjusted hazard ratios were 0.80 (95% CI: 0.62-1.02) for total CVD and 0.74 (0.55-0.99) for coronary heart disease. Conclusions: There is an inverse association between adherence to the Mediterranean diet and the incidence of fatal and non-fatal CVD in initially healthy middle-aged adults.
Authors: Toledo, Estefanía Ainhoa; Lopez-del Burgo, C; Ruiz-Zambrana, A; et al.
Journal: FERTILITY AND STERILITY
ISSN 0015-0282  Vol. 96  Nº 5  2011  pp. 1149 - 1153
Authors: Verberne, L.; de Irala, J; et al.
Journal: PLOS ONE
ISSN 1932-6203  Vol. 6  Nº 1  2011  pp. e16268
Emerging evidence relates some nutritional factors to depression risk. However, there is a scarcity of longitudinal assessments on this relationship. Objective: To evaluate the association between fatty acid intake or the use of culinary fats and depression incidence in a Mediterranean population. Material and Methods: Prospective cohort study (1999-2010) of 12,059 Spanish university graduates (mean age: 37.5 years) initially free of depression with permanently open enrolment. At baseline, a 136-item validated food frequency questionnaire was used to estimate the intake of fatty acids (saturated fatty acids (SFA), polyunsaturated fatty acids (PUFA), trans unsaturated fatty acids (TFA) and monounsaturated fatty acids (MUFA) and culinary fats (olive oil, seed oils, butter and margarine) During follow-up participants were classified as incident cases of depression if they reported a new clinical diagnosis of depression by a physician and/or initiated the use of antidepressant drugs. Cox regression models were used to calculate Hazard Ratios (HR) of incident depression and their 95% confidence intervals (CI) for successive quintiles of fats. Results: During follow-up (median: 6.1 years), 657 new cases of depression were identified. Multivariable-adjusted HR (95% CI) for depression incidence across successive quintiles of TFA intake were: 1 (ref), 1.08 (0.82-1.43), 1.17 (0.88-1.53), 1.28 (0.97-1.68), 1.42 (1.09-1.84) with a significant dose-response relationship (p for trend = 0.003). Results did not substantially change after adjusting for potential lifestyle or dietary confounders, including adherence to a Mediterranean Dietary Pattern. On the other hand, an inverse and significant dose-response relationship was obtained for MUFA (p for trend = 0.05) and PUFA (p for trend = 0.03) intake. Conclusions: A detrimental relationship was found between TFA intake and depression risk, whereas weak inverse associations were found for MUFA, PUFA and olive oil. These findings suggest that cardiovascular disease and depression may share some common nutritional determinants related to subtypes of fat intake.
Authors: Sánchez, A; Pimenta, AM; et al.
Journal: OBESITY
ISSN 1930-7381  Vol. 18  Nº 7  2010  pp. 1443 - 1448
This study included 11,825 participants of a Spanish dynamic prospective cohort based on former students from University of Navarra, registered professionals from some Spanish provinces, and university graduates from other associations, followed-up for 6.1 years. We aimed to assess the association between childhood or young adult overweight/obesity and the risk of depression. Participants were asked to select which of nine figures most closely represented their body shape at ages 5 and 20 years. Childhood and young adult overweight/obesity was defined as those cases in which participants reported body shape corresponding to the figures 6¿9 (more obese categories) at age 5 or 20, respectively. A subject was classified as incident case of depression if he/she was initially free of depression and reported physician-made diagnosis of depression and/or the use of antidepressant medication in at least one of biannual follow-up questionnaires. The association between childhood and young adult overweight/obesity and incidence of depression was estimated by multiple-adjusted hazard ratio (HR) and its 95% confidence interval (95% CI). Overweight/obesity at age 5 years predicted an increased risk for adult depression (HR = 1.50, 95% CI = 1.06¿2.12), and a stronger association was observed at age 20 years ((HR = 2.22, 95% CI = 1.22¿4.08), (subjects younger than 30 years at recruitment were excluded from this last analysis)). Childhood or young adult overweight/obesity was associated with elevated risk of adult depression. These results, if causal and confirmed in other prospective studies, support treating childhood and young adult overweight/obesity as part of comprehensive adult depression prevention efforts.
Authors: Fernández-Ballart, JD; Piñol, JL; Zazpe I; et al.
Journal: British Journal of Nutrition (Print Edition)
ISSN 0007-1145  Vol. 103  Nº 12  2010  pp. 1808 - 1816
The aim of the present study was to assess reproducibility and relative validity of a self-administered FFQ used in the PREDIMED Study, a clinical trial for primary prevention of CVD by Mediterranean diet in a population at high cardiovascular risk. The FFQ was administered twice (FFQ1 and FFQ2) to explore reproducibility at 1 year. Four 3 d dietary records (DR) were used as reference to explore validity; participants therefore recorded their food intake over 12 d in the course of 1 year. The degree of misclassification in the FFQ was also evaluated by a contingency table of quintiles comparing the information from the FFQ2 and the DR. A total of 158 men and women (aged 55¿80 years) were asked not to modify their dietary habits during the study period. Reproducibility for food groups, energy and nutrient intake, explored by the Pearson correlation coefficient (r) ranged 0·50¿0·82, and the intraclass correlation coefficient (ICC) ranged from 0·63 to 0·90. The FFQ2 tended to report higher energy and nutrient intake than the DR. The validity indices of the FFQ in relation to the DR for food groups and energy and nutrient intake ranged (r) from 0·24 to 0·72, while the range of the ICC was between 0·40 and 0·84. With regard to food groups, 68¿83 % of individuals were in the same or adjacent quintile in both methods, a figure which decreased to 55¿75 % for energy and nutrient intake. We concluded that FFQ measurements had good reproducibility and a relative validity similar to those of FFQ used in other prospective studies.
Authors: Guembe, M. J.; Toledo, Estefanía Ainhoa; Barba, Joaquín; et al.
Journal: ATHEROSCLEROSIS
ISSN 0021-9150  Vol. 211  Nº 2  2010  pp. 612 - 617
OBJECTIVE: To assess the association between the metabolic syndrome (MetSd) and asymptomatic cardiovascular disease and determine if the MetSd or its single risk factors perform better in discriminating prevalent asymptomatic cardiovascular disease. METHODS: A total of 880 community-dwelling subjects (423 with and 457 without MetSd according to ATPIII) underwent a physical examination, an echocardiography and an ultrasound examination of carotid arteries and blood and urine samples were collected. Associations between the subclinical organ damage markers and the MetSd were addressed with non-conditional logistic regression. AUCs of ROCs were used to compare the models' ability to discriminate asymptomatic cardiovascular disease. RESULTS: The MetSd was independently associated with carotid subclinical atherosclerosis, increased left ventricular mass index and cardiac dysfunction. The MetSd did not discriminate prevalent increased carotid intima-media thickness better than abdominal obesity and impaired fasting glucose [AUC=0.75 (95% CI: 0.71-0.78) and 0.75 (0.71-0.79), respectively; p=0.55]. The MetSd performed worse than abdominal obesity in discriminating increased left ventricular mass index among males younger than 65 years [AUC=0.66 (95% CI: 0.62-0.69) and 0.69 (0.66-0.73), respectively; p=0.02]. No differences between the ability of MetSd or its components in discriminating increased left ventricular mass index were observed among older men or women. The discrimination ability for microalbuminuria for the MetSd or impaired fasting glucose was not statistically different [AUC=0.67 (95% CI: 0.60-0.74) and 0.69 (0.62-0.76), respectively; p=0.18]. CONCLUSION: This study supports the association between the MetSd and asymptomatic cardiovascular disease. The construct of the MetSd might not be better than its single components in addressing cardiovascular risk.
Authors: Toledo, Estefanía Ainhoa; Hu, FB; et al.
Journal: American Journal of Clinical Nutrition
ISSN 0002-9165  Vol. 92  Nº 6  2010  pp. 1484 - 1493
Authors: Konstantinidou, V.; Covas, M. I.; Muñoz-Aguayo, D.; et al.
Journal: FASEB JOURNAL
ISSN 0892-6638  Vol. 24  Nº 7  2010  pp. 2546 - 2557
The aim of the study was to assess whether benefits associated with the traditional Mediterranean diet (TMD) and virgin olive oil (VOO) consumption could be mediated through changes in the expression of atherosclerosis-related genes. A randomized, parallel, controlled clinical trial in healthy volunteers (n=90) aged 20 to 50 yr was performed. Three-month intervention groups were as follows: 1) TMD with VOO ( TMD+VOO), 2) TMD with washed virgin olive oil (TMD+WOO), and 3) control with participants' habitual diet. WOO was similar to VOO, but with a lower polyphenol content (55 vs. 328 mg/kg, respectively). TMD consumption decreased plasma oxidative and inflammatory status and the gene expression related with both inflammation [INF-gamma (INF gamma), Rho GTPase-activating protein15 (ARHGAP15), and interleukin-7 receptor (IL7R)] and oxidative stress [adrenergic beta(2)-receptor (ADRB2) and polymerase (DNA-directed) kappa (POLK)] in peripheral blood mononuclear cells. All effects, with the exception of the decrease in POLK expression, were particularly observed when VOO, rich in polyphenols, was present in the TMD dietary pattern. Our results indicate a significant role of olive oil polyphenols in the down-regulation of proatherogenic genes in the context of a TMD. In addition, the benefits associated with a TMD and olive oil polyphenol consumption on cardiovascular risk can be mediated through nutrigenomic effects.-Konstantinidou, V., Covas, M.-I., Munoz-Aguayo, D., Khymenets, O., de la Torre, R., Saez, G., del Carmen Tormos, M., Toledo, E., Marti, A., Ruiz-Gutierrez, V., Ruiz Mendez, M. V., Fito, M. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the Mediterranean diet: a randomized controlled trial.
Authors: Toledo, Estefanía Ainhoa; Carmona de la Torre, F.A.; et al.
Journal: Public Health Nutrition
ISSN 1368-9800  Vol. 13  Nº 3  2010  pp. 338 - 349
Objective: To study the association between adherence to several a priori-defined healthy food patterns and the risk of hypertension. Design: Prospective, multipurpose, dynamic cohort study (recruitment permanently open). We followed up 10800 men and women (all of them University graduates), who were initially free of hypertension, for a variable period (range 2-6 years, median 4-6 years). During follow-up, 640 participants reported a new medical diagnosis of hypertension. Baseline diet was assessed using a validated 136-item FFQ. Validated information about non-dietary potential confounders was also gathered. We calculated adherence to fifteen different hypothesis-oriented food patterns and assessed the association between each of them and incident hypertension using multivariable Cox models. Setting: The SUN (Seguimiento Universidad de Navarra - University of Navarra Follow-up) Project, Spain. Subjects : Participants recruited to the SUN cohort before October 2005 were eligible for inclusion; after excluding those with self-reported hypertension or CVD at baseline, or with extreme total energy intake, data of 10800 were analysed. Results: Higher adherence to the DASH (Dietary Approaches to Stop Hypertension) diet (range of the score: 0 to 5) was significantly associated with a lower risk for developing hypertension (P for trend = 0.02). The other food patterns showed no significant association with incident hypertension. Conclusions: Our results support a long-term protection of the DASH diet against the incidence of hypertension, but we found no evidence of a similar inverse association with hypertension for any other a priori-defined healthy food pattern.
Authors: Basterra, Francisco Javier; Forga, Luis; Bes-Rastrollo, Maira; et al.
Journal: Revista española de cardiología. (Ed. impresa)
ISSN 0300-8932  Vol. 63  Nº 1  2010  pp. 20 - 27
Authors: Reina, G; Toledo, Estefanía Ainhoa; Carlos, Silvia;
Book title:  Conceptos de salud pública y estrategias preventivas: un manual para ciencias de la salud
2018  pp. 171 - 176
Authors: Martínez, Miguel Ángel; Carlos, Silvia; Toledo, Estefanía Ainhoa; et al.
Book title:  Piédrola Gil. Medicina Preventiva y Salud Pública
2016  pp. 169 - 180
Authors: Carlos, Silvia; Toledo, Estefanía Ainhoa; Martínez, Miguel Ángel;
Book title:  Conceptos de salud pública y estrategias preventivas. Un manual para ciencias de la salud
2013  pp. 225 - 230
Authors: Toledo, Estefanía Ainhoa; de Irala, J; Martínez, Miguel Ángel;
Title: Tabaco
Book title:  Conceptos de salud pública y estrategias preventivas: un manual para ciencias de la salud
2013  pp. 303 - 309
Authors: Rodríguez, María Cristina; Toledo, Estefanía Ainhoa;
Book title:  Conceptos de salud pública y estrategias preventivas: un manual para ciencias de la salud
2013  pp. 407 - 411
Authors: Reina, G; Toledo, Estefanía Ainhoa; Carlos, Silvia;
Book title:  Conceptos de salud pública y estrategias preventivas. Un manual para Ciencias de la Salud
2013  pp. 177 - 184
Authors: Martínez, Miguel Ángel; Toledo, Estefanía Ainhoa; Sánchez Tainta, Ana; et al.
Book title:  Compendio de salud pública
2011  pp. 435 - 448
Authors: Toledo, Estefanía Ainhoa; de Irala, J; Martínez, Miguel Ángel;
Title: Tabaco
Book title:  Compendio de salud pública
2011  pp. 377 - 384
Authors: Carlos, Silvia; Toledo, Estefanía Ainhoa; Martínez, Miguel Ángel;
Book title:  Compendio de salud pública
2011  pp. 279 - 284
Authors: Martínez, Miguel Ángel; Toledo, Estefanía Ainhoa; Carlos, Silvia;
Book title:  Compendio de salud pública
2011  pp. 493 - 502
Authors: Bes-Rastrollo, Maira, (Coordinador); Carlos, Silvia, (Coordinador); et al.
2013