Association between type 2 diabetes and depressive symptoms after a 1-year follow-up in an older adult Mediterranean population.

OBJECTIVES: To examine the cross-sectional association between baseline depressive symptoms and the presence of type 2 diabetes (T2D), and its association with glycated hemoglobin (HbA1c) and other metabolic variables, and the prospective association of depressive symptoms and HbA1c after 1 year of follow-up. METHODS: n = 6224 Mediterranean older adults with overweight/obesity and metabolic syndrome (48% females, mean age 64.9 ± 4.9 years) were evaluated in the framework of the PREDIMED-Plus study cohort. Depressive symptoms were assessed using the Beck Depression Inventory-II and HbA1c was used to measure metabolic control. RESULTS: The presence of T2D increased the likelihood of higher levels of depressive symptoms (χ2 = 15.84, p = 0.001). Polynomial contrast revealed a positive linear relationship (χ2 = 13.49, p = 0.001), the higher the depressive symptoms levels, the higher the prevalence of T2D. Longitudinal analyses showed that the higher baseline depressive symptoms levels, the higher the likelihood of being within the HbA1c ≥ 7% at 1-year level (Wald-χ2 = 24.06, df = 3, p < .001, for the full adjusted model). Additionally, depressive levels at baseline and duration of T2D predicted higher HbA1c and body mass index, and lower physical activity and adherence to Mediterranean Diet at 1 year of follow-up. CONCLUSIONS: This study supports an association between T2D and the severity of depressive symptoms, suggesting a worse metabolic control from mild severity levels in the short-medium term, influenced by lifestyle habits related to diabetes care. Screening for depressive symptoms and a multidisciplinary integrative therapeutic approach should be ensured in patients with T2D.

Intensive Weight-Loss Lifestyle Intervention Using Mediterranean Diet and COVID-19 Risk in Older Adults: Secondary Analysis of PREDIMED-Plus Trial.

OBJECTIVES: We tested the effects of a weight-loss intervention encouraging energy-reduced MedDiet and physical activity (PA) in comparison to ad libitum MedDiet on COVID-19 incidence in older adults. DESIGN: Secondary analysis of PREDIMED-Plus, a prospective, ongoing, multicentre randomized controlled trial. SETTING: Community-dwelling, free-living participants in PREDIMED-Plus trial. PARTICIPANTS: 6,874 Spanish older adults (55-75 years, 49% women) with overweight/obesity and metabolic syndrome. INTERVENTION: Participants were randomised to Intervention (IG) or Control (CG) Group. IG received intensive behavioural intervention for weight loss with an energy-reduced MedDiet intervention and PA promotion. CG was encouraged to consume ad libitum MedDiet without PA recommendations. MEASUREMENTS: COVID-19 was ascertained by an independent Event Committee until December 31, 2021. COX regression models compared the effect of PREDIMED-Plus interventions on COVID-19 risk. RESULTS: Overall, 653 COVID-19 incident cases were documented (IG:317; CG:336) over a median (IQR) follow-up of 5.8 (1.3) years (inclusive of 4.0 (1.2) years before community transmission of COVID-19) in both groups. A significantly lowered risk of COVID-19 incidence was not evident in IG, compared to CG (fully-adjusted HR (95% CI): 0.96 (0.81,1.12)). CONCLUSIONS: There was no evidence to show that an intensive weight-loss intervention encouraging energy-reduced MedDiet and PA significantly lowered COVID-19 risk in older adults with overweight/obesity and metabolic syndrome in comparison to ad libitum MedDiet. Recommendations to improve adherence to MedDiet provided with or without lifestyle modification suggestions for weight loss may have similar effects in protecting against COVID-19 risk in older adults with high cardiovascular risks.

Surgical treatment trends and outcomes for anal fistula: fistulotomy is still accurate and safe. Results from a nationwide observational study.

PURPOSE: The aim of the present study was to analyse current surgical treatment preferences for anal fistula (AF) and its subtypes and nationwide results in terms of success and complications. METHODS: A retrospective multicentre observational cohort study was conducted. The study period was 1 year (2019), with a follow-up period of at least 1 year. A descriptive analysis of patient characteristics and trends regarding technical options was performed. Univariate and multivariate Cox regression models were used to analyse factors associated with healing and faecal incontinence (FI). RESULTS: Fifty-one hospitals were involved, providing data on 1628 patients with AF. At a median follow-up of 18.3 (9.9-28.3) months, 1231 (75.9%) patients achieved healing, while 390 (24.1%) did not; failure was catalogued as persistence in 279 (17.2.0%) patients and as recurrence in 111 (6.8%). On multivariate analysis, factors associated with healing were fistulotomy (OR 5.5; 95% CI 3.8-7.9; p < 0.001), simple fistula (OR 2.1; 95% CI 1.5-2.8; p < 0.001), single tract (HR 1.9; 95% CI 1.3-2.8; p < 0.001) and number of preparatory surgeries (none vs. 3; HR 1.8; 95% CI 1.2-2.8; p = 0.006). Regarding de novo FI, in the multivariate analysis previous anal surgery (OR 1.5, 95% CI 1.0-2.4, p = 0.037), age (OR 1.02, 95% CI 1.00-1.04, p = 0.002) and being female (OR 1.7, 95% CI 1.1-2.5, p = 0.008) were statistically related. CONCLUSIONS: Anal fistulotomy is the most used procedure for AF, especially for simple AF, with a favourable overall balance between healing and continence impairment. Sphincter-sparing or minimally invasive sphincter-sparing techniques resulted in lower rates of healing. In spite of their intended sphincter-sparing design, a certain degree of FI was observed for several of these techniques.

Elimination of Interface Energy Barriers Using Dendrimer Polyelectrolytes with Fractal Geometry.

In this work we study conjugated polyelectrolyte (CPE) films based on polyamidoamine (PAMAM) dendrimers of generations G1 and G3. These fractal macromolecules are compared to branched polyethylenimine (b-PEI) polymer using methanol as the solvent. All of these materials present a high density of amino groups, which protonated by methoxide counter-anions create strong dipolar interfaces. The vacuum level shift associated to these films on n-type silicon was 0.93 eV for b-PEI, 0.72 eV for PAMAM G1 and 1.07 eV for PAMAM G3. These surface potentials were enough to overcome Fermi level pinning, which is a typical limitation of aluminium contacts on n-type silicon. A specific contact resistance as low as 20 mΩ·cm2 was achieved with PAMAM G3, in agreement with the higher surface potential of this material. Good electron transport properties were also obtained for the other materials. Proof-of-concept silicon solar cells combining vanadium oxide as a hole-selective contact with these new electron transport layers have been fabricated and compared. The solar cell with PAMAM G3 surpassed 15% conversion efficiency with an overall increase of all the photovoltaic parameters. The performance of these devices correlates with compositional and nanostructural studies of the different CPE films. Particularly, a figure-of-merit (Vσ) for CPE films that considers the number of protonated amino groups per macromolecule has been introduced. The fractal geometry of dendrimers leads to a geometric increase in the number of amino groups per generation. Thus, investigation of dendrimer macromolecules seems a very good strategy to design CPE films with enhanced charge-carrier selectivity.

Epidemiology, oncologic results and risk stratification model for metachronous peritoneal metastases after surgery for pT4 colon cancers: results from an observational retrospective multicentre long-term follow-up study.

PURPOSE: Metachronous peritoneal metastases (MPM) following a curative surgery procedure for pT4 colon cancer is a challenging condition. Current epidemiological studies on this topic are scarce. METHODS: A retrospective multicentre trial was designed. All consecutive patients who underwent operations to treat pT4 cancers between 2015 and 2017 were reviewed. Demographic, clinical, operative, pathological and oncological follow-up variables were included. MPM were described as any oncological disease at the peritoneum, clearly different from a local recurrence. Univariate and multivariate Cox regression models were constructed. A risk stratification model was created on a cumulative factor basis. According to the calculated hazard ratio (HR), a scoring system was designed (HR < 3, 1 point; HR > 3, 2 points) and a scale from 0 to 6 was calculated for peritoneal disease-free rate (PDF-R). A risk stratification model was also created on the basis of these calculations. RESULTS: Fifty different hospitals were involved, which included a total of 1356 patients. Incidence of MPM was 13.6% at 50 months median follow-up. The strongest independent risk factors for MPM were positive pN stage [HR 3.72 (95% CI 2.56-5.41; p < 0.01) for stage III disease], tumour perforation [HR 1.91 (95% CI 1.26-2.87; p < 0.01)], mucinous or signet ring cell histology [HR 1.68 (95% CI 1.1-2.58; p = 0.02)], poorly differentiated tumours [HR 1.54 (95% CI 1.1-2.2; p = 0.02)] and emergency surgery [HR 1.42 (95% CI 1.01-2.01; p = 0.049)]. In the absence of additional risk factors, pT4 tumours showed 98% and 96% PDF-R in 1-year and 5-year periods based on Kaplan-Meier curves. CONCLUSIONS: Cumulative MPM incidence was 13.6% at 5-year follow-up. The sole presence of a pT4 tumour resulted in high rates of PDF-R at 1-year and 5-year follow-up (98% and 96% respectively). Five additional risk factors different from pT4 status itself were identified as possible MPM indicators during follow-up.

Mid- and long-term changes in satiety-related hormones, lipid and glucose metabolism, and inflammation after a Mediterranean diet intervention with the goal of losing weight: A randomized, clinical trial.

Background: Obesity is produced by the enlargement of the adipose tissue. Functioning as an endocrine organ, it releases and receives information through a complex network of cytokines, hormones, and substrates contributing to a low-chronic inflammation environment. Diet and healthy habits play key roles in the prevention of obesity and its related pathologies. In this regard, there is a need to switch to healthier and more appetizing diets, such as the Mediterranean one. Objective: To compare the mid-and long-term effects of two Mediterranean diet (MedDiet) interventions, one energy-reduced plus physical activity promotion versus a non-restrictive diet, on peripheral satiety-related hormones, weight loss, glucose/lipid metabolism, and pro-inflammatory markers in subjects with obesity/overweight and metabolic syndrome. Materials and methods: A randomized, lifestyle intervention was conducted in 23 Spanish centers, with a large cohort of patients presenting metabolic syndrome. Our study is a subproject set in IMIM (Hospital del Mar Research Institute). Participants were men and women, aged 55-75 and 60-75, respectively, who at baseline met at least three metabolic syndrome components. Subjects were assigned to two intervention groups: (1) an intensive lifestyle intervention with an energy-reduced MedDiet and physical activity promotion (intervention group) with the aim of weight loss; and (2) a normocaloric MedDiet (control). We quantified in a subsample of 300 volunteers from Hospital del Mar Research Institute (Barcelona), following analytes at baseline, 6 months, and 1 year: glucose, HbA1c, triglycerides, total cholesterol, high-density lipoprotein cholesterol, LDL cholesterol, C-peptide, ghrelin, GLP-1, glucagon, insulin, leptin, PAI-1, resistin, and visfatin. Anthropometric and classical cardiovascular risk factors were also determined. A multivariate statistical model was employed to compare the two groups. Linear mixed-effect models were performed to compare changes in risk factors and biomarkers between intervention groups and over time. Results: Compared to participants in the control group, those in intervention one showed greater improvements in weight, waist circumference, insulin (P < 0.001), glucose metabolism-related compounds (P < 0.05), triglyceride-related lipid profile (P < 0.05), leptin, blood pressure, and pro-inflammatory markers such as PAI-1 (P < 0.001) at mid-and/or long-term. High-sensitivity C-reactive protein, resistin, and vifastin also decreased in both groups. Conclusion: A weight loss intervention employing a hypocaloric MedDiet and physical activity promotion has beneficial effects on adiposity, glucose metabolism, lipid profile, leptin, and pro-inflammatory markers, such as PAI-1 in both mid-and long-term.

Caffeinated coffee consumption and risk of atrial fibrillation in two Spanish cohorts.

AIMS: The association between caffeinated coffee consumption and atrial fibrillation remains unclear. Recent studies suggest an inverse association only between a moderate caffeinated coffee consumption and atrial fibrillation, but others have reported no association. The aim of our study was to prospectively assess the association between caffeinated coffee consumption and atrial fibrillation in two Spanish cohorts, one of adults from a general population and another of elderly participants at high cardiovascular risk. METHODS AND RESULTS: We included 18,983 and 6479 participants from the 'Seguimiento Universidad de Navarra' (SUN) and 'Prevención con Dieta Mediterránea' (PREDIMED) cohorts, respectively. Participants were classified according to their caffeinated coffee consumption in three groups: ≤3 cups/month, 1-7 cups/week, and >1 cup/day. We identified 97 atrial fibrillation cases after a median follow-up of 10.3 years (interquartile range 6.5-13.5), in the SUN cohort and 250 cases after 4.4 years median follow-up (interquartile range 2.8-5.8) in the PREDIMED study. No significant associations were observed in the SUN cohort although a J-shaped association was suggested. A significant inverse association between the intermediate category of caffeinated coffee consumption (1-7 cups/week) and atrial fibrillation was observed in PREDIMED participants with a multivariable-adjusted hazard ratio = 0.53 (95% confidence interval 0.36-0.79) when compared with participants who did not consume caffeinated coffee or did it only occasionally. No association was found for higher levels of caffeinated coffee consumption (>1 cup per day), hazard ratio = 0.79 (95% confidence interval 0.49-1.28). In the meta-analysis of both PREDIMED and SUN studies, the hazard ratio for intermediate consumption of caffeinated coffee was 0.60 (95% confidence interval 0.44-0.82) without evidence of heterogeneity. Similar findings were found for the association between caffeine intake and atrial fibrillation risk. CONCLUSION: Intermediate levels of caffeinated coffee consumption (1-7 cups/week) were associated with a reduction in atrial fibrillation risk in two prospective Mediterranean cohorts.

Health-related quality of life in individuals with metabolic syndrome: a cross-sectional study / Calidad de vida relacionada con la salud en individuos con síndrome metabólico: un estudio descriptivo

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a combination of various cardiovascular risk factors with a major impact on morbidity and premature mortality. However, the impact of MetS on self-reported health-related quality of life (HRQoL) is unknown. This study evaluated the HRQoL in a Spanish adult population aged 55 years and older with MetS. METHOD: A cross-sectional analysis was performed with baseline data from the PREDIMED-Plus multicentre randomized trial. The participants were 6430 men and women aged 55-75 years with overweight/obesity (body mass index ≥27 and ≤40kg/m2) and MetS. The SF-36 questionnaire was used as a tool to measure HRQoL. Scores were calculated on each scale of the SF-36 by gender and age. RESULTS: Participants showed higher scores in the social function (mean 85.9, 95% CI; 85.4-86.4) and emotional role scales (mean 86.8, 95% CI; 86.0-87.5). By contrast, the worst scores were obtained in the aggregated physical dimensions. In addition, men obtained higher scores than women on all scales. Among men, the worst score was obtained in general health (mean 65.6, 95% CI; 65.0-66.2), and among women, in body pain (mean 54.3, 95%CI; 53.4-55.2). A significant decrease was found in the aggregated physical dimensions score among participants 70-75 years old, but an increased one in the aggregated mental dimensions, compared to younger participants. CONCLUSIONS: Our results reflect that the MetS may negatively affect HRQoL in the aggregated physical dimensions, body pain in women, and general health in men. However, this adverse association was absent for the psychological dimensions of HRQoL, which were less affected

INTRODUCCIÓN Y OBJETIVOS: El síndrome metabólico (SM) es la combinación de diversos factores de riesgo cardiovascular que pueden derivar en un mayor impacto en la morbimortalidad prematura. Sin embargo, el impacto del SM en la calidad de vida relacionada con la salud (CVRS) es desconocido. El objetivo de este estudio es evaluar la CVRS en la población adulta española de 55 años o más con SM. MÉTODOS: Se realizó un análisis transversal con los datos del ensayo PREDIMED-Plus. Seis mil cuatrocientos treinta varones y mujeres entre 55-75 años con sobrepeso/obesidad y SM. El instrumento de medida de la CVRS fue el cuestionario SF-36. Cada escala del SF-36 fue descrita y estratificada por sexo. RESULTADOS: Los participantes mostraron valores más altos en las escalas función social (media: 85,9; IC 95%: 85,4-86,4) y rol emocional (media: 86,8; IC 95%: 86,0-87,5). En los varones, la peor puntuación fue en la dimensión salud general (media: 65,6; IC 95%: 65,0-66,2) y en las mujeres el dolor corporal (media: 54,3; IC 95%: 53,4-55,2). Además, los varones obtuvieron puntuaciones más altas en todas las escalas. En la escala función física en varones se encontró una disminución significativa de la CVRS en los participantes entre 70 y 75 años en comparación con los más jóvenes. Las peores puntuaciones se obtuvieron en las dimensiones físicas agregadas. CONCLUSIONES: El SM afecta de manera negativa a la CVRS en las dimensiones agregadas físicas, haciendo especial hincapié en la esfera dolor corporal en mujeres y salud general en varones. Sin embargo, las esferas psicológicas se encuentran menos afectadas por el SM

Health-related quality of life in individuals with metabolic syndrome: A cross-sectional study.

INTRODUCTION AND OBJECTIVES: Metabolic syndrome (MetS) is a combination of various cardiovascular risk factors with a major impact on morbidity and premature mortality. However, the impact of MetS on self-reported health-related quality of life (HRQoL) is unknown. This study evaluated the HRQoL in a Spanish adult population aged 55 years and older with MetS. METHOD: A cross-sectional analysis was performed with baseline data from the PREDIMED-Plus multicentre randomized trial. The participants were 6430 men and women aged 55-75 years with overweight/obesity (body mass index ≥27 and ≤40kg/m2) and MetS. The SF-36 questionnaire was used as a tool to measure HRQoL. Scores were calculated on each scale of the SF-36 by gender and age. RESULTS: Participants showed higher scores in the social function (mean 85.9, 95% CI; 85.4-86.4) and emotional role scales (mean 86.8, 95% CI; 86.0-87.5). By contrast, the worst scores were obtained in the aggregated physical dimensions. In addition, men obtained higher scores than women on all scales. Among men, the worst score was obtained in general health (mean 65.6, 95% CI; 65.0-66.2), and among women, in body pain (mean 54.3, 95%CI; 53.4-55.2). A significant decrease was found in the aggregated physical dimensions score among participants 70-75 years old, but an increased one in the aggregated mental dimensions, compared to younger participants. CONCLUSIONS: Our results reflect that the MetS may negatively affect HRQoL in the aggregated physical dimensions, body pain in women, and general health in men. However, this adverse association was absent for the psychological dimensions of HRQoL, which were less affected.

Longitudinal changes in Mediterranean diet and transition between different obesity phenotypes.

BACKGROUND & AIMS: Little is known about the impact of specific dietary patterns on the development of obesity phenotypes. We aimed to determine the association of longitudinal changes in adherence to the traditional Mediterranean diet (MedDiet) with the transition between different obesity phenotypes. METHODS: Data of 5801 older men and women at high cardiovascular risk from PREDIMED trial were used. Adherence to MedDiet was measured with the validated 14p-Mediterranean Diet Adherence Screener (MEDAS). Using the simultaneous combination of metabolic health- and body size-related parameters participants were categorized into one of four phenotypes: metabolically healthy and abnormal obese (MHO and MAO), metabolically healthy and abnormal non-obese (MHNO and MANO). Cox regression models with yearly repeated measures during 5-year of follow-up were built with use of Markov chain assumption. RESULTS: Each 2-point increase in MEDAS was associated with the following transitions: in MAO participants, with a 16% (95% CI 3-31%) greater likelihood of becoming MHO; in MHO participants with a 14% (3-23%) lower risk of becoming MAO; in MHNO participants with a 18% (5-30%) lower risk of becoming MHO. In MANO women, but not in men, MEDAS was associated with 20% (5-38%) greater likely of becoming MHNO (p for interaction by gender 0.014). No other significant associations were observed. CONCLUSIONS: Better adherence to the traditional MedDiet is associated with transitions to healthier phenotypes, promoting metabolic health improvement in MAO, MANO (only in women), and MHO, as well as protecting against obesity incidence in MHNO subjects.

Mediterranean alcohol-drinking pattern, low to moderate alcohol intake and risk of atrial fibrillation in the PREDIMED study.

BACKGROUND AND AIMS: There is ongoing controversy about the effect of a low to moderate alcohol consumption on atrial fibrillation (AF). Our aim is to assess the association between adherence to a Mediterranean alcohol drinking pattern and AF incidence. METHODS AND RESULTS: A total 6527 out of the 7447 participants in the PREDIMED trial met our inclusion criteria. A validated frequency food questionnaire was used to measure alcohol consumption. Participants were classified as non-drinkers, Mediterranean alcohol drinking pattern (MADP) (10-30 g/d in men and 5-15 g/day in women, preferably red wine consumption with low spirits consumption), low-moderate drinking (<30 g/day men y and < 15 g/day women), and heavy drinking. We performed multivariable Cox regression models to estimate hazard ratios (HR) with 95% confidence intervals (95% CI) of incident AF according to alcohol drinking patterns. After a mean follow up of 4.4 years, 241 new incident AF cases were confirmed. Alcohol consumption was not associated to AF incidence among low-moderate drinkers (HR: 0.96; 95%CI: 0.67-1.37), adherents to MADP (HR: 1.15 95%CI: 0.75-1.75), or heavy drinkers (HR: 0.92; 95%CI: 0.53-1.58), compared with non-drinkers. CONCLUSIONS: In a high cardiovascular risk adult population, a Mediterranean alcohol consumption pattern (low to moderate red wine consumption) was not associated with an increased incidence of AF. CLINICAL TRIALS: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

Prospects for strongly coupled atom-photon quantum nodes.

We discuss the trapping of cold atoms within microscopic voids drilled perpendicularly through the axis of an optical waveguide. The dimensions of the voids considered are between 1 and 40 optical wavelengths. By simulating light transmission across the voids, we find that appropriate shaping of the voids can substantially reduce the associated loss of optical power. Our results demonstrate that the formation of an optical cavity around such a void could produce strong coupling between the atoms and the guided light. By bringing multiple atoms into a single void and exploiting collective enhancement, cooperativities ~400 or more should be achievable. The simulations are carried out using a finite difference time domain method. Methods for the production of such a void and the trapping of cold atoms within it are also discussed.

La dieta mediterránea, óptima contra las enfermedades cardiovasculares, pero poco seguida por supervivientes de un evento coronario isquémico en un país mediterráneo / The Mediterranean diet, optimal against cardiovascular disease but adopted by few survivors of an ischemic coronary event in a Mediterranean country

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Extra virgin olive oil consumption reduces the risk of osteoporotic fractures in the PREDIMED trial.

BACKGROUND & AIMS: The incidence of osteoporotic fractures is lower in countries in the Mediterranean basin. Virgin olive oil, a key component of the Mediterranean Diet (MDiet), with recognised beneficial effects on metabolism and cardiovascular health, may decrease the risk of osteoporotic fractures. The aim to this study was to explore the effect of chronic consumption of total olive oil and its varieties on the risk of osteoporosis-related fractures in a middle-aged and elderly Mediterranean population. METHODS: We included all participants (n = 870) recruited in the Reus (Spain) centre of the PREvención con DIeta MEDiterránea (PREDIMED) trial. Individuals, aged 55-80 years at high cardiovascular risk, were randomized to a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or a low-fat diet. The present analysis was an observational cohort study nested in the trial. A validated food frequency questionnaire was used to assess dietary habits and olive oil consumption. Information on total osteoporotic fractures was obtained from a systematic review of medical records. The association between yearly repeated measurements of olive oil consumption and fracture risk was assessed by multivariate Cox proportional hazards. RESULTS: We documented 114 incident cases of osteoporosis-related fractures during a median follow-up of 8.9 years. Treatment allocation had no effect on fracture risk. Participants in the highest tertile of extra-virgin olive oil consumption had a 51% lower risk of fractures (HR:0.49; 95% CI:0.29-0.81. P for trend = 0.004) compared to those in the lowest tertile after adjusting for potential confounders. Total and common olive oil consumption was not associated with fracture risk. CONCLUSIONS: Higher consumption of extra-virgin olive oil is associated with a lower risk of osteoporosis-related fractures in middle-aged and elderly Mediterranean population at high cardiovascular risk.

Adherence to Mediterranean diet is associated with methylation changes in inflammation-related genes in peripheral blood cells

Epigenetic processes, including DNA methylation, might be modulated by environmental factors such as the diet, which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events. Meanwhile, Mediterranean diet (MedDiet) has demonstrated favourable effects on cardiovascular risk, blood pressure, inflammation and other complications related to excessive adiposity. Some of these effects could be mediated by epigenetic modifications. Therefore, the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells. A subset of 36 individuals was selected within the Prevención con Dieta Mediterránea (PREDIMED)-Navarra study, a randomised, controlled, parallel trial with three groups of intervention in high cardiovascular risk volunteers, two with a MedDiet and one low-fat control group. Changes in methylation between baseline and 5 years were studied. DNA methylation arrays were analysed by several robust statistical tests and functional classifications. Eight genes related to inflammation and immunocompetence (EEF2, COL18A1, IL4I1, LEPR, PLAGL1, IFRD1, MAPKAPK2, PPARGC1B) were finally selected as changes in their methylation levels correlated with adherence to MedDiet and because they presented sensitivity related to a high variability in methylation changes. Additionally, EEF2 methylation levels positively correlated with concentrations of TNF-alfa and CRP. This report is apparently the first showing that adherence to MedDiet is associated with the methylation of the reported genes related to inflammation with a potential regulatory impact

The PREDIMED trial, Mediterranean diet and health outcomes: How strong is the evidence?

AIMS: To address potential controversies on the health benefits of the Mediterranean diet (MedDiet) after PREDIMED, a randomized trial of MedDiet for primary cardiovascular prevention. We have focused on: a) the PREDIMED study design, b) analysis of PREDIMED data and c) interpretation of its results. DATA SYNTHESIS: Regarding the design of the trial, its early termination and between-group differences in the intensity of the intervention are potential causes of concern. The planned duration was 6 years but the trial was prematurely stopped when an interim analysis at 4.8-year provided sufficient evidence of benefit for the two MedDiets. In the MedDiet groups supplemented with extra-virgin olive oil or mixed-nuts, the primary composite endpoint (myocardial infarction, stroke, or cardiovascular death) was reduced by 30% and 28% respectively, as compared with the control group. Final results did not change after taking into account the different intensity of educational efforts during the trial. Other potential doubts related to data analysis (e.g., intention to treat versus a per-protocol approach, and consequences of dropouts) should not be causes of concern. Finally, we addressed alternative interpretations of the effect on all-cause mortality. The protocol-defined primary endpoint was a composite cardiovascular endpoint, not all-cause mortality. To analyze total mortality, we would have needed a much larger sample size and longer follow-up. Therefore, the PREDIMED results cannot be used to draw firm conclusions on MedDiets and all-cause mortality. CONCLUSIONS: The PREDIMED study was designed to overcome three major problems of previous nutritional research: a) residual confounding, addressed by using a randomized design; b) single-nutrient approaches, by randomizing an overall dietary pattern; and c) the limitations of assessing only intermediate risk markers, by using hard clinical end-points.

A Mediterranean diet supplemented with extra virgin olive oil or nuts improves endothelial markers involved in blood pressure control in hypertensive women.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Egg consumption and cardiovascular disease according to diabetic status: The PREDIMED study.

BACKGROUND: Eggs are a major source of dietary cholesterol and their consumption has been sometimes discouraged. A relationship between egg consumption and the incidence of cardiovascular disease (CVD) has been suggested to be present exclusively among patients with type2 diabetes. AIMS: To assess the association between egg consumption and CVD in a large Mediterranean cohort where approximately 50% of participants had type 2 diabetes. METHODS: We prospectively followed 7216 participants (55-80 years old) at high cardiovascular risk from the PREDIMED (PREvención con DIeta MEDiterránea) study for a mean of 5.8 years. All participants were initially free of CVD. Yearly repeated measurements of dietary information with a validated 137-item food-frequency questionnaire were used to assess egg consumption and other dietary exposures. The endpoint was the rate of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes). RESULTS: A major cardiovascular event occurred in 342 participants. Baseline egg consumption was not significantly associated with cardiovascular events in the total population. Non-diabetic participants who ate on average >4 eggs/week had a hazard ratio (HR) of 0.96 (95% confidence interval, 0.33-2.76) in the fully adjusted multivariable model when compared with non-diabetic participants who reported the lowest egg consumption (<2 eggs/week). Among diabetic participants, the HR was 1.33 (0.72-2.46). There was no evidence of interaction by diabetic status. HRs per 500 eggs of cumulative consumption during follow-up were 0.94 (0.66-1.33) in non-diabetics and 1.18 (0.90-1.55) in diabetics. CONCLUSIONS: Low to moderated egg consumption was not associated with an increased CVD risk in diabetic or non-diabetic individuals at high cardiovascular risk. This trial was registered at controlled-trials.com as ISRCTN35739639.