Association between polymorphisms in the leptin promoter and leptin receptor genes and cancer in a mediterranean population of the PREDIMED study

Plasma Metabolites Associated with Frequent Red Wine Consumption: A Metabolomics Approach within the PREDIMED Study

SCOPE: The relationship between red wine (RW) consumption and metabolism is poorly understood. We aimed to assess the systemic metabolomic profiles in relation to frequent RW consumption as well as the ability of a set of metabolites to discriminate RW consumers. METHODS AND RESULTS: Cross-sectional analysis of 1,157 participants. Subjects were divided as non-RW consumers versus RW consumers (> 1 glass/day RW (100 mL/day)). Plasma metabolomics analysis was performed using LC-MS. Associations between 386 identified metabolites and RW consumption were assessed using elastic net regression analysis taking into consideration baseline significant covariates. Ten-cross-validation (CV) was perform…

Additional file 1: of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Detailed metabolomic analysis procedure ([51, 52]). (DOCX 15 kb)

Association between the APOA2 promoter polymorphism and body weight in Mediterranean and Asian populations: replication of a gene–saturated fat interaction

Objective: The APOA2 gene has been associated with obesity and insulin resistance (IR) in animal and human studies with controversial results. We have reported an APOA2–saturated fat interaction determining body mass index (BMI) and obesity in American populations. This work aims to extend our findings to European and Asian populations. Methods: Cross-sectional study in 4602 subjects from two independent populations: a high-cardiovascular risk Mediterranean population (n=907 men and women; aged 67±6 years) and a multiethnic Asian population (n=2506 Chinese, n=605 Malays and n=494 Asian Indians; aged 39±12 years) participating in a Singapore National Health Survey. Anthropometric, clinical, …

Mediterranean Diet Reduces the Adverse Effect of the TCF7L2-rs7903146 Polymorphism on Cardiovascular Risk Factors and Stroke Incidence

OBJECTIVE Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of the Mediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. RESEARCH DESIGN AND METHODS A randomized trial (two MedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at b…

Leisure-time physical activity, sedentary behaviors, sleep, and cardiometabolic risk factors at baseline in the PREDIMED-PLUS intervention trial: A cross-sectional analysis.

Limited data exists on the interrelationships between physical activity (PA), sedentary behaviors and sleep concerning cardiometabolic risk factors in aged adults at high cardiovascular disease risk. Our aim was to examine independent and joint associations between time spent in leisure-time PA, sedentary behaviors and sleep on the prevalence of obesity, type 2 diabetes (T2D) and components of the metabolic syndrome (MetS) in Mediterranean individuals at high cardiovascular risk. Cross-sectional analyses were performed on baseline data from 5776 Spanish adults (aged 55-75y in men; 60-75y in women) with overweight/ obesity and MetS, from October 2013 to October 2016, in the PREDIMED-PLUS tri…

How does the Mediterranean diet promote cardiovascular health? Current progress toward molecular mechanisms

Epidemiological evidence supports a health-promoting effect of the Mediterranean Diet (MedDiet), especially in the prevention of cardiovascular diseases. These cardiovascular benefits have been attributed to a number of components of the MedDiet such as monounsaturated fatty acids, antioxidant vitamins and phytochemicals. However, the underlying mechanisms remain unknown. Likewise, little is known about the genes that define inter-individual variation in response to the MedDiet, although the TCF7L2 gene is emerging as an illustrative candidate for determining relative risk of cardiovascular events in response to the MedDiet. Moreover, omics technologies are providing evidence supporting pot…

Additional file 6: Figure S4. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) to discriminate between the baseline and final states in group 3 (suspected NAFLD reversion cases). Model diagnostics (A = 6, R2X = 0.628, Q2X = 0.235) (DOCX 42 kb)

Erythrocyte deformability in morbid obesity before bariatric surgery. Influence of abdominal obesity.

Although there are several studies dealing with erythrocyte deformability (ED) in obese patients, research on this topic in morbidly obese subjects is scarce. In these studies ED seems to be decreased, although the cause remains unknown. A case-control study in 76 morbid obese subjects (23 women and 53 men, aged 44 ± 13 years) and in 79 normal-weight controls (30 women and 49 men, aged 43 ± 13 years) was undertaken. ED has been determined by ektacytometric techniques in a Rheodyn SSD, by means of the elongation index (EI) at 12, 30 and 60 Pascals, along with anthropometric, lipidic, metabolic and inflammatory parameters. EI was statistically lower in morbidly obese subjects than in controls…

Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial.

Background: Dietary intervention success requires strong participant adherence, but very few studies have examined factors related to both short-term and long-term adherence. A better understanding of predictors of adherence is necessary to improve the design and execution of dietary intervention trials. This study was designed to identify participant characteristics at baseline and study features that predict short-term and long-term adherence with interventions promoting the Mediterranean-type diet (MedDiet) in the PREvencion con DIeta MEDiterranea (PREDIMED) randomized trial. Methods: Analyses included men and women living in Spain aged 55-80 at high risk for cardiovascular disease. Part…

MetProc: Separating Measurement Artifacts from True Metabolites in an Untargeted Metabolomics Experiment

High-throughput metabolomics using liquid chromatography and mass spectrometry (LC/MS) provides a useful method to identify biomarkers of disease and explore biological systems. However, the majority of metabolic features detected from untargeted metabolomics experiments have unknown ion signatures, making it critical that data should be thoroughly quality controlled to avoid analyzing false signals. Here, we present a postalignment method relying on intermittent pooled study samples to separate genuine metabolic features from potential measurement artifacts. We apply the method to lipid metabolite data from the PREDIMED (PREvención con DIeta MEDi-terránea) study to demonstrate clear remova…

Fatty Acids Composition of Blood Cell Membranes and Peripheral Inflammation in the PREDIMED Study: A Cross-Sectional Analysis

There is limited evidence from epidemiological studies for the inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes. Therefore, this study examined associations between baseline (n = 282) and 1-year (n = 143) changes in the levels of fatty acids in blood cell membranes with circulating inflammatory markers in older adults at high cardiovascular risk. The data for this cross-sectional analysis was obtained from a case-control study within the PREDIMED study. Linear regression with elastic net penalty was applied to test associations between measured fatty acids and inflammatory markers. Several fatty acids were associated with interferon-&gamma

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

Abstract 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 ≤40 kg/m2) and MetS. The SF-36 questionnaire was used as a tool to measure HRQoL. Scores were calculate…

Conceptos básicos en biología molecular relacionados con la genética y la epigenética

Resumen La observacion de que «lo mismo no sirve para todos» en la prevencion y el tratamiento de las enfermedades cardiovasculares, entre otras, ha propulsado el concepto de medicina de precision. Su objetivo es proporcionar las mejores intervenciones basadas en la informacion adicional que aporta el genoma. El genoma humano se compone de miles de millones de pares de bases que contienen un codigo que controla como se expresan los genes. Este codigo depende de reguladores no estaticos que rodean el ADN y constituyen el epigenoma. Ademas, los factores ambientales tambien desempenan un papel importante en esta compleja regulacion. Se presenta una perspectiva general sobre los conceptos basic…

Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population: the PREDIMED study.

The beneficial impact of walnuts on human health has been attributed to their unique chemical composition. In order to characterize the dietary walnut fingerprinting, spot urine samples from two sets of 195 (training) and 186 (validation) individuals were analyzed by an HPLC-q-ToF-MS untargeted metabolomics approach, selecting the most discriminating metabolites by multivariate data analysis (VIP ≥ 1.5). Stepwise logistic regression analysis was used to design a multimetabolite prediction biomarker model. The global performance of the model and each included metabolite in it was evaluated by receiver operating characteristic curves, using the area under the curve (AUC) values. Dietary expos…

Polyphenol Levels Are Inversely Correlated with Body Weight and Obesity in an Elderly Population after 5 Years of Follow Up (The Randomised PREDIMED Study).

Overweight and obesity have been steadily increasing in recent years and currently represent a serious threat to public health. Few human studies have investigated the relationship between polyphenol intake and body weight. Our aim was to assess the relationship between urinary polyphenol levels and body weight. A cross-sectional study was performed with 573 participants from the PREDIMED (Prevención con Dieta Mediterránea) trial (ISRCTN35739639). Total polyphenol levels were measured by a reliable biomarker, total urinary polyphenol excretion (TPE), determined by the Folin-Ciocalteu method in urine samples. Participants were categorized into five groups according to their TPE at the fifth …

Gene–alcohol interactions in the metabolic syndrome

Abstracts Aims Recent studies have reported that moderate alcohol consumption is associated with a lesser prevalence of the metabolic syndrome (MetS). However, this relationship is still confusing and the presence of gene–environment interactions has been suggested. Our aim is to summarize evidence for gene–alcohol interactions in the MetS. Data synthesis Research in gene–alcohol interactions applied to MetS is very complex due to the difficulties surrounding the definition of phenotype, environment and genotype, as well as in estimating the influence of the social context. In the MetS there is a constellation of metabolic disturbances the definition of which is still changing. Thus, most s…

Prediction of cardiovascular disease by the framingham-REGICOR equation in the high-risk PREDIMED cohort: Impact of the mediterranean diet across different risk strata

Background-The usefulness of cardiovascular disease (CVD) predictive equations in different populations is debatable. We assessed the efficacy of the Framingham-REGICOR scale, validated for the Spanish population, to identify future CVD in participants, who were predefined as being at high-risk in the PREvención con DIeta MEDiterránea (PREDIMED) study-a nutrition-intervention primary prevention trial-and the impact of adherence to the Mediterranean diet on CVD across risk categories. Methods and Results-In a post hoc analysis, we assessed the CVD predictive value of baseline estimated risk in 5966 PREDIMED participants (aged 55-74 years, 57% women; 48% with type 2 diabetes mellitus). Major …

Gender-Specific Association of a Perilipin Gene Haplotype with Obesity Risk in a White Population

Objective: Perilipin is a class of protein-coating lipid droplets in adipocytes and steroidogenic cells. Our purpose was to examine the association between common single-nucleotide polymorphisms (SNPs) at the perilipin (PLIN) locus and obesity, as well as related phenotypes, in unrelated American adults. Research Methods and Procedures: Four PLIN SNPs (PLIN 6209T>C, 11482G>A, 13041A>G, and 14995A>T) were typed in 734 white subjects (373 men and 361 women) attending a residential lifestyle intervention program. The baseline anthropometric and biochemical measures were used. Obesity was defined as BMI ≥ 30 kg/m2. Results: Multivariate analysis demonstrated that, in women, two of the SNPs (130…

Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial.

OBJECTIVE - : The Prevención con Dieta Mediterránea (PREDIMED) trial showed that a Mediterranean diet (MedDiet) supplemented with either extra virgin olive oil or 30 g/d of mixed nuts reduced incident cardiovascular events compared with a control (low fat) diet. The mechanisms of cardiovascular protection afforded by MedDiets remain to be uncovered. We assessed the effect of both supplemented MedDiets on internal carotid intima-media thickness (ICA-IMT) and plaque height, the ultrasound features that best predict future cardiovascular events, in subjects at high cardiovascular risk. APPROACH AND RESULTS - : In a PREDIMED subcohort (n=175), plaque height and carotid IMT of 3 prespecified seg…

Obese Subjects Carrying the 11482G>A Polymorphism at the Perilipin Locus Are Resistant to Weight Loss after Dietary Energy Restriction

Dietary treatment of obesity could be improved if predictive information about the individual's genetic response to diet was available. Adipose tissue has been the focus of efforts to identify candidate genes. Perilipin is a major protein found in adipocytes, and perilipin knockout mice are lean and resistant to diet-induced obesity.The objective of the study was to examine the association of several polymorphisms at the perilipin (PLIN) locus with obesity and weight reduction in response to a low-energy diet in obese patients.This study was a 1-yr randomized (depending on the PLIN genotype) trial with three follow-up evaluations.The study was conducted at a university research center.One h…

Metabolic Syndrome Features and Excess Weight Were Inversely Associated with Nut Consumption after 1-Year Follow-Up in the PREDIMED-Plus Study.

PREDIMED-PLUS investigators: et al.

Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Background Limited prospective studies have examined changes in non-alcoholic fatty-liver disease (NAFLD) related serum-metabolites and none the effects of NAFLD-reversion. We aimed to evaluate whether perturbations in metabolites indicate predisposition to NAFLD development and to assess the effects of NAFLD reversion on metabolite profiles. Methods A targeted liquid-chromatography tandem mass-spectrometry metabolic profiling (n = 453 metabolites) approach was applied, using serum from 45 subjects of the PREDIMED study, at baseline and after a median 3.8-year follow-up. NAFLD was determined using the hepatic steatosis index; with three groups classified and studied: Group 1, not characteri…

The Mediterranean diet protects against waist circumference enlargement in 12Ala carriers for the PPARgamma gene: 2 years' follow-up of 774 subjects at high cardiovascular risk.

The PPARγ gene regulates insulin sensitivity and adipogenesis. The Pro12Ala polymorphism of this gene has been related to fat accumulation. Our aim was to analyse the effects of a 2-year nutritional intervention with Mediterranean-style diets on adiposity in high-cardiovascular risk patients depending on the Pro12Ala polymorphism of the PPARγ gene. The population consisted of a substudy (774 high-risk subjects aged 55–80 years) of the Prevención con Dieta Mediterránea (PREDIMED) randomised trial aimed at assessing the effect of the Mediterranean diet for CVD prevention. There were three nutritional intervention groups: two of them of a Mediterranean-style diet and the third was a control gr…

Influence of lipids and obesity on haemorheological parameters in patients with deep vein thrombosis.

It is not well established whether haemorheological alterations constitute independent risk factors for deep vein thrombosis (DVT).We have determined in 149 DVT patients and in 185 control subjects the body mass index (BMI), the haemorheological profile: blood viscosity (BV), plasma viscosity (PV), fibrinogen (Fg), erythrocyte aggregation (EA), erythrocyte deformability (ED) and plasma lipids. In the crude analysis BMI, Fg, PV, EA, triglycerides (TG) and ApoB were statistically higher and HDL cholesterol (HDL-Chol) statistically lower in DVT patients than in controls. No differences in BV and ED were observed.After BMI adjustment, Fg, PV and EA remained statistically higher in DVT cases tha…

Plasma Metabolites Associated with Coffee Consumption: A Metabolomic Approach within the PREDIMED Study

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 metabolit…

Nutrition in the genomics era: cardiovascular disease risk and the Mediterranean diet.

The effect of dietary changes on phenotypes (i.e., plasma lipid measures, body weight and blood pressure) differs significantly between individuals. This phenomenon has been more extensively researched in relation to changes in dietary fat and plasma lipid concentrations for the prevention of cardiovascular disease (CVD) compared to other pathological conditions. Although common knowledge associates low fat diets with reductions in total and plasma LDL cholesterol, the clinical evidence shows dramatic inter-individual differences in response that are partially due to genetic factors. The discovery of the cardioprotective and other healthy properties of the Mediterranean diet has popularized…

Fenofibrate effect on triglyceride and postprandial response of apolipoprotein A5 variants: the GOLDN study.

Objective— Apolipoprotein A5 ( APOA5 ) is a key determinant of plasma triglyceride (TG) concentrations. Genetic variation at the APOA5 locus could be responsible for some of the observed differences in response to fenofibrate therapy. Methods and Results— We examined the association between tag SNPs (−1131T>C and 56C>G) at APOA5 and TG and HDL-C response to fenofibrate and a postprandial lipid challenge in 791 men and women participating in the GOLDN study. After 3-week drug treatment, APOA5 56G carriers displayed significant decrease in TG ( P =0.006), and increase in HDL-C ( P =0.002) levels relative to their basal values in the fasting state when compared with noncarriers (a TG re…

Associations Between the Modified Food Standard Agency Nutrient Profiling System Dietary Index and Cardiovascular Risk Factors in an Elderly Population.

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm- NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic b…

Saturated fat intake and alcohol consumption modulate the association between the APOE polymorphism and risk of future coronary heart disease: a nested case-control study in the Spanish EPIC cohort

The association is still not clear between the common APOE polymorphism and coronary heart disease (CHD) risk, nor its modulation by diet. Thus, our aim was to study the association between the APOE genotypes and incident CHD and how dietary fat and alcohol consumption modify these effects. We performed a nested case-control study in the Spanish European Prospective Investigation into Cancer and Nutrition cohort. Healthy men and women (41,440, 30-69 years) were followed up over a 10-year period, with the incident CHD cases being identified. We analyzed 534 incident CHD cases and 1123 controls. APOE, dietary intake and plasma lipids were determined at baseline. The APOE polymorphism was sign…

Polymorphisms cyclooxygenase-2 -765G>C and interleukin-6 -174G>C are associated with serum inflammation markers in a high cardiovascular risk population and do not modify the response to a Mediterranean diet supplemented with virgin olive oil or nuts

Inflammation is involved in cardiovascular diseases. Some studies have found that the Mediterranean diet (MD) can reduce serum concentrations of inflammation markers. However, none of these studies have analyzed the influence of genetic variability in such a response. Our objective was to study the effect of the -765G>C polymorphism in the cyclooxygenase-2 (COX-2) gene and the -174G>C polymorphism in the interleukin-6 (IL-6) gene on serum concentrations of IL-6, C-reactive protein, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule-1 as well as their influence on the response to a nutritional intervention with MD. An intervention study in a high cardiovascular ri…

Plasma lipidomic profiles and cardiovascular events in a randomized intervention trial with the Mediterranean diet.

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 …

Metformin Use and Cognitive Function in Older Adults With Type 2 Diabetes Following a Mediterranean Diet Intervention

Background and Purpose: Both adherence to the Mediterranean diet (MedDiet) and the use of metformin could benefit the cognitive performance of individuals with type 2 diabetes, but evidence is still controversial. We examined the association between metformin use and cognition in older adults with type 2 diabetes following a MedDiet intervention. Methods: Prospective cohort study framed in the PREDIMED-Plus-Cognition sub-study. The PREDIMED-Plus clinical trial aims to compare the cardiovascular effect of two MedDiet interventions, with and without energy restriction, in individuals with overweight/obesity and metabolic syndrome. The present sub-study included 487 cognitively normal subjects…

Associations of LPL and APOC3 gene polymorphisms on plasma lipids in a mediterranean population: Interaction with tobacco smoking and the APOE locus

We conducted a cross-sectional study in a Spanish population (n = 1,029) to investigate associations between the LPL and APOC3 gene loci (LPL-HindIII, LPL-S447X, and APOC3-SstI) and plasma lipid levels and their interaction with APOE polymorphisms and smoking. Carriers of the H− or the X447 allele had higher levels of HDL cholesterol (HDL-C), and lower levels of TG, after adjustment for age, body mass index, alcohol, smoking, exercise, and education (P < 0.01). The APOC3 polymorphism presented additive effects to the LPL variants on TG and HDL-C levels in men, and on TG in women. The most and the least favorable haplotype combinations were H−/X447/S1 and H+/S447/S2, respectively. These comb…

Interacciones dieta-genotipo entre el consumo de grasas y polimorfismos comunes determinando el metabolismo lipídico

Las recomendaciones dietéticas actuales referentes al consumo de grasas en la dieta han sido realizadas sin tener en cuenta las posibles diferencias genéticas de las personas que podrían ser las responsables de las diferentes respuestas interindividuales que frecuentemente se observan ante la misma dieta. La presencia de variabilidad genética ha sido puesta de manifiesto para todos los genes relacionados con el metabolismo lipídico, por lo que existe un ingente número de genes y de variantes genéticas para ser incluidas en los estudios sobre interacciones dieta-genotipo en el ámbito específico del consumo de grasas y aceites. Se revisarán algunos ejemplos sobre interacciones grasa-genotipo.…

Utilizing nutritional genomics to tailor diets for the prevention of cardiovascular disease: a guide for upcoming studies and implementations.

Introduction: Personalized diets based on an individual’s genome to optimize the success of dietary intervention and reduce genetic cardiovascular disease (CVD) risk, is one of the challenges most frequently discussed in the scientific community. Areas covered: The authors gathered literature-based evidence on nutritional genomics and CVD phenotypes, our own results and research experience to provide a critical overview of the current situation of using nutritional genomics to tailor diets for CVD prevention and to propose guidelines for future studies and implementations. Expert commentary: Hundreds of studies on gene-diet interactions determining CVD intermediate (plasma lipids, hypertens…

Metabolic syndrome pathophysiology: The role of adipose tissue

Several pathophysiological explanations for the metabolic syndrome have been proposed involving insulin resistance, chronic inflammation and ectopic fat accumulation following adipose tissue saturation. However, current concepts create several paradoxes, including limited cardiovascular risk reduction with intensive glucose control in diabetics, therapies that result in weight gain (PPAR agonists), and presence of some of the metabolic traits among some lipodystrophies. We propose the functional failure of an organ, in this case, the adipose tissue as a model to interpret its manifestations and to reconcile some of the apparent paradox. A cornerstone of this model is the failure of the adip…

Mediterranean Diet Maintained Platelet Count within a Healthy Range and Decreased Thrombocytopenia-Related Mortality Risk: A Randomized Controlled Trial

There is little information on the dietary modulation of thrombosis-related risk factors such as platelet count. We aimed to assess the effects of Mediterranean diet (MedDiet) on platelet count and related outcomes in an older population at high cardiovascular risk. In participants of the PREDIMED (PREvención con DIeta MEDiterránea) study, we assessed whether an intervention with a MedDiet enriched with extra-virgin olive oil or nuts, relative to a low-fat control diet, modulated platelet count (n = 4189), the risk of developing thrombocytosis and thrombocytopenia (n = 3086), and the association between these alterations and all-cause mortality (median follow-up time: 3.0 years). Although p…

Cystinuria subtype and nephrolithiasis

Polyunsaturated fatty acids interact with the PPARA-L162V polymorphism to affect plasma triglyceride and apolipoprotein C-III concentrations in the Framingham Heart Study.

Peroxisome proliferator-activated receptor alpha (PPARalpha) is a nuclear transcription factor regulating multiple genes involved in lipid metabolism. It was shown that a common leucine to valine (L162V) substitution at the PPARalpha gene (PPARA) is functional and affects transactivation activity of PPARalpha ligands, such as PUFA, on a concentration-dependent basis. The current study examined this gene-nutrient interaction in relation to plasma lipid variables in a population-based study consisting of 1003 men and 1103 women participating in the Framingham cohort and consuming their habitual diets. We found significant gene-nutrient interactions between the L162V polymorphism and total PUF…

Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporat…

Oxidative stress is associated with an increased antioxidant defense in elderly subjects: a multilevel approach.

© 2014 Fonseca et al. Background: Studies of associations between plasma GSH-Px activity and cardiovascular risk factors have been done in humans, and contradictory results have been reported. The aim of our study was to assess the association between the scavenger antioxidant enzyme glutathione peroxidase (GSH-Px) activity in plasma and the presence of novel and classical cardiovascular risk factors in elderly patients. Copyright: Methods: We performed a cross-sectional study with baseline data from a subsample of the PREDIMED (PREvención con DIeta MEDiterránea) study in Spain. Participants were 1,060 asymptomatic subjects at high risk for cardiovascular disease (CVD), aged 55 to 80, selec…

Plasma Metabolites From Choline Pathway and Risk of Cardiovascular Disease in the PREDIMED (Prevention With Mediterranean Diet) Study.

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 …

The Effect of Physical Activity and High Body Mass Index on Health-Related Quality of Life in Individuals with Metabolic Syndrome

© 2020 by the authors.

Retraction and Republication: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90.

To the Editor: Because of irregularities in the randomization procedures, we wish to retract the following article: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet. N Engl J Med 2013;368:1279-90. DOI: 10.1056/NEJMoa1200303.1 We have reanalyzed the data and have published a new report: Primary Prevention of Cardiovascular Disease with a Mediterranean Diet Supplemented with Extra-Virgin Olive Oil or Nuts. N Engl J Med. DOI: 10.1056/NEJMoa1800389.2 . . .

Additional file 1: of Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial

Table S1. Odds of high adherence with the MedDiet intervention at two and three years of follow-up. Table S2. Odds of high adherence with the MedDiet intervention using alternate adherence score cut-points. Table S3. Odds of adherence with olive oil and nut consumption after 1 and 4 years of follow-up. Table S4. Odds of high adherence with the MedDiet intervention at one yeara, restricting the analyses to those participants recruited before 2006. Table S5. Adherence at one year of follow-up according to a 14-point dietary adherence score and year of recruitment into PREDIMED. Table S6. Odds of high adherence with the MedDiet intervention at one and four years of follow-upa, with alternate r…

Leisure time physical activity is associated with improved HDL functionality in high cardiovascular risk individuals: a cohort study.

Abstract Aims Physical activity has consistently been shown to improve cardiovascular health and high-density lipoprotein-cholesterol levels. However, only small and heterogeneous studies have investigated the effect of exercise on high-density lipoprotein functions. Our aim is to evaluate, in the largest observational study to date, the association between leisure time physical activity and a range of high-density lipoprotein functional traits. Methods The study sample consisted of 296 Spanish adults at high cardiovascular risk. Usual leisure time physical activity and eight measures of high-density lipoprotein functionality were averaged over two measurements, one year apart. Multivariabl…

Asociaciones de la concentración de adiponectina sérica con parámetros antropométricos, bioquímicos y presión arterial en población de alto riesgo cardiovascular

Introduccion La adiponectinemia se ha asociado inversamente con obesidad abdominal, un perfil lipidico mas favorable y menor resistencia a la insulina. Sin embargo, recientes estudios en poblacion de alto riesgo cardiovascular, especialmente con funcion renal alterada, muestran que concentraciones elevadas son un indicador desfavorable. Nuestro objetivo ha sido estudiar la asociacion entre adiponectinemia y parametros antropometricos, bioquimicos y presion arterial (PA) en pacientes de alto riesgo cardiovascular. Pacientes y metodos Se estudio a 185 pacientes (133 mujeres y 52 varones), participantes del estudio PREDIMED (edad media de 65,5 ± 4,3 anos). Se obtuvieron datos clinicos, antropo…

Meta-Analysis of the INSIG2 Association with Obesity Including 74,345 Individuals: Does Heterogeneity of Estimates Relate to Study Design?

The INSIG2 rs7566605 polymorphism was identified for obesity (BMI≥30 kg/m2) in one of the first genome-wide association studies, but replications were inconsistent. We collected statistics from 34 studies (n = 74,345), including general population (GP) studies, population-based studies with subjects selected for conditions related to a better health status (‘healthy population’, HP), and obesity studies (OB). We tested five hypotheses to explore potential sources of heterogeneity. The meta-analysis of 27 studies on Caucasian adults (n = 66,213) combining the different study designs did not support overall association of the CC-genotype with obesity, yielding an odds ratio (OR) of 1.05 (p-va…

Single tube optimisation of APOE genotyping based on melting curve analysis

Objectives: To develop and validate a single-tube protocol for APOE genotyping using fluorescent probes. Design and methods: We have designed and validated a hybrid, single-tube, SimpleProbe/FRET probe protocol that takes advantage of the different probe wavelength emissions. Results: Our method offers high quality outcomes, minimum interferences between probe signals and is 100% concordant with the reference protocol. Conclusions: This method is cheaper, faster and more reliable and versatile than other alternatives proposed. © 2008 Elsevier Inc. All rights reserved.

Effect on gut microbiota of a 1-y lifestyle intervention with Mediterranean diet compared with energy-reduced Mediterranean diet and physical activity promotion: PREDIMED-Plus Study

ABSTRACT Background The Mediterranean diet is a well-recognized healthy diet that has shown to induce positive changes in gut microbiota. Lifestyle changes such as diet along with physical activity could aid in weight loss and improve cardiovascular risk factors. Objectives To investigate the effect of an intensive lifestyle weight loss intervention on gut microbiota. Methods This is a substudy of the PREDIMED-Plus (Prevención con Dieta Mediterránea-Plus), a randomized controlled trial conducted in overweight/obese men and women (aged 55–75 y) with metabolic syndrome. The intervention group (IG) underwent an intensive weight loss lifestyle intervention based on an energy-restricted Mediterr…

Nut Consumptions as a Marker of Higher Diet Quality in a Mediterranean Population at High Cardiovascular Risk

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&ndash

DNA methylation of the CYP1A1 and GSTP1 genes and incidence of major cancers (lung, breast and colon) in the PREDIMED-Valencia study

MOESM1 of CLOCK gene variation is associated with incidence of type-2 diabetes and cardiovascular diseases in type-2 diabetic subjects: dietary modulation in the PREDIMED randomized trial

Additional file 1: Figure S1. Flow-chart. Figure S2. Cumulative T2D-free survival by CLOCK-rs4580704 genotypes depending on the dietary intervention group. Figure S3. Cumulative stroke-free survival by CLOCK-rs4580704 genotypes. Table S1. Characteristics of the PREDIMED study participants at baseline according to the dietary intervention groups. Table S2. Characteristics of the PREDIMED study participants at baseline according to the T2D status. Table S3. Incidence rate and hazard ratios (HR) for total cardiovascular diseases (CVD) depending on the CLOCK-rs4580704. Table S4. Incidence rate and hazard ratios (HR) for stroke depending on the CLOCK-rs4580704 in T2D subjects and stratified by d…

Sex-Specific Differences in the Control of Serum Concentrations of Glycine in Subjects with Metabolic Syndrome and Mendelian Randomization Analysis for Obesity

OBJECTIVES: Glycine is a novel circulating marker for metabolic diseases associated with lower type-2 diabetes and protection against obesity in some studies. Circulating glycine levels are genetically determined under the control of several loci. The locus most strongly associated is the carbamoyl-phosphate synthase I (CPS1). Interestingly, some sex-specific genome-wide association studies (GWAS) showed differences in the effect of the main single nucleotide polymorphisms (SNPs) in this locus on glycine levels (significant sex * CPS1 interactions). However, the potential mechanisms explaining this sex-heterogeneity are unknown. Therefore, our aims were: 1) to analyze whether the sex * CPS1…

Soluble transferrin receptor and risk of type 2 diabetes in the obese and nonobese.

Background Studies evaluating the relationship between soluble transferrin receptor (sTfR), a biomarker inversely related to body iron stores, and risk of type 2 diabetes mellitus (T2DM) are scarce and inconclusive. Furthermore, sTfR concentrations have been observed to be significantly higher in obese than in nonobese individuals. Therefore, the aim of this study was to assess the relationship between sTfR and the risk of T2DM in obese and nonobese subjects. Design A nested case–control study of 153 cases of newly diagnosed diabetic subjects, 73 obese and 80 nonobese, and 306 individually matched controls, 138 obese and 166 nonobese, who did not develop T2DM for a median 6-year follow-up (…

The 1258 GA polymorphism in the neuropeptide Y gene is associated with greater alcohol consumption in a Mediterranean population.

Abstract Neuropeptide Y (NPY) is a neurotransmitter widely distributed in the central nervous system. Several studies have demonstrated that increases of NPY are associated with reduced alcohol intake and anxiety manifestations. The Leu7Pro polymorphism in the NPY has been associated with alcohol consumption, but evidence is scarce. In the Spanish Mediterranean population, this variant is not polymorphic. Thus, our aim is to identify novel functional variants in the NPY and to investigate the impact of these markers and others previously described on alcohol consumption in this population. A total of 911 subjects (321 men and 590 women) from the Spanish Mediterranean population were recruit…

Manifestaciones fenotípicas de la cistinuria: estudio de 20 familias en la Comunidad Valenciana

Fundamento El objetivo de este trabajo fue realizar una caracterizacion fenotipica de los pacientes con cistinuria en la Comunidad Valenciana en el contexto de su genealogia y abordar desde esta perspectiva la amplia heterogeneidad de esta enfermedad. Sujetos y metodo A partir de 29 individuos que habian sido diagnosticados de cistinuria con anterioridad a este estudio se logro la colaboracion de 20 familias. Se recogio una muestra de orina de cada individuo, se analizo el sedimento y se cuantificaron los aminoacidos mediante cromatografia de alta resolucion. El analisis genetico se llevo a cabo mediante reaccion en cadena de la polimerasa (PCR) y analisis de patrones de polimorfismos de re…

Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a mediterranean population

Abstract Background Tobacco use has been reported to be the main cause of 90% of male and 80% of female lung cancers, as well as a relevant risk factor for other cancers such as oropharynx, larynx, esophagus, stomach, liver, pancreas, kidney, bladder, and colorectum. Smoking directly affects DNA methylation and although several genes have been reported to be differentially methylated in smokers, gender differences and population-specific differences remain to be further investigated. Our aim was to undertake global and sex-specific genome-wide epigenomic studies (EWAS) in a Mediterranean population to identify the main smoking DNA-methylated genes. Methods We analyzed 88 participants in the…

Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial

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 l…

SLC23A2 Gene Variation, Vitamin C Levels, and Glaucoma

Abstract Primary open-angle glaucoma (POAG) is a multifactorial disease in which both genetic and environmental factors are involved. Among the environmental factors associated with POAG, nutritional factors are particularly important since nutrition is essential for maintaining good health. Researchers can study the interactions between nutrition and genes by means of nutritional genomics, but nutrigenomics studies regarding eye diseases are very scarce. This research group recently published one of the first studies on nutrigenomics in POAG. It was found that the rs1279683 polymorphism in the SLC23A2 gene, which encodes a vitamin C transporter, is associated with a higher risk of POAG. Si…

Impacto de Life's Simple 7 en la incidencia de eventos cardiovasculares mayores en adultos españoles con alto riesgo de la cohorte del estudio PREDIMED

Resumen Introduccion y objetivos La estrategia Life's Simple 7 de la American Heart Association propuso 7 metricas de salud cardiovascular ideal: indice de masa corporal (IMC)  Metodos La metrica de dieta saludable se definio como alcanzar al menos 9 puntos en una escala validada de 14 puntos de adhesion a dieta mediterranea. Se definio evento cardiovascular mayor incidente como infarto de miocardio, ictus o muerte de causa cardiovascular. Se uso regresion de Cox para estimar hazard ratios (HR) ajustadas multivariables con intervalos de confianza del 95% (IC95%) para categorias sucesivas de metricas de salud cardiovascular. Resultados Tras seguir a 7.447 participantes durante una mediana de…

Effects of Walnut Consumption for 2 Years on Lipoprotein Subclasses Among Healthy Elders

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study

Background and aims: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. Methods and results: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there…

A metabolomics-driven approach to predict cocoa product consumption by designing a multimetabolite biomarker model in free-living subjects from the PREDIMED study

Scope The aim of the current study was to apply an untargeted metabolomics strategy to characterize a model of cocoa intake biomarkers in a free-living population. Methods and results An untargeted HPLC-q-ToF-MS based metabolomics approach was applied to human urine from 32 consumers of cocoa or derived products (CC) and 32 matched control subjects with no consumption of cocoa products (NC). The multivariate statistical analysis (OSC-PLS-DA) showed clear differences between CC and NC groups. The discriminant biomarkers identified were mainly related to the metabolic pathways of theobromine and polyphenols, as well as to cocoa processing. Consumption of cocoa products was also associated wit…

Genetic variation at the perilipin (PLIN) locus is associated with obesity-related phenotypes in White women

Perilipin coats intracellular lipid droplets and modulates adipocyte lipolysis. We have evaluated the association between several polymorphisms at the perilipin (PLIN) locus (PLIN1 : 6209T > C, PLIN4 : 11482G > A, PLIN5 : 13041A > G, and PLIN6 : 14995A > T) with obesity-related phenotypes in 1589 White subjects randomly selected from a general Spanish population. In women (n = 801), the less common alleles of PLIN1 and PLIN4, in strong linkage disequilibrium (D' : 0.96), were significantly associated with lower body mass index. Carriers of the allele 2 (6209C) at the PLIN1 locus weighed significantly less (-2.2 kg; p = 0.007) than women homozygotes for the wild-type genotype. The same was t…

High Plasma Glutamate and a Low Glutamine-to-Glutamate Ratio Are Associated with Increased Risk of Heart Failure but Not Atrial Fibrillation in the Prevención con Dieta Mediterránea (PREDIMED) Study

[Background] Although the association between glutamate and glutamine in relation to cardiometabolic disorders has been evaluated, the role of these metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unknown.

Amelogenin test: From forensics to quality control in clinical and biochemical genomics.

Abstract Background The increasing number of samples from the biomedical genetic studies and the number of centers participating in the same involves increasing risk of mistakes in the different sample handling stages. We have evaluated the usefulness of the amelogenin test for quality control in sample identification. Methods Amelogenin test (frequently used in forensics) was undertaken on 1224 individuals participating in a biomedical study. Concordance between referred sex in the database and amelogenin test was estimated. Additional sex-error genetic detecting systems were developed. Results The overall concordance rate was 99.84% (1222/1224). Two samples showed a female amelogenin test…

Effect of an Intensive Weight-Loss Lifestyle Intervention on Kidney Function: A Randomized Controlled Trial

Introduction: Large randomized trials testing the effect of a multifactorial weight-loss lifestyle intervention including Mediterranean diet (MedDiet) on renal function are lacking. Here, we evaluated the 1-year efficacy of an intensive weight-loss intervention with an energy-reduced MedDiet (erMedDiet) plus increased physical activity (PA) on renal function. Methods: Randomized controlled "PREvención con DIeta MEDiterránea-Plus"(PREDIMED-Plus) trial is conducted in 23 Spanish centers comprising 208 primary care clinics. Overweight/obese (n = 6,719) adults aged 55-75 years with metabolic syndrome were randomly assigned (1:1) to an intensive weight-loss lifestyle intervention with an erMedDi…

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits: A Mendelian Randomization Study.

Key Points Question Is birth weight associated with type 2 diabetes and glycemic traits? Findings This mendelian randomization study found that a 1-SD decrease in birth weight due to the genetic risk score was associated with a higher risk of type 2 diabetes among European and East Asian populations. In addition, a 1-SD decrease in birth weight was associated with a 0.189-SD increase in fasting glucose concentration, but not with fasting insulin, 2-hour glucose, or hemoglobin A1c level. Meaning A genetic predisposition to lower birth weight was associated with an increased risk of type 2 diabetes and increased fasting glucose, suggesting potential mechanisms through which perturbation of th…

Associations of the FTO rs9939609 and the MC4R rs17782313 polymorphisms with type 2 diabetes are modulated by diet, being higher when adherence to the Mediterranean diet pattern is low

Background: Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Methods: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes c…

Thrombotic events in systemic lupus erythematosus. Its association with acquired and inherited thrombophilic defects.

Systemic lupus erythematosus (SLE) is characterised by increased venous and arterial thrombotic risk. Although antiphospholipid antibodies (APAs) have been shown to be related with thrombotic tendency in these patients, in more than 40% of them, thrombosis occurs without the presence of such antibodies. We analysed the association of venous and arterial thrombotic events with acquired (anticardiolipin antibodies (ACAs) and lupus anticoagulant (LA)) and inherited (antithrombin (AT), protein C (PC), protein S (PS) deficiencies, factor V Leiden and the prothrombin G20210A mutation), thrombophilic risk factors in 86 SLE patients and 89 healthy controls. Patients showed a higher significant perc…

Chromium Exposure and Risk of Cardiovascular Disease in High Cardiovascular Risk Subjects　― Nested Case-Control Study in the Prevention With Mediterranean Diet (PREDIMED) Study ―

BACKGROUND: Epidemiological data on chromium (Cr) exposure and the risk of cardiovascular disease (CVD) are still limited. Toenail Cr level (TCL) provides a time-integrated measure reflecting long-term Cr exposure. We measured TCL to assess the hypothesis that long-term Cr exposure was inversely associated with incident CVD in a population at high risk for CVD.Methods and Results:The associations between TCL and CVD were evaluated in a case-control study nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. We randomly selected 147 of the 288 patients diagnosed with CVD during follow-up and matched them on age and sex to 271 controls. Instrumental neutron activation analys…

Plasma Acylcarnitines and Risk of Type 2 Diabetes in a Mediterranean Population at High Cardiovascular Risk

[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.

Validating a Rapid Method for Detecting Common Polymorphisms in the APOA5 Gene by Melting Curve Analysis Using LightTyper

The recently identified apolipoprotein A-V gene (APOA5) has been shown to play an important role in hypertriglyceridemia (1). Genetic variation in APOA5 has been consistently associated with plasma triglyceride concentrations in several studies (2)(3)(4). Moreover, some studies have demonstrated additional associations with lipoprotein subclasses, remnant-like particles, and cardiovascular disease risk (4)(5)(6). Several single-nucleotide polymorphisms (SNPs) in the human APOA5 gene have been detected with differing frequencies depending on the population analyzed (7)(8), and Klos et al.(7) have also suggested context-dependent associations in different populations. Overall, 5 common SNPs, …

Increased Consumption of Virgin Olive Oil, Nuts, Legumes, Whole Grains, and Fish Promotes HDL Functions in Humans

[Scope] To evaluate whether increases in the consumption of cardioprotective food groups (virgin olive oil, nuts, fruits/vegetables, legumes, whole grains, fish, and wine) are associated with improvements in high‐density lipoprotein (HDL) functions in high cardiovascular risk subjects.

Mercury exposure and risk of cardiovascular disease: a nested case-control study in the PREDIMED (PREvention with MEDiterranean Diet) study

Background: Substantial evidence suggests that consuming 1-2 servings of fish per week, particularly oily fish (e.g., salmon, herring, sardines) is beneficial for cardiovascular health due to its high n-3 polyunsaturated fatty acid content. However, there is some concern that the mercury content in fish may increase cardiovascular disease risk, but this relationship remains unclear. Methods: The PREDIMED trial included 7477 participants who were at high risk for cardiovascular disease at baseline. In this study, we evaluated associations between mercury exposure, fish consumption and cardiovascular disease. We randomly selected 147 of the 288 cases diagnosed with cardiovascular disease duri…

Influence of the APOA5 locus on plasma triglyceride, lipoprotein subclasses, and CVD risk in the Framingham Heart Study

Several polymorphisms in the APOA5 gene have been associated with increased plasma triglyceride (TG) concentrations. However, associations between APOA5 and lipoprotein subclasses, remnant-like particles (RLPs), and cardiovascular disease (CVD) risk have been less explored. We investigated associations of five APOA5 single-nucleotide polymorphisms (SNPs; −1131T>C, −3A>G, 56C>G IVS3+ 476G>A, and 1259T>C) with lipoprotein subfractions and CVD risk in 1,129 men and 1,262 women participating in the Framingham Heart Study. Except for the 56C>G SNP, the other SNPs were in significant linkage disequilibria, resulting in three haplotypes (11111, 22122, and 11211) representing 98% of the population.…

Cross-sectional assessment of nut consumption and obesity, metabolic syndrome and other cardiometabolic risk factors: the PREDIMED study

INTRODUCTION: Prospective studies have consistently suggested that nut consumption is inversely related to fatal and non-fatal coronary heart disease. Limited data are available on the epidemiological associations between nut intake and cardiometabolic risk factors. OBJECTIVE: To evaluate associations between frequency of nut consumption and prevalence of cardiometabolic risk factors [obesity, metabolic syndrome (MetS), type-2 diabetes, hypertension, and dyslipidemia] in a Mediterranean population at high cardiovascular risk. MATERIALS AND METHODS: Cross-sectional study of 7,210 men and women (mean age, 67 y) recruited into the PREDIMED study. MetS was defined by the harmonized ATPIII and I…

A high dietary glycemic index increases total mortality in a Mediterranean population at high cardiovascular risk

© 2014 Castro-Quezada et al. Objective: Different types of carbohydrates have diverse glycemic response, thus glycemic index (GI) and glycemic load (GL) are used to assess this variation. The impact of dietary GI and GL in all-cause mortality is unknown. The objective of this study was to estimate the association between dietary GI and GL and risk of all-cause mortality in the PREDIMED study. Material and Methods: The PREDIMED study is a randomized nutritional intervention trial for primary cardiovascular prevention based on community-dwelling men and women at high risk of cardiovascular disease. Dietary information was collected at baseline and yearly using a validated 137-item food freque…

Short-Term Effects on Gene-Expression and on DNA-Methylation at the Genome-Wide Level of the Iberian Ham Intake and Compared With Orange Intake: A Crossover Randomized Trial

OBJECTIVES: Diet regulates gene expression and methylation profiles by several mechanisms. However, studies analyzing the simultaneous effect of specific foods on gene-expression and DNA methylation at the genome-wide level are very scarce. Therefore our aims were: To study the short-term transcriptomics and epigenomcis effects at the genome-wide level of the Iberian ham intake compared with orange intake in the same subjects. METHODS: We carried out a cross-over randomized trial (registered at ISRCTN17906849) in 33 healhty volunteers (aged 18–50 years and 50% females) of European ancestry. After 12h fasting, participants were randomly allocated to eat 67.5 g of Iberian ham (100% pure iberi…

Candidate Gene and Genome-Wide Association Studies for Circulating Leptin Levels Reveal Population and Sex-Specific Associations in High Cardiovascular Risk Mediterranean Subjects

Leptin is a hormone crucial in the regulation of food intake and body-weight maintenance. However, the genes and gene variants that influence its plasma levels are still not well known. Results of studies investigating polymorphisms in candidate genes have been inconsistent, and, in addition, very few genome-wide association studies (GWAS) have been undertaken. Our aim was to investigate the genes and gene variants most associated with plasma leptin concentrations in a high-cardiovascular-risk Mediterranean population. We measured plasma leptin in 1011 men and women, and analyzed the genetic factors associated using three approaches: (1) Analyzing the single nucleotide polymorphisms (SNPs) …

Polymorphisms at theSRBIlocus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) fo…

The TaqIB and −629C&gt;A polymorphisms at the cholesteryl ester transfer protein locus: associations with lipid levels in a multiethnic population. The 1998 Singapore National Health Survey

The Singapore population comprises Chinese, Malays and Asian Indians. Within this population, Asian Indians have the highest rates of coronary heart disease, whereas Chinese have the lowest. Conversely, Indians have the lowest high-density lipoprotein cholesterol (HDL-C) concentrations, followed by Malays and Chinese. We studied the TaqIB and -629C>A polymorphisms at the CETP locus in 1300 Chinese, 364 Malay and 282 Asian Indian men, and in 1558 Chinese, 397 Malay and 306 Asian Indian women, to determine whether these polymorphisms are responsible for the ethnic difference in HDL-C concentration. The frequency of the B2 allele in Chinese, Malays and Indians was 0.384, 0.339 and 0.449 in men…

Additional file 5: Figure S3. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) to discriminate between the baseline and final states in group 2 (suspected cases of NAFLD). Model diagnostics (A = 6, R2X = 0.624, Q2X = 0.179) (DOCX 39 kb)

PPAR-alpha L162V and PGC-1 G482S gene polymorphisms, but not PPAR-gamma P12A, are associated with alcohol consumption in a Spanish Mediterranean population.

Abstract Background Peroxisome Proliferator-Activated Receptors (PPARs) and its co-activators are regulatory elements of the cellular lipid homeostasis and have been associated with feeding behavior modulation. Animal models suggest that these genes may be involved in alcohol consumption regulation. However, no studies in humans exist. Our aim is to estimate the possible association between polymorphisms in the PPAR-α , PPAR-γ and PPAR-γ co-activator 1A ( PGC-1A ) genes and alcohol consumption in humans. Methods We have conducted a cross-sectional study between the PPAR-α L162V, PPAR-γ P12A and PGC-1A G482S polymorphisms, and alcohol consumption in a general Mediterranean Spanish population…

The rs1466113 Polymorphism in the Somatostatin Receptor 2 Gene Is Associated with Obesity and Food Intake in a Mediterranean Population

&lt;i&gt;Background:&lt;/i&gt; A genome-wide association study identified rs1466113 (G&gt;C) in the somatostatin receptor 2 (SSTR2) gene as one of the polymorphisms most significantly associated with body mass index (BMI). As replication is required, we examined the association between this polymorphism and anthropometric variables and food intake in a Mediterranean population. &lt;i&gt;Methods:&lt;/i&gt; We studied 945 high cardiovascular-risk subjects (340 men and 605 women) aged 67 ± 6 years, participating in the PREDIMED-Valencia Study. Demographic, clinical, biochemical, dietary, genetic and anthropometric data were obtained. &lt;i&gt;Results:&lt;/i&gt; We found recessive effects for t…

Mediterranean diet and heart rate: the PREDIMED randomised trial

A higher heart rate (HR) has been associated with increased total and cardiovascular mortality [1] and [2]. Clinical trials support the beneficial effect of decreasing HR in patients with heart failure [3] and ischaemic heart disease [4]. A recent cross-sectional study showed that closer adherence to the Mediterranean diet (MeDiet) was related to lower HR [5]. We evaluated the association between adherence to the MeDiet (measured with a score from 0 to 14 obtained by a validated screener [6]) and HR using both a cross-sectional and a longitudinal analysis of the PREDIMED trial [7] and [8].

Erythrocyte Membrane Phosphatidylserine Exposure in Obesity

It has been suggested that increased erythrocyte membrane phosphatidylserine (PS) exposure could contribute to hypercoagulability and hemorheological disturbances in obesity. The aim of our study was to evaluate PS exposure in obese patients and in a control group and to correlate this with hemorheological properties, i.e., erythrocyte aggregability (EA) and deformability, and to evaluate the effect of weight loss on these parameters. An anthropometric and analytical evaluation was performed at baseline and after 3 months on a diet (very low-calorie diet for 4 weeks and low-calorie diet for 2 months) on 49 severe or morbid obese patients (37 women, 12 men) and 55 healthy volunteers (39 wome…

Vitamin K dietary intake is associated with cognitive function in an older adult Mediterranean population.

Abstract Background In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. Methods In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Foo…

Adherence to the Mediterranean Lifestyle and Desired Body Weight Loss in a Mediterranean Adult Population with Overweight: A PREDIMED-Plus Study

Background. Body weight dissatisfaction is a hindrance to following a healthy lifestyle and it has been associated with weight concerns. Objectives. The aim of this study was to assess the association between the adherence to the Mediterranean lifestyle (diet and exercise) and the desired body weight loss in an adult Mediterranean population with overweight. Methods. Cross-sectional analysis in 6355 participants (3268 men; 3087 women) with metabolic syndrome and BMI (Body mass index) between 27.0 and 40.0 kg/m2 (55–75 years old) from the PREDIMED-Plus trial. Desired weight loss was the percentage of weight that participants wished to lose. It was categorized into four cut-offs of this perce…

Association of olfatory dysfunction with plasma lipids and blood pressure in a high cardiovascular risk population: sex-specific analysis

Abstract Background Impaired sense of smell is a predictor of morbidity and mortality, including cardiovascular diseases. Likewise, several studies have reported sex-specific associations between olfactory function and cardiometabolic measures including plasma lipids and blood pressure. Thus, in a representative sample of US adults from the National Health and Nutrition Examination Survey (NHANES) study, olfactory dysfunction was associated with significantly higher total cholesterol (TC) and LDL-C among older men, but significantly lower TC among older women. However, considering that more studies in diverse population are needed, our aim was to analyze the association between the olfactor…

Consumption of iogurt, low-fat milk, and other low-fat dairy products is associated with lower risk of metabolic syndrome incidence in an elderly mediterranean population.

Background: The association between consumption of dairy products and the risk of developing metabolic syndrome (MetS) is unclear. Objective: The purpose of this study was to evaluate the associations between consumption of dairy products (total and different subtypes) and incident MetS in a Mediterranean population at high cardiovascular disease risk. Methods: We prospectively analyzed 1868 men and women (55–80 y old) without MetS at baseline, recruited from different PREDIMED (Prevenci´ on con Dieta Mediterr´ anea) centers between October 2003 and June 2009 and followed up until December 2010. MetS was defined according to updated, harmonized criteria. At baseline and yearly thereafter, w…

Low-fat dairy products and blood pressure: follow-up of 2290 older persons at high cardiovascular risk participating in the PREDIMED study

High blood pressure (BP) has been ranked as the most important risk factor worldwide regarding attributable deaths. Dietary habits are major determinants of BP. Among them, frequent intake of low-fat dairy products may protect against hypertension. Our aim was to assess the relationship between low-fat dairy product intake and BP levels and their changes after 12-month follow-up in a cohort of asymptomatic older persons at high cardiovascular risk recruited into a large-scale trial assessing the effects of Mediterranean diets on cardiovascular outcomes. Data from 2290 participants, including 1845 with hypertension, were available for analyses. Dairy products were not a specific part of the …

Apolipoprotein A2 Polymorphism Interacts with Intakes of Dairy Foods to Influence Body Weight in 2 U.S. Populations

The interaction between a functional apolipoprotein A2 gene (APOA2) variant and saturated fatty acids (SFAs) for the outcome of body mass index (BMI) is among the most widely replicated gene-nutrient interactions. Whether this interaction can be extrapolated to food-based sources of SFAs, specifically dairy foods, is unexplored. Cross-sectional analyses were performed in 2 U.S. population–based samples. We evaluated interactions between dairy foods and APOA2 −265T > C (rs5082) for BMI in the Boston Puerto Rican Health Study (n = 955) and tested for replication in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 1116). Dairy products were evaluated as total dairy, hig…

Abstract MP04: Taste Perception Profiles Are Associated With Patterns Of Adherence To A Mediterranean Diet Among Older Adults With Metabolic Syndrome

Objective: Evidence suggests perception of sweet, salt, sour, bitter, and umami tastes may be independently related to food preferences and intake. Our objective was to determine whether a collective measure of taste perception for all 5 tastes—“taste perception profiles”—was related to adherence to a Mediterranean diet (MedD). Methods: Participants were 367 older adults (55-75 years; 55% female) with metabolic syndrome from PREDIMED-Plus, Valencia. A data-driven clustering approach identified six taste perception profiles from baseline taste perception scores: Low All ( n = 85), High Bitter ( n = 41), High Umami ( n = 61), Low Bitter &amp; Umami ( n = 59), High All But Bitter ( n = 72) an…

Metabolomics of the tryptophan-kynurenine degradation pathway and risk of atrial fibrillation and heart failure: potential modification effect of Mediterranean diet.

BACKGROUND: The tryptophan–kynurenine pathway is linked to inflammation. We hypothesize that metabolites implicated in this pathway may be associated with the risk of heart failure (HF) or atrial fibrillation (AF) in a population at high risk of cardiovascular disease. OBJECTIVES: We aimed to prospectively analyze the associations of kynurenine-related metabolites with the risk of HF and AF and to analyze a potential effect modification by the randomized interventions of the PREDIMED (Prevención con Dieta Mediterránea) trial with Mediterranean diet (MedDiet). METHODS: Two case–control studies nested within the PREDIMED trial were designed. We selected 324 incident HF cases and 502 incident …

Dietary Inflammatory Index and liver status in subjects with different adiposity levels within the PREDIMED trial.

Summary Background & aims To assess the possible association between a validated Dietary Inflammatory Index (DII) and specific dietary components with suitable non-invasive markers of liver status in overweight and obese subjects within the PREDIMED study. Methods A cross-sectional study encompassing 794 randomized overweight and obese participants (mean ± SD age: 67.0 ± 5.0 y, 55% females) from the PREDIMED (PREvencion con DIeta MEDiterranea) trial was conducted. DII is a validated tool evaluating the effect of diet on six inflammatory biomarkers (IL-1b, IL-4, IL-6, IL-10, TNF-α and C-reactive protein). Furthermore, a validated 137-item food-frequency-questionnaire was used to obtain the i…

Additional file 4: Figure S2. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) model to discriminate between the baseline and final states in group 1 (participants not meeting the NAFLD criteria at baseline and at the end of follow-up). Model diagnostics (A = 6, R2X = 0.621, Q2X = 0.160) (DOCX 43 kb)

Polimorfismos en el gen de la apolipoproteína E y riesgo de hipercolesterolemia: un estudio de casos y controles en una población laboral de Valencia

Fundamento El gen de la apolipoproteina E (apoE) presenta tres variantes comunes (alelos ɛ2, ɛ3, ɛ4), cuya frecuencia alelica y asociacion con los lipidos plasmaticos varia segun las poblaciones. Nuestro objetivo fue estimar la asociacion entre estas variantes geneticas y el riesgo de hipercolesterolemia en la poblacion mediterranea espanola. Pacientes y metodo Se ha realizado un estudio de casos y controles en una poblacion laboral de Valencia. Se identificaron 330 casos (148 varones y 182 mujeres) con hipercolesterolemia moderada (colesterol total > 200 mg/dl o con tratamiento hipolipemiante) y un intervalo de edad entre 20–60 anos. Se seleccionaron 330 controles normocolesterolemicos apa…

Fiber intake and all-cause mortality in the Prevención con Dieta Mediterránea (PREDIMED) study

Background: 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 …

Thyroid hormone receptor alpha gene variants increase the risk of developing obesity and show gene-diet interactions.

Thyroid hormone receptor-beta resistance has been associated with metabolic traits. THRA gene sequencing of an obese woman (index case) who presented as empirical thyroid hormone receptor-α (THRA) resistance, disclosed a polymorphism (rs12939700) in a critical region involved in TRα alternative processing.THRA gene variants were evaluated in three independent europid populations (i) in two population cohorts at baseline (n=3417 and n=2265), 6 years later (n=2139) and (ii) in 4734 high cardiovascular risk subjects (HCVR, PREDIMED trial).The minor allele of the index case polymorphism (rs12939700), despite having a very low frequency (4%), was significantly associated with higher body mass in…

Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk: Two Case-Control Studies in the PREDIMED Trial

OBJECTIVES: To prospectively analyze the associations between urea cycle metabolites and incident atrial fibrillation (AF) or heart failure (HF), and to evaluate the effect of a Mediterranean diet (MD) intervention on such associations. METHODS: We designed two nested case-control studies within the PREDIMED trial, a randomized controlled trial aimed to evaluate the effect of two MD interventions, supplemented with either extra virgin olive oil (EVOO) or nuts, on cardiovascular disease (CVD). Fasting blood samples were collected at baseline and urea cycle metabolites (arginine, citrulline, and ornithine) and methylarginines (asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA…

A Multi-Locus Genetic Risk Score for Primary Open-Angle Glaucoma (POAG) Variants Is Associated with POAG Risk in a Mediterranean Population: Inverse Correlations with Plasma Vitamin C and E Concentrations

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. The genetics of POAG are complex, and population-specific effects have been reported. Although many polymorphisms associated with POAG risk have been reported, few studies have analyzed their additive effects. We investigated, in a southern European Mediterranean population, the association between relevant POAG polymorphisms, identified by initial genome-wide association studies (GWASs) and POAG risk, both separately and as an aggregated multi-locus genetic risk score (GRS). Also, bearing in mind that oxidative stress is a factor increasingly recognized in the pathogenesis of POAG, we analyzed the potential assoc…

MicroRNAs and Drinking : Association between the Pre-miR-27a rs895819 Polymorphism and Alcohol Consumption in a Mediterranean Population

Recently, microRNAs (miRNA) have been proposed as regulators in the different processes involved in alcohol intake, and differences have been found in the miRNA expression profile in alcoholics. However, no study has focused on analyzing polymorphisms in genes encoding miRNAs and daily alcohol consumption at the population level. Our aim was to investigate the association between a functional polymorphism in the pre-miR-27a (rs895819 A>G) gene and alcohol consumption in an elderly population. We undertook a cross-sectional study of PREvención con DIeta MEDiterránea (PREDIMED)-Valencia participants (n = 1007, including men and women aged 67 7 years) and measured their alcohol consumption (to…

BOGENVI: A Biomedical Ontology for Modelling Gene*Environment Interactions on Intermediate Phenotypes in Nutrigenomics Research

Nutritional Genomics is demanding computing models and technological platforms in order to support acquisition, storage, management and presentation of all the information generated coming from heterogeneous sources: genotypes, environmental factors (diet and other life-style factors) and phenotypes (intermediate and final phenotypes). Our aim is to build a biomedical ontology in order to modelling gene*environment interactions on intermediate phenotypes by means of formalising and integrating genomic, environmental and phenotypic data, in the field of research on Nutritional Genomics applied to cardiovascular diseases and associated phenotypes. This ontology is part of a Health Information…

Modulación de la expresión fenotípica del paciente con cistinuria: influencia de la intervención terapéutica y de la dieta

OBJETIVOS El fenotipo final del paciente con cistinuria depende, por una parte, de la ausencia o defecto molecular mas o menos grave en el transporte de cistina y aminoacidos dibasicos; y por otra parte tambien de factores ambientales. El objetivo del presente estudio es conocer el efecto de la modulacion de diversos factores ambientales (pH urinario, ingesta de liquido, tratamiento farmacologico y en especial la dieta) sobre el fenotipo final del paciente con cistinuria. METODOS Se estudiaron 45 sujetos diagnosticados como pacientes con cistinuria (25 hombres y 20 mujeres), 42 individuos pertenecientes al arbol genealogico de estos pacientes con cistinuria (15 hombres y 27 mujeres) y 90 co…

Genetic polymorphism related to exfoliative glaucoma is also associated with primary open-angle glaucoma risk

Background To investigate the possible association of the rs2165241 polymorphism (C > T) in LOXL1 gene with the risk of primary open-angle glaucoma in a Mediterranean population. Methods The analysis of genetic polymorphisms was performed by standard TaqMan allelic discrimination technique, using a 7900HT Sequence Detection System (Applied Biosystems). Results In a recessive genetic model, the T allele of the rs2165241 polymorphism was significantly associated with the risk of primary open-angle glaucoma (TT vs. CC: odds ratios = 2.19, 95% confidence interval = [1.33–3.62]). After multivariate logistic regression model adjusted by age and weight, the magnitude of the association decreased b…

The Mediterranean diet improves the systemic lipid and DNA oxidative damage in metabolic syndrome individuals. A randomized, controlled, trial.

Summary Background & aims Metabolic syndrome (MetS), in which a non-classic feature is an increase in systemic oxidative biomarkers, presents a high risk of diabetes and cardiovascular disease (CVD). Adherence to the Mediterranean Diet (MedDiet) is associated with a reduced risk of MetS. However, the effect of the MedDiet on biomarkers for oxidative damage has not been assessed in MetS individuals. We have investigated the effect of the MedDiet on systemic oxidative biomarkers in MetS individuals. Methods Randomized, controlled, parallel clinical trial in which 110 female with MetS, aged 55–80, were recruited into a large trial (PREDIMED Study) to test the efficacy of the traditional MedDie…

Relevant associations of the glucokinase regulatory protein/glucokinase gene variation with TAG concentrations in a high-cardiovascular risk population: modulation by the Mediterranean diet

The SNP rs1260326 (P446L) and rs1799884 ( − 30G&gt;A) for the glucokinase regulatory protein (GCKR) and glucokinase (GCK) genes, respectively, have been associated with opposing effects on TAG and glucose concentrations. However, their genetic modulation by diet (dietary patterns or foods) remains to be investigated. We studied 945 high-cardiovascular risk subjects aged 67 (sd 6) years who participated in the PREvención con DIeta MEDiterránea-Valencia Study. Demographic, clinical, biochemical and genetic data were obtained. Adherence to the Mediterranean diet (MD) and food intake were measured by validated questionnaires. Carriers of the L allele of GKCR had significantly higher TAG concent…

Total and Subtypes of Dietary Fat Intake and its Association with Components of the Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Risk

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&ndash

Choline Metabolism and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Study

Abstract Background Few studies have examined the associations of trimethylamine-N-oxide (TMAO) and its precursors (choline, betaine, dimethylglycine, and L-carnitine) with the risk of atrial fibrillation (AF) and heart failure (HF). This study sought to investigate these associations. Methods Prospective associations of these metabolites with incident AF and HF were examined among participants at high cardiovascular risk in the PREDIMED study (PREvención con DIeta MEDiterránea) after follow-up for about 10 years. Two nested case-control studies were conducted, including 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma levels of TMAO an…

Influence of social factors on avoidable mortality: a hospital-based case-control study.

Objective. The effect of socioeconomic factors on avoidable mortality at an individual level is not well known, since most studies showing this association are based on aggregate data. The purpose of this study was to determine socioeconomic differences between those patients who die of avoidable causes and those who do not die. Methods. A matched case-control study was carried out regarding in-hospital avoidable mortality (Holland's medical care indicators) that occurred in a university hospital serving a Spanish-Mediterranean population during a 30-month period. Results. We studied 82 cases of death from avoidable causes and 300 controls matched on medical care indicators and age. The var…

IS COMPLYING WITH THE RECOMMENDATIONS OF SODIUM INTAKE BENEFICIAL FOR HEALTH? EVIDENCE FROM THE PREDIMED STUDY

CLOCK gene variation is associated with incidence of type‑2 diabetes and cardiovascular diseases in type‑2 diabetic subjects: dietary modulation in the PREDIMED randomized trial

Background: Circadian rhythms regulate key biological processes influencing metabolic pathways. Disregulation is associated with type 2 diabetes (T2D) and cardiovascular diseases (CVD). Circadian rhythms are generated by a transcriptional autoregulatory feedback loop involving core clock genes. CLOCK (circadian locomotor output cycles protein kaput), one of those core genes, is known to regulate glucose metabolism in rodent models. Cross-sectional studies in humans have reported associations between this locus and obesity, plasma glucose, hypertension and T2D prevalence, supporting its role in cardiovascular risk. However, no longitudinal study has investigated the association between CLOCK…

Cross-sectional associations of objectively-measured sleep characteristics with obesity and type 2 diabetes in the PREDIMED-Plus trial.

Study Objectives: To examine independent and combined associations of sleep duration and sleep variability with body composition, obesity and type 2 diabetes (T2D) in elders at high cardiovascular risk. Methods: Cross-sectional analysis of 1986 community-dwelling elders with overweight/obesity and metabolic syndrome from PREDIMEDPlus trial. Associations of accelerometry-derived sleep duration and sleep variability with body mass index (BMI), waist circumference (WC) and body composition were assessed fitting multivariable-adjusted linear regression models. Prevalence ratios (PR) and 95% confidence intervals (CI) for obesity and T2D were obtained using multivariable-adjusted Cox regression w…

Blood pressure values and depression in hypertensive individuals at high cardiovascular risk

Background: Hypertension and depression are both important risk factors for cardiovascular diseases. Nevertheless, the association of blood pressure on and depression has not been completely established. This study aims to analyze whether depression may influence the control of blood pressure in hypertensive individuals at high cardiovascular risk. Methods: Cross-sectional study, embedded within the PREDIMED clinical trial, of 5954 hypertensive patients with high cardiovascular risk factor profiles. The relationship between blood pressure control and depression was analyzed. A multivariate analysis (logistic and log-linear regression), adjusting for potential confounders (socio-demographic …

Role of HDL function and LDL atherogenicity on cardiovascular risk: a comprehensive examination

[Background] High-density lipoprotein (HDL) functionality and low-density lipoprotein (LDL) atherogenic traits can describe the role of both particles on cardiovascular diseases more accurately than HDL- or LDL-cholesterol levels. However, it is unclear how these lipoprotein properties are particularly affected by different cardiovascular risk factors.

Increases in Plasma Tryptophan Are Inversely Associated with Incident Cardiovascular Disease in the Prevención con Dieta Mediterránea (PREDIMED) Study123

Background: During development of cardiovascular disease (CVD), interferon-γ-mediated inflammation accelerates degradation of tryptophan into downstream metabolites. A Mediterranean diet (MedDiet) consisting of a high intake of extra-virgin 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 Prevención con Dieta Medite…

Legume consumption is inversely associated with type 2 diabetes incidence in adults: A prospective assessment from the PREDIMED study

Background & aims: Legumes, a low-energy, nutrient-dense and low glycemic index food, have shown beneficial effects on glycemic control and adiposity. As such, legumes are widely recommended in diabetic diets, even though there is little evidence that their consumption protects against type 2 diabetes. Therefore the aim of the present study was to examine the associations between consumption of total legumes and specific subtypes, and type 2 diabetes risk. We also investigated the effect of theoretically substituting legumes for other protein- or carbohydrate-rich foods. Methods: Prospective assessment of 3349 participants in the PREvención con DIeta MEDiterránea (PREDIMED) study without ty…

Haemorheological parameters in young patients with acute myocardial infarction

The role played by hemorheological alterations on acute myocardial infarction (AMI) in young patients remains a question of debate. We have carried out a case-control study of 84 AMI patients aged45 years and 135 sex and age matched controls, in which blood viscosity (BV), plasma viscosity (PV), erythrocyte aggregation (EA) performed with the Myrenne (EA0, EA1) and the Sefam aggregometer (Ta, AI10, gammaD), erythrocyte deformability (ED) along with fibrinogen (Fbg), C-reactive protein (CRP) and plasmatic lipids i.e. total cholesterol (T-Chol) and triglycerides (TG) were determined. AMI patients showed higher, Fbg, TG, EA0, EA1, IA10, gammaD and lower Ta than controls (p=0.029, p0.001, p=0.0…

Additional file 5: Figure S3. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) to discriminate between the baseline and final states in group 2 (suspected cases of NAFLD). Model diagnostics (A = 6, R2X = 0.624, Q2X = 0.179) (DOCX 39 kb)

Additional file 11: Figure S9. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Volcano plot [−log10 (p-value) vs. log2 (fold-change)] for the comparison between the baseline and final states in group 3 (suspected NAFLD reversion cases). Abbreviations: AA, amino acids; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; MUFA, monounsaturated fatty acids; NAE, N-acyl ethanolamines; FFAox, free fatty acid oxidised; AC, acyl carnitines; PC, phosphatidylcholine; LPC, lysophosphatidylcholine; PE, phatidylethanolamine; LPE, lysophosphatidylethanolamine; PI, phatidylinositols; LPI, lysophosphatidylinositols; Cer, ceramides; SM, sphingomyelin; ChoE, cholesteryl esters; Chol, cholesterol; TAG, triacylglycerols; DAG, diacylglycerols, BA, bile acids; CMH, monohexosylce…

The Eveningness Chronotype and Lower Adherence to the Mediterranean Diet Are Associated With Depressive Symptoms in Older Subjects With Metabolic Syndrome

OBJECTIVES: Studies have shown the importance of depression as a risk factor for several diseases. Likewise, currently there is great interest on the role of chronotype in depressive disorders. Similarly, associations between diet and depression have been reported. However, very few studies have analyzed the combined effect of diet and chronotype on depression. Our aim was to investigated the joint influence of the morning/evening chronotype and adherence to the Mediterranean diet (MeDiet) on depressive symptoms in older subjects with metabolic syndrome. METHODS: We analyzed 465 PREDIMED Plus-Valencia study participants (aged 55–75). We assessed depressive symptoms by the Beck Depression In…

Lifestyles and risk factors associated with adherence to the Mediterranean diet: a baseline assessment of the PREDIMED trial

Background: The traditional Mediterranean dietary pattern (MedDiet) is associated with longevity and low rates of cardiovascular disease (CVD). However, there is little information on who is more likely to follow this food pattern. Aim: To evaluate how different factors are associated with lower MedDiet adherence in older Spanish subjects. Methods: We included 7305 participants (men aged 55-80 y, women 60-80 y) at high-risk of CVD recruited into the PREDIMED trial (ISRCTN35739639). Socioeconomic, anthropometric, lifestyle characteristics and CVD risk factors were recorded. A validated 14-item questionnaire was used to evaluate MedDiet adherence at baseline. Multivariate models were used to …

Data-Driven Clustering Approach to Derive Taste Perception Profiles from Sweet, Salt, Sour, Bitter, and Umami Perception Scores: An Illustration among Older Adults with Metabolic Syndrome.

BACKGROUND Current approaches to studying relations between taste perception and diet quality typically consider each taste-sweet, salt, sour, bitter, umami-separately or aggregately, as total taste scores. Consistent with studying dietary patterns rather than single foods or total energy, an additional approach may be to study all 5 tastes collectively as "taste perception profiles." OBJECTIVE We developed a data-driven clustering approach to derive taste perception profiles from taste perception scores and examined whether profiles outperformed total taste scores for capturing individual variability in taste perception. METHODS The cohort included 367 community-dwelling adults [55-75 y; 5…

Impact of Consuming Extra-Virgin Olive Oil or Nuts within a Mediterranean Diet on DNA Methylation in Peripheral White Blood Cells within the PREDIMED-Navarra Randomized Controlled Trial: A Role for Dietary Lipids

DNA methylation could be reversible and mouldable by environmental factors, such as dietary exposures. The objective was to analyse whether an intervention with two Mediterranean diets, one rich in extra-virgin olive oil (MedDiet + EVOO) and the other one in nuts (MedDiet + nuts), was influencing the methylation status of peripheral white blood cells (PWBCs) genes. A subset of 36 representative individuals were selected within the PREvención con DIeta MEDiterránea (PREDIMED-Navarra) trial, with three intervention groups in high cardiovascular risk volunteers: MedDiet + EVOO, MedDiet + nuts, and a low-fat control group. Methylation was assessed at baseline and at five-year follow-up. Ingenui…

Plasma Metabolomic Profiles of Glycemic Index, Glycemic Load, and Carbohydrate Quality Index in the PREDIMED Study

Background The quality of carbohydrate consumed, assessed by the glycemic index (GI), glycemic load (GL), or carbohydrate quality index (CQI), affects the postprandial glycemic and insulinemic responses, which have been implicated in the etiology of several chronic diseases. However, it is unclear whether plasma metabolites involved in different biological pathways could provide functional insights into the role of carbohydrate quality indices in health. Objectives We aimed to identify plasma metabolomic profiles associated with dietary GI, GL, and CQI. Methods The present study is a cross-sectional analysis of 1833 participants with overweight/obesity (mean age = 67 y) from 2 case-cohort s…

Association of Taste Perception for Sweet, Salt, Sour, Bitter and Umami and Food Intake Among Community-dwelling Adults in the PREDIMED-PLUS Trial (P18-065-19)

OBJECTIVES: To investigate the association between taste perception for sweet, salt, sour, bitter and umami and food category intakes. We hypothesized that greater taste perception will be inversely associated with the amount consumed. METHODS: A cross-sectional baseline analysis was performed on community-dwelling overweight adults with metabolic syndrome (N = 367, 55–75y) from the PREDIMED-PLUS Trial, University of Valencia Center, Spain. Taste perception was determined by challenging subjects with standard solutions of sweet, salt, sour, bitter and umami (400 mM sucrose, 200 mM NaCl, 34 mM citric acid, 5.6 mM phenylthiocarbamide (PTC), 200 mM monopotassium glutamate, respectively) and ev…

Glycemic Dysregulations Are Associated With Worsening Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-up in the PREDIMED-Plus Study

The authors wish to thank the PREDIMED-Plus participants and staff for their engagement, as well as to the primary care centers involved in the study. We also thank the Cerca Programme of the Generalitat de Catalunya, and the CIBEROBN, CIBERESP and CIBERDEM initiatives of Instituto de Salud Carlos III in Spain, and the collaborators in the PRIME consortium for helpful input. The first version of the present article has been published in the public repository Research Square as a preprint publication of our work (44). We particularly thank Stephanie Nishi for her assistance with manuscript language revision.

Polymorphism of the Transcription Factor 7-Like 2 Gene (TCF7L2) Interacts with Obesity on Type-2 Diabetes in the PREDIMED Study Emphasizing the Heterogeneity of Genetic Variants in Type-2 Diabetes Risk Prediction: Time for Obesity-Specific Genetic Risk Scores

Nutrigenetic studies analyzing gene-diet interactions of the TCF7L2-rs7903146 C > T polymorphism on type-2 diabetes (T2D) have shown controversial results. A reason contributing to this may be the additional modulation by obesity. Moreover, TCF7L2-rs7903146 is one of the most influential variants in T2D-genetic risk scores (GRS). Therefore, to increase the predictive value (PV) of GRS it is necessary to first see whether the included polymorphisms have heterogeneous effects. We comprehensively investigated gene-obesity interactions between the TCF7L2-rs7903146 C > T polymorphism on T2D (prevalence and incidence) and analyzed other T2D-polymorphisms in a sub-sample. We studied 7018 PREDIMED …

Benefits of the Mediterranean diet: Epidemiological and molecular aspects

Abstract More than 50 years after the Seven Countries Study, a large number of epidemiological studies have explored the relationship between the Mediterranean diet (MD) and health, through observational, case-control, some longitudinal and a few experimental studies. The overall results show strong evidence suggesting a protective effect of the MD mainly on the risk of cardiovascular disease (CVD) and certain types of cancer. The beneficial effects have been attributed to the types of food consumed, total dietary pattern, components in the food, cooking techniques, eating behaviors and lifestyle behaviors, among others. The aim of this article is to review and summarize the knowledge deriv…

Interplay between cognition and weight reduction in individuals following a Mediterranean Diet: Three-year follow-up of the PREDIMED-Plus trial

Background & aims: Some cognitive profiles might facilitate successful weight loss and its maintenance. Also, weight reductions may result in cognitive benefits. However, little work to date has examined the interactions between cognition and weight changes in the context of interventions with the Mediterranean diet (MedDiet). We studied the within-subject longitudinal relationships between cognition, body mass index (BMI), physical activity (PA), and quality of life (QoL), in older adults following a MedDiet. Methods: The PREDIMED-Plus is a primary prevention trial testing the effect of a lifestyle intervention program with an energy-restricted MedDiet (er-MedDiet), weight-loss goals and P…

Chronological Age Interacts with the Circadian Melatonin Receptor 1B Gene Variation, Determining Fasting Glucose Concentrations in Mediterranean Populations. Additional Analyses on Type-2 Diabetes Risk

Gene-age interactions have not been systematically investigated on metabolic phenotypes and this modulation will be key for a better understanding of the temporal regulation in nutrigenomics. Taking into account that aging is typically associated with both impairment of the circadian system and a decrease in melatonin secretion, we focused on the melatonin receptor 1B (MTNR1B)-rs10830963 C&gt

Additional file 7: Figure S5. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Heatmap representing individual metabolomic features obtained from the comparisons between the three baseline states in groups 1, 2 and 3.Heatmapcolor codes for log2 (fold-change) and ANOVA and Tukey’s Honestly Significance Difference post hoc test p-values are indicated at the bottom of the Figure. Darker green and red colors indicate higher drops or elevations of the metabolite levels in every comparison. Grey lines correspond to significant fold-changes of individual metabolites, darker grey colors have been used to highlight higher significances (p

Relationship between olive oil consumption and ankle-brachial pressure index in a population at high cardiovascular risk.

[Background and aims]: The aim of this study was to ascertain the association between the consumption of different categories of edible olive oils (virgin olive oils and olive oil) and olive pomace oil and ankle-brachial pressure index (ABI) in participants in the PREDIMED-Plus study, a trial of lifestyle modification for weight and cardiovascular event reduction in individuals with overweight/obesity harboring the metabolic syndrome.

Plasma Metabolomics Profiles are Associated with the Amount and Source of Protein Intake: A Metabolomics Approach within the PREDIMED Study.

SCOPE: The plasma metabolomics profiles of protein intake has been rarely investigated. We aimed to identify the distinct plasma metabolomics profiles associated with overall intakes of protein as well as with intakes from animal and plant protein sources. METHODS AND RESULTS: Cross-sectional analysis using data from 1,833 participants at high risk of cardiovascular disease. Plasma metabolomics analysis was performed using LC-MS. Associations between 385 identified metabolites and the intake of total, animal protein (AP) and plant protein (PP), and plant-to-animal ratio (PR) were assessed using elastic net continuous regression analyses. A double 10-cross-validation (CV) procedure was used …

The Mediterranean Diet decreases LDL atherogenicity in high cardiovascular risk individuals: a randomized controlled trial.

cope Traditional Mediterranean diet (TMD) protects against cardiovascular disease through several mechanisms such as decreasing LDL cholesterol levels. However, evidence regarding TMD effects on LDL atherogenic traits (resistance against oxidation, size, composition, cytotoxicity) is scarce. Methods and results We assessed the effects of a 1-year intervention with a TMD on LDL atherogenic traits in a random sub-sample of individuals from the PREDIMED study (N = 210). We compared two TMDs: one enriched with virgin olive oil (TMD-VOO, N = 71) and another with nuts (TMD-Nuts, N = 68), versus a low-fat control diet (N = 71). After the TMD-VOO intervention, LDL resistance against oxidation incre…

DNA methylomes reveal biological networks involved in human eye development, functions and associated disorders

This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are…

A-6G polymorphism of the angiotensinogen gene and body weight changes in essential hypertension: a prospective study

Walnut Consumption, Plasma Metabolomics, and Risk of Type 2 Diabetes and Cardiovascular Disease

BACKGROUND: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. OBJECTIVES: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. METHODS: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseli…

Effects of a psychosocial intervention at one-year follow-up in a PREDIMED-plus sample with obesity and metabolic syndrome

This study examines if overweight/obesity are related to higher impulsivity, food addiction and depressive symptoms, and if these variables could be modified after 1 year of a multimodal intervention (diet, physical activity, psychosocial support). 342 adults (55-75 years) with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus Cognition study were randomized to the intervention or to the control group (lifestyle recommendations). Cognitive and psychopathological assessments were performed at baseline and after 1-year follow-up. At baseline, higher impulsivity was linked to higher food addiction and depressive symptoms, but not to body mass index (BMI). Food addiction n…

Cytoskeletal transgelin 2 contributes to gender-dependent adipose tissue expandability and immune function

During adipogenesis, preadipocytes' cytoskeleton reorganizes in parallel with lipid accumulation. Failure to do so may impact the ability of adipose tissue (AT) to shift between lipid storage and mobilization. Here, we identify cytoskeletal transgelin 2 (TAGLN2) as a protein expressed in AT and associated with obesity and inflammation, being normalized upon weight loss. TAGLN2 was primarily found in the adipose stromovascular cell fraction, but inflammation, TGF-β, and estradiol also prompted increased expression in human adipocytes. Tagln2 knockdown revealed a key functional role, being required for proliferation and differentiation of fat cells, whereas transgenic mice overexpressing Tagl…

Efecto del polimorfismo de la apolipoproteína E en el perfil lipoproteico y riesgo cardiovascular en una población mediterránea

Fundamento La asociacion de las variantes comunes del gen de la apolipoproteina E (apo E)con arteriosclerosis varia segun las poblaciones. Nuestro objetivo fue estimar la asociacion entreestas variantes geneticas (alelos e2, e3 y e4) con las concentraciones de lipidos plasmaticosy el riesgo de enfermedad cardiovascular (ECV) en una poblacion mediterranea espanola. Pacientes y metodo Se ha realizado un estudio transversal en 486 individuos (144 varones y342 mujeres) procedentes de poblacion general mediterranea (7-85 anos). Se determino el genotipode la apo E y variables antropometricas, bioquimicas y del estilo de vida. Resultados La frecuencia alelica para e2 y e4 fue baja (0,052; interval…

Additional file 3: of Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial

Consort 2010 Checklist. (DOC 219 kb)

Long Daytime Napping Is Associated with Increased Adiposity and Type 2 Diabetes in an Elderly Population with Metabolic Syndrome.

The authors especially thank the PREDIMED-Plus participants for their enthusiastic collaboration, the PREDIMED-Plus personnel for their outstanding support, and the personnel of all associated primary care centers for their exceptional effort. Centros de Investigación Biomédica en Red: Obesidad y Nutrición (CIBEROBN), Centros de Investigación Biomédica en Red: Epidemiología y Salud Pública (CIBERESP) and Centros de Investigación Biomédica en Red: Diabetes y Enfermedades Metabólicas asociadas (CIBERDEM) are initiatives of Instituto de Salud Carlos III (ISCIII), Madrid, Spain. We thank the PREDIMED-Plus Biobank Network, part of the National Biobank Platform of ISCIII for storing and managing …

The 3-year effect of the mediterranean diet intervention on inflammatory biomarkers related to cardiovascular disease

The intervention with the Mediterranean diet (MD) pattern has evidenced short-term anti-inflammatory effects, but little is known about its long-term anti-inflammatory properties at molecular level. This study aims to investigate the 3-year effect of MD interventions compared to low-fat diet (LFD) on changes on inflammatory biomarkers related to atherosclerosis in a free-living population with a high-risk of cardiovascular disease (CD). Participants (n = 285) in the PREDIMED trial were randomly assigned into three intervention groups: MD with extra-virgin olive oil (EVOO) or MD-Nuts, and a LFD. Fourteen plasma inflammatory biomarkers were determined by Luminex assays. An additional pilot st…

Association between the 2018 WCRF/AICR and the Low-Risk Lifestyle Scores with Colorectal Cancer Risk in the Predimed Study

Limited longitudinal studies have been conducted to evaluate colorectal cancer (CRC) incidence based on the updated 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) recommendations or other global lifestyle indices, and none in aged populations at high cardiovascular risk. We aimed to assess the association between CRC incidence and adherence to two emerging lifestyles indices (2018 WCRF/AICR score and another low-risk lifestyle (LRL) score comprising smoking status, alcohol consumption, physical activity, diet, and body mass index) in the Spanish PREvencion con DIeta MEDiterranea (PREDIMED) cohort. We studied 7216 elderly men and women at high cardiovascul…

Estudio de investigación cualitativa sobre las diferencias entre hombres y mujeres en la percepción de la obesidad, sus causas, abordaje y repercusiones para la salud

Introducción: aunque la obesidad es un problema de salud multidimensional, pocos estudios de investigación cualitativa han analizado el discurso de personas obesas con perspectiva de género para conocer con mayor  profundidad información difícilmente obtenible con técnicas cuantitativas.Objetivo: analizar el discurso de personas obesas mediante grupos de discusión en cuanto a factores que subyacen en la obesidad, percepción del riesgo de patologías, pérdida peso y otros factores relevantes.Métodos: se realizaron dos grupos de discusión en sesiones separadas, homogéneos por sexo, con un total de 14 participantes. Un moderador dirigió la sesión contemplando las distintas dimensiones del probl…

Energy Balance and Risk of Mortality in Spanish Older Adults

Clinical data on the direct health effects of energy deficit or surplus beyond its impact on body weight are scarce. We aimed to assess the association with all-cause, cardiovascular and cancer mortality of (1) sustained energy deficit or surplus, calculated according to each individual’s en-ergy intake (EI) and theoretical energy expenditure (TEE), and (2) mid-term change in total EI in a prospective study. In 7119 participants in the PREDIMED Study (PREvención con DIeta MEDi-terránea) with a mean age of 67 years, energy intake was derived from a 137-item food frequency questionnaire. TEE was calculated as a function of age, sex, height, body weight and physical ac-tivity. The main exposur…

Non-targeted metabolomic biomarkers and metabotypes of type 2 diabetes: A cross-sectional study of PREDIMED trial participants

Aim. - To characterize the urinary metabolomic fingerprint and multi-metabolite signature associated with type 2 diabetes (T2D), and to classify the population into metabotypes related to T2D. Methods. - A metabolomics analysis using the 1 H-NMR-based, non-targeted metabolomic approach was conducted to determine the urinary metabolomic fingerprint of T2D compared with non-T2D participants in the PREDIMED trial. The discriminant metabolite fingerprint was subjected to logistic regression analysis and ROC analyses to establish and to assess the multi-metabolite signature of T2D prevalence, respectively. Metabotypes associated with T2D were identified using the k-means algorithm. Results. - A …

Polymorphisms of the renin-angiotensin system influence height in normotensive women in a Spanish population.

The objective of this study was to analyze the influence of the polymorphisms G-6A of the angiotensinogen gene, insertion/deletion (I/D) of the angiotensin-converting enzyme, and C573T of the angiotensin II AT1 receptor gene on a healthy, middle-age population. A total of 370 (194 women) healthy normotensive Caucasian subjects, aged 25-50 yr old, were selected from the general population. A significant association was found between height and the C573T polymorphism in women (P0.001). After adjustment for age, this association remained significant (P0.002). Thus, the lowest height values were from subjects carrying TT genotype (CC, 1.627 +/- 0.008 m; CT, 1.595 +/- 0.006 m; TT, 1.586 +/- 0.01…

Association of plasma markers of cholesterol homeostasis with metabolic syndrome components. A cross-sectional study.

Abstract Background and aims Increased plasma phytosterols, which reflect enhanced cholesterol absorption, have been related to an increased risk of cardiovascular disease (CVD). However, high CVD risk conditions, such as obesity, diabetes and the metabolic syndrome (MetS) have been associated with reduced cholesterol absorption. We investigated associations between plasma noncholesterol sterols and MetS components. Methods and results With a cross-sectional design, we related MetS components to plasma noncholesterol sterol-to-cholesterol ratios measured by gas chromatography in 674 dyslipidemic patients and 361 healthy subjects participating in a prospective cohort study. Plasma phytostero…

Lipidomic profiling identifies signatures of metabolic risk

Background: Metabolic syndrome (MetS), the clustering of metabolic risk factors, is associated with cardiovascular disease risk. We sought to determine if dysregulation of the lipidome may contribute to metabolic risk factors. Methods: We measured 154 circulating lipid species in 658 participants from the Framingham Heart Study (FHS) using liquid chromatography-tandem mass spectrometry and tested for associations with obesity, dysglycemia, and dyslipidemia. Independent external validation was sought in three independent cohorts. Follow-up data from the FHS were used to test for lipid metabolites associated with longitudinal changes in metabolic risk factors. Results: Thirty-nine lipids were…

Dietary intake of vitamin K is inversely associated with mortality risk

Vitamin K has been related to cardiovascular disease and cancer risk. However, data on total mortality are scarce. The aimof the present study was to assess the association between the dietary intake of different types of vitamin K and mortality in a Mediterranean population at high cardiovascular disease risk. A prospective cohort analysis was conducted in 7216 participants from the PREDIMED (Prevención con Dieta Mediterránea) study (median follow-up of 4.8 y). Energy and nutrient intakes were evaluated using a validated 137-item food frequency questionnaire. Dietary vitamin K intake was calculated annually using the USDA food composition database and other published sources. Deaths were a…

Heterogeneity of the Stearoyl-CoA desaturase-1 (SCD1) Gene and Metabolic Risk Factors in the EPIC-Potsdam Study

Background: Stearoyl-CoA desaturase-1 (SCD1) is an enzyme involved in lipid metabolism. In mice and humans its activity has been associated with traits of the metabolic syndrome, but also with the prevention of saturated fatty acids accumulation and subsequent inflammation, whereas for liver fat content inconsistent results have been reported. Thus, variants of the gene encoding SCD1 (SCD1) could potentially modify metabolic risk factors, but few human studies have addressed this question. Methods: In a sample of 2157 middle-aged men and women randomly drawn from the Potsdam cohort of the European Prospective Investigation into Cancer and Nutrition, we investigated the impact of 7 SCD1 tagg…

Additional file 3: Figure S1. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) model to discriminate between the three baseline states in groups 1, 2 and 3. Model diagnostics (A = 8, R2X = 0.651, Q2X = 0.264) (DOCX 43 kb)

Effect of the polymorphism rs2066844 of the NOD2 gene on colon cancer incidence in a high cardiovascular risk population: Modulation by gender

Association of the rs4988235 in the lactase gene with obesity and its modulation by dairy products in a Mediterranean population

The -13910C>T polymorphism (rs4988235) upstream from the lactase (LCT) gene, strongly associated with lactase persistence (LP) in Europeans, is emerging as a new candidate for obesity. We aimed to analyze the association of this polymorphism with obesity-related variables and its modulation by dairy product intake in an elderly population. We studied 940 high-cardiovascular risk Spanish subjects (aged 67 ± 7 years). Dairy product consumption was assessed by a validated questionnaire. Anthropometric variables were directly measured, and metabolic syndrome-related variables were obtained. Prevalence of genotypes was: 38.0% CC (lactase nonpersistent (LNP)), 45.7% CT, and 16.3% TT. The CC genot…

Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial

[Background] The Fas apoptotic pathway has been implicated in type 2 diabetes and cardiovascular disease. Although a polymorphism (rs7138803; G > A) near the Fas apoptotic inhibitory molecule 2 (FAIM2) locus has been related to obesity, its association with other cardiovascular risk factors and disease remains uncertain.

Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case-control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. C…

Legume consumption and risk of all-cause, cardiovascular, and cancer mortality in the PREDIMED study.

BACKGROUND & AIMS: Limited prospective studies have examined the association between legumes consumption and mortality, whereas scarce, if at all, previous studies have evaluated such associations taking into consideration specific grain legumes. We aimed to investigate the association between total legumes consumption and grain legumes species (dry beans, chickpeas, lentils, and fresh peas) with all-cause, cardiovascular disease (CVD), cancer and other-cause mortality among elderly Mediterranean individuals at high CVD risk. METHODS: We prospectively assessed 7216 participants from the PREvención con DIeta MEDiterránea study. Dietary intake was assessed at baseline and yearly during follow…

Mediterranean Diet and Invasive Breast Cancer Risk Among Women at High Cardiovascular Risk in the PREDIMED Trial

Importance Breast cancer is the leading cause of female cancer burden, and its incidence has increased by more than 20% worldwide since 2008. Some observational studies have suggested that the Mediterranean diet may reduce the risk of breast cancer. Objective To evaluate the effect of 2 interventions with Mediterranean diet vs the advice to follow a low-fat diet (control) on breast cancer incidence. Design, Setting, and Participants The PREDIMED study is a 1:1:1 randomized, single-blind, controlled field trial conducted at primary health care centers in Spain. From 2003 to 2009, 4282 women aged 60 to 80 years and at high cardiovascular disease risk were recruited after invitation by their p…

Seafood Consumption, Omega-3 Fatty Acids Intake, and Life-Time Prevalence of Depression in the PREDIMED-Plus Trial.

Background: The aim of this analysis was to ascertain the type of relationship between fish and seafood consumption, omega-3 polyunsaturated fatty acids (&omega

Gene-Environment Interactions: Defining the Playfield

Milk and Dairy Products Intake Is Related to Cognitive Impairment at Baseline in Predimed Plus Trial

Scope: To examine the association between milk and dairy products intake and the prevalence of cognitive decline among Spanish individuals at high cardiovascular risk. Methods and results: Cross-sectional analyses are performed on baseline data from 6744 adults (aged 55-75 years old). Intake of milk and dairy products is estimated using a food frequency questionnaire grouped into quartiles. The risk of developing cognitive impairment is based on the Mini-Mental State Examination (MMSE). A higher prevalence of cognitive decline was found in subjects who consumed more grams. Patients with worse MMSE score (10-24) consumed a mean of 395.14 ± 12.21 g, while patients with better MMSE score (27-3…

Comparación de las frecuencias de los alelos factor V Leiden (G1691A) y protrombina-G20210A entre pacientes con trombosis venosa profunda y población general mediterránea española

Background: Factor V leiden and the -G20210A variant of prothrombin gene are associated to a higher risk of deep venous thrombosis. Aim: To assess the frequency of factor V Leiden (G1691A) and prothrombin -G20210A alleles in patients with deep venous thrombosis (DVT) and in the general population from Spain. Material and methods: Factor V Leiden (g1691a) and prothrombin-g20210a alleles were genotyped in 493 individuals from the Spanish general populations and in 131 patients with DVT. The presence of DVT was confirmed by phlebography. Allelic frequencies and the DVT risk associated with these variants were estimated. Results: Allelic frequencies for the factor V Leiden (G1691A) allele were …

Retracted: Effect of a high-fat Mediterranean diet on bodyweight and waist circumference: a prespecified secondary outcomes analysis of the PREDIMED randomised controlled trial

Summary Background Because of the high density of fat, high-fat diets are perceived as likely to lead to increased bodyweight, hence health-care providers are reluctant to recommend them to overweight or obese individuals. We assessed the long-term effects of ad libitum, high-fat, high-vegetable-fat Mediterranean diets on bodyweight and waist circumference in older people at risk of cardiovascular disease, most of whom were overweight or obese. Methods PREDIMED was a 5 year parallel-group, multicentre, randomised, controlled clinical trial done in primary care centres affiliated to 11 hospitals in Spain. 7447 asymptomatic men (aged 55–80 years) and women (aged 60–80 years) who had type 2 di…

The Mediterranean diet, plasma metabolome, and cardiovascular disease risk.

Abstract Aims To investigate whether metabolic signature composed of multiple plasma metabolites can be used to characterize adherence and metabolic response to the Mediterranean diet and whether such a metabolic signature is associated with cardiovascular disease (CVD) risk. Methods and results Our primary study cohort included 1859 participants from the Spanish PREDIMED trial, and validation cohorts included 6868 participants from the US Nurses’ Health Studies I and II, and Health Professionals Follow-up Study (NHS/HPFS). Adherence to the Mediterranean diet was assessed using a validated Mediterranean Diet Adherence Screener (MEDAS), and plasma metabolome was profiled by liquid chromatogr…

Additional file 2: of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Estimation of the index of enzyme activities. (DOCX 11 kb)

Changes in arginine are inversely associated with type 2 diabetes: A case-cohort study in the PREDIMED trial

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…

Cancer Signaling Transcriptome Is Upregulated in Type 2 Diabetes Mellitus

We aimed to explore the differences in the whole transcriptome of peripheral blood mononuclear cells between elderly individuals with and without type 2 diabetes (T2D). We conducted a microarray-based transcriptome analysis of 19 individuals with T2D and 15 without. Differentially expressed genes according to linear models were submitted to the Ingenuity Pathway Analysis system to conduct a functional enrichment analysis. We established that diseases, biological functions, and canonical signaling pathways were significantly associated with T2D patients when their logarithms of Benjamini&ndash

Polyphenol intake and cardiovascular risk in the PREDIMED-Plus trial. A comparison of different risk equations

Abstract Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food…

Relative validity of a semi-quantitative food-frequency questionnaire in an elderly Mediterranean population of Spain

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 a…

genuMet: distinguish genuine untargeted metabolic features without quality control samples

AbstractMotivationLarge-scale untargeted metabolomics experiments lead to detection of thousands of novel metabolic features as well as false positive artifacts. With the incorporation of pooled QC samples and corresponding bioinformatics algorithms, those measurement artifacts can be well quality controlled. However, it is impracticable for all the studies to apply such experimental design.ResultsWe introduce a post-alignment quality control method called genuMet, which is solely based on injection order of biological samples to identify potential false metabolic features. In terms of the missing pattern of metabolic signals, genuMet can reach over 95% true negative rate and 85% true posit…

Association of the rs4567312 variant in the leptin receptor gene with plasma leptin concentrations and lung cancer incidence in the PREDIMED study

Arylesterase Activity and Antioxidant Status Depend on PON1-Q192R and PON1-L55M Polymorphisms in Subjects with Increased Risk of Cardiovascular Disease Consuming Walnut-Enriched Meat

Human paraoxonase (PON1) exists in 2 major polymorphic forms and has been shown to protect LDL and HDL against oxidation. The aim of this study was to assess the differences between subjects at increased risk of cardiovascular disease (CVD), taking into account the effects of PON1-Q192R and PON1-L55M polymorphisms on 1) basal serum arylesterase activity, lipid peroxidation (LPO), and LDL-cholesterol (LDL-C), HDL-C, total cholesterol (TC), and oxidized-LDL (ox-LDL) concentrations; 2) the relations between arylesterase activity and lipid variables; and 3) the effect of walnut-enriched meat (WM) consumption on arylesterase activity and lipid variables. Twenty-three Caucasians at increased risk…

Dietary habits and geographic variation in stomach cancer mortality in Spain

Following examination of the geographical pattern of stomach cancer incidence in Spain, the possible relationship between diet and stomach cancer has been assessed using an ecological model which looks into the relationship between the consumption of different foods and the nutrient intake in each of the 50 Spanish provinces during the period 1964-65, and the mortality rate for stomach cancer in these same 50 provinces during a period 20 years later (1984-86). The geographical pattern of stomach cancer mortality has been arrived at using the standardized mortality ratios (SMRs) calculated for each province. The per capita consumption of foods was obtained from the National Institute for Sta…

Effect of a 2-year diet intervention with walnuts on cognitive decline. The Walnuts And Healthy Aging (WAHA) study: a randomized controlled trial

Background Walnut consumption counteracts oxidative stress and inflammation, 2 drivers of cognitive decline. Clinical data concerning effects on cognition are lacking. Objectives The Walnuts And Healthy Aging study is a 2-center (Barcelona, Spain; Loma Linda, CA) randomized controlled trial examining the cognitive effects of a 2-y walnut intervention in cognitively healthy elders. Methods We randomly allocated 708 free-living elders (63-79 y, 68% women) to a diet enriched with walnuts at ∼15% energy (30-60 g/d) or a control diet (abstention from walnuts). We administered a comprehensive neurocognitive test battery at baseline and 2 y. Change in the global cognition composite was the primary…

Mediterranean dietary pattern and depression: the PREDIMED randomized trial

Background: A few observational studies have found an inverse association between adherence to a Mediterranean diet and the risk of depression. Randomized trials with an intervention based on this dietary pattern could provide the most definitive answer to the findings reported by observational studies. The aim of this study was to compare in a randomized trial the effects of two Mediterranean diets versus a low-fat diet on depression risk after at least 3 years of intervention. Methods: This was a multicenter, randomized, primary prevention field trial of cardiovascular disease (Prevencion con Dieta Mediterranea (PREDIMED Study)) based on community-dwelling men aged 55 to 80 years and wome…

Polimorfismos genéticos del sistema renina-angiotensina e hipertensión arterial esencial en la población española

Fundamento Analizar la asociacion entre los principales polimorfismos geneticos descritos en el sistema renina-angiotensina y la hipertension arterial (hta) esencial en una muestra de poblacion espanola. Pacientes y metodo Estudio de casos y controles con 185 hipertensos esenciales (edad [de] 39,6 [7,5] anos, 52% mujeres, presion arterial sistolica [pas] de 151,2 [17,4] mmhg, presion arterial diastolica [pad] de 96,0 [9,4] mmhg) y 350 controles normotensos apareados por edad y sexo de una muestra de poblacion general de la Comunidad Valenciana (edad 39,4 [8,0] anos, 51,7% mujeres, PAS de 116,0 [12,0] mmhg, pad de 69,6 [8,5] mmhg). Se realizo pcr para la determinacion de los polimorfismos i/…

Waist-to-height ratio and cardiovascular risk factors in elderly individuals at high cardiovascular risk

Introduction: Several anthropometric measurements have been associated with cardiovascular disease, type-2 diabetes mellitus and other cardiovascular risk conditions, such as hypertension or metabolic syndrome. Waist-to-height-ratio has been proposed as a useful tool for assessing abdominal obesity, correcting other measurements for the height of the individual. We compared the ability of several anthropometric measurements to predict the presence of type-2 diabetes, hyperglycemia, hypertension, atherogenic dyslipidemia or metabolic syndrome. Materials and Methods: In our cross-sectional analyses we included 7447 Spanish individuals at high cardiovascular risk, men aged 55-80 years and wome…

Mediterranean, DASH, and MIND dietary patterns and cognitive function: The 2-year longitudinal changes in an older Spanish cohort

Wu, L., and Sun, D. (2017). Adherence to Mediterranean diet and risk of developing cognitive disorders: an updated systematic review and meta-analysis of prospective cohort studies. Sci. Rep. 7:41317. doi: 10.1038/srep41317 Wu, Z., Phyo, A. Z. Z., Al-harbi, T., Woods, R. L., and Ryan, J. (2020). Distinct cognitive trajectories in late life and associated predictors and outcomes: a systematic review. J. Alzheimer’s Dis. Rep. 4, 459–478. doi: 10.3233/ADR-200232 Conflict of Interest: SKN was a volunteer member of the not-for profit group Plant Based Canada. JS-S reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, Departament de Salut P…

One-Year Changes in Urinary Microbial Phenolic Metabolites and the Risk of Type 2 Diabetes—A Case-Control Study

The intake of polyphenols has been associated with a risk reduction of type 2 diabetes. Nevertheless, to the best of our knowledge, the molecules that might be metabolically active after ingestion are only starting to be investigated regarding this metabolic disease. To investigate the association between one-year changes in urinary microbial phenolic metabolites (MPM) and the incidence of type 2 diabetes, we performed a case-control study using data and samples of the PREDIMED trial including 46 incident type 2 diabetes cases of 172 randomly selected participants. Eight urinary MPMs were quantified in urine by liquid chromatography coupled to mass spectrometry and used to assess their asso…

Polymorphisms in the Serotonin (5-Hydroxytryptamine (5-HT)) Type 2A Receptor (5-HTR2A) Gene, Other Related Genes and Anthropometry

Serotonin or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter, which helps to regulate many physiological processes such as sleep, appetite, eating disorders, thermoregulation, hormone secretion, mood, anxiety, etc. The serotonin and related genes, such as the 5-HT2A receptor gene (HTR2A), the 5-HT transporter gene (SLC6A4), the 5-HT2C receptor gene (HTR2C), or the 5-HT1A receptor (HTR1A) gene, are re-emerging as powerful candidates for studying the association between food intake and anthropometry. Variations in all of these genes need to be studied to better understand the effects of serotonin and its receptors on anthropometry. The most widely studied polymorphism is the −1438G…

Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case–Cohort Study

Abstract 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 Prevención con Dieta Mediterránea (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 …

Type 2 diabetes and cognitive impairment in an older population with overweight or obesity and metabolic syndrome: baseline cross-sectional analysis of the PREDIMED-plus study

This study cross-sectionally examines in the elderly population: (a) the association of type 2 diabetes with executive function (EF); (b) the effect of BMI on both type 2 diabetes and EF; (c) the association between glycaemia control and EF in type 2 diabetes. 6823 older individuals with overweight/obesity and metabolic syndrome participating in the PREDIMED-PLUS study, were assessed with a battery of cognitive tests and a medical interview. ANOVA showed a significantly worse performance on EF in type 2 diabetes vs. non-diabetic individuals. Two complementary models were displayed: (1) in the whole sample, the presence of type 2 diabetes, depressive symptoms and BMI had a direct negative ef…

Effects of Polyphenol, Measured by a Biomarker of Total Polyphenols in Urine, on Cardiovascular Risk Factors After a Long-Term Follow-Up in the PREDIMED Study

Several epidemiological studies have shown an inverse association between the consumption of polyphenol-rich foods and risk of cardiovascular diseases. However, accuracy and reliability of these studies may be increased using urinary total polyphenol excretion (TPE) as a biomarker for total polyphenol intake. Our aim was to assess if antioxidant activity, measured by a Folin-Ciocalteu assay in urine, is correlated with an improvement in cardiovascular risk factors (blood pressure and serum glucose, cholesterol, HDL-cholesterol, LDL-cholesterol, and triglyceride concentrations) in an elderly population at high risk. A longitudinal study was performed with 573 participants (aged 67.3 ± 5.9) f…

Association of physical activity with body mass index, waist circumference and incidence of obesity in older adults

Background There is limited, and inconsistent, data on the prospective association between physical activity and surrogate markers of adiposity in older adults. We aim to determine the prospective association of leisure time physical activity (LTPA) with body mass index (BMI), waist circumference (WC) and the incidence of obesity. Methods This prospective analysis included 7144 individuals with a mean age of 67 ± 6.2 years, from the PREvencion con DIeta MEDiterranea (PREDIMED) study. BMI and WC were measured and LTPA was recorded using the Minnesota Leisure Time Physical Activity Questionnaire. Exposure and outcome variables were calculated as cumulative average of repeated measurements. Re…

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,…

Taste Perception Profiles and Adiposity in Older Adults with Metabolic Syndrome – PREDIMED-Plus

OBJECTIVES: In humans, perception for each taste (sweet, salt, sour, bitter and umami) has been independently related to food preferences and intake. Yet, the collective influence of perception of all 5 tastes on diet and cardiometabolic health remains unexplored. Therefore, our objective was to investigate the relations between a collective measure of taste perception – “taste perception profiles” – and adiposity. METHODS: We analyzed baseline data of 367 older adults (55–75 years; 55% female) with metabolic syndrome (MetS) participating in the PREDIMED-Plus Valencia trial. Taste perception was assessed for sweet, salt, sour, bitter and umami using sucrose, NaCl, citric acid, phenylthiocar…

Dietary Diversity and Nutritional Adequacy among an Older Spanish Population with Metabolic Syndrome in the PREDIMED-Plus Study: A Cross-Sectional Analysis

Dietary guidelines emphasize the importance of a varied diet to provide an adequate nutrient intake. However, an older age is often associated with consumption of monotonous diets that can be nutritionally inadequate, increasing the risk for the development or progression of diet-related chronic diseases, such as metabolic syndrome (MetS). To assess the association between dietary diversity (DD) and nutrient intake adequacy and to identify demographic variables associated with DD, we cross-sectionally analyzed baseline data from the PREDIMED-Plus trial: 6587 Spanish adults aged 55&ndash

A short screener is valid for assessing mediterranean diet adherence among older spanish men and women

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Associations between serum uric acid concentrations and metabolic syndrome and its components in the PREDIMED study.

Several studies have demonstrated a relationship between increased serum uric acid (SUA) concentrations and the prevalence of metabolic syndrome (MetS) in the oriental population. However, to the best of our knowledge, the association between SUA and MetS has never been investigated in elderly European individuals at high cardiovascular risk. The aim of this study was to conduct a cross-sectional and prospective evaluation of the associations between SUA concentrations and the MetS in elderly individuals at high cardiovascular risk.Men and women (55-80 years of age) from different PREDIMED (Prevención con DIeta MEDiterránea) recruiting centers were studied. Baseline cross-sectional (n = 441…

Dietary glycemic index and glycemic load are positively associated with risk of developing metabolic syndrome in middle-aged and elderly adults

© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society. Objectives To evaluate how glycemic index (GI) and glycemic load (GL) are associated with the metabolic syndrome (MetS) and its features in middle-aged and elderly adults at high cardiovascular risk. Design Prospective, longitudinal, population-based cohort. Setting PREvenciõn con DIeta MEDiterránea study. Participants Men and women (N = 6,606) divided into three age groups (<65, 65-74, ≥75). Measurements Energy and nutrient intake was evaluated using a validated 137-item food frequency questionnaire. MetS and its features were defined in accordance with the criteria of the American Heart Association …

Association between dietary fibre intake and fruit, vegetable or whole-grain consumption and the risk of CVD: results from the PREvención con DIeta MEDiterránea (PREDIMED) trial

Prospective studies assessing the association between fibre intake or fibre-rich food consumption and the risk of CVD have often been limited by baseline assessment of diet. Thus far, no study has used yearly repeated measurements of dietary changes during follow-up. Moreover, previous studies included healthy and selected participants who did not represent subjects at high cardiovascular risk. We used yearly repeated measurements of diet to investigate the association between fibre intake and CVD in a Mediterranean cohort of elderly adults at high cardiovascular risk. We followed-up 7216 men (55-80 years) and women (60-80 years) initially free of CVD for up to 7 years in the PREvención con…

Reduced circulating sTWEAK levels are associated with metabolic syndrome in elderly individuals at high cardiovascular risk

BACKGROUND: The circulating soluble TNF-like weak inducer of apoptosis (sTWEAK) is a cytokine that modulates inflammatory and atherogenic reactions related to cardiometabolic risk. We investigated the association between sTWEAK levels and metabolic syndrome (MetS) and its components in older subjects at high cardiovascular risk. METHODS: Cross-sectional analysis of 452 non-diabetic individuals (men and women aged 55-80 years) at high cardiovascular risk. MetS was defined by AHA/NHLBI and IDF criteria. Logistic regression analyses were used to estimate odds ratios (ORs) for MetS and its components by tertiles of serum sTWEAK concentrations measured by ELISA. RESULTS: sTWEAK concentrations we…

A lifestyle intervention with an energy-restricted Mediterranean diet and physical activity enhances HDL function: a substudy of the PREDIMED-Plus randomized controlled trial

Background Consumption of a Mediterranean diet, adequate levels of physical activity, and energy-restricted lifestyle interventions have been individually associated with improvements in HDL functions. Evidence of intensive interventions with calorie restriction and physical activity is, however, scarce. Objectives To determine whether an intensive lifestyle intervention with an energy-restricted Mediterranean diet plus physical activity enhanced HDL function compared to a non-hypocaloric Mediterranean eating pattern without physical activity. Methods In 391 older adults with metabolic syndrome (mean age, 65 years; mean BMI, 33.3 kg/m2) from 1 of the Prevencion con Dieta Mediterranea-Plus t…

Differential effects of the C1431T and Pro12Ala PPARgamma gene variants on plasma lipids and diabetes risk in an Asian population.

We investigated the association of C1431T and Pro12Ala polymorphisms at the peroxisome proliferator-activated receptor γ (PPARγ) locus with plasma lipids and insulin resistance-related variables, according to diabetes status, in a large and representative Asian population from Singapore consisting of 2,730 Chinese, 740 Malays, and 568 Indians. Moreover, we estimated the diabetes risk and examined gene-nutrient interactions between these variants and the ratio of polyunsaturated fatty acid to saturated fat (SFA) in determining body mass index (BMI) and fasting insulin. We found differential effects of these gene variants. The Pro12Ala polymorphism was more associated with plasma lipids and f…

Total and subtypes of dietary fat intake and risk of type 2 diabetes mellitus in the Prevención con Dieta Mediterránea (PREDIMED) study.

Background: The associations between dietary fat and cardiovascular disease have been evaluated in several studies, but less is known about their influence on the risk of diabetes.Objective: We examined the associations between total fat, subtypes of dietary fat, and food sources rich in saturated fatty acids and the incidence of type 2 diabetes (T2D).Design: A prospective cohort analysis of 3349 individuals who were free of diabetes at baseline but were at high cardiovascular risk from the PREvencion con DIeta MEDiterranea (PREDIMED) study was conducted. Detailed dietary information was assessed at baseline and yearly during the follow-up using a food frequency questionnaire. Multivariable…

Additional file 9: Figure S7. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Volcano plot [−log10 (p-value) vs. log2 (fold-change)] for the comparison between the baseline and final states in group 1 (not meeting the NAFLD criteria at baseline and during the follow-up).Abbreviations: AA, amino acids; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; MUFA, monounsaturated fatty acids; NAE, N-acyl ethanolamines; FFAox, free fatty acid oxidised; AC, acyl carnitines; PC, phosphatidylcholine; LPC, lysophosphatidylcholine; PE, phatidylethanolamine; LPE, lysophosphatidylethanolamine; PI, phatidylinositols; LPI, lysophosphatidylinositols; Cer, ceramides; SM, sphingomyelin; ChoE, cholesteryl esters; Chol, cholesterol; TAG, triacylglycerols; DAG, diacylglycerols,…

Variaciones en el gen SLC7A9: impacto de trece mutaciones frecuentes en la etiología de la cistinuria en población mediterránea española

Fundamento y objetivo Investigar la presencia de mutaciones en el gen SLC7A9, descritas como mas prevalentes en otras poblaciones, en familias con cistinuria en poblacion mediterranea espanolay su asociacion con manifestaciones clinicas de la enfermedad. Pacientes y metodo Se estudio a 20 familias con cistinuria (6 tipo I, 12 tipo no I y 2 de tipo desconocido), incluidos 48 pacientes con cistinuria y 44 familiares. Se aislo el ADN y se realizoel analisis molecular de 13 mutaciones en el gen SLC7A9 (P52L, N58_G79del22, G63R,G105R, T123M, V170M, A182T, V188M, c.614dupA, G259R, L283F, A316V y R333W). Seestudio la asociacion de estas mutaciones con las concentraciones de aminoacidos en orina,fo…

The rs9939609-fto polymorphism is associated with methylation levels in both men and women from a high cardiovascular risk population

Perspective: Essential study quality descriptors for data from nutritional epidemiologic research

Pooled analysis of secondary data increases the power of research and enables scientific discovery in nutritional epidemiology. Information on study characteristics that determine data quality is needed to enable correct reuse and interpretation of data. This study aims to define essential quality characteristics for data from observational studies in nutrition. First, a literature review was performed to get an insight on existing instruments that assess the quality of cohort, case-control, and cross-sectional studies and dietary measurement. Second, 2 face-to-face workshops were organized to determine the study characteristics that affect data quality. Third, consensus on the data descrip…

Dietary magnesium intake is inversely associated with mortality in adults at high cardiovascular disease risk

The relation between dietary magnesium intake and cardiovascular disease (CVD) or mortality was evaluated in several prospective studies, but few of them have assessed the risk of all-cause mortality, which has never been evaluated in Mediterranean adults at high cardiovascular risk. The aim of this study was to assess the association between magnesium intake and CVD and mortality risk in a Mediterranean population at high cardiovascular risk with high averagemagnesium intake. The present study included 7216 men and women aged 55-80 y fromthe PREDIMED (Prevencíon con Dieta Mediterŕanea) study, a randomized clinical trial. Participants were assigned to 1 of 2 Mediterranean diets (supplemente…

MOESM1 of Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study

Additional file 1: Table S1. Associations of total inactive time with adiposity indicators and cardio-metabolic risk factors (with further adjustment for light physical activity, instead of moderate-to-vigorous physical activity). Table S2. Associations of total inactive time with adiposity indicators and cardio-metabolic risk factors (with further adjustment for light physical activity, instead of moderate-to-vigorous physical activity and waist circumference as an indicator of adiposity). Table S3. Prevalence ratio of metabolic syndrome parameters according to tertiles of sedentary time (with further adjustment for light physical activity, instead of moderate-to-vigorous physical activity…

Transcriptional response to a Mediterranean diet intervention exerts a modulatory effect on neuroinflammation signaling pathway.

Background: The Traditional Mediterranean Diet (TMD) is known to have beneficial effects on several chronic diseases. However, data concerning the whole transcriptome modulation of the TMD are scar...

Psychological and metabolic risk factors in older adults with a previous history of eating disorder: A cross-sectional study from the Predimed-Plus study

Goals To explore affective and cognitive status, later in life, in individuals with and without previous history of eating disorder (ED), and also its association with higher risk for metabolic syndrome (MetS) symptomatology. Methods A cross-sectional analysis of 6756 adults, aged 55-75 years with overweight/obesity and MetS participating in the Predimed-Plus study was conducted. Participants completed self-reported questionnaires to examine lifetime history of ED, according to DSM-5 criteria, and other psychopathological and neurocognitive factors. Anthropometric and metabolic measurements were also collected. Results Of the whole sample, 24 individuals (0.35%) reported a previous history …

Influence of lifestyle factors and staple foods from the Mediterranean diet on non-alcoholic fatty liver disease among older individuals with metabolic syndrome features

Objective: Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver morbidity. This condition often is accompanied by obesity, diabetes, and metabolic syndrome (MetS). The aim of this study was to evaluate the connection between lifestyle factors and NAFLD in individuals with MetS. Methods: A cross-sectional study with 328 participants (55-75 y of age) diagnosed with MetS participating in the PREDIMED-Plus trial was conducted. NAFLD status was evaluated using the non-invasive hepatic steatosis index (HSI). Sociodemographic, clinical, and dietary data were collected. Adherence to the Mediterranean diet (mainly assessed by the consumption of olive oil, nuts, legumes…

Dairy consumption, plasma metabolites, and risk of type 2 diabetes.

Background Epidemiologic studies have reported a modest inverse association between dairy consumption and the risk of type 2 diabetes (T2D). Whether plasma metabolite profiles associated with dairy consumption reflect this relationship remains unknown. Objectives We aimed to identify the plasma metabolites associated with total and specific dairy consumption, and to evaluate the association between the identified multi-metabolite profiles and T2D. Methods The discovery population included 1833 participants from the Prevencion con Dieta Mediterranea (PREDIMED) trial. The confirmatory cohorts included 1522 PREDIMED participants at year 1 of the trial and 4932 participants from the Nurses' Hea…

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study.

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout perio…

Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects.

The first results of the PREDIMED (PREvencion con Dieta MEDiterranea) randomized trial, after 3-month intervention, showed that the Mediterranean Diet (MD), supplemented with either virgin olive oil (VOO) or nuts, reduced systolic blood pressure, serum cholesterol and triacylglycerol (TG) concentrations and increased high-density lipoprotein (HDL)-cholesterol when compared to a control (low-fat diet) group. Serum TG levels are an independent risk factor for coronary heart disease and are strongly determined by very low-density lipoprotein (VLDL) composition, which can be specifically modified by dietary lipid source. Within the context of the PREDIMED study, we assessed the VLDL composition…

Anthropometric Variables as Mediators of the Association of Changes in Diet and Physical Activity With Inflammatory Profile

AbstractBackgroundMechanisms underlying the associations of high levels of physical activity (PA) and adherence to the Mediterranean diet (MedDiet) with a better inflammatory profile remain unclear. Our objective was to assess the mediating role of changes in body mass index (BMI) and waist circumference (WC), as markers of body fat in the association of changes in PA and adherence to the MedDiet, with changes in the inflammatory profile.MethodThis study included 489 adults, aged 55–75 years, from the PREDIMED-Plus multicenter lifestyle intervention trial. An inflammatory score was calculated, based on 8 blood biomarkers: high-sensitivity C-reactive protein, interleukin 6, interleukin 8, in…

High Fruit and Vegetable Consumption and Moderate Fat Intake Are Associated with Higher Carotenoid Concentration in Human Plasma

This research was funded by CICYT [AGL2016-75329-R] and CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovación y Universidades, (AEI/FEDER, UE), Generalitat de Catalunya (GC) [2017SGR196]. The PREDIMED-Plus trial was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated Fondo de Investigaciones Sanitarias projects lead by J.S.-S. and J.V., including the following projects: PI13…

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

Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease. OBJECTIVE: To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease. SUBJECTS/METHODS: A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were meas…

Additional file 3: Figure S1. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) model to discriminate between the three baseline states in groups 1, 2 and 3. Model diagnostics (A = 8, R2X = 0.651, Q2X = 0.264) (DOCX 43 kb)

Adherence to the mediterranean diet modulates the association between the abca1 gene, plasma lipids and diabetes in a high-risk population

Reduction in the Incidence of Type 2 Diabetes With the Mediterranean Diet

OBJECTIVE To test the effects of two Mediterranean diet (MedDiet) interventions versus a low-fat diet on incidence of diabetes. RESEARCH DESIGN AND METHODS This was a three-arm randomized trial in 418 nondiabetic subjects aged 55–80 years recruited in one center (PREDIMED-Reus, northeastern Spain) of the Prevención con Dieta Mediterránea [PREDIMED] study, a large nutrition intervention trial for primary cardiovascular prevention in individuals at high cardiovascular risk. Participants were randomly assigned to education on a low-fat diet (control group) or to one of two MedDiets, supplemented with either free virgin olive oil (1 liter/week) or nuts (30 g/day). Diets were ad libitum, and no…

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 o…

Effect of the polymorphisms rs1476413, rs1801131, rs4846052 and rs6541003 of the MTHFR gene on prostate cancer in a high cardiovascular risk population

Interactions between dietary n-3 fatty acids and genetic variants and risk of disease

Nutritional genomics has undergone rapid development and the concept is now very popular with the general public. Therefore, there is increasing demand for knowledge on adapting dietary composition to the genome. Our aim has been to undertake a systematic review so as to find out the level of evidence existing on whether the effects of n-3 fatty acids on health can be modulated by genetic variation. A systematic literature search was conducted on studies that jointly analyse the effect of one or more genetic variants in candidate genes and n-3 fatty acids. Both observational and experimental studies were included. Results are classified in accordance with whether the study was undertaken on…

A 14-item Mediterranean diet assessment tool and obesity indexes among high-risk subjects: the PREDIMED trial

Objective Independently of total caloric intake, a better quality of the diet (for example, conformity to the Mediterranean diet) is associated with lower obesity risk. It is unclear whether a brief dietary assessment tool, instead of full-length comprehensive methods, can also capture this association. In addition to reduced costs, a brief tool has the interesting advantage of allowing immediate feedback to participants in interventional studies. Another relevant question is which individual items of such a brief tool are responsible for this association. We examined these associations using a 14-item tool of adherence to the Mediterranean diet as exposure and body mass index, waist circum…

Associations between dietary polyphenols and type 2 diabetes in a cross-sectional analysis of the PREDIMED-Plus Trial: role of body mass index and sex

Overweight and obesity are important risk factors for type 2 diabetes (T2D). Moving towards healthier diets, namely, diets rich in bioactive compounds, could decrease the odds of suffering T2D. However, those individuals with high body mass index (BMI) may have altered absorption or metabolism of some nutrients and dietary components, including polyphenols. Therefore, we aimed to assess whether high intakes of some classes of polyphenols are associated with T2D in a population with metabolic syndrome and how these associations depend on BMI and sex. This baseline cross-sectional analysis includes 6633 participants from the PREDIMED-Plus trial. Polyphenol intakes were calculated from food fr…

Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations.

OBJECTIVE—Using the genome-wide association approach, we recently identified the glucokinase regulatory protein gene (GCKR, rs780094) region as a novel quantitative trait locus for plasma triglyceride concentration in Europeans. Here, we sought to study the association of GCKR variants with metabolic phenotypes, including measures of glucose homeostasis, to evaluate the GCKR locus in samples of non-European ancestry and to fine- map across the associated genomic interval. RESEARCH DESIGN AND METHODS—We performed association studies in 12 independent cohorts comprising &amp;gt;45,000 individuals representing several ancestral groups (whites from Northern and Southern Europe, whites from the …

Fluid and total water intake in a senior mediterranean population at high cardiovascular risk: demographic and lifestyle determinants in the PREDIMED-Plus Study

Purpose: We aimed to evaluate associations between compliance with recommendations for total water intake (TWI) and total water intake from fluids (TWIF), and some socio-demographic and lifestyle factors of a senior Mediterranean population at high cardiovascular risk. Methods: Cross-sectional analysis with data of 1902 participants from the PREDIMED-Plus study. A validated 32-item Spanish fluid-intake questionnaire was used to assess beverage consumption and water intake. Multivariable logistic regression models were used to assess the odds ratio (OR) and the 95% confidence interval (CI) for complying with European Food Safety Agency recommendations for TWI and TWIF according to various so…

White fish reduces cardiovascular risk factors in patients with metabolic syndrome: the WISH-CARE study, a multicenter randomized clinical trial.

Reduction of cardiovascular risk with high consumption of fish in diet is still a matter of debate, and concerns about heavy metal contamination have limited consumption of oily fish. We aimed to evaluate the effect of regular ingestion of white fish on cardiovascular risk factors in patients with metabolic syndrome.Multicenter randomized crossover clinical trial including 273 individuals with metabolic syndrome. An 8-week only-one dietary intervention: 100 g/d of white fish (Namibia hake) with advice on a healthy diet, compared with no fish or seafood with advice on a healthy diet. Outcomes were lipid profile, individual components of the metabolic syndrome, serum insulin concentrations, h…

Plasma Arginine/Asymmetric Dimethylarginine Ratio and Incidence of Cardiovascular Events: A Case-Cohort Study.

CONTEXT: Arginine, its methylated metabolites, and other metabolites related to the urea cycle have been independently associated with cardiovascular risk, but the potential causal meaning of these associations (positive for some metabolites and negative for others) remains elusive due to a lack of studies measuring metabolite changes over time. OBJECTIVE: To examine the association between baseline and 1-year concentrations of urea cycle metabolites and cardiovascular disease (CVD) in a case-cohort setting. DESIGN: A case-cohort study was nested within the Prevención con Dieta Mediterránea trial. We used liquid chromatography-tandem mass spectrometry to assess metabolite levels at baseline…

Basic Concepts in Molecular Biology Related to Genetics and Epigenetics.

The observation that "one size does not fit all" for the prevention and treatment of cardiovascular disease, among other diseases, has driven the concept of precision medicine. The goal of precision medicine is to provide the best-targeted interventions tailored to an individual's genome. The human genome is composed of billions of sequence arrangements containing a code that controls how genes are expressed. This code depends on other nonstatic regulators that surround the DNA and constitute the epigenome. Moreover, environmental factors also play an important role in this complex regulation. This review provides a general perspective on the basic concepts of molecular biology related to g…

Dietary Marine ω-3 Fatty Acids and Incident Sight-Threatening Retinopathy in Middle-Aged and Older Individuals With Type 2 Diabetes Prospective Investigation From the PREDIMED Trial

IMPORTANCE: Diabetic retinopathy (DR) is a devastating complication of individuals with type 2 diabetes mellitus. The retina is rich in long-chain ω−3 polyunsaturated fatty acids (LCω3PUFAs), which are substrate for oxylipins with anti-inflammatory and antiangiogenic properties. Experimental models support dietary LCω3PUFA protection against DR, but clinical data are lacking. OBJECTIVE: To determine whether LCω3PUFA intake relates to a decreased incidence of sight-threatening DR in individuals with type 2 diabetes older than 55 years. DESIGN, SETTING, AND PARTICIPANTS: In late 2015, we conceived a prospective study within the randomized clinical trial Prevención con Dieta Mediterránea (PRED…

Predisposición genética en el consumo de alcohol: el caso de la Alcohol Deshidrogenasa 1C

Introduccion: El consumo de alcohol se presenta frecuentemente asociado a determinados delitos, siendo en unas ocasiones atenuante o eximente, y en otras una infraccion penal per se. Se han identificado numerosos factores geneticos y ambientales que predisponen al consumo de alcohol. Nuestro objetivo ha sido estudiar la prevalencia del polimorfismo Ile349Val en la alcohol deshidrogenasa 1C que da lugar a la isoforma gamma 2 (metabolizador lento), y estudiar su asociacion con el consumo de alcohol asi como reflexionar sobre la dimension de la implicacion de estas variantes geneticas en la Medicina Legal. Material y Metodos: Se ha genotipado el polimorfismo Ile 349Val en 869 individuos proced…

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

[Background]: Hypertension can be prevented by adopting healthy dietary patterns. Our aim was to assess the 4-year effect on blood pressure (BP) control of a randomized feeding trial promoting the traditional Mediterranean dietary pattern.

Replacing red meat and processed red meat for white meat, fish, legumes or eggs is associated with lower risk of incidence of metabolic syndrome.

BACKGROUND & AIMS: Few studies have assessed the association between consumption of red meat (RM) and processed red meats (PRM) and the incidence of metabolic syndrome (MetS) and results have been inconsistent. We investigated associations between total consumption of meat and its subtypes and incident MetS and estimated the effect of substituting RM or PRM for alternative protein-rich foods. METHODS: We analyzed 1868 participants (55-80 years-old) recruited into the PREDIMED study who had no MetS at baseline and were followed for a median of 3.2 years. MetS was defined using updated harmonized criteria. Anthropometric variables, dietary habits, and blood biochemistry were determined at bas…

Gut and microbial resveratrol metabolite profiling after moderate long-term consumption of red wine versus dealcoholized red wine in humans by an optimized ultra-high-pressure liquid chromatography tandem mass spectrometry method

Resveratrol exerts a variety of biological and pharmacological activities, which are observed despite its extremely low bioavailability and rapid clearance from the circulation due to extensive sulfation and glucuronidation in the intestine and liver. In order to more accurately quantify all known resveratrol metabolites, a sensitive and optimized analytical assay was developed and validated by pure standards. Methodology improvements aimed to the chromatographic detection of disulfates and sulfoglucuronides, improving resolution of sulfates, by using a buffered solution, with recovery values of resveratrol and its metabolites, even of sulfates, of 99%. The adapted methodology was then appl…

Interaction of Diet/Lifestyle Intervention and TCF7L2 Genotype on Glycemic Control and Adiposity among Overweight or Obese Adults: Big Data from Seven Randomized Controlled Trials Worldwide

Objective . The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene ( TCF7L2 ). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods . From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or ob…

Metabolic, Affective and Neurocognitive Characterization of Metabolic Syndrome Patients with and without Food Addiction. Implications for Weight Progression.

According to the food addiction (FA) model, the consumption of certain types of food could be potentially addictive and can lead to changes in intake regulation. We aimed to describe metabolic parameters, dietary characteristics, and affective and neurocognitive vulnerabilities of individuals with and without FA, and to explore its influences on weight loss progression. The sample included 448 adults (55-75 years) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus cognition sub-study. Cognitive and psychopathological assessments, as well as dietary, biochemical, and metabolic measurements, were assessed at baseline. Weight progression was evaluated after a 3-year follow u…

Leisure-Time physical activity, sedentary behaviour and diet quality are associated with metabolic syndrome severity: the PREDIMED-Plus Study

The authors especially thank the PREDIMED-Plus participants for their enthusiastic collaboration, the PREDIMED-Plus personnel for outstanding support, and the personnel of all associated primary care centres for their exceptional effort. CIBEROBN, CIBERESP and CIBERDEM are initiatives of Instituto de Salud Carlos III, Spain. We thank the PREDIMED-Plus Biobank Network, part of the National Biobank Platform of Instituto de Salud Carlos III for storing and managing biological samples.

Body weight changes and the A-6G polymorphism of the angiotensinogen gene

BACKGROUND: The objective of the study was to analyze the relationship of polymorphisms of the angiotensinogen gene with changes in body weight during 3 y of antihypertensive treatment, in a group of young adults with essential hypertension. METHODS: Essential hypertensives, less than 50 y old, never previously treated with antihypertensive drugs and in the absence of diabetes mellitus were included. After the initial evaluation, patients were treated using only non-pharmacological measures (n=29), β-blockers (n=40) or angiotensin-converting enzyme inhibitors (n=66). Resting blood pressure, biochemical profile and body weight at the beginning and yearly were measured. The polymorphism A-6G …

High fat diets for weight loss among subjects with elevated fasting glucose levels: The PREDIMED study

Abstract Aim We studied fasting plasma glucose (FPG) as a determinant of weight change on high-fat diets in the PREDIMED trial. Methods A total of 3,622 participants were randomized to receive one of two Mediterranean diets (n = 2,616) or a control diet (n = 1,006) for 5 years and had complete data for baseline FPG and body-weight development. Weight change by pre-treatment FPG categories ( Results The two Mediterranean diets contained 41.5 E% fat, 16.5 E% protein, and 40 E% carbohydrate whereas the control diet contained 37.8 E% fat, 16.8 E% protein and 43.2 E% carbohydrate. In the Mediterranean diet groups, participants with FPG≥115 lost 1.04 kg (95% CI 0.68; 1.41, n = 1115) whereas parti…

Significant associations of the rs2943634 (2q36.3) genetic polymorphism with adiponectin, high density lipoprotein cholesterol and ischemic stroke.

Abstract Background rs2943634 C/A single nucleotide polymorphism (SNP), located in a non coding region of chromosome 2q36.3, has been associated with coronary artery disease in two genome wide association studies. Our goal was to investigate its relation with myocardial infarction (MI) and ischemic stroke (IS), as well as with 12 intermediate risk phenotypes, in a population-based prospective cohort study. Methods rs2943634 was genotyped in a case–cohort study including a random sample of 1891 individuals (subcohort) and all incident MI (n = 211) and IS (n = 144) cases during a mean follow-up of 8.2 ± 2.2 years, nested within the European Prospective Investigation into Cancer and Nutrition …

Cross-Sectional Associations between HDL Structure or Function, Cell Membrane Fatty Acid Composition, and Inflammation in Elderly Adults.

Background Cell membrane fatty acid composition has been related to inflammation and cardiovascular risk. Dysregulation of HDL functionis also considered a cardiovascular risk factor. Objective We aimed to investigate whether the content of cell membrane fatty acids and HDL functionality are linked to each other as well as to inflammation. Methods This cross-sectional analysis involved 259 participants (67.9 y) with overweight/obesity (body mass index 29.5 kg/m2) from a coronary heart disease case-control study nested within the PREDIMED trial for which HDL functional parameters (Apolipoproteins (Apo) A-1, A-IV and C-III, cholesterol efflux capacity (CEC), HDL oxidative inflammatory index (…

Impact of cardiovascular risk factors on oxidative stress and DNA damage in a high risk Mediterranean population

The impact of classic cardiovascular risk factors on oxidative stress status in a high-risk cardiovascular Mediterranean population of 527 subjects was estimated. Oxidative stress markers (malondialdehyde, 8-oxo-7′8′-dihydro-2′-deoxyguanosine, oxidized/reduced glutathione ratio) together with the activity of antioxidant enzyme triad (superoxide dismutase, catalase, glutathione peroxidase) were analysed in circulating mononuclear blood cells. Malondialdehyde, oxidized glutathione and the ratio of oxidized to reduced glutathione were signifi cantly higher while catalase and glutathione peroxidase activities were signifi cantly lower in high cardiovascular risk participants than in controls. S…

Mediterranean Diet and atherothrombosis biomarkers: a randomized controlled trial

Scope To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. Methods and results In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1‐year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet‐VOO; n = 120) or nuts (MedDiet‐Nuts; n = 119) versus a low‐fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1‐year differences in biomarkers. Differences are observed between 1‐year changes in the MedDiet‐VOO…

Fruit and Vegetable Consumption is Inversely Associated with Plasma Saturated Fatty Acids at Baseline in Predimed Plus Trial

I.D.-L. is supported by the [FI_B 00256] from the FI-AGAUR Research Fellowship Program, Generalitat de Catalunya and M.M.-M is supported by the FPU17/00513 grant. a.-H. is supported by the [CD17/00122] grant and S.K.N. is supported by a Canadian Institutes of Health Research (CIHR) Fellowship. We also thank all the volunteers for their participation in and the personnel for their contribution to the PREDIMED-Plus trial. This research was funded by CiCYT [AGL2016-75329-R] and CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovacion y Universidades, (AEI/FEDER, UE), Generalitat de Catalunya (GC) [2017SGR196]. The PREDIMED-Plus trial was supported by t…

Mediterranean Diet and White Blood Cell Count—A Randomized Controlled Trial

We aimed to assess the effects of the antioxidant-rich Mediterranean diet (MedDiet) on white blood cell count. Our study population included participants in the PREvención con DIeta MEDiterránea study (average age 67 years old, 58% women, high cardiovascular risk). We assessed whether a MedDiet intervention enriched in extra-virgin olive oil or nuts, versus a low-fat control diet, modified the incidence of leukocytosis (&gt

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

[Background and aims]: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. [Methods and results]: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects …

Dieta mediterránea hipocalórica y factores de riesgo cardiovascular: análisis transversal de PREDIMED-Plus

Resumen Introduccion y objetivos Los beneficios cardiovasculares de la dieta mediterranea se han evaluado bajo supuestos de ingesta total de energia ad libitum (sin restriccion de energia). En el presente trabajo se estudia basalmente la cohorte de un gran ensayo en marcha denominado PREDIMED-Plus y la asociacion entre la adherencia a la dieta mediterranea hipocalorica segun la escala de 17 puntos (MedDiet) de este ensayo con la prevalencia inicial de factores de riesgo cardiovascular (FRCV). Metodos Evaluacion transversal de los participantes de PREDIMED-Plus (6.874 adultos mayores con sobrepeso/obesidad y sindrome metabolico). Se evaluo a los participantes para determinar la prevalencia d…

Hypertensive status and lipoprotein oxidation in an elderly population at high cardiovascular risk.

BACKGROUND: In elderly individuals, hypertension is a main risk factor for cardiovascular disease and oxidative damage is increased. Our aim was to assess the relationship between the degree of in vivo low-density lipoprotein (oxLDL) oxidation and the hypertensive status in a elderly population at high cardiovascular risk. METHODS: Cross-sectional study with baseline data from the PREDIMED (PREvención con DIeta MEDiterránea) trial, an intervention study directed at testing the efficacy of the Mediterranean diet on the primary prevention of cardiovascular disease. Participants were 1,130 subjects at high cardiovascular risk aged 55-80. At baseline, in vivo circulating oxLDL was measured, and…

Associations of the MCM6-rs3754686 proxy for milk intake in Mediterranean and American populations with cardiovascular biomarkers, disease and mortality: Mendelian randomization

Controversy persists on the association between dairy products, especially milk, and cardiovascular diseases (CVD). Genetic proxies may improve dairy intake estimations, and clarify diet-disease relationships through Mendelian randomization. We meta-analytically (n T (nonpersistence>persistence), dairy intake, and CVD biomarkers in American (Hispanics, African-American and Whites) and Mediterranean populations. Moreover, we analyzed longitudinal associations with milk, CVD and mortality in PREDIMED), a randomized Mediterranean diet (MedDiet) intervention trial (n = 7185). The MCM6-rs3754686/MCM6-rs309180 (as proxy), LP-allele (T) was strongly associated with higher milk intake, but inconsis…

A High Intake of Saturated Fatty Acids Strengthens the Association between the Fat Mass and Obesity-Associated Gene and BMI123

Evidence that physical activity (PA) modulates the association between the fat mass and obesity-associated gene (FTO) and BMI is emerging; however, information about dietary factors modulating this association is scarce. We investigated whether fat and carbohydrate intake modified the association of FTO gene variation with BMI in two populations, including participants in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n = 1069) and in the Boston Puerto Rican Health (BPRHS) study (n = 1094). We assessed energy, nutrient intake, and PA using validated questionnaires. Genetic variability at the FTO locus was characterized by polymorphisms rs9939609 (in the GOLDN) and rs11…

Association between a healthy lifestyle and general obesity and abdominal obesity in an elderly population at high cardiovascular risk.

DOI: 10.1016/j.ypmed.2011.06.008 https://www-sciencedirect-com.sabidi.urv.cat/science/article/pii/S0091743511002349?via%3Dihub Filiació URV: SI BACKGROUND: Diet, smoking and physical activity are important modifiable lifestyle factors that can influence body weight and fat accumulation. We assessed the relationship between lifestyle and obesity risk in a baseline analysis of the PREDIMED study, a randomized dietary primary prevention trial conducted in Spain. METHODS: 7000 subjects at high cardiovascular risk were assessed cross-sectionally. A healthy lifestyle pattern (HLP) was determined using a score including: adherence to the Mediterranean diet, moderate alcohol consumption, expending …

Carbohydrate quality changes and concurrent changes in cardiovascular risk factors: a longitudinal analysis in the PREDIMED-Plus randomized trial.

[Background]: Overall quality of dietary carbohydrate intake rather than total carbohydrate intake may determine the risk of cardiovascular disease (CVD).

Plasma Ceramides, Mediterranean Diet, and Incident Cardiovascular Disease in the PREDIMED Trial

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 (Prevención con Dieta Mediterránea), 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 supplemente…

Additional file 4: Figure S2. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) model to discriminate between the baseline and final states in group 1 (participants not meeting the NAFLD criteria at baseline and at the end of follow-up). Model diagnostics (A = 6, R2X = 0.621, Q2X = 0.160) (DOCX 43 kb)

Additional file 8: Figure S6. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Heatmap representing individual metabolomic features obtained from all the comparisons made between the final and the baseline states in groups 1, 2 and 3. Heatmapcolor codes for log2 (fold-change) and Student’s t-test p-values are indicated at the bottom of the Figure. Darker green and red colors indicate higher drops or elevations of the metabolite levels in every comparison. Grey lines correspond to significant fold-changes of individual metabolites, darker grey colors have been used to highlight higher significances (p

Frequent Consumption of Sugar- and Artificially Sweetened Beverages and Natural and Bottled Fruit Juices Is Associated with an Increased Risk of Metabolic Syndrome in a Mediterranean Population at High Cardiovascular Disease Risk.

Background: The relation between the consumption of sweetened beverages and metabolic syndrome (MetS) is controversial. Objective: This analysis evaluated the associations between intakes of sugar-sweetened beverages (SSBs), artificially sweetened beverages, and natural and bottled fruit juices and the incidence of MetS in elderly individuals at high risk of cardiovascular disease (CVD) and without MetS at baseline. Methods: We prospectively examined 1868 participants free of MetS at baseline from the PREDIMED (PREvención con DIeta MEDiterránea) study. MetS was defined by using the updated harmonized criteria of the International Diabetes Federation, the American Heart Association, and Nati…

Effect of a Mediterranean Diet Intervention on Dietary Glycemic Load and Dietary Glycemic Index: The PREDIMED Study

© 2014 Ana Isabel Rodríguez-Rejón et al. Objective. To compare the one year effect of two dietary interventions with MeDiet on GL and GI in the PREDIMED trial. Methods. Participants were older subjects at high risk for cardiovascular disease. This analysis included 2866 nondiabetic subjects. Diet was assessed with a validated 137-item food frequency questionnaire (FFQ). The GI of each FFQ item was assigned by a 5-step methodology using the International Tables of GI and GL Values. Generalized linear models were fitted to assess the relationship between the intervention group and dietary GL and GI at one year of follow-up, using control group as reference. Results. Multivariate-adjusted mode…

Glycolysis/gluconeogenesis- and tricarboxylic acid cycle–related metabolites, Mediterranean diet, and type 2 diabetes

Background: Glycolysis/gluconeogenesis and tricarboxylic acid (TCA) cycle metabolites have been associated with type 2 diabetes (T2D). However, the associations of these metabolites with T2D incidence and the potential effect of dietary interventions remain unclear. Objectives: We aimed to evaluate the association of baseline and 1-y changes in glycolysis/gluconeogenesis and TCA cycle metabolites with insulin resistance and T2D incidence, and the potential modifying effect of Mediterranean diet (MedDiet) interventions. Methods: We included 251 incident T2D cases and 638 noncases in a nested case-cohort study within the PREDIMED Study during median follow-up of 3.8 y. Participants were alloc…

Dietary Polyphenol Intake is Associated with HDL-Cholesterol and A Better Profile of other Components of the Metabolic Syndrome: A PREDIMED-Plus Sub-Study

Dietary polyphenol intake is associated with improvement of metabolic disturbances. The aims of the present study are to describe dietary polyphenol intake in a population with metabolic syndrome (MetS) and to examine the association between polyphenol intake and the components of MetS. This cross-sectional analysis involved 6633 men and women included in the PREDIMED (PREvenci&oacute

Nutrigenética, nutrigenómica y dieta mediterránea: una nueva visión para la gastronomía

Both nutrigenetics and nutrigenomics are disciplines that form part of what is known as Nutritional Genomics, which, in the widest sense, provides the framework for integrating different omics with food and nutrition sciences. After decades of nutrigenetic and nutrigenomic studies, there is a large enough amount of knowledge to consider its application in so-called precision nutrition. This new discipline seeks to take into account the particular characteristics of the individual in order to provide the best diet for preventing or treating a disease. Omic markers are considered to be of importance to that personalization. There are many foods, nutrients and dietary patterns that have been r…

Baja prevalencia del polimorfismo Leu7Pro en el péptido señal del preproneuropéptido Y en la población mediterránea española

Fundamento y objetivo: Un polimorfismo comun, Leu7Pro, en el peptido senal del neuropeptido Y se ha asociado con concentraciones elevadas de colesterol y arteriosclerosis en Finlandia. Nuestro objetivo fue estimar la prevalencia de dicho polimorfismo en la poblacion espanola. Pacientes y metodo: Se ha realizado un diseno transversal en 1.000 individuos procedentes de poblacion mediterranea espanola. Se estudiaron dos muestras independientes compuestas por 486 individuos (muestra 1) y por 514 (muestra 2). Se determino el polimorfismo Leu7Pro. Resultados: Solo se detecto un individuo portador de la variante Leu7Pro (0,1%). La frecuencia alelica para el alelo Pro7 en la poblacion estudiada fue…

Yogurt consumption and abdominal obesity reversion in the PREDIMED study.

Yogurt consumption and abdominal obesity reversion in the PREDIMED study. BACKGROUND AND AIMS: Evidence on the association yogurt consumption and obesity is not conclusive. The aim of this study was to prospectively evaluate the association between yogurt consumption, reversion of abdominal obesity status and waist circumference change in elderly. METHODS AND RESULTS: 4545 individuals at high cardiovascular risk were prospectively followed. Total, whole-fat and low-fat yogurt consumption were assessed using food frequency questionnaires. Generalized estimating equations were used to analyze the association between yogurt consumption and waist circumference change (measured at baseline and y…

Dietary Quality Changes According to the Preceding Maximum Weight: A Longitudinal Analysis in the PREDIMED-Plus Randomized Trial

One-year dietary quality change according to the preceding maximum weight in a lifestyle intervention program (PREDIMED-Plus trial, 55–75-year-old overweight or obese adults; n = 5695) was assessed. A validated food frequency questionnaire was used to assess dietary intake. A total of 3 groups were made according to the difference between baseline measured weight and lifetime maximum reported weight: (a) participants entering the study at their maximum weight, (b) moderate weight loss maintainers (WLM), and (c) large WLM. Data were analyzed by General Linear Model. All participants improved average lifestyle. Participants entering the study at their maximum weight were the most susceptible …

Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

[Background]: The pandemic of cardiovascular disease (CVD) and type 2 diabetes (T2D) requires the identification of new predictor biomarkers. Biomarkers potentially modifiable with lifestyle changes deserve a special interest. Our aims were to analyze: (a) The associations of lysine, 2-aminoadipic acid (2-AAA) or pipecolic acid with the risk of T2D or CVD in the PREDIMED trial; (b) the effect of the dietary intervention on 1-year changes in these metabolites, and (c) whether the Mediterranean diet (MedDiet) interventions can modify the effects of these metabolites on CVD or T2D risk. [Methods]: Two unstratified case-cohort studies nested within the PREDIMED trial were used. For CVD analyses…

Association Between Lifestyle and Hypertriglyceridemic Waist Phenotype in the PREDIMED-Plus Study.

Objective: The hypertriglyceridemic waist (HTGW) phenotype is characterized by abdominal obesity and high levels of triglycerides. In a cross-sectional assessment of PREDIMED-Plus trial participants at baseline, HTGW phenotype prevalence was evaluated, associated risk factors were analyzed, and the lifestyle of individuals with metabolic syndrome and HTGW was examined. Methods: A total of 6,874 individuals aged 55 to 75 with BMI ≥ 27 and < 40 kg/m2 were included and classified by presence (HTGW+ ) or absence (HTGW- ) of HTGW (waist circumference: men ≥ 102 cm, women ≥ 88 cm; fasting plasma triglycerides ≥ 150 mg/dL). Analytical parameters and lifestyle (energy intake and expenditure) were a…

The effect of the APOE polymorphism on HDL-C concentrations depends on the cholesterol ester transfer protein gene variation in a Southern European population.

Abstract Background Apolipoprotein E (ApoE) locus has consistently shown a significant association with low-density lipoprotein cholesterol (LDL-C). However, its impact on high-density lipoprotein cholesterol (HDL-C) has been highly controversial suggesting that it may be context-dependent. We examined the gene–gene interaction between the common ApoE and the CETP polymorphisms in determining HDL-C concentrations in men and women from the general population. Methods 550 unrelated Caucasian subjects were randomly selected from a Mediterranean Region in Spain. Plasma lipids, anthropometric, clinical and lifestyle variables were measured. Common ApoE and CETP-TaqIB polymorphisms were determine…

Effect of walnut-enriched meat on the relationship between VCAM, ICAM, and LTB4 levels and PON-1 activity in ApoA4 360 and PON-1 allele carriers at increased cardiovascular risk

Cardiovascular risk depends largely on paraoxonase (PON-1) and apolipoprotein A4 (APOA4) gene polymorphisms. To compare the effects of consumption of walnut-enriched meat versus low-fat meat (LM) on selected soluble adhesion molecules and leukotrienes (LTB4). In all 22 subjects at increased cardiovascular risk were taken. It is a non-blinded, cross-over, placebo-controlled study. Two 5-week experimental periods separated by 4–6 week wash-out interval. Participants consumed walnut-enriched meat during one period and LM during the other. Diet characteristics, HDLc, Apo A1, paraoxonase, sVCAM-1, sICAM-1 and LTB4 were analysed. PON-1 55, PON-1 192 and APOA4 360 polymorphism effects were also as…

Impact of psychosocial factors on cardiovascular morbimortality: a prospective cohort study

[Background] Whilst it is well known that psychosocial determinants may contribute to cardiovascular diseases (CVD), data from specific groups are scarce. The present study aims to determine the contribution of psychosocial determinants in increasing the risk of cardiovascular events (myocardial infarction and stroke), and death from CVD, in a high risk adult population.

Dietary fat interacts with the -514CT polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: the 1998 Singapore National Health Survey.

We have previously reported an interaction between -514CT polymorphism at the hepatic lipase (HL) gene and dietary fat on high-density lipoprotein-cholesterol (HDL-C) metabolism in a representative sample of white subjects participating in the Framingham Heart Study. Replication of these findings in other populations will provide proof for the relevance and consistency of this marker as a tool for risk assessment and more personalized cardiovascular disease prevention. Therefore, we examined this gene-nutrient interaction in a representative sample of Singaporeans (1324 Chinese, 471 Malays and 375 Asian Indians) whose dietary fat intake was recorded by a validated questionnaire. When no str…

Plasma viscosity and related cardiovascular risk factors in a Spanish Mediterranean population

Plasma viscosity (PV) constitutes an independent important predictor of initial and recurrent cardiac events and mortality. It has been suggested that there is a geographical variation in PV values related to coronary event rates. Little information exists regarding PV in Spain. Therefore, our objective was to determine PV in a large sample of randomly selected subjects from the Spanish population and to study which demographic or cardiovascular risk factors (CVRF) influence levels of PV in this population.1277 subjects (503 males, 774 females) aged 43+/-14 years (range: 20-70) were randomly selected from an Eastern Spanish population. These subjects were free of cardiovascular diseases and…

Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial

© 2014 Elsevier B.V. Background and aim: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. Methods and results: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and …

SEQPACKER: A Biologist-Friendly User Interface to Manipulate Nucleotide Sequences in Genomic Epidemiology

The aim of this paper is to present a new integrated bioinformatics tool for manipulating nucleotide sequences with a user-friendly graphical interface. This tool is named “SeqPacker” because it uses DNA/RNA sequences. In addition, SeqPacker can be seen as a kind of nucleotide chain editor using standardized technologies, nucleotide representation standards, and high platform portability in support of research in Genomic Epidemiology. SeqPacker is written in JAVA as free and stand-alone software for several computer platforms.

Association between taste perception and adiposity in overweight or obese older subjects with metabolic syndrome and identification of novel taste-related genes.

BACKGROUND The relation between taste perception, diet, and adiposity remains controversial. Additionally, there is a lack of knowledge on the polymorphisms influencing taste given the scarcity of genome-wide association studies (GWASs) published. OBJECTIVES We studied the relation between perception of the basic tastes, i.e., sweet, salty, bitter, sour, and umami (separately and jointly in a "taste score"), and anthropometric measurements in older subjects with metabolic syndrome (MetS). GWASs were undertaken to identify genes associated with basic tastes and their score. METHODS Taste perception was cross-sectionally determined by challenging subjects (381 older individuals with MetS) wit…

Additional file 10: Figure S8. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Volcano plot [−log10 (p-value) vs. log2 (fold-change)] for the comparison between the baseline and final states in group 2 (suspected cases of NAFLD). Abbreviations: AA, amino acids; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; MUFA, monounsaturated fatty acids; NAE, N-acyl ethanolamines; FFAox, free fatty acid oxidised; AC, acyl carnitines; PC, phosphatidylcholine; LPC, lysophosphatidylcholine; PE, phatidylethanolamine; LPE, lysophosphatidylethanolamine; PI, phatidylinositols; LPI, lysophosphatidylinositols; Cer, ceramides; SM, sphingomyelin; ChoE, cholesteryl esters; Chol, cholesterol; TAG, triacylglycerols; DAG, diacylglycerols, BA, bile acids; CMH, monohexosylceramides…

Gene-environment interactions of CETP gene variation in a high cardiovascular risk Mediterranean population

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the −4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D'= 0.88; P < 0.001). They were i…

Intake of Total Polyphenols and Some Classes of Polyphenols Is Inversely Associated with Diabetes in Elderly People at High Cardiovascular Disease Risk

Background: Higher consumption of some polyphenols has been associated with a reduced risk of diabetes. However, no studies have evaluated the relation between all polyphenol subclasses and the incidence of diabetes.Objective: We aimed to prospectively examine the associations between the intake of total polyphenols and different groups of polyphenols (flavonoids, phenolic acids, stilbenes, lignans, and others) on the risk of incident diabetes in the PREDIMED (Prevencion con Dieta Mediterranea) trial.Methods: This was an observational cohort analysis of the nondiabetic participants in the PREDIMED trial. This study was a multicenter, controlled, randomized, parallel-group feeding trial to a…

Isotemporal substitution of inactive time with physical activity and time in bed: cross-sectional associations with cardiometabolic health in the PREDIMED-Plus study

Background: This study explored the association between inactive time and measures of adiposity, clinical parameters, obesity, type 2 diabetes and metabolic syndrome components. It further examined the impact of reallocating inactive time to time in bed, light physical activity (LPA) or moderate-to-vigorous physical activity (MVPA) on cardio-metabolic risk factors, including measures of adiposity and body composition, biochemical parameters and blood pressure in older adults. Methods: This is a cross-sectional analysis of baseline data from 2189 Caucasian men and women (age 55-75 years, BMI 27-40 Kg/m(2)) from the PREDIMED-Plus study (http://www.predimedplus.com/). All participants had >= 3…

Papel de las ómicas en la nutrición de precisión: fortalezas y debilidades

Precision medicine has taken huge strides forward in recent years. Although there is still no generally accepted single definition, it basically considers the particular characteristics of each person as relevant in order to better adapt therapeutic or preventive measures in a more personalized fashion. Likewise, the concept of precision nutrition has gathered strength, in which the aim is to provide the best dietary recommendations to prevent or treat a disease in accordance with the characteristics of the individual in question. Of special importance among these characteristics are those based on omics. Initially genomics, and now epigenomics, metabolomics, proteomics and transcriptomics …

Modelo conceptual bioinformático aplicado al análisis genómico de las enfermedades cardiovasculares

Fundamento El analisis genomico actualmente necesita de la concurrencia de disciplinas muy alejadas del campo de la biologia molecular, entre ellas la ciencia de la computacion, base de la bioinformatica. Las herramientas bioinformaticas trabajan fundamentalmente con modelos abstractos de la informacion genomica. Este trabajo tiene por objetivo la obtencion de un modelo conceptual de la informacion genomica cuya finalidad es la construccion de sistemas de software bioinformaticos para el analisis de las enfermedades cardiovasculares. Metodos Se han aplicado 2 enfoques complementarios en ingenieria del software: el paradigma de la orientacion a objetos, aplicando el metodo unificado de desar…

Use of Different Food Classification Systems to Assess the Association between Ultra-Processed Food Consumption and Cardiometabolic Health in an Elderly Population with Metabolic Syndrome (PREDIMED-Plus Cohort)

The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014–2019; agreement #340918; granted to M.Á.M.-G.); the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI…

Physical activity is associated with better global cognition and frontal function in overweight/obese older adults with metabolic syndrome

Background There is epidemiological evidence of an association between the metabolic syndrome (MetS), a cluster of cardiovascular risk factors related to central adiposity and insulin resistance, and cognitive impairment and dementia. On the other hand, there is evidence for a beneficial effect of physical activity on cognitive outcomes in older adult populations. In a cross-sectional study, we evaluated the relationship between aerobic physical activity and cognition in a cohort of overweight/obese older adults with MetS at risk for dementia. Cognitive function was assessed in a subsample of 82 subjects (men 55–75 y; women 60–75 y), with MetS and a BMI ≥27 to < 40 kg/m2 enrolled in the PRE…

Sleep Duration is Inversely Associated with Serum Uric Acid Concentrations and Uric Acid to Creatinine Ratio in an Elderly Mediterranean Population at High Cardiovascular Risk

The aim of the study was to evaluate sleep duration and sleep variability in relation to serum uric acid (SUA) concentrations and SUA to creatinine ratio. This is a cross-sectional analysis of baseline data from 1842 elderly participants with overweight/obesity and metabolic syndrome in the (Prevencion con Dieta Mediterranea) PREDIMED-Plus trial. Accelerometry-derived sleep duration and sleep variability were measured. Linear regression models were fitted to examine the aforementioned associations. A 1 hour/night increment in sleep duration was inversely associated with SUA concentrations ( = -0.07, p = 0.047). Further adjustment for leukocytes attenuated this association (p = 0.050). Each …

Fitoesteroles plasmáticos: marcadores de una dieta saludable y un riesgo cardiometabólico menor en la población española del estudio EPIC

Resumen Introduccion Las concentraciones elevadas de fitoesteroles plasmaticos, que reflejan una mayor absorcion intestinal de colesterol se han relacionado con un aumento del riesgo cardiovascular. Sin embargo, una situacion de riesgo alto, el sindrome metabolico (SM), se asocia a un aumento de la sintesis y una disminucion de la absorcion de colesterol y, por tanto, a una menor fitoesterolemia. En este estudio hemos investigado la relacion entre los fitoesteroles del plasma y la dieta y la presencia de factores de riesgo cardiovascular, incluidos los componentes del SM. Metodos y resultados En un estudio transversal, se evaluaron la ingesta de fitoesteroles y concentraciones plasmaticas d…

Effects of a Mediterranean Diet and physical activity on atherothrombosis biomarkers in high cardiovascular risk individuals

Objective. Following a Mediterranean diet (MedDiet) and being physically active decrease cardiovascular risk. However, their individual and combined effects on atherothrombosis biomarkers are unexplored. Approach and Results. In 358 random volunteers from the PREDIMED trial (Prevencion con Dieta Mediterranea), we assessed the 1-year effects of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; N=120) or nuts (MedDiet-Nuts; N=119) versus a low-fat control diet (N=119), on atherothrombosis markers. In a secondary, observational approach, we studied the associations of 1-year changes in MedDiet adherence, physical activity (PA) levels, and their combination, with 1-year…

Protective effect of homovanillyl alcohol on cardiovascular disease and total mortality: virgin olive oil, wine, and catechol-methylathion

Background: Hydroxytyrosol is a phenolic compound that is present in virgin olive oil (VOO) and wine. Hydroxytyrosol-related foods have been shown to protect against cardiovascular disease (CVD).Objective: We investigated the associations between hydroxytyrosol and its biological metabolite, 3-O-methyl-hydroxytyrosol, also known as homovanillyl alcohol (HVAL), with CVD and total mortality.Design: We included 1851 men and women with a mean ± SD age of 66.8 ± 6 y at high risk of CVD from prospective cohort data. The primary endpoint was a composite of myocardial infarction, stroke, and death from cardiovascular causes; the secondary endpoint was all-cause mortality. Twenty-four-hour urinary h…

Phenolic and microbial-targeted metabolomics to discovering and evaluating wine intake biomarkers in human urine and plasma

The discovery of biomarkers of intake in nutritional epidemiological studies is essential in establishing an association between dietary intake (considering their bioavailability) and diet-related risk factors for diseases. The aim is to study urine and plasma phenolic and microbial profile by targeted metabolomics approach in a wine intervention clinical trial for discovering and evaluating food intake biomarkers. High-risk male volunteers (n = 36) were included in a randomized, crossover intervention clinical trial. After a washout period, subjects received red wine or gin, or dealcoholized red wine over four weeks. Fasting plasma and 24-h urine were collected at baseline and after each i…

Additional file 6: Figure S4. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Principal component analysis (PCA) to discriminate between the baseline and final states in group 3 (suspected NAFLD reversion cases). Model diagnostics (A = 6, R2X = 0.628, Q2X = 0.235) (DOCX 42 kb)

Additional file 9: Figure S7. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Volcano plot [−log10 (p-value) vs. log2 (fold-change)] for the comparison between the baseline and final states in group 1 (not meeting the NAFLD criteria at baseline and during the follow-up).Abbreviations: AA, amino acids; SFA, saturated fatty acids; PUFA, polyunsaturated fatty acids; MUFA, monounsaturated fatty acids; NAE, N-acyl ethanolamines; FFAox, free fatty acid oxidised; AC, acyl carnitines; PC, phosphatidylcholine; LPC, lysophosphatidylcholine; PE, phatidylethanolamine; LPE, lysophosphatidylethanolamine; PI, phatidylinositols; LPI, lysophosphatidylinositols; Cer, ceramides; SM, sphingomyelin; ChoE, cholesteryl esters; Chol, cholesterol; TAG, triacylglycerols; DAG, diacylglycerols,…

Association between glucokinase regulatory protein (GCKR) and apolipoprotein A5 (APOA5) gene polymorphisms and triacylglycerol concentrations in fasting, postprandial, and fenofibrate-treated states.

Background: Hypertriglyceridemia is a risk factor for cardiovascular disease. Variation in the apolipoprotein A5 (APOA5) and glucokinase regulatory protein (GCKR) genes has been associated with fasting plasma triacylglycerol. Objective: We investigated the combined effects of the GCKR rs780094C→T, APOA5 −1131T→C, and APOA5 56C→G single nucleotide polymorphisms (SNPs) on fasting triacylglycerol in several independent populations and the response to a high-fat meal and fenofibrate interventions. Design: We used a cross-sectional design to investigate the association with fasting triacylglycerol in 8 populations from America, Asia, and Europe (n = 7730 men and women) and 2 intervention studies…

Mediterranean Diet Improves High-Density Lipoprotein Function in High-Cardiovascular-Risk Individuals: A Randomized Controlled Trial.

Background: The biological functions of high-density lipoproteins (HDLs) contribute to explaining the cardioprotective role of the lipoprotein beyond quantitative HDL cholesterol levels. A few small-scale interventions with a single antioxidant have improved some HDL functions. However, to date, no long-term, large-scale, randomized controlled trial has been conducted to assess the effects of an antioxidant-rich dietary pattern (such as a traditional Mediterranean diet [TMD]) on HDL function in humans. Methods: This study was performed in a random subsample of volunteers from the PREDIMED Study (Prevención con Dieta Mediterránea; n=296) after a 1-year intervention. We compared the effects …

Metabolomic Pattern Analysis after Mediterranean Diet Intervention in a Nondiabetic Population: A 1- and 3-Year Follow-up in the PREDIMED Study

The Mediterranean diet (MD) is considered a dietary pattern with beneficial effects on human health. The aim of this study was to assess the effect of an MD on urinary metabolome by comparing subjects at 1 and 3 years of follow-up, after an MD supplemented with either extra-virgin olive oil (MD + EVOO) or nuts (MD + Nuts), to those on advice to follow a control low-fat diet (LFD). Ninety-eight nondiabetic volunteers were evaluated, using metabolomic approaches, corresponding to MD + EVOO (n = 41), MD + Nuts (n = 27), or LFD (n = 30) groups. The (1)H NMR urinary profiles were examined at baseline and after 1 and 3 years of follow-up. Multivariate data analysis (OSC-PLS-DA and HCA) methods we…

Low Serum Choline Concentrations Are Associated with Worse Cognitive Performance in Subjects with Metabolic Syndrome

OBJECTIVES: Choline is an essential nutrient critical for components of the cell membrane, such as choline-containing phospholipids (phosphatidylcholine and sphingomyelin), and in synthesis of the neurotransmitter acetylcholine. Choline has been shown to exert neuroprotective effects, but the association between serum choline and cognitive performance has been scarcely investigated. Our aims are: 1) To study the association between serum total choline, phosphatidylcholine and sphingomyelin with cognitive performance in subjects with metabolic syndrome; and 2) to analyze genetic variants and dietary intake most associated with cholines in this population. METHODS: We analyzed 426 subjects (a…

Bitter, Sweet, Salty, Sour and Umami Taste Perception Decreases with Age: Sex-Specific Analysis, Modulation by Genetic Variants and Taste-Preference Associations in 18 to 80 Year-Old Subjects

There is growing interest in relating taste perception to diet and healthy aging. However, there is still limited information on the influence of age, sex and genetics on taste acuity as well as on the relationship between taste perception and taste preferences. We have analysed the influence of age on the intensity rating of the five basic tastes: sweet, salty, bitter, sour and umami (separately and jointly in a &ldquo

Influence of a Mediterranean Dietary Pattern on Body Fat Distribution: Results of the PREDIMED-Canarias Intervention Randomized Trial

Objective: To assess the influence of a Mediterranean dietary pattern (MeDiet) on anthropometric and body composition parameters in one of the centers of the PREDIMED randomized dietary trial. Subjects/Settings: 351 Canarian free-living subjects aged 55 to 80 years, with type 2 diabetes or ≥3 cardiovascular risk factors. Intervention: Participants were randomly assigned to one of 3 different dietary interventions: MeDiet + extra-virgin olive oil (EVOO), MeDiet + nuts (walnuts, almonds, and hazelnuts), or a control low-fat diet. Total energy intake was ad libitum. Outcome measures: Measures included changes in anthropometric measures (weight, body mass index [BMI] and waist circumference [WC…

Longitudinal association of telomere length and obesity indices in an intervention study with a Mediterranean diet: the PREDIMED-NAVARRA trial

Background: Telomeres are nucleoprotein structures that protect the ends of eukaryote chromosomes. Shorter telomere length (TL) is associated with some age-related human disorders, but its relationship with obesity or adiposity parameters remains unclear. Objective: The aim of this study was to assess the relationship between TL and changes in adiposity indices after a 5-year nutritional intervention. Design and subjects: TL was measured by quantitative real-time PCR in 521 subjects (55-80 years, 55% women). Participants were randomly selected from the PREDIMED-NAVARRA centre after they completed a 5-year intervention programme. Anthropometric parameters were directly measured by trained pe…

A Polymorphism in a Gene Encoding Perilipin 4 Is Associated with Height but not with Bone Measures in Individuals from the Framingham Osteoporosis Study

There is increasing interest in identifying new pathways and candidate genes that confer susceptibility to osteoporosis. There is evidence that adipogenesis and osteogenesis may be related, including a common bone marrow progenitor cell for both adipocytes and osteoblasts. Perilipin 1 (PLIN1) and Perilipin 4 (PLIN4) are members of the PATS family of genes and are involved in lipolysis of intracellular lipid deposits. A previous study reported gender-specific associations between one polymorphism of PLIN1 and bone mineral density (BMD) in a Japanese population. We hypothesized that polymorphisms in PLIN1 and PLIN4 would be associated with bone measures in adult Caucasian participants of the …

Dysfunctional High-Density Lipoproteins Are Associated With a Greater Incidence of Acute Coronary Syndrome in a Population at High Cardiovascular Risk

Background: Studies have failed to establish a clear link between high-density lipoprotein (HDL) cholesterol and cardiovascular disease, leading to the hypothesis that the atheroprotective role of HDL lies in its biological activity rather than in its cholesterol content. However, to date, the association between HDL functional characteristics and acute coronary syndrome has not been investigated comprehensively. Methods: We conducted a case-control study nested within the PREDIMED (Prevención con Dieta Mediterránea) cohort, originally a randomized trial in which participants followed a Mediterranean or low-fat diet. Incident acute coronary syndrome cases (N=167) were individually matched …

Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk.

Background and aims Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. Methods and results Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin–Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), c…

The Effect of a Mediterranean Diet on the Incidence of Cataract Surgery

Background: Cataract is a leading cause of vision impairment worldwide, and surgery is the only available treatment. The process that initiates lens opacification is dependent on the oxidative stress experienced by the lens components. A healthy overall dietary pattern, with the potential to reduce oxidative stress, has been suggested as a means to decrease the risk of developing cataract. We aimed to investigate the hypothesis that an intervention with a Mediterranean diet (MedDiet) rather than a low-fat diet could decrease the incidence of cataract surgery in elderly subjects. Methods: We included 5802 men and women (age range: 55-80 years) from the Prevencion con Dieta Mediterronea study…

Mediterranean diet supplemented with nuts reduces waist circumference and shifts lipoprotein subfractions to a less atherogenic pattern in subjects at high cardiovascular risk

[Objective]: The PREDIMED trial showed that Mediterranean diets supplemented with either extra-virgin olive oil or nuts reduced incident cardiovascular events compared to a control diet. Consumption of both supplemental foods has been associated with reduced LDL-cholesterol, but it is unknown whether they can shift lipoprotein subfractions to a less atherogenic pattern. We investigated changes in adiposity and lipoprotein subfractions after consumption of the PREDIMED diets.

A Guide to Applying the Sex-Gender Perspective to Nutritional Genomics

Precision nutrition aims to make dietary recommendations of a more personalized nature possible, to optimize the prevention or delay of a disease and to improve health. Therefore, the characteristics (including sex) of an individual have to be taken into account as well as a series of omics markers. The results of nutritional genomics studies are crucial to generate the evidence needed so that precision nutrition can be applied. Although sex is one of the fundamental variables for making recommendations, at present, the nutritional genomics studies undertaken have not analyzed, systematically and with a gender perspective, the heterogeneity/homogeneity in gene-diet interactions on the diffe…

Sensibilidad, especificidad y valor predictivo del análisis genético de variantes en el gen SLC3A1 aplicado al diagnóstico de cistinuria en población española

Objetivo Estimar la validez clinica del analisis de las mutaciones puntuales R452W, M467T, 114C > A, 231T > A, 1136 + 3delT y 1332 + 7T > C en el gen SLC3A1, asi como de sus posibles haplotipos aplicados al diagnostico de cistinuria en poblacion mediterranea espanola. Material y metodos Se han estudiado 48 pacientes con cistinuria, 44 familiares sin cistinuria y 81 controles sanos. Se realizo un analisis genetico para la identificacion de variantes en el gen SLC3A1. Se calculo la sensibilidad, especificidad y valor predictivo para cada variante genetica y para los posibles haplotipos. Resultados La especificidad de las mutaciones M467T, R452W y 231T > A aplicadas al diagnostico de cistinuri…

Polyphenol-Rich Foods in the Mediterranean Diet are Associated with Better Cognitive Function in Elderly Subjects at High Cardiovascular Risk

Brain oxidative processes play a major role in age-related cognitive decline, thus consumption of antioxidant-rich foods might help preserve cognition. Our aim was to assess whether consumption of antioxidant-rich foods in the Mediterranean diet relates to cognitive function in the elderly. In asymptomatic subjects at high cardiovascular risk (n = 447; 52% women; age 55-80 y) enrolled in the PREDIMED study, a primary prevention dietary-intervention trial, we assessed food intake and cardiovascular risk profile, determined apolipoprotein E genotype, and used neuropsychological tests to evaluate cognitive function. We also measured urinary polyphenols as an objective biomarker of intake. Asso…

Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans

Blood concentrations of lipoproteins and lipids are heritable1 risk factors for cardiovascular disease2,3. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue4) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipo…

Polyphenol intake from a Mediterranean diet decreases inflammatory biomarkers related to atherosclerosis: a substudy of the PREDIMED trial

High dietary polyphenol intake is associated with reduced all-cause mortality and a lower incidence of cardiovascular events. However, the mechanisms involved are not fully understood. The aim of the present substudy of the PREvencion con DIetaMEDiterranea (Prevention with Mediterranean diet; PREDIMED) trial was to analyse the relationship between polyphenol intake measured by total urinary polyphenol excretion (TPE), and circulating inflammatory biomarkers and cardiovascular risk factors in elderly individuals. A substudy of 1139 high-risk participants was carried out within the PREDIMED trial. The subjects were randomly assigned to a low-fat control diet or to two Mediterranean diets, sup…

Identification of novel SLC3A1 gene mutations in Spanish cystinuria families and association with clinical phenotypes

Cystinuria is an inherited metabolic disease characterized by an abnormal urinary excretion of cystine and dibasic amino acids, leading to kidney stone formation. Incidence of cystinuria in the Mediterranean Spanish population is one of the highest in the world. In view of the low prevalence of previously reported mutations in the SLC3A1 gene, analyses to identify novel variants were carried out on 20 cystinuria families. Additionally, we investigated the possible association between these molecular variants and clinical phenotypes. Genomic DNA from 48 cystinuria patients, 44 healthy relatives and 81 unrelated controls from the East Mediterranean coast of Spain was screened by conformation …

Gazpacho consumption is associated with lower blood pressure and reduced hypertension in a high cardiovascular risk cohort. Cross-sectional study of the PREDIMED trial.

[Background and aim]: Hypertension is a major public health problem and a leading cause of death and disability in both developed and developing countries, affecting one-quarter of the world's adult population. Our aim was to evaluate whether the consumption of gazpacho, a Mediterranean vegetable-based cold soup rich in phytochemicals, is associated with lower blood pressure (BP) and/or reduced prevalence of hypertension in individuals at high cardiovascular risk.

Mediterranean Diet and Cardiovascular Health: Teachings of the PREDIMED Study123

The PREDIMED (Prevención con Dieta Mediterránea) study was designed to assess the long-term effects of the Mediterranean diet (MeDiet) without any energy restriction on incident cardiovascular disease (CVD) as a multicenter, randomized, primary prevention trial in individuals at high risk. Participants were randomly assigned to 3 diet groups: 1) MeDiet supplemented with extra-virgin olive oil (EVOO); 2) MeDiet supplemented with nuts; and 3) control diet (advice on a low-fat diet). After 4.8 y, 288 major CVD events occurred in 7447 participants; crude hazard ratios were 0.70 (95% CI: 0.53, 0.91) for the MeDiet + EVOO and 0.70 (95% CI: 0.53, 0.94) for the MeDiet + nuts compared with the contr…

Education modulates the association of the FTO rs9939609 polymorphism with body mass index and obesity risk in the Mediterranean population

Objective To define whether the rs9939609 FTO (fat mass and obesity associated) single nucleotide polymorphism (SNP) is associated with anthropometric measurements and its modulation by educational level in a Mediterranean population. Methods We studied 3 independent adult samples: a random sample (n = 1580) from the general population (GP), obese hospital patients (OHP) (n = 203) and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and height were directly measured. Education and physical activity (PA) were measured using questionnaires. Results The rs9939609 presented heterogeneous associations with BMI. In the GP, the minor A-allele was significantly associated wit…

Association between M467T and 114 C--A variants within the SLC3A1 gene and some phenotypical traits in cystinuria patients from Spain.

Cystinuria is an inherited metabolic disease characterized by an abnormal urinary excretion of cystine and dibasic amino acids. Formation of renal calculi, recurrent infections and renal failure are the main complications of this disease. The SLC3A1 gene, which codes for a dibasic amino acid transporter protein, is involved in the pathogenesis of cystinuria. We investigated the possible association between molecular variants (M467T, E483X, T216 M and 114 C--A) within the SLC3A1 gene and some phenotypical traits in a Spanish area. The study population consisted of 45 cystinuria patients, 42 cystinuria relatives and 81 healthy control subjects. Only the M467T mutation was found in chromosomes…

Ultra-Performance Liquid Chromatography-Ion Mobility Separation-Quadruple Time-of-Flight MS (UHPLC-IMS-QTOF MS) Metabolomics for Short-Term Biomarker Discovery of Orange Intake: A Randomized, Controlled Crossover Study

A major problem with dietary assessments is their subjective nature. Untargeted metabolomics and new technologies can shed light on this issue and provide a more complete picture of dietary intake by measuring the profile of metabolites in biological samples. Oranges are one of the most consumed fruits in the world, and therefore one of the most studied for their properties. The aim of this work was the application of untargeted metabolomics approach with the novel combination of ion mobility separation coupled to high resolution mass spectrometry (IMS-HRMS) and study the advantages that this technique can bring to the area of dietary biomarker discovery, with the specific case of biomarker…

Plasma metabolites predict both insulin resistance and incident type 2 diabetes: a metabolomics approach within the Prevención con Dieta Mediterránea (PREDIMED) study

Background Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). Objectives The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. Methods We used a case-cohort study nested within the Prevencion con Dieta Mediterranea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem m…

Association Between Fatty Acids of Blood Cell Membranes and Incidence of Coronary Heart Disease

Objective— To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk. Approach and Results— This is a case-control study nested in the PREDIMED trial (Prevención con Dieta Mediterránea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year. Conditional logistic regression was used to estimate odds ratios (ORs) and…

Mediterranean Diet and Age-Related Cognitive Decline

IMPORTANCE: Oxidative stress and vascular impairment are believed to partly mediate age-related cognitive decline, a strong risk factor for development of dementia. Epidemiologic studies suggest that a Mediterranean diet, an antioxidant-rich cardioprotective dietary pattern, delays cognitive decline, but clinical trial evidence is lacking. OBJECTIVE: To investigate whether a Mediterranean diet supplemented with antioxidant-rich foods influences cognitive function compared with a control diet. DESIGN, SETTING, AND PARTICIPANTS: Parallel-group randomized clinical trial of 447 cognitively healthy volunteers from Barcelona, Spain (233 women [52.1%]; mean age, 66.9 years), at high cardiovascular…

Metabolites related to purine catabolism and risk of type 2 diabetes incidence; modifying effects of the TCF7L2-rs7903146 polymorphism

Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid rat…

Efecto del polimorfismo +2138InsCAGACC en el gen del receptor 3 de la melanocortina en el riesgo de obesidad en población española

Objetivo El receptor 3 de la melanocortina (MC3R) ha sido implicado en la regulacion de la homeostasis energetica y en el peso corporal. Nuestro objetivo es conocer si el polimorfismo +2138InsCAGACC en dicho gen se asocia con el riesgo de obesidad en poblacion espanola. Material y metodo Se ha realizado un estudio de casos y controles con 303 casos de obesidad y 606 controles apareados por sexo y edad. Se determinaron variables antropometricas y del estilo de vida y el polimorfismo +2138InsCAGACC en el gen del MC3R. Resultados La frecuencia alelica para la variante +2138InsCAGACC para el total de la poblacion fue de 0,29, y resulto ligeramente menos frecuente en el grupo de casos que en el …

Hyperhomocysteinemia, obesity and cryptogenic stroke

BACKGROUND: The pathogenic role of hyperhomocysteinemia in cryptogenic stroke is not well established. We aimed to determine homocysteine levels in patients with cryptogenic stroke considering the possible variables that may act as confounders and analyze the influence of obesity on this association. PATIENTS AND METHODS: We conducted a case-control study in 123 patients with cryptogenic stroke aged 42 ± 12 years and in 153 control subjects aged 42 ± 13 years. Serum homocysteine was determined by fluorescence polarization immunoassay. RESULTS: Patients showed statistically higher levels of homocysteine, creatinine and higher BMI than controls (p = 0.045, p = 0.014, p = 0.013), respectively.…

Impacto de la apolipoproteína A5 en el riesgo cardiovascular: Modulaciones genéticas y ambientales

Triglyceride concentrations are an independent risk factor for coronary heart disease. Apolipoprotein A5 gene (APOA5) has an important role determining triglyceride metabolism and it is a potential cardiovascular risk. However the mechanisms for these actions are not well-known. Despite the different allelic frequency of its major polymorphisms in different populations, multiple studies have shown consistent associations between these variants and fasting triglycerides. Variations in the APOA5 gene have also been associated with postprandial triglycerides, as well as with different sizes of lipoproteins and other markers. Moreover, some of the APOA5 gene variants have been associated with i…

Advances in Integrating Traditional and Omic Biomarkers When Analyzing the Effects of the Mediterranean Diet Intervention in Cardiovascular Prevention

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 a…

Baseline adherence to the Mediterranean diet and major cardiovascular events: Prevención con dieta mediterránea trial

Lifestyle modification, particularly dietary changes, is the cornerstone of population-based strategies for cardiovascular disease (CVD) prevention.1 Recently the Prevención con Dieta Mediterránea (PREDIMED) study,2 a 5-year randomized primary prevention trial (isrctn.org Identifier: ISRCTN35739639), showed a 30% reduction in incident CVD with Mediterranean diet (MeDiet) intervention in comparison with a control diet. At quarterly visits throughout the study, a validated 14-item MeDiet screening tool (Table 1) was used to assess conformity with this dietary pattern.3 Close monitoring of adherence to dietary instructions for CVD prevention is difficult in the clinical setting. Short dietary …

trans -Lycopene from tomato juice attenuates inflammatory biomarkers in human plasma samples: An intervention trial

cope : To evaluate the effects of carotenoids from tomato juice (TJ) on inflammatory biomarkers, by performing a 4-week dose-response nutritional trial in a population at high cardiovascular risk. Methods and results : An open, prospective, randomized, cross-over, and controlledclinical trial was carried out with 28 volunteers (mean age 69.7 ± 3.1 years; mean BMI 31.5 ± 3.6 kg/m2) at high cardiovascular risk, which were assigned to consume daily for 4 weeks in random order: 200 mL (LD) or 400 mL (HD) of TJ, or water as a control (C), with a 21-day wash-out period between each intervention. Blood samples were collected at baseline (B) and after each intervention. Endpoints included significa…

Effectiveness of the physical activity intervention program in the PREDIMED-Plus study: a randomized controlled trial

[Background] The 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 PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial, we assessed the initial effectiveness of the PA component.

Effect of the polymorphism rs2470893 of the CYP1A1 gene on ovarian and endometrial cancer in Mediterranean women

Dietary total antioxidant capacity and mortality in the PREDIMED study

PURPOSE: The aim of the present study was to assess the association between the dietary total antioxidant capacity, the dietary intake of different antioxidants and mortality in a Mediterranean population at high cardiovascular disease risk. METHODS: A total of 7,447 subjects from the PREDIMED study (multicenter, parallel group, randomized controlled clinical trial), were analyzed treating data as an observational cohort. Different antioxidant vitamin intake and total dietary antioxidant capacity were calculated from a validated 137-item food frequency questionnaire at baseline and updated yearly. Deaths were ascertained through contact with families and general practitioners, review of med…

Association between the rs6950982 polymorphism near the SERPINE1 gene and blood pressure and lipid parameters in a high-cardiovascular-risk population: interaction with Mediterranean diet

The SERPINE1 (serpin peptidase inhibitor, clade E, member 1) gene, better known by its previous symbol PAI-1 (plasminogen activator inhibitor 1), has been associated with cardiovascular phenotypes with differing results. Our aim was to examine the association between the rs6950982 (G  A) near the SERPINE1 gene, blood pressure (BP) and plasma lipid concentrations as well as the modulation of the polymorphism effects by adherence to Mediterranean diet (AMD). We studied 945 high-cardiovascular-risk subjects. Biochemical, clinical, dietary and genetic data (rs6950982) were obtained. We also determined the common rs1799768 (4G/5G), for checking independent effects. AMD was measured by a validate…

Asociación entre índice tobillo-brazo y rendimiento cognitivo en participantes del estudio PREDIMED-Plus: estudio transversal

Resumen Introduccion y objetivos El indice tobillo-brazo (ITB) es un indicador de enfermedad arterial periferica (EAP). El objetivo de este estudio es evaluar la asociacion entre la EAP medida con el ITB y el rendimiento cognitivo de individuos con sobrepeso u obesidad y sindrome metabolico. Metodos Estudio transversal realizado con los datos basales del estudio PREDIMED-Plus, en el que se incluyo a un total de 4.898 participantes (tras excluir a aquellos sin medicion de ITB) de entre 55 y 75 anos, con sobrepeso u obesidad y sindrome metabolico. En la visita basal se midio el ITB segun un protocolo estandarizado, asi como otros factores de riesgo cardiovascular (diabetes mellitus, dislipemi…

Empirically-derived food patterns and the risk of total mortality and cardiovascular events in the PREDIMED study.

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 fo…

Anti-Inflammatory Effects of the Mediterranean Diet in the Early and Late Stages of Atheroma Plaque Development

Objective.To evaluate the long-term effects of a Mediterranean diet (MeDiet) intervention on the plasma concentrations of inflammatory and plaque stability-related molecules in elderly people at high risk for cardiovascular disease.Design and Setting. 66 participants from primary care centers affiliated with the Hospital Clinic of Barcelona were randomized into 3 groups: MeDiet plus extra virgin olive oil (EVOO) or nuts and a low-fat diet (LFD). At baseline and at 3 and 5 years, we evaluated the changes in the plasma concentrations of 24 inflammatory biomarkers related to the different stages of the atherosclerotic process by Luminex®.Results.At 3 and 5 years, both MeDiet groups showed a si…

Statistical and biological gene-lifestyle interactions of MC4R and FTO with diet and physical activity on obesity: new effects on alcohol consumption

Background: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associati…

Effects of dietary fiber intake on risk factors for cardiovascular disease in subjects at high risk

Background: Epidemiological studies and feeding trials with supplements suggest that fibre intake is associated with a reduction in cardiovascular risk. However, the effects of changes in dietary fibre on risk factor levels have not been evaluated in free-living individuals. Thus, the effects of changes in dietary fibre intake on cardiovascular risk factors were assessed over 3 months in free-living high-risk subjects. Methods: 772 high-risk subjects (age 69±5 years) were assigned to a low-fat diet or two Mediterranean-style diets. All participants received behavioural and nutritional education, including recommendations for increasing the consumption of vegetables, fruits, and legumes. Cha…

Gender specific associations of the Trp64Arg mutation in the beta3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation

Abstract. Corella D, Guillen M, Portoles O, Sorli JV, Alonso V, Folch J, Saiz C (School of Medicine, University of Valencia, Valencia, Spain). Gender specific associations of the Trp64Arg mutation in the β3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. J Intern Med 2001; 250: 348–360. Objective. To investigate the association between the Trp64Arg β3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. Design and subject. Cross-sectional study in 1063 (476 men and 587 wome…

Plasma branched-chain amino acids and incident cardiovascular disease in the PREDIMED Trial

Abstract BACKGROUND The role of branched-chain amino acids (BCAAs) in cardiovascular disease (CVD) remains poorly understood. We hypothesized that baseline BCAA concentrations predict future risk of CVD and that a Mediterranean diet (MedDiet) intervention may counteract this effect. METHODS We developed a case-cohort study within the Prevención con Dieta Mediterránea (PREDIMED), with 226 incident CVD cases and 744 noncases. We used LC-MS/MS to measure plasma BCAAs (leucine, isoleucine, and valine), both at baseline and after 1 year of follow-up. The primary outcome was a composite of incident stroke, myocardial infarction, or cardiovascular death. RESULTS After adjustment for potential conf…

Common cholesteryl ester transfer protein gene variation related to high-density lipoprotein cholesterol is not associated with decreased coronary heart disease risk after a 10-year follow-up in a Mediterranean cohort: Modulation by alcohol consumption.

Despite the consistent association between cholesteryl ester transfer protein (CETP) gene variation and plasma HDL-C, huge controversy still rages on its association with coronary heart disease (CHD). We investigated the association between the CETP-TaqIB polymorphism, HDL-C and incident CHD in a Mediterranean population.A nested case-control study among participants of the Spanish EPIC cohort was performed. 41,440 healthy individuals (30-69 years) were followed up over a 10-year period, incident CHD cases being identified. We analyzed 557 confirmed CHD cases and 1180 healthy controls.Despite B2B2 subjects having the highest HDL-C concentrations and B1B1, the lowest (P0.001), no protective …

Olive oil intake and risk of cardiovascular disease and mortality in the PREDIMED Study

[Background] It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk.

Additional file 1: Table S1. of Mercury exposure and risk of cardiovascular disease: a nested case-control study in the PREDIMED (PREvention with MEDiterranean Diet) study

Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to those who were not diagnosed with cardiovascular disease within one year of follow-up. Table S2. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to those who were diagnosed with cardiovascular disease within 5 years of toenail collection. Table S3. Relative Risk of Cardiovascular Disease, according to quartiles of toenail mercury, among case participants and matched controls in the PREDIMED trial, restricted to par…

Influence of Demographic and Lifestyle Variables on Plasma Magnesium Concentrations and Their Associations with Cardiovascular Risk Factors in a Mediterranean Population.

Several studies have shown that a low magnesium (Mg) intake in the diet is associated with greater cardiovascular risk and greater risk of diabetes. However, the results are not consistent in all populations. To minimize the biases derived from diet measurement, more objective biomarkers of magnesium status have been proposed. Although there is still no ideal biomarker for Mg, several studies have shown that plasma Mg concentrations could be a relatively acceptable biomarker for cardiovascular risk assessment. However, further studies are required to better characterize this marker in different populations. Our aim was to analyze the association between plasma Mg concentrations (measured th…

Effect of a traditional Mediterranean diet on apolipoproteins B, A-I, and their ratio: a randomized, controlled trial.

Objectives: Apolipoprotein (Apo)B, ApoA-I, and their ratio could predict coronary heart disease (CHD) risk more accurately than conventional lipid measurements. Our aim was to assess the effect of a traditional Mediterranean diet (TMD) on apolipoproteins. Methods: High-cardiovascular risk subjects (n=551, 308 women and 243 men), aged 55-80 years, were recruited into a large, multicenter, randomized, controlled, parallel-group, clinical trial (The PREDIMED Study) aimed at testing the efficacy of TMD on primary cardiovascular disease prevention. Participants assigned to a low-fat diet (control) (n=177), or TMDs (TMD. +. virgin olive oil (VOO), n=181 or TMD. +. nuts, n=193) received nutritiona…

Plasma lipidome patterns associated with cardiovascular risk in the PREDIMED trial: A case-cohort study.

Abstract 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 4.8years of median follow-up. We repeatedly measured 202 plasma known lipid metabolites at baseline and after 1-year of intervention. Principal component an…

Additional file 2: of Predictors of short- and long-term adherence with a Mediterranean-type diet intervention: the PREDIMED randomized trial

Figure S1. Validated 14-item questionnaire of mediterranean diet adherence (DOCX 205 kb)

Risk factors differentially associated with non-alcoholic fatty liver disease in males and females with metabolic syndrome.

espanolIntroduccion: el higado graso no alcoholico (HGNA) es una enfermedad hepatica cronica mas prevalente en los paises occidentales. Objetivos: evaluar factores de riesgo asociados a HGNA en hombres y mujeres diagnosticados con SM estratificados segun terciles del indice de esteatosis hepatica (HSI). Metodos: analisis transversal del estudio PREDIMED Plus (incluyendo unicamente informacion del nodo Navarra-Nutricion). Un total de 278 participantes (141 hombres y 137 mujeres) con SM fueron estratificados segun terciles de HSI. El estudio analizo variables clinicas, bioquimicas e informacion sobre el estilo de vida, como grado de adherencia a la dieta mediterranea y practica de actividad f…

Dietary fat intake and risk of cardiovascular disease and all-cause mortality in a population at high risk of cardiovascular disease.

Background Dietary fat quality and fat replacement are more important for cardiovascular disease (CVD) prevention than is total dietary fat intake. Objective The aim was to evaluate the association between total fat intake and fat subtypes with the risk of CVD (myocardial infarction, stroke, or death from cardiovascular causes) and cardiovascular and all-cause death. We also examined the hypothetical effect of the isocaloric substitution of one macronutrient for another. Design We prospectively studied 7038 participants at high CVD risk from the PREvencion con DIeta MEDiterranea (PREDIMED) study. The trial was conducted from 2003 to 2010, but the present analysis was based on an expanded fo…

Tomato sauce enriched with olive oil exerts greater effects on cardiovascular disease risk factors than raw tomato and tomato sauce: a randomized trial

Epidemiological studies have observed a negative association between tomato intake and the incidence of cardiovascular disease. As tomato sauces are usually cooked with the addition of oil, some studies have pointed out that both processes may increase the bioavailability of the bioactive compounds. However, the effect of consumption of raw tomatoes and tomato sauces on inflammation biomarkers and adhesion molecules related to atherosclerosis remains unknown. The aim of this study was to test the postprandial effects of a single dose of raw tomatoes (RT), tomato sauce (TS) and tomato sauce with refined olive oil (TSOO) on cardiovascular disease risk factors. We performed an open, prospectiv…

Additional file 8: Figure S6. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Heatmap representing individual metabolomic features obtained from all the comparisons made between the final and the baseline states in groups 1, 2 and 3. Heatmapcolor codes for log2 (fold-change) and Student’s t-test p-values are indicated at the bottom of the Figure. Darker green and red colors indicate higher drops or elevations of the metabolite levels in every comparison. Grey lines correspond to significant fold-changes of individual metabolites, darker grey colors have been used to highlight higher significances (p

Dietary Intake of n-6 Fatty Acids Modulates Effect of Apolipoprotein A5 Gene on Plasma Fasting Triglycerides, Remnant Lipoprotein Concentrations, and Lipoprotein Particle Size

Background— Apolipoprotein A5 gene (APOA5) variation is associated with plasma triglycerides (TGs). However, little is known about whether dietary fat modulates this association. Methods and Results— We investigated the interaction between APOA5 gene variation and dietary fat in determining plasma fasting TGs, remnant-like particle (RLP) concentrations, and lipoprotein particle size in 1001 men and 1147 women who were Framingham Heart Study participants. Polymorphisms –1131T>C and 56C>G, representing 2 independent haplotypes, were analyzed. Significant gene–diet interactions between the –1131T>C polymorphism and polyunsaturated fatty acid (PUFA) intake were found (PG polymorphism. The –1131…

The Mediterranean Diet and Cardiovascular Epidemiology

The Mediterranean diet was first considered to be a low-saturated fat diet that conveyed protection against coronary heart disease by lowering plasma total cholesterol levels. Later, the emphasis shifted away from the low-saturated-fat content of this diet toward its high content of olive oil and its overall constellation of characteristics. Moreover, there is now evidence that the Mediterranean diet benefits not only the risk for coronary heart disease but also cancer occurrence, total mortality, and longevity.

Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with plasma lipid levels in a healthy Spanish population.

Genetic variants at the cholesteryl ester transfer protein (CETP) locus have been associated with CETP activity and mass, as well as plasma high density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I levels. We have examined allele frequencies and lipid associations for the common CETP TaqIB polymorphism in a sample of 514 healthy subjects (231 men, mean age 37.4 years, and 283 women, mean age 35.7 years) residing in Valencia (Spain). The frequency of the less common TaqIB2 allele (0.351; 95% CI: 0.322-0. 380) was significantly lower than those reported for Northern European populations. Consistent with previous studies, we found a significant association of the TaqIB polymorphism w…

Advances in Understanding the Molecular Basis of the Mediterranean Diet Effect

Posted with permission from the Annual Review of Food Science and Technology, Volume 9 by Annual Reviews, http://www.annualreviews.org. Increasingly, studies showing the protective effects of the Mediterranean diet (MedDiet) on different diseases (cardiovascular, diabetes, some cancers, and even total mortality and aging indicators) are being published. The scientific evidence level for each outcome is variable, and new studies are needed to better understand the molecular mechanisms whereby the MedDiet may exercise its effects. Here, we present recent advances in understanding the molecular basis of MedDiet effects, mainly focusing on cardiovascular diseases but also discussing other relat…

EPIGENOMICS AND METABOLOMICS MECHANISMS FOR A GENE X DIET INTERACTION MODULATING AGE-RELATED OBESITY

A functional variant in the apolipoprotein AII (APOA2) gene (rs5082) predisposes homozygous carriers to age-related obesity when habitual saturated fat (SFA) intake is high. We used epigenomics, transcription and metabolomics analyses to identify currently unknown mechanisms underlying this well-replicated gene x diet interaction. We conducted an epigenome-wide scan to compare genetically at-risk to low-risk individuals with low (<22 g/d) or high (≥22 g/d) SFA intake in the Boston Puerto Rican Health Study and validated the findings in the GOLDN Study and the Framingham Heart Study. In these three populations, we identified genotype-dependent differential methylation, only with high SFA int…

Transcriptomic autophagy-related gene signature investigation for type 2 diabetes in Mediterranean subjects

Abstract Background Autophagy (involving degradation and clearance of damaged organelles and compounds) plays a role in type 2 diabetes (T2D). There are three main types of autophagy and several genes involved. These genes have been well studied in animal models, but there are few transcriptomic studies in humans. Our aim is to analyze the differential gene expression, and the functional enrichment of the main autophagy-related genes (ARG) in T2D subjects from a Mediterranean population Methods We analyzed 120 White-European subjects (mean age 61,4 years; 50% women; 24 T2D) from Valencia, Spain. Clinical and lifestyle data were obtained. ARN was isolated from blood. Transcriptome-wide gene …

Adherence to a Mediterranean-type diet and reduced prevalence of clustered cardiovascular risk factors in a cohort of 3204 high-risk patients

Background The Mediterranean food pattern (MeDiet) has been suggested to have beneficial effects on cardiovascular risk factors. Scarcity of assessment of this effect on large samples of patients at high risk is, however, observed. Our objective was to estimate the association between adherence to MeDiet and the prevalence of risk factors in 3204 asymptomatic high-risk patients. Design Cross-sectional assessment of baseline characteristics of participants in a primary prevention trial. Methods Participants were assessed by their usual primary-care physicians to ascertain the prevalence of diet-related cardiovascular risk factors (diabetes, hypertension, dyslipidemia, or obesity) using stand…

The case for strategic international alliances to harness nutritional genomics for public and personal health

Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need …

Association of Mediterranean diet with peripheral artery disease: the PREDIMED randomized trial.

Association of Mediterranean Diet With Peripheral Artery Disease: The PREDIMED Randomized Trial The role of nutrition in preventing peripheral artery disease (PAD) remains elusive. 1 Mediterranean diets reduce the risk of myocardial infarction and stroke. 2,3. They also may reduce the risk of PAD, but this hypothesis has never been tested in a randomized trial. We assessed the association of Mediterranean diets with the occurrence of symptomatic PAD in an exploratory, nonprespecified analysis of a randomized trial...

Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort

Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake (P = 0.026). HDL-cholesterol level increased, …

Red Blood Cell Eicosapentaenoic Acid Inversely Relates to MRI-Assessed Carotid Plaque Lipid Core Burden in Elders at High Cardiovascular Risk

Supplemental marine omega-3 eicosapentaenoic acid (EPA) has an anti-atherosclerotic effect. Clinical research on EPA supplied by the regular diet and atherosclerosis is scarce. In the framework of the PREvención con DIeta MEDiterránea (PREDIMED) trial, we conducted a cross-sectional study in 161 older individuals at high vascular risk grouped into different stages of carotid atherosclerosis severity, including those without ultrasound-detected atheroma plaque (n = 38), with plaques <2.0 mm thick (n = 65), and with plaques ≥2.0 mm (n = 79). The latter were asked to undergo contrast-enhanced 3T magnetic resonance imaging (MRI) and were subsequently grouped into absence (n = 31) or presence (n…

Dietary inflammatory index and all-cause mortality in large cohorts: The SUN and PREDIMED studies

[Background]: Inflammation is known to be related to the leading causes of death including cardiovascular disease, several types of cancer, obesity, type 2 diabetes, depression-suicide and other chronic diseases. In the context of whole dietary patterns, the Dietary Inflammatory Index (DII®) was developed to appraise the inflammatory potential of the diet. [Objective]: We prospectively assessed the association between DII scores and all-cause mortality in two large Spanish cohorts and valuated the consistency of findings across these two cohorts and results published based on other cohorts.

Epigenomics and metabolomics reveal the mechanism of the APOA2-saturated fat intake interaction affecting obesity

BACKGROUND: The putative functional variant −265T>C (rs5082) within the APOA2 promoter has shown consistent interactions with saturated fatty acid (SFA) intake to influence the risk of obesity. OBJECTIVE: The aim of this study was to implement an integrative approach to characterize the molecular basis of this interaction. DESIGN: We conducted an epigenome-wide scan on 80 participants carrying either the rs5082 CC or TT genotypes and consuming either a low-SFA (C genotype, promoting an APOA2 expression difference between APOA2 genotypes on a high-SFA diet, and modulating BCAA and tryptophan metabolic pathways. These findings identify potential mechanisms by which this highly reproducible ge…

Genotype patterns at CLU, CR1, PICALM and APOE, cognition and Mediterranean diet: the PREDIMED-NAVARRA trial.

The traditional Mediterranean diet (MedDiet) has shown beneficial effects on cognitive decline. Nevertheless, diet–gene interactions have been poorly evaluated. We aimed to investigate diet–gene interaction in the PREDIMED-NAVARRA randomized trial. A total of 522 participants (67 ± 6 years at baseline) enrolled in the PREDIMED-NAVARRA trial were randomly allocated to one of three diets: two MedDiets (supplemented with either extra-virgin olive oil or nuts) or a low-fat diet. They were evaluated with the Mini-Mental State Examination (MMSE) and the Clock Drawing Test (CDT) after 6.5 years of intervention. Subjects were genotyped for CR1-rs3818361, CLU-rs11136000, PICALM-rs3851179 and Apolipo…

Additional file 7: Figure S5. of Serum metabolites in non-alcoholic fatty-liver disease development or reversion; a targeted metabolomic approach within the PREDIMED trial

Heatmap representing individual metabolomic features obtained from the comparisons between the three baseline states in groups 1, 2 and 3.Heatmapcolor codes for log2 (fold-change) and ANOVA and Tukey’s Honestly Significance Difference post hoc test p-values are indicated at the bottom of the Figure. Darker green and red colors indicate higher drops or elevations of the metabolite levels in every comparison. Grey lines correspond to significant fold-changes of individual metabolites, darker grey colors have been used to highlight higher significances (p

Perilipin polymorphism interacts with saturated fat and carbohydrates to modulate insulin resistance

Macronutrient intakes and genetic variants have been shown to interact to alter the risk of insulin resistance, but replication of gene-nutrient interactions across independent populations may be difficult to achieve. Saturated fat and carbohydrate were previously shown to interact with genotype for insulin resistance for a variant of perilipin (PLIN), the major adipocyte-associated protein and a regulator of adipocyte metabolism. We investigated the same interaction for PLIN 11482G>A (rs894160) on insulin resistance in US men(n=462) and women(n=508) (mean ±SD, 49±16 years). In multivariate linear regression models, we found a significant (PA for HOMA-IR (homeostasis model assessment of ins…

Identification of a new locus and validation of previously reported loci showing differential methylation associated with smoking. The REGICOR study.

Smoking increases the risk of many diseases and could act through changes in DNA methylation patterns. The aims of this study were to determine the association between smoking and DNA methylation throughout the genome at cytosine-phosphate-guanine (CpG) site level and genomic regions. A discovery cross-sectional epigenome-wide association study nested in the follow-up of the REGICOR cohort was designed and included 645 individuals. Blood DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip. Smoking status was self-reported using a standardized questionnaire. We identified 66 differentially methylated CpG sites associated with smoking, located in 38 genes. In most of …

Microbial metabolomic fingerprinting in urine after regular dealcoholized red wine consumption in humans.

The regular consumption of dealcoholized red wine (DRW) has demonstrated benefits in cardiovascular risk factors. The analysis of phenolic metabolites formed in the organism, especially those that could come from microbiota metabolism, would help to understand these benefits. The aim of this study was to determine the widest urinary metabolomic fingerprinting of phenolics and microbial-derived phenolic acids (n = 61) after regular intake of DRW in men at high cardiovascular risk by UPLC-MS/MS using a targeted approach. Up to 49 metabolites, including phase II and microbial phenolic metabolites, increased after DRW consumption compared to baseline (P < 0.05). The highest percentage of increa…

Homocysteine levels and the metabolic syndrome in a Mediterranean population: A case-control study

Hyperhomocysteinemia (HH) and metabolic syndrome (MS) are associated with increased cardiovascular risk. However, whether there is a link between MS or its components and homocysteine levels in a population without cardiovascular disease is not well established. We conducted a case-control study in 61 MS patients (41 males, 20 females, aged 51 ± 11 years) and in 98 controls without MS (59 males, 39 females, aged 50 ± 10 years) to ascertain the association between MS and HH, and with inflammatory markers. MS was classified according to the updated ATPIII criteria [17]. No differences in homocysteine levels were observed when comparing MS patients and controls (12.0 ± 3.18 μM vs. 11.9 ± 3.5 μ…

Mediterranean diet and risk of heart failure: results from the PREDIMED randomized controlled trial

Aims The aim of this study was to evaluate the effect of the Mediterranean diet (MedDiet) on the incidence of heart failure (HF), a pre-specified secondary outcome in the PREDIMED (PREvencion con DIeta MEDiterranea) primary nutrition-intervention prevention trial. Methods and results Participants at high risk of cardiovascular disease were randomly assigned to one of three diets: MedDiet supplemented with extra-virgin olive oil (EVOO), MedDiet supplemented with nuts, or a low-fat control diet. Incident HF was ascertained by a Committee for Adjudication of events blinded to group allocation. Among 7403 participants without prevalent HF followed for a median of 4.8 years, we observed 29 new H…

Obesity indexes and total mortality among elderly subjects at high cardiovascular risk: The PREDIMED study

Background: Different indexes of regional adiposity have been proposed for identifying persons at higher risk of death. Studies specifically assessing these indexes in large cohorts are scarce. It would also be interesting to know whether a dietary intervention may counterbalance the adverse effects of adiposity on mortality. Methods: We assessed the association of four different anthropometric indexes (waist-to-height ratio (WHtR), waist circumference (WC), body mass index (BMI) and height) with all-cause mortality in 7447 participants at high cardiovascular risk from the PREDIMED trial. Forty three percent of them were men (55 to 80 years) and 57% were women (60 to 80 years). All of them …

Physical fitness and physical activity association with cognitive function and quality of life: baseline cross-sectional analysis of the PREDIMED-Plus trial

Controlled Trial (ISRCTN89898870, https://www.isrctn.com/ISRCTN89898870?q=ISRCTN89898870&filters=&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search) on 07/24/2014.

Dietary intake in population with metabolic syndrome: is the prevalence of inadequate intake influenced by geographical area? cross-sectional analysis from PREDIMED-Plus Study

Inadequate diet influences chronic diseases such as cardiovascular disease (CVD), the leading cause of death in Spain. CVD figures vary from one geographical region to another

Polyphenol intake and mortality risk: a re-analysis of the PREDIMED trial

[Background] Polyphenols may lower the risk of cardiovascular disease (CVD) and other chronic diseases due to their antioxidant and anti-inflammatory properties, as well as their beneficial effects on blood pressure, lipids and insulin resistance. However, no previous epidemiological studies have evaluated the relationship between the intake of total polyphenols intake and polyphenol subclasses with overall mortality. Our aim was to evaluate whether polyphenol intake is associated with all-cause mortality in subjects at high cardiovascular risk.

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome.

Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GW…

Taste Perception Profiles Are Associated With Adherence to Empirically Derived Dietary Patterns Among Older Adults With Metabolic Syndrome

OBJECTIVES: Understanding individual-level drivers of food intake is critical when personalizing dietary guidance. One likely driver is taste perception; yet, limited data relate perception of all 5 tastes (sweet, salt, sour, bitter, umami) to dietary patterns (DPs). Our aim was to determine whether a multivariable measure of taste perception, taste perception profiles, was associated with adherence to empirically derived DPs. METHODS: Participants were 367 community-dwelling adults with metabolic syndrome from PREDIMED-Plus, Valencia (55–75 years; 55% female). Six taste perception profiles were derived from 5 taste perception scores via a data-driven clustering approach: Low All (23%), Hig…

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 cardi…

Dairy product consumption and risk of type 2 diabetes in an elderly Spanish Mediterranean population at high cardiovascular risk.

PURPOSE The possible effects of dairy consumption on diabetes prevention remain controversial. The aim of this study was to investigate the association between the dairy consumption and type 2 diabetes (T2D) risk in an elderly Mediterranean population at high cardiovascular risk. METHODS: We prospectively followed 3,454 non-diabetic individuals from the PREDIMED study. Dairy consumption was assessed at baseline and yearly using food frequency questionnaires and categorized into total, low-fat, whole-fat, and subgroups: milk, yogurt, cheeses, fermented dairy, concentrated full fat, and processed dairy. Hazard ratios (HRs) were calculated using Cox proportional hazards regression models. RESU…

Lack of association between hemorheological alterations and upper-extremity deep vein thrombosis.

Introduction: There is an association between rheological alterations and lower extremity deep vein thrombosis, although no research has been carried out regarding the possible influence of rheological alterations in the development of venous thrombosis in the upper limbs. Materials and methods: We have determined in 54 patients (23 male, 31 female; aged 35 ± 11 years) with primary upper extremity deep vein thrombosis (UEDVT), and in a well matched control group of 87 subjects (41 male, 46 female; aged 36 ± 12 years) the rheological profile (blood viscosity, plasma viscosity, fibrinogen, erythrocyte aggregation, erythrocyte de- formability) along with plasma lipids (total cholesterol and tr…

The tomato sauce making process affects the bioaccessibility and bioavailability of tomato phenolics: A pharmacokinetic study

Tomato sauce is the most commonly consumed processed tomato product worldwide, but very little is known about how the manufacturing process may affect the phenolic composition and bioavailability after consumption. In a prospective randomised, cross-over intervention study, we analysed the plasma and urinary levels of tomato phenolic compounds and their metabolites after acute consumption of raw tomatoes and tomato sauce, enriched or not with refined olive oil during production. Respectively, eleven and four phenolic metabolites were found in urine and plasma samples. The plasma concentration and urinary excretion of naringenin glucuronide were both significantly higher after the consumptio…

High dietary protein intake is associated with an increased body weight and total death risk.

Summary Background & aims High dietary protein diets are widely used to manage overweight and obesity. However, there is a lack of consensus about their long-term efficacy and safety. Therefore, the aim of this study was to assess the effect of long-term high-protein consumption on body weight changes and death outcomes in subjects at high cardiovascular risk. Methods A secondary analysis of the PREDIMED trial was conducted. Dietary protein was assessed using a food-frequency questionnaire during the follow-up. Cox proportional hazard models were used to estimate the multivariate-adjusted hazard ratio (HR) and 95% confidence intervals (95%CI) for protein intake in relation to the risk of bo…

MOESM1 of Lysine pathway metabolites and the risk of type 2 diabetes and cardiovascular disease in the PREDIMED study: results from two case-cohort studies

Additional file 1. Additional figures and tables.