0000000001159627
AUTHOR
Fernando Arós
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…
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…
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…
Urinary Tartaric Acid, a Biomarker of Wine Intake, Correlates with Lower Total and LDL Cholesterol.
Postmenopausal women are at higher risk of developing cardiovascular diseases due to changes in lipid profile and body fat, among others. The aim of this study was to evaluate the association of urinary tartaric acid, a biomarker of wine consumption, with anthropometric (weight, waist circumference, body mass index (BMI), and waist-to-height ratio), blood pressure, and biochemical variables (blood glucose and lipid profile) that may be affected during the menopausal transition. This sub-study of the PREDIMED (Prevención con Dieta Mediterránea) trial included a sample of 230 women aged 60–80 years with high cardiovascular risk at baseline. Urine samples were diluted and filtered, and tartari…
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 …
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…
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 …
Is complying with the recommendations of sodium intake beneficial for health in individuals at high cardiovascular risk? Findings from the PREDIMED study
Background: Excess sodium intake is associated with high blood pressure, a major risk factor for cardiovascular disease (CVD). It is unknown whether decreasing sodium intake to ,2300 mg/d has an effect on CVD or all-cause mortality. Objective: The objective was to assess whether reductions in sodium intake to ,2300 mg/d were associated with either an increased or a decreased risk of fatal and nonfatal CVD and all-cause mortality. Design: This observational prospective study of the PREvencicon DIeta MEDiterr� (PREDIMED) trial included 3982 participants at high CVD risk. Sodium intake was evaluated with a validated food- frequency questionnaire and categorized as low (,1500 mg/d), in- termedi…
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 …
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…
Dairy product consumption and risk of colorectal cancer in an older mediterranean population at high cardiovascular risk.
Prospective studies have reported an inverse association between the consumption of total dairy products and milk and the risk of colorectal cancer (CRC). Nonetheless, there is little and inconsistent evidence regarding subtypes of dairy product and CRC risk. We assessed the associations between the consumption of total dairy products, their different subtypes and CRC risk in older Mediterranean individuals at high cardiovascular risk. We analyzed data from 7,216 men and women (55-80 years) without CRC at baseline from the PREvencion con DIeta MEDiterranea study. Individuals were recruited between 2003 and 2009 and followed up until December 2012. At baseline and yearly thereafter, consumpt…
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…
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…
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.
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…
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…
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…
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…
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].
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 …
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…
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 …
Longitudinal association of changes in diet with changes in body weight and waist circumference in subjects at high cardiovascular risk: the PREDIMED trial
Background Consumption of certain foods is associated with long-term weight gains and abdominal fat accumulation in healthy, middle-aged and young, non-obese participants. Whether the same foods might be associated with changes in adiposity in elderly population at high cardiovascular risk is less known. Objective Using yearly repeated measurements of both food habits and adiposity parameters, we aimed to investigate how changes in the consumption of specific foods were associated with concurrent changes in weight or waist circumference (WC) in the PREDIMED trial. Design We followed-up 7009 participants aged 55-70 years at high cardiovascular risk for a median time of 4.8 years. A validated…
Mediterranean Diet and Physical Activity Decrease the Initiation of Cardiovascular Drug Use in High Cardiovascular Risk Individuals: A Cohort Study
Our aim was to assess whether long-term adherence to a Mediterranean diet (MedDiet) and leisure-time physical activity (LTPA) were associated with a lower initiation of cardiovascular drug use. We studied the association between cumulative average of MedDiet adherence and LTPA and the risk of cardiovascular drug initiation in older adults at high cardiovascular risk (PREvención con DIeta MEDiterránea trial participants) non-medicated at baseline: glucose-lowering drugs (n = 4437), antihypertensives (n = 2145), statins (n = 3977), fibrates (n = 6391), antiplatelets (n = 5760), vitamin K antagonists (n = 6877), antianginal drugs (n = 6837), and cardiac glycosides (n = 6954). One-point increas…
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…
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 …
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…
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 …
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…
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)
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…
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…
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…
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…
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…
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…
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…
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…
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 …
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
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…
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…
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…
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…
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…
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…
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…
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.
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…
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 …
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…
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…
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…
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.
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 …
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…
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…
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…
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 …
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.
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…
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…
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…
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…
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…
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)
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…
MOESM1 of Longitudinal association of changes in diet with changes in body weight and waist circumference in subjects at high cardiovascular risk: the PREDIMED trial
Additional file 1: Figure S1. Flow chart summarizing selection of PREDIMED participants for the present study. Figure S2. Directed acyclic graph (DAG). Table S1. Characterization of food items belonging to each food group. Table S2. Correlations matrix between food groups (serving/d) within each global dietary score (GDS). Table S3. Sensitivity analyses: Association of yearly changes in food groups intake with concurrent changes in waist circumference over 5-year of follow-up by sex. Table S4. Sensitivity analysis: association of changes in global dietary score (GDS) with body weight and waist circumference changes over 5-year of follow-up. Table S5. Sensitivity analysis: association of cha…
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…
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.
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…