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Background: Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m2. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results: At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The eff

Diets rich in polyphenols has been associated with better cognitive performance. The aim of this study is to assess the relationship between microbial phenolic metabolites (MPM) in urine and cognition in the context of an older population at high cardiovascular risk.A cross-sectional analysis is conducted in 400 individuals of the PREDIMED-Plus study. Liquid chromatography coupled to mass spectrometry is used to identify urinary MPM. Mediterranean diet (MedDiet) adherence is estimated with a 17-item questionnaire and cognitive function is evaluated with a battery of neuropsychological tests. Multivariable-adjusted linear regression models are fitted to assess the relationship of urinary MPM with the MedDiet and cognitive tests. Protocatechuic acid and enterolactone glucuronide are associated with higher adherence to the MedDiet. Regarding cognitive function, protocatechuic acid, vanillic acid glucuronide, 3-hydroxybenzoic acid, enterodiol glucuronide, and enterolactone glucuronide are directly associated with a global composite score of all the cognitive tests. Furthermore, protocatechuic acid and enterolactone glucuronide are associated with higher scores in the Mini-Mental State Examination, whereas enterodiol glucuronide is associated with improved Clock Drawing Test scores.These results suggest that the MedDiet is linked to MPM associated with better cognitive performance in an older population.© 2023 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.

Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD.The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models.Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period.This study identified a set of

Background & aims: Short telomeres have been observed in chronic disease patients. Identifying environmental and lifestyle factors that could reduce telomere attrition is crucial for disease prevention. The aim of this work was to determine whether weight-loss induced by an energy-reduced Mediterranean diet (erMedDiet) and physical activity (PA) could modify telomere length (TL). Methods: In 317 randomized non-smoker participants (mean age, 65.8 ± 4.98 years) with metabolic syndrome from two “Prevención con Dieta Mediterránea-Plus” (PREDIMED-Plus) trial centers, we evaluated MedDiet adherence, PA, anthropometric variables and TL at baseline and after a 3-year intervention using an intensive lifestyle program (IG) with an erMedDiet and PA or an unrestricted MedDiet without PA promotion (CG). Results: Participants in the IG displayed greater 3-year weight reductions (−3.7 ± 4 kg, P < 0.001) compared to those in the CG. No differences in TL changes between groups were observed in the cohort as a whole. However, an interaction was observed between the intervention group and sex for TL changes (pinteraction = 0.039). Women in the IG showed an increase in TL after 3-y (+0.25 ± 0.9, relative units) compared to women in the CG (−0.07 ± 1.0) (pANCOVA = 0.036), whereas no differences between groups were observed in men. Women in the IG had a lower risk of telomere shortening after the intervention (OR = 0.17, 95%CI: 0.05–0.64, p = 0.008) compared to women in the CG. Conclusions: A 3-year lifestyle intervention based on an erMedDiet and PA slowed telomere shortening in women but not in men. Trial registration: ISRCTN, ISRCTN89898870. Registered 24 July 2014- Retrospectively registered, https://www.isrctn.com/ISRCTN89898870.

Metabolic syndrome (MetS) has become a growing risk factor of some non-communicable diseases. Increase of greenhouse gas emissions affects the planet.To assess the association between MetS severity and amount of carbon dioxide (CO2) emitted in an adult population.Cross-sectional study (n = 6646; 55-76-year-old-men; 60-75-year-old-women with MetS).Dietary habits were assessed using a pre-validated semi quantitative 143-item food frequency questionnaire. The amount of CO2 emitted due to the production of food consumed by person and day was calculated using a European database, and the severity of the MetS was calculated with the MetS Severity Score.Higher glycaemia levels were found in people with higher CO2 emissions. The risk of having high severe MetS was related to high CO2 emissions.Low CO2 emissions diet would help to reduce MetS severity. Advantages for both health and the environment were found following a more sustainable diet.ISRCTN, ISRCTN89898870 . Registered 05 September 2013.© 2023. The Author(s).

Background: Dietary flavonoid intake is associated with a reduced risk of some cardiometabolic disorders, attributed in part to their claimed anti-inflammatory activity. Our aim was to investigate the potential association between specific urine flavonoid metabolites, liver enzymes, and inflammatory status in individuals with metabolic syndrome (MetS). Methods: In this cross-sectional study, clinical and dietary data from 267 participants, aged 55 to 75 years, participating in the PREDIMED Plus study (PREvención con DIeta MEDiterránea) were analyzed. At the baseline, spot urine samples were collected and seven urinary flavonoid metabolites were quantified using ultra-performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS). Liver enzymes, inflammatory scores, and urinary flavonoid concentrations were inverse normally transformed. Results: Adjusted linear regression models showed an inverse association between urinary citrus flavanone concentrations and gamma-glutamyl transferase (GGT) (all p-values <0.05). Naringenin 7'-GlcUA was significantly associated with a lower aggregate index of systemic inflammation (AISI) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.025) and systemic inflammation index (SII) (Bper 1SD = -0.14; 95% CI: -0.27 to -0.02; p-value = 0.028). To investigate the relationship between flavanone subclasses and GGT levels, we fitted a score of citrus-flavanones, and subjects were stratified into quartiles. The highest values of the citrus-flavanone score (per 1-SD increase) were associated with lower GGT levels (Bper 1SD = -0.41; 95% CI: -0.74 to -0.07), exhibiting a linear trend across quartiles (p-trend = 0.015). Conclusion: This cross-sectional study showed that higher urinary excretion of citrus-flavanon

Research related to sustainable diets is is highly relevant to provide better understanding of the impact of dietary intake on the health and the environment.To assess the association between the adherence to an energy-restricted Mediterranean diet and the amount of CO2 emitted in an older adult population.Using a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary CO2 emissions in 6646 participants was assessed.Food intake and adherence to the erMedDiet was assessed using validated food frequency questionnaire and 17-item Mediterranean questionnaire. Sociodemographic characteristics were documented. Environmental impact was calculated through greenhouse gas emissions estimations, specifically CO2 emissions of each participant diet per day, using a European database. Participants were distributed in quartiles according to their estimated CO2 emissions expressed in kg/day: Q1 (≤2.01 kg CO2), Q2 (2.02-2.34 kg CO2), Q3 (2.35-2.79 kg CO2) and Q4 (≥2.80 kg CO2).More men than women induced higher dietary levels of CO2 emissions. Participants reporting higher consumption of vegetables, fruits, legumes, nuts, whole cereals, preferring white meat, and having less consumption of red meat were mostly emitting less kg of CO2 through diet. Participants with higher adherence to the Mediterranean Diet showed lower odds for dietary CO2 emissions: Q2 (OR 0.87; 95%CI: 0.76-1.00), Q3 (OR 0.69; 95%CI: 0.69-0.79) and Q4 (OR 0.48; 95%CI: 0.42-0.55) vs Q1 (reference).The Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO2 emissions. Mediterranean Diet index may be used as a pollution level index.© 2023. The Author(s).

The potential role of the lipidome in atrial fibrillation (AF) development is still widely unknown. We aimed to assess the association between lipidome profiles of the Prevención con Dieta Mediterránea (PREDIMED) trial participants and incidence of AF. We conducted a nested case–control study (512 incident centrally adjudicated AF cases and 735 controls matched by age, sex, and center). Baseline plasma lipids were profiled using a Nexera X2 U-HPLC system coupled to an Exactive Plus orbitrap mass spectrometer. We estimated the association between 216 individual lipids and AF using multivariable conditional logistic regression and adjusted the p values for multiple testing. We also examined the joint association of lipid clusters with AF incidence. Hitherto, we estimated the lipidomics network, used machine learning to select important network-clusters and AF-predictive lipid patterns, and summarized the joint association of these lipid patterns weighted scores. Finally, we addressed the possible interaction by the randomized dietary intervention. Forty-one individual lipids were associated with AF at the nominal level (p < 0.05), but no longer after adjustment for multiple-testing. However, the network-based score identified with a robust data-driven lipid network showed a multivariable-adjusted ORper+1SD of 1.32 (95% confidence interval: 1.16–1.51; p < 0.001). The score included PC plasmalogens and PE plasmalogens, palmitoyl-EA, cholesterol, CE 16:0, PC 36:4;O, and TG 53:3. No interaction with the dietary intervention was found. A multilipid score, primarily made up of plasmalogens, was associated with an increased risk of AF. Future studies are needed to get further insights into the lipidome role on AF. Current Controlled Trials number, ISRCTN35739639.

Background and aims: The American Heart Association proposed 7 ideal cardiovascular health metrics (Life's Simple 7 [LS7]) namely, not smoking, body mass index <25 kg/m2, healthy diet, moderate physical activity ≥150 min/week, total blood cholesterol <200 mg/dL, blood pressure <120/80 mmHg and fasting blood glucose <100 mg/dL. Our objective was to assess the association between these LS7 metrics and the incidence of atrial fibrillation (AF). Methods and results: A total of 6,479 participants of the PREDIMED study were included. We calculated the participants’ baseline LS7 index ranging 0–7 points to categorize them according to their adherence to these LS7 health metrics. Multivariable Cox regression models were used to estimate Hazard Ratios (HR) and their 95% Confidence Intervals (95% CI). After a median follow-up of 4.8 years, we identified 250 incident cases of AF. After adjusting for potential confounders, adherence to LS7 index was not associated with the incidence of AF (adjusted HR 0.90 [95% CI: 0.56–1.45] for highest vs. lowest LS7 categories). Body mass index <25 kg/m2 was the only health metric individually associated with a lower risk of AF (HR 0.36 [95% CI: 0.16–0.78]). Conclusions: In a high cardiovascular risk Spanish population, adherence to American Heart Association's LS7 metrics was not associated with the risk of incident AF. Clinical Trials number: ISRCTN35739639.

Olive oil consumption has been inversely associated with the risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, the impact of olive oil consumption on plasma metabolites remains poorly understood. This study aims to identify plasma metabolites related to total and specific types of olive oil consumption, and to assess the prospective associations of the identified multi-metabolite profiles with the risk of T2D and CVD.The discovery population included 1837 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) trial with available metabolomics data at baseline. Olive oil consumption was determined through food-frequency questionnaires (FFQ) and adjusted for total energy. A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation sample. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known candidate metabolites and olive oil consumption were assessed using elastic net regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite-weighted models and FFQ-derived olive oil consumption in each pair of training-validation data sets within the discovery sample. We further estimated the prospective associations of the identified plasma multi-metabolite profile with incident T2D and CVD using multivariable Cox regression models.We identified a metabolomic signature for the consumption of total olive oil (with 74 metabolites), VOO (with 78 metabolites), and COO (with 17 metabolites), including several lipids, acylcarnitines, and amino acids. 10-CV Pearson correlation coefficients between total olive oil consumption derived from FFQs and

Anemia causes hypo-oxygenation in the brain, which could lead to cognitive disorders. We examined dietary iron intake as well as anemia markers (i.e., hemoglobin, hematocrit, mean corpuscular volume) and diabetes coexistence in relation to neuropsychological function and quality of life. In this study, 6117 community-dwelling adults aged 55-75 years (men) and 60-75 years (women) with overweight/obesity and metabolic syndrome were involved. We performed the Mini-Mental State Examination (MMSE), the Trail Making Test parts A and B (TMT-A/B), Semantic Verbal Fluency of animals (VFT-a), Phonological Verbal Fluency of letter P (VFT-p), Digit Span Test (DST), the Clock Drawing Test (CDT), and the Short Form-36 Health Survey (SF36-HRQL test). Dietary iron intake did not influence neuropsychological function or quality of life. However, anemia and lower levels of anemia markers were associated with worse scores in all neurophysiological and SF36-HRQL tests overall, but were especially clear in the MMSE, TMT-B (cognitive flexibility), and the physical component of the SF36-HRQL test. The relationships between anemia and diminished performance in the TMT-A/B and VFT tasks were notably pronounced and statistically significant solely among participants with diabetes. In brief, anemia and reduced levels of anemia markers were linked to inferior cognitive function, worse scores in different domains of executive function, as well as a poorer physical, but not mental, component of quality of life. It was also suggested that the coexistence of diabetes in anemic patients may exacerbate this negative impact on cognition. Nevertheless, dietary iron intake showed no correlation with any of the outcomes. To make conclusive recommendations for clinical practice, our findings need to be thoro

A healthy lifestyle (HL) has been inversely related to type 2 diabetes (T2D) and cardiovascular disease (CVD). However, few studies have identified a metabolite profile associated with HL. The present study aims to identify a metabolite profile of a HL score and assess its association with the incidence of T2D and CVD in individuals at high cardiovascular risk.In a subset of 1833 participants (age 55-80y) of the PREDIMED study, we estimated adherence to a HL using a composite score based on the 2018 Word Cancer Research Fund/American Institute for Cancer Research recommendations. Plasma metabolites were analyzed using LC-MS/MS methods at baseline (discovery sample) and 1-year of follow-up (validation sample). Cross-sectional associations between 385 known metabolites and the HL score were assessed using elastic net regression. A 10-cross-validation procedure was used, and correlation coefficients or AUC were assessed between the identified metabolite profiles and the self-reported HL score. We estimated the associations between the identified metabolite profiles and T2D and CVD using multivariable Cox regression models.The metabolite profiles that identified HL as a dichotomous or continuous variable included 24 and 58 metabolites, respectively. These are amino acids or derivatives, lipids, and energy intermediates or xenobiotic compounds. After adjustment for potential confounders, baseline metabolite profiles were associated with a lower risk of T2D (hazard ratio [HR] and 95% confidence interval (CI): 0.54, 0.38-0.77 for dichotomous HL, and 0.22, 0.11-0.43 for continuous HL). Similar results were observed with CVD (HR, 95% CI: 0.59, 0.42-0.83 for dichotomous HF and HR, 95%CI: 0.58, 0.31-1.07 for continuous HL). The reduction in the risk of T2D and CVD was maintained o

Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet.PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes.Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after addition

Scope Dairy consumption has been suggested to impact cognition; however, evidence is limited and inconsistent. This study aims to longitudinally assess the association between dairy consumption with cognitive changes in an older Spanish population at high cardiovascular disease risk. Methods and results Four thousand six hundred sixty eight participants aged 55-75 years, completed a validated food frequency questionnaire at baseline and a neuropsychological battery of tests at baseline and 2-year follow-up. Multivariable linear regression models are used, scaled by 100 (i.e., the units of beta correspond to 1 SD/100), to assess associations between baseline tertile daily consumption and 2-year changes in cognitive performance. Participants in the highest tertile of total milk and whole-fat milk consumption have a greater decline in global cognitive function (beta: -4.71, 95% CI: -8.74 to -0.69, p-trend = 0.020 and beta: -6.64, 95% CI: -10.81 to -2.47, p-trend = 0.002, respectively) compared to those in the lowest tertile. No associations are observed between low fat milk, yogurt, cheese or fermented dairy consumption, and changes in cognitive performance. Conclusion Results suggest there are no clear prospective associations between consumption of most commonly consumed dairy products and cognition, although there may be an association with a greater rate of cognitive decline over a 2-year period in older adults at high cardiovascular disease risk for whole-fat milk.

Scope Consumption of meat has been associated with a higher risk of type 2 diabetes (T2D), but if plasma metabolite profiles associated with these foods reflect this relationship is unknown. The objective is to identify a metabolite signature of consumption of total meat (TM), red meat (RM), processed red meat (PRM), and fish and examine if they are associated with T2D risk. Methods and results The discovery population includes 1833 participants from the PREDIMED trial. The internal validation sample includes 1522 participants with available 1-year follow-up metabolomic data. Associations between metabolites and TM, RM, PRM, and fish are evaluated with elastic net regression. Associations between the profiles and incident T2D are estimated using Cox regressions. The profiles included 72 metabolites for TM, 69 for RM, 74 for PRM, and 66 for fish. After adjusting for T2D risk factors, only profiles of TM (Hazard Ratio (HR): 1.25, 95% CI: 1.06-1.49), RM (HR: 1.27, 95% CI: 1.07-1.52), and PRM (HR: 1.27, 95% CI: 1.07-1.51) are associated with T2D. Conclusions The consumption of TM, its subtypes, and fish is associated with different metabolites, some of which have been previously associated with T2D. Scores based on the identified metabolites for TM, RM, and PRM show a significant association with T2D risk.

Objective: Tryptophan can be catabolised to various metabolites through host kynurenine and microbial indole pathways. We aimed to examine relationships of host and microbial tryptophan metabolites with incident type 2 diabetes (T2D), host genetics, diet and gut microbiota. Method: We analysed associations between circulating levels of 11 tryptophan metabolites and incident T2D in 9180 participants of diverse racial/ethnic backgrounds from five cohorts. We examined host genome-wide variants, dietary intake and gut microbiome associated with these metabolites. Results: Tryptophan, four kynurenine-pathway metabolites (kynurenine, kynurenate, xanthurenate and quinolinate) and indolelactate were positively associated with T2D risk, while indolepropionate was inversely associated with T2D risk. We identified multiple host genetic variants, dietary factors, gut bacteria and their potential interplay associated with these T2D-relaetd metabolites. Intakes of fibre-rich foods, but not protein/tryptophan-rich foods, were the dietary factors most strongly associated with tryptophan metabolites. The fibre-indolepropionate association was partially explained by indolepropionate-associated gut bacteria, mostly fibre-using Firmicutes. We identified a novel association between a host functional LCT variant (determining lactase persistence) and serum indolepropionate, which might be related to a host gene-diet interaction on gut Bifidobacterium, a probiotic bacterium significantly associated with indolepropionate independent of other fibre-related bacteria. Higher milk intake was associated with higher levels of gut Bifidobacterium and serum indolepropionate only among genetically lactase non-persistent individuals. Conclusion: Higher milk intake among lactase non-persistent individuals

Olive oil consumption has been shown to lower cardiovascular disease risk, but its associations with total and cause-specific mortality are unclear.The purpose of this study was to evaluate whether olive oil intake is associated with total and cause-specific mortality in 2 prospective cohorts of U.S. men and women.The authors used multivariable-adjusted Cox proportional-hazards models to estimate HRs for total and cause-specific mortality among 60,582 women (Nurses' Health Study, 1990-2018) and 31,801 men (Health Professionals Follow-up Study, 1990-2018) who were free of cardiovascular disease or cancer at baseline. Diet was assessed by a semiquantitative food frequency questionnaire every 4 years.During 28 years of follow-up, 36,856 deaths occurred. The multivariable-adjusted pooled HR for all-cause mortality among participants who had the highest consumption of olive oil (>0.5 tablespoon/day or >7 g/d) was 0.81 (95% CI: 0.78-0.84) compared with those who never or rarely consumed olive oil. Higher olive oil intake was associated with 19% lower risk of cardiovascular disease mortality (HR: 0.81; 95% CI: 0.75-0.87), 17% lower risk of cancer mortality (HR: 0.83; 95% CI: 0.78-0.89), 29% lower risk of neurodegenerative disease mortality (HR: 0.71; 95% CI: 0.64-0.78), and 18% lower risk of respiratory disease mortality (HR: 0.82; 95% CI: 0.72-0.93). In substitution analyses, replacing 10 g/d of margarine, butter, mayonnaise, and dairy fat with the equivalent amount of olive oil was associated with 8%-34% lower risk of total and cause-specific mortality. No significant associations were observed when olive oil was compared with other vegetable oils combined.Higher olive oil intake was associated with lower risk of total and cause-specific mortality. Replacing margarine, butte

Background: Tricarboxylic acid (TCA) cycle deregulation may predispose to cardiovascular diseases, but the role of TCA cycle-related metabolites in the development of atrial fibrillation (AF) and heart failure (HF) remains unexplored. This study sought to investigate the association of TCA cycle-related metabolites with risk of AF and HF. Methods: We used two nested case-control studies within the PREDIMED study. During a mean follow-up for about 10 years, 512 AF and 334 HF incident cases matched by age (±5 years), sex and recruitment center to 616 controls and 433 controls, respectively, were included in this study. Baseline plasma levels of citrate, aconitate, isocitrate, succinate, malate and D/L-2-hydroxyglutarate were measured with liquid chromatography-tandem mass spectrometry. Multivariable conditional logistic regression models were fitted to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for metabolites and the risk of AF or HF. Potential confounders included smoking, family history of premature coronary heart disease, physical activity, alcohol intake, body mass index, intervention groups, dyslipidemia, hypertension, type 2 diabetes and medication use. Results: Comparing extreme quartiles of metabolites, elevated levels of succinate, malate, citrate and D/L-2-hydroxyglutarate were associated with a higher risk of AF [ORQ4 vs. Q1 (95% CI): 1.80 (1.21–2.67), 2.13 (1.45–3.13), 1.87 (1.25–2.81) and 1.95 (1.31–2.90), respectively]. One SD increase in aconitate was directly associated with AF risk [OR (95% CI): 1.16 (1.01–1.34)]. The corresponding ORs (95% CI) for HF comparing extreme quartiles of malate, aconitate, isocitrate and D/L-2-hydroxyglutarate were 2.15 (1.29–3.56), 2.16 (1.25–3.72), 2.63 (1.56–4.44) and 1.82 (1.10–3.04), respectively. The

© The European Society of Cardiology 2020. Aims: The association between caffeinated coffee consumption and atrial fibrillation remains unclear. Recent studies suggest an inverse association only between a moderate caffeinated coffee consumption and atrial fibrillation, but others have reported no association. The aim of our study was to prospectively assess the association between caffeinated coffee consumption and atrial fibrillation in two Spanish cohorts, one of adults from a general population and another of elderly participants at high cardiovascular risk. Methods and results: We included 18,983 and 6479 participants from the ‘Seguimiento Universidad de Navarra’ (SUN) and ‘Prevención con Dieta Mediterránea’ (PREDIMED) cohorts, respectively. Participants were classified according to their caffeinated coffee consumption in three groups: ≤3 cups/month, 1–7 cups/week, and >1 cup/day. We identified 97 atrial fibrillation cases after a median follow-up of 10.3 years (interquartile range 6.5–13.5), in the SUN cohort and 250 cases after 4.4 years median follow-up (interquartile range 2.8–5.8) in the PREDIMED study. No significant associations were observed in the SUN cohort although a J-shaped association was suggested. A significant inverse association between the intermediate category of caffeinated coffee consumption (1–7 cups/week) and atrial fibrillation was observed in PREDIMED participants with a multivariable-adjusted hazard ratio = 0.53 (95% confidence interval 0.36–0.79) when compared with participants who did not consume caffeinated coffee or did it only occasionally. No association was found for higher levels of caffeinated coffee consumption (>1 cup per day), hazard ratio = 0.79 (95% confidence interval 0.49–1.28). In the meta-analysis of both PREDIMED and SU

© American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email: journals.permissions@oup.com. 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 and its precursors were semi-quantitatively profiled with liquid chromatography tandem mass spectrometry. Odds ratios were estimated with multivariable conditional logistic regression models. RESULTS: After adjustment for classical risk factors and accounting for multiple testing, participants in the highest quartile vs. the lowest quartile of baseline choline and betaine levels had a higher risk of AF [OR (95% CI): 1.85 (1.30-2.63) and 1.57 (1.09-2.24), respectively]. The corresponding OR for AF for extreme quartiles of dimethylglycine was 1.39 (0.99-1.96). One SD increase in log-transformed dimethylglycine was positively associated with AF risk (OR, 1.17; 1.03-1.33). The corresponding ORs for HF for extreme quartiles of choline, betaine, and dimethylglycine were 2.51 (1.57-4.03), 1.65 (1.00-2.71) and 1.65 (1.04-2.61), respectively. TMAO and L-carnitine levels were not associated with AF or HF. CONCLUSIONS: Our findings support the role of the choline metabolic

Epidemiological data on iron status and cardiovascular disease (CVD) are still controversial. The aim of this study was to determine whether low serum iron (SI) levels are associated with an increased odds of first CVD event in a population at high cardiovascular risk.Case-control study design nested within the "PREvención con DIeta MEDiterránea" (PREDIMED) trial. A total of 207 participants diagnosed with CVD (myocardial infarction, stroke or cardiovascular death) during follow-up period (2003-2010) were matched by sex, age and intervention group to 436 controls by incidence density sampling. Median time between serum sample collection and subsequent CVD event occurrence was 0.94 years. Inductively coupled plasma mass spectrometry analysis was used to determine SI levels. In-person interviews, medical record reviews, and validated questionnaires were used to assess covariates. Multivariable-adjusted odds ratios (ORs) of CVD were calculated with conditional logistic regression.Mean SI levels were higher in men than in women (1224.0 ?g/L vs. 1093.8 ?g/L; p < 0.001). Among women, but not in men, the mean SI concentration was lower in cases than in controls (1008.5 ?g/L vs. 1132.9 ?g/L; p = 0.030). There was a gradual decrease in the multivariable-adjusted ORs of CVD with increasing SI levels (highest vs. lowest quartile: OR = 0.55, 95% CI: 0.32-0.93; ptrend = 0.020). This inverse relationship was more pronounced among women (highest vs. lowest quartile: OR = 0.15, 95% CI: 0.03-0.69; ptrend = 0.011).The present findings are consistent with previously reported inverse associations between SI and CVD. SI levels as an independent marker of short-term cardiovascular risk may be useful for risk assessment in older populations.www.controlled-trials.com; International Standard Ra

Vulvodynia is a chronic dysesthesia or discomfort of the vulva (burning, irritation, pain) lasting more than three months, with no clinical or laboratory findings that justify the symptoms. A prevalence of 4 % is estimated in general population. Its etiology is still unknown. It is probably multifactorial and multiple theories are postulated (neuropathic, inflammatory...). The diagnosis is fundamentally clinical and by exclusion. Its treatments are varied, not having any of them alone widely demonstrate satisfactory and validated results with randomized studies. The individualization of each case is important to adapt one or another therapy. The repercussion and possible relationship of this disease with patients’ quality of life and psycho-emotional aspects must be taken into account. Among these therapies, not only lifestyle habits, hygiene and pharmacotherapy are important, but also physiotherapeutic aspects of the female genital area and pelvic floor are., La vulvodinia es una disestesia o malestar crónico de la vulva (quemazón, irritación, ardor, dolor) de más de tres meses de duración, sin hallazgos clínicos ni de laboratorio que justifiquen la sintomatología. Se estima una prevalencia poblacional de un 4 %. Su etiología es aún desconocida, probablemente, multifactorial y en la que se postulan múltiples teorías (neuropática, inflamatoria, etc.). El diagnóstico es fundamentalmente clínico y de exclusión. Sus tratamientos son variados, no habiéndose demostrado resultados ampliamente satisfactorios, validados y con estudios aleatorizados con ninguno de ellos de forma aislada. Es importante la individualización de cada caso para adecuar una u otra terapia. Debe tenerse en cuenta la repercusión y relación posible de esta enfermedad con la calidad de vida y los aspectos psicoemocionales de la paciente. Entre estas terapias, no solo son importantes los hábitos de vida, la higiene y la farmacoterapia, sino también aspectos fisioterapéuticos de la zona genital y el suelo pélvico de la mujer.

Metabolic syndrome (MetS) components are strongly associated with increased risk of non-alcoholic fatty liver disease (NAFLD) development. Several studies have supported that resveratrol is associated with anti-inflammatory and antioxidant effects on health status. The main objective of this study was to assess the putative associations between some urinary resveratrol phase II metabolites, cardiometabolic, and liver markers in individuals diagnosed with MetS. In this cross-sectional study, 266 participants from PREDIMED Plus study (PREvención con DIeta MEDiterránea) were divided into tertiles of total urinary resveratrol phase II metabolites (sum of five resveratrol conjugation metabolites). Urinary resveratrol metabolites were analyzed by ultra- performance liquid chromatography coupled to triple quadrupole mass spectrometry (UPLC-Q-q-Q MS), followed by micro-solid phase extraction (µ-SPE) method. Liver function markers were assessed using serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT). Moreover, lipid profile was measured by triglycerides, very-low-density lipoprotein cholesterol (VLDL-c), and total cholesterol/high-density lipoprotein ratio (total cholesterol/HDL). Linear regression adjusted models showed that participants with higher total urine resveratrol concentrations exhibited improved lipid and liver markers compared to the lowest tertile. For lipid determinations: log triglycerides (?T3= -0.15, 95% CI; -0.28, -0.02, p-trend = 0.030), VLDL-c, (?T3= -4.21, 95% CI; -7.97, -0.46, p-trend = 0.039), total cholesterol/HDL ratio Moreover, (?T3= -0.35, 95% CI; -0.66, -0.03, p-trend = 0.241). For liver enzymes: log AST (?T3= -0.12, 95% CI; -0.22, -0.02, p-trend = 0.011, and log GGT (?T3= -0.24, 95

Copyright © The Author(s) 2019. BACKGROUND: Overall quality of dietary carbohydrate intake rather than total carbohydrate intake may determine the risk of cardiovascular disease (CVD). OBJECTIVE: We examined 6- and 12-mo changes in carbohydrate quality index (CQI) and concurrent changes in several CVD risk factors in a multicenter, randomized, primary-prevention trial (PREDIMED-Plus) based on an intensive weight-loss lifestyle intervention program. METHODS: Prospective analysis of 5373 overweight/obese Spanish adults (aged 55-75 y) with metabolic syndrome (MetS). Dietary intake information obtained from a validated 143-item semiquantitative food-frequency questionnaire was used to calculate 6- and 12-mo changes in CQI (categorized in quintiles), based on 4 criteria (total dietary fiber intake, glycemic index, whole grain/total grain ratio, and solid carbohydrate/total carbohydrate ratio). The outcomes were changes in intermediate markers of CVD. RESULTS: During the 12-mo follow-up, the majority of participants improved their CQI by increasing their consumption of fruits, vegetables, legumes, fish, and nuts and decreasing their consumption of refined cereals, added sugars, and sugar-sweetened beverages. After 6 mo, body weight, waist circumference (WC), systolic and diastolic blood pressure (BP), fasting blood glucose, glycated hemoglobin (HbA1c), triglyceride levels, triglycerides and glucose (TyG) index, and TyG-WC decreased across successive quintiles of improvement in the CQI. After 12 mo, improvements were additionally observed for HDL cholesterol and for the ratio of total to HDL cholesterol. Favorable improvements (expressed in common units of SD and 95% CI) for quintile 5 compared with quintile 1 of CQI change were observed for most risk factors, including TyG-WC

© 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism Background & aims: Little is known about the impact of specific dietary patterns on the development of obesity phenotypes. We aimed to determine the association of longitudinal changes in adherence to the traditional Mediterranean diet (MedDiet) with the transition between different obesity phenotypes. Methods: Data of 5801 older men and women at high cardiovascular risk from PREDIMED trial were used. Adherence to MedDiet was measured with the validated 14p-Mediterranean Diet Adherence Screener (MEDAS). Using the simultaneous combination of metabolic health- and body size-related parameters participants were categorized into one of four phenotypes: metabolically healthy and abnormal obese (MHO and MAO), metabolically healthy and abnormal non-obese (MHNO and MANO). Cox regression models with yearly repeated measures during 5-year of follow-up were built with use of Markov chain assumption. Results: Each 2-point increase in MEDAS was associated with the following transitions: in MAO participants, with a 16% (95% CI 3–31%) greater likelihood of becoming MHO; in MHO participants with a 14% (3–23%) lower risk of becoming MAO; in MHNO participants with a 18% (5–30%) lower risk of becoming MHO. In MANO women, but not in men, MEDAS was associated with 20% (5–38%) greater likely of becoming MHNO (p for interaction by gender 0.014). No other significant associations were observed. Conclusions: Better adherence to the traditional MedDiet is associated with transitions to healthier phenotypes, promoting metabolic health improvement in MAO, MANO (only in women), and MHO, as well as protecting against obesity incidence in MHNO subjects.

© 2020, The Author(s). Physical activity (PA) has been hypothesized to be effective to maintaining cognitive function and delay cognitive decline in the elderly, but physical fitness (PF) could be a better predictor of cognitive function. We aimed to study the association between PA and PF with cognitive function and quality of life using cross-sectional data from 6874 participants of the PREDIMED-Plus trial (64.9 ± 4.9 years, 48.5% female). PF and PA were measured with a Chair Stand Test, the REGICOR and Rapid Assessment Physical Activity questionnaires. Cognitive function was measured with Mini-mental State Examination, Control Oral Word Association Test, Trail Making Test and Digit Span tests; whereas health-related quality of life was assessed with the SF36-HRQL test. Cognitive and quality of life scores were compared among PF quartiles and PA levels (low, moderate and high) with ANCOVA and with Chair Stand repetitions and energy expenditure from total PA with multivariable linear regression adjusted for confounding factors. PF associated with higher scores in phonemic and semantic verbal fluency tests and with lower TMT A time. However, PA was not associated with the neurocognitive parameters evaluated. Both PF and PA levels were strongly associated with a better quality of life. We concluded that PF, but not PA, is associated with a better cognitive function. This trial was retrospectively registered at the International Standard Randomized 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.

© 2020 The Author(s). Published by Oxford University Press on behalf of the American Society for Nutrition. 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. Objectives: We examined associations of glutamate, glutamine, and the glutamine-to-glutamate ratio with AF and HF incidence in a Mediterranean population at high cardiovascular disease (CVD) risk. Methods: The present study used 2 nested case-control studies within the PREDIMED (Prevención con Dieta Mediterránea) study. During ∼10 y of follow-up, there were 509 AF incident cases matched to 618 controls and 326 HF incident cases matched to 426 controls. Plasma concentrations of glutamate and glutamine were semiquantitatively profiled with LC-tandem MS. ORs were estimated with multivariable conditional logistic regression models. Results: In fully adjusted models, per 1-SD increment, glutamate was associated with a 29% (95% CI: 1.08, 1.54) increased risk of HF and glutamine-to-glutamate ratio with a 20% (95% CI: 0.67, 0.94) decreased risk. Glutamine-to-glutamate ratio was also inversely associated with HF risk (OR per 1-SD increment: 0.80; 95% CI: 0.67, 0.94) when comparing extreme quartiles. Higher glutamate concentrations were associated with a worse cardiometabolic risk profile, whereas a higher glutamine-to-glutamate ratio was associated with a better cardiometabolic risk profile. No associations between the concentrations of these metabolites and AF were observed. Conclusions: Our findings suggest that high plasma glutamate concentrations possibly resulting from alterations in the glutamate-glutamine cycle may contribu

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.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 and Pearson correlations coefficients between multi-metabolite weighted models and reported protein intake in each pair of training-validation datasets were calculated. A wide set of metabolites was consistently associated with each protein source evaluated. These metabolites mainly consisted of amino acids and their derivatives, acylcarnitines, different organic acids and lipid species. Few metabolites overlapped among protein sources (i.e. C14:0 SM, C20:4 carnitine, GABA and allantoin) but none of them towards the same direction. Regarding AP and PP approaches, C20:4 carnitine and dimethylglycine were positively associated with PP but negatively associated with AP. However, allantoin, C14:0 SM, C38:7 PE plasmalogen, GABA, metronidazole and trigonelline (N-methylnicotinate) behaved contrary. Ten-CV Pearson correlations coefficients between self-reported protein intake and plasma metabolomics profiles ranged from 0.21 for PR to 0.32 for total protein.Different sets of metabolites were associated with total, animal and plant protein intake. Further studies are needed to assess the contribution of these metabolites

© 2019, The Author(s). 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 ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.

Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D).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.We used a case-cohort study nested within the Prevención con Dieta Mediterránea (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 mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR-related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models.We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous)

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, we selected 696 non-cases and 221 incident CVD cases; for T2D, we included 610 non-cases and 243 type 2 diabetes incident cases. Metabolites were quantified using liquid chromatography-tandem mass spectrometry, at baseline and after 1-year of intervention. RESULTS: In weighted Cox regression models, we found that baseline lysine (HR+1 SD increase = 1.26; 95% CI 1.06-1.51) and 2-AAA (HR+1 SD increase = 1.28; 95% CI 1.05-1.55) were both associated with a higher risk of T2D, but not with CVD. A significant interaction (p = 0.032) between baseline lysine and T2D on the risk of CVD was observed: subjects with prevalent T2D and high levels of lysine exhibited the highest risk of CVD. The intervention with MedDiet did not have a significant effect on 1-year changes of the metabolites. CONCLUSIONS: Our results provide an independent prospective replication of the association of 2-AAA with future risk of T2D. We show an association of lysine with subsequent CVD risk, which is apparently diabetes-dependent. No evidence of effects of MedDiet intervention on lysine, 2-AAA or pipecolic acid changes

© 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University Background and aims: There is ongoing controversy about the effect of a low to moderate alcohol consumption on atrial fibrillation (AF). Our aim is to assess the association between adherence to a Mediterranean alcohol drinking pattern and AF incidence. Methods and results: A total 6527 out of the 7447 participants in the PREDIMED trial met our inclusion criteria. A validated frequency food questionnaire was used to measure alcohol consumption. Participants were classified as non-drinkers, Mediterranean alcohol drinking pattern (MADP)(10–30 g/d in men and 5–15 g/day in women, preferably red wine consumption with low spirits consumption), low-moderate drinking (<30 g/day men y and < 15 g/day women), and heavy drinking. We performed multivariable Cox regression models to estimate hazard ratios (HR)with 95% confidence intervals (95% CI)of incident AF according to alcohol drinking patterns. After a mean follow up of 4.4 years, 241 new incident AF cases were confirmed. Alcohol consumption was not associated to AF incidence among low-moderate drinkers (HR: 0.96; 95%CI: 0.67–1.37), adherents to MADP (HR: 1.15 95%CI: 0.75–1.75), or heavy drinkers (HR: 0.92; 95%CI: 0.53–1.58), compared with non-drinkers. Conclusions: In a high cardiovascular risk adult population, a Mediterranean alcohol consumption pattern (low to moderate red wine consumption)was not associated with an increased incidence of AF. Clinical trials: URL: http://www.controlled-trials.com. Unique identifier: ISRCTN35739639.

Research examining associations between objectively-measured napping time and type 2 diabetes (T2D) is lacking. This study aimed to evaluate daytime napping in relation to T2D and adiposity measures in elderly individuals from the Mediterranean region. A cross-sectional analysis of baseline data from 2190 elderly participants with overweight/obesity and metabolic syndrome, in the PREDIMED-Plus trial, was carried out. Accelerometer-derived napping was measured. Prevalence ratios (PR) and 95% confidence intervals (CI) for T2D were obtained using multivariable-adjusted Cox regression with constant time. Linear regression models were fitted to examine associations of napping with body mass index (BMI) and waist circumference (WC). Participants napping ?90 min had a higher prevalence of T2D (PR 1.37 (1.06, 1.78)) compared with those napping 5 to <30 min per day. Significant positive associations with BMI and WC were found in those participants napping ?30 min as compared to those napping 5 to <30 min per day. The findings of this study suggest that longer daytime napping is associated with higher T2D prevalence and greater adiposity measures in an elderly Spanish population at high cardiovascular risk.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Background: Nut consumption has been associated with improved nutrient adequacy and diet quality in healthy adult populations but this association has never been explored in individuals at high cardiovascular risk. Objective: to assess the associations between consumption of nuts and nutrient adequacy and diet quality in a Mediterranean population at high cardiovascular risk. Design: baseline assessment of nutritional adequacy in participants (n = 6060, men and women, with ages 55-75 years old, with overweight/obesity and metabolic syndrome) in the PREDIMED-PLUS primary cardiovascular prevention randomized trial. Methods: nut intake was assessed using a validated food frequency questionnaire. Participants who reported consuming zero quantity of nuts were classified as ‘non-nut consumers’. ‘Nut consumers’ were participants who reported consuming any quantity of nuts. Nineteen micronutrients were examined (vitamins B1, B2, B3, B6, B12, A, C, D, E and folic acid; Ca, K, P, Mg, Fe, Se, Cr, Zn, and iodine). The proportion of micronutrient inadequacy was estimated using the estimated average requirements (EAR) or adequate intake (AI) cut-points. Diet quality was also assessed using a 17-item Mediterranean dietary questionnaire (Mediterranean diet score, MDS), a carbohydrate quality index (CQI) and a fat quality index (FQI). Results: eighty-two percent of participants were nut consumers (median of nut consumption 12.6 g/day; interquartile range: 6.0-25.2). Nut consumers were less likely to be below the EAR for vitamins A, B1, B2, B6, C, D, E, folic acid, and Ca, Mg, Se and Zn than non-nut consumers. Nut consumers were also more likely to be above the AI for K and Cr than non-nut consumers. Nut consumers had lower preval

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 55-75 years, with overweight/obesity who also had MetS. An energy-adjusted dietary diversity score (DDS) was calculated using a 143-item validated semi-quantitative food frequency questionnaire (FFQ). Nutrient inadequacy was defined as an intake below 2/3 of the dietary reference intake (DRI) forat least four of 17 nutrients proposed by the Institute of Medicine (IOM). Logistic regression models were used to evaluate the association between DDS and the risk of nutritionally inadequate intakes. In the higher DDS quartile there were more women and less current smokers. Compared with subjects in the highest DDS quartile, those in the lowest DDS quartile had a higher risk of inadequate nutrient intake: odds ratio (OR) = 28.56 (95% confidence interval (CI) 20.80-39.21). When we estimated food varietyfor each of the food groups, participants in the lowest quartile had a higher risk of inadequate nutrient intake for the groups of vegetables, OR = 14.03 (95% CI 10.55-18.65), fruits OR = 11.62 (95% CI 6.81-19.81), dairy products OR = 6.54 (95% CI 4.64-9.22) and protein foods OR = 6.60 (95% CI 1.96-22.24). As DDS decreased, the risk of inadequate nutrients intake rose. Given the impact of nutrient intake a

Background Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. Methods In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. Results A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intent

Background: Perturbed lipid metabolic pathways may play important roles in the development of cardiovascular disease (CVD). However, existing epidemiological studies have focused more on discovering individual lipid metabolites for CVD risk prediction rather than assessing metabolic pathways. Methods: This study included a subcohort of 787 participants and all 230 incident CVD cases from the PREDIMED trial. Applying a network-based analytical method, we identified lipid subnetworks and clusters from a global network of 200 lipid metabolites and linked these subnetworks/clusters to CVD risk. Results: Lipid metabolites with more double bonds clustered within one subnetwork, whereas lipid metabolites with fewer double bonds clustered within other subnetworks. We identified 10 lipid clusters that were divergently associated with CVD risk. The hazard ratios [HRs, 95% confidence interval (CI)] of CVD per a 1-standard deviation (SD) increment in cluster score were 1.39 (1.17-1.66) for the hydroxylated phosphatidylcholine (HPC) cluster and 1.24 (1.11-1.37) for a cluster that included diglycerides and a monoglyceride with stearic acyl chain. Every 1-SD increase in the score of cluster that included highly unsaturated phospholipids and cholesterol esters was associated with an HR for CVD of 0.81 (95% CI, 0.67-0.98). Despite a suggestion that MedDiet modified the association between a subnetwork that included most lipids with a high degree of unsaturation and CVD, changes in lipid subnetworks/clusters during the first-year follow-up were not significantly different between intervention groups. Conclusions: The degree of unsaturation was a major determinant of the architecture of lipid metabolic network. Lipid clusters that strongly predicted CVD risk, such as the HPC cluster, warr

© 2018 by the American Diabetes Association. OBJECTIVE: Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. RESEARCH DESIGN AND METHODS: We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. RESULTS: Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend ≤0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs. CONCLUSIONS: Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another pro