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The production and consumption of ultra-processed foods (UPF) has increased considerably during the last years worldwide. Collective evidence shows the association between UPF consumption and adverse health outcomes, including inflammatory gastro-intestinal disorders and obesity. The gut microbiota has been suggested as potential mediator of the effects of UPF consumption on metabolism and health. However, few studies have been conducted in order to elucidate these aspects. Therefore, the aim of the present study was to assess the cross-sectional associations between UPF consumption and gut microbiota in a population of senior subjects (n = 645) within the frame of the PREDIMED-Plus trial. Eligible participants were men and women (aged 55–75 years), without documented history of cardiovascular disease at enrollment, with overweight/obesity (body mass index ≤ 27 and

Abstract Background 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. Methods 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. Results 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. Conclusions This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. Trial registration: ISRCTN35739639.

Abstract Background SARS-CoV-2 is the causative agent of COVID-19 identified in December 2019, an acute infectious respiratory disease that can cause persistent neurological and musculoskeletal symptoms such as headache, fatigue, myalgias difficulty concentrating, among others including acute cerebrovascular disease with a prevalence of 1–35%. The aim of this study is to evaluate the impact of COVID-19 in undergraduate students on their academic performance as an indicator of their intellectual ability and performance in a university that maintained 100% face-to-face teaching during the 2020–2021 academic year. Methods A total of 7,039 undergraduate students were analyzed in a prospective cohort study at the University of Navarra. A questionnaire including sociodemographic and behavioral questions was sent. PCRs were performed throughout the academic year for the diagnosis of SARS-CoV-2 infection and students’ academic results were provided by the academic center, adjusted descriptive and multivariate models were performed to assess the association. Results A total of 658 (9.3%) participants were diagnosed with COVID-19, almost 4.0% of them achieved outstanding academic results, while uninfected students did so in 7.3%. SARS-CoV-2 infection was associated with a significant decrease in having outstanding academic results (OR = 0.57; 95% CI: 0.38–0.86). Conclusion Having COVID-19 disease, decreased academic performance in undergraduate students. Therefore, it is necessary to prevent infection even in the youngest sections of the population.

Background Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention. Methods and Results We studied 503 participants from the PREDIMED‐Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy‐reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow‐up. Cross‐sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m2 [95% CI, 0.18–1.11]) and lower left atrial reservoir and contractile strain (−0.44% [95% CI, −0.87 to −0.01]; and −0.44% [95% CI, −0.75 to −0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow‐up were associated with left atrial enlargement (0.71 mL/m2 [95% CI, 0.17–1.26]). Conclusions In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function. Registration URL: http://www.controlled‐trials.com; Unique identifier: ISRCTN89898870.

Abstract Background 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. Methods 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:

Abstract Experimental studies reported biochemical actions underpinning aging processes and mortality, but the relevant metabolic alterations in humans are not well understood. Here we examine the associations of 243 plasma metabolites with mortality and longevity (attaining age 85 years) in 11,634 US (median follow-up of 22.6 years, with 4288 deaths) and 1878 Spanish participants (median follow-up of 14.5 years, with 525 deaths). We find that, higher levels of N2,N2-dimethylguanosine, pseudouridine, N4-acetylcytidine, 4-acetamidobutanoic acid, N1-acetylspermidine, and lipids with fewer double bonds are associated with increased risk of all-cause mortality and reduced odds of longevity; whereas L-serine and lipids with more double bonds are associated with lower mortality risk and a higher likelihood of longevity. We further develop a multi-metabolite profile score that is associated with higher mortality risk. Our findings suggest that differences in levels of nucleosides, amino acids, and several lipid subclasses can predict mortality. The underlying mechanisms remain to be determined.

Several studies have tried to analyse the association between all-cause mortality and different risk factors, (especially those which are modifiable, such as smoking, diet or exercise), to develop public health preventive strategies. However, a specific analysis of predictors of premature and late mortality is needed to give more precise recommendations. Considering that there are risk factors which exert an influence on some diseases and not on others, we expect that, similarly, they may have a different impact depending on the timing of mortality, separating premature (≤65 years) from late mortality (>65 years). Thus, we prospectively followed-up during a median of 12 years a cohort of 20,272 university graduates comprising an ample range of ages at inception. Time-dependent, covariate-adjusted Cox models were used to estimate adjusted hazard ratios (HR) and their 95 % confidence intervals (CI) for each predictor. The strongest independent predictor of mortality at any age was physical activity which was associated with reduced risk of total, premature and late mortality (range of HRs when comparing the highest vs. the lowest level: 0.24 to 0.48). Specific strong predictors for premature mortality were smoking, HR: 4.22 (95 % CI: 2.42–7.38), and the concurrence of ≥2 metabolic conditions at baseline, HR: 1.97 (1.10–3.51). The habit of sleeping a long nap (≥30 min/d), with HR: 2.53 (1.30–4.91), and poor adherence to the Mediterranean Diet (≤3 points in a 0 to 8 score vs. ≥6 points), with HR: 2.27 (1.08–4.76), were the strongest specific predictors for late mortality. Smoking, diet quality or lifestyles, probably should be differentially assessed as specific predictors for early and late mortality. In the era of precision medicine, this approach will allow tailored recommendations appropriate to each person's age and baseline condition.

BackgroundThe COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity.MethodsWe assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown.ResultsDuring the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants’ follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60–0.91]) and after (0.72 cm [95% CI: 0.56–0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: –0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: –0.30 to –0.04]).ConclusionMitigating strategies to enforce the intervention and patient’s follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity.Clinical trial registrationhttps://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870.

Background and aimsFront-of-Pack (FoP) nutrition labelling has been established as a policy, empowering consumers to choose healthy food options for preventing diet-related non-communicable diseases. This study aimed to evaluate the association between the nutrient profile underlying the Chilean warning label score and all-cause mortality and to conduct a calibration with the Nutri-Score in a large cohort of Spanish university graduates.Materials and methodsThis prospective cohort study analysed 20,666 participants (8,068 men and 12,598 women) with a mean (standard deviation) age of 38 years (±12.4) from the SUN cohort. Dietary food intake was assessed by a validated semi-quantitative food-frequency questionnaire at baseline and after 10 years of follow-up. The warning label score was calculated by considering the threshold of nutrients (sugar, saturated fat, and sodium) and energy density per 100 g/ml of product, as established by Chilean Legislation. Participants were classified according to quartiles of consumption of daily label score: Q1 (≤5.0), Q2 (>5.0–7.1), Q3 (>7.1–9.8), and Q4 (>9.8). Time-dependent, multivariable-adjusted Cox models were applied. To compare the performance of the warning label score and Nutri-Score to predict mortality, we used the Akaike information criterion (AIC) and Bayesian information criterion (BIC) methods.ResultsDuring a median of 12.2 years of follow-up, 467 deaths were identified. A higher score in the warning label values (lower nutritional quality) was associated with an increased risk of all-cause mortality [HR (95% CI) Q4 vs. Q1: 1.51 (1.07–2.13); p-trend = 0.010] and cancer mortality [HR (95% CI) Q4 vs. Q1: 1.91 (1.18–3.10); p-trend = 0.006]. However, no statistically significant association was found for cardiovascular mortality. Furthermore, the warning label score and Nutri-Score exhibited comparable AIC and BIC values, showing similar power of prediction for mortality.ConclusionA diet with a higher warning label score (>9.8 per day) was a good predictor of all cases and cancer mortality in a large Spanish cohort of university graduates. Also, the warning label score was capable to predict mortality as well as the Nutri-Score. Our findings support the validity of the warning label score as a FoP nutrition labelling policy since it can highlight less healthy food products.

Systemic inflammation is associated with an increased risk of non-communicable diseases, such as cardiovascular diseases and diabetes. Circulating fatty acids (FA) are known to be related to these conditions, possibly through their role in inflammation, although different types of FAs can have opposite effects on inflammatory mediators. The aim of the present study was to analyze the association of plasma FAs with inflammatory biomarkers in a PREDIMED trial subsample after one year of intervention. In a one-year longitudinal study of 91 participants of the PREDIMED trial (Barcelona-Clinic center), plasma FAs and inflammatory biomarkers were analyzed using gas chromatography and ELISA, respectively. In baseline plasma, a multivariable-adjusted ordinary least squares regression model showed that n-3 polyunsaturated FAs concentrations were inversely associated with concentrations of soluble intercellular adhesion molecule-1 (sICAM-1) and E-selectin, whereas the level of the most abundant saturated FA, palmitic acid, was directly associated with concentrations of interleukin-6 (IL-6) (β = 0.48 pg/mL, 95% CI: 0.03, 0.93 per 1-SD increase, p-value = 0.037). After one year of nutritional intervention, changes of plasma diet-derived total saturated FAs and palmitic acid were directly associated with changes in IL-6 (β = 0.59 pg/mL [95% CI: 0.28, 0.89] per 1-SD, p-value = 0.001; β = 0.64 pg/mL, 95% CI: 0.31, 0.98, p-value = 0.001), respectively, after correction for multiple testing. Our findings suggest that saturated FAs of dietary origin, especially palmitic acid, are directly involved in the increase of IL-6 in plasma.

(1) Background: Metabolic Syndrome (MetS) affects over a third of the United States population, and has similar prevalence in Europe. Dietary approaches to prevention are important. Coffee consumption has been inversely associated with mortality and chronic disease; however, its relation to the risk of MetS is unclear. We aimed to investigate the association between coffee consumption and incident MetS in the ‘Seguimiento Universidad de Navarra’ cohort. (2) Methods: From the SUN project, we included 10,253 participants initially free of MetS. Coffee consumption was assessed at baseline, and the development of MetS was assessed after 6 years of follow-up. All data were self-reported by participants. MetS was defined according to the Harmonizing Definition. We used multivariable logistic regression models to estimate odds ratios and 95% confidence intervals for incident MetS according to four categories of coffee consumption:

BackgroundThe Internet has become the main source of information on health issues, and information now determines the therapeutic preferences of patients. For this reason, it is relevant to analyze online information discussing psychotherapy.ObjectiveTo investigate tweets posted by 25 major US media outlets between 2009 and 2019 concerning psychotherapy.MethodsWe investigated tweets posted by 25 major US media outlets about psychotherapy between January 2009 and December 2019 as well as the likes generated. In addition, we measured the sentiment analysis of these tweets.ResultsMost of the tweets analyzed focused on Mindfulness (5,498), while a low number were related to Psychoanalysis (376) and even less to Cognitive-Behavioral Therapy (61). Surprisingly, Computer-supported therapy, Psychodynamic therapy, Systemic therapy, Acceptance and commitment therapy, and Dialectical behavior therapy did not generate any tweet. In terms of content, efficacy was the main focus of the posted tweets, receiving Cognitive-Behavioral Therapy and Mindfulness a positive appraisal.ConclusionsUS media outlets focused their interest on Mindfulness which may have contributed to the growing popularity in the past years of this therapeutic modality.

Abstract 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 137-item semi-quantitative Food Frequency Questionnaire was used for dietary assessment with yearly repeated measurements. We longitudinally assessed associations between yearly changes in food consumption (serving/d) and concurrent changes in weight (kg) or WC (cm). Results Yearly increments in weight were observed with increased consumption (kg per each additional increase in 1 serving/d) for refined grains (0.32 kg/serving/d), red meat (0.24), potatoes (0.23), alcoholic beverages (0.18), processed meat (0.15), white bread (0.07) and sweets (0.04); whereas inverse associations were detected for increased consumption of low-fat yogurt (− 0.18), and low-fat milk (− 0.06). Annual WC gain (cm per each additional increase in 1 serving/d) occurred with increased consumption of snacks, fast-foods and pre-prepared dishes (0.28), processed meat (0.18), alcoholic beverages (0.13), and sweets (0.08); whereas increased consumption of vegetables (− 0.23), and nuts (− 0.17), were associated with reductions in WC. Conclusions In this assessment conducted in high-risk subjects using yearly repeated measurements of food habits and adiposity, some ultra-processed foods, refined carbohydrates (including white bread), potatoes, red meats and alcohol were associated with higher weight and WC gain, whereas increases in consumption of low-fat dairy products and plant foods were associated with less gain in weight and WC. Trial registration This study was registered at controlled-trials.com with International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005.

Effective prevention and risk prediction are important for peripheral artery disease (PAD) due to its poor prognosis and the huge disease burden it produces. Circulating amino acids (AA) and their metabolites may serve as biomarkers of PAD risk, but they have been scarcely investigated. The objective was to prospectively analyze the associations of baseline levels of plasma AA (and their pathways) with subsequent risk of PAD and the potential effect modification by a nutritional intervention with the Mediterranean diet (MedDiet). A matched case-control study was nested in the PREDIMED trial, in which participants were randomized to three arms: MedDiet with tree nut supplementation group, MedDiet with extra-virgin olive oil (EVOO) supplementation group or control group (low-fat diet). One hundred and sixty-seven PAD cases were matched with 250 controls. Plasma AA was measured with liquid chromatography/mass spectrometry at the Broad Institute. Baseline tryptophan, serine and threonine were inversely associated with PAD (ORfor 1 SD increase = 0.78 (0.61–0.99); 0.67 (0.51–0.86) and 0.75 (0.59–0.95), respectively) in a multivariable-adjusted conditional logistic regression model. The kynurenine/tryptophan ratio was directly associated with PAD (ORfor 1 SD increase = 1.50 (1.14–1.98)). The nutritional intervention with the MedDiet+nuts modified the association between threonine and PAD (p-value interaction = 0.018) compared with the control group. However, subjects allocated to the MedDiet+EVOO group were protected against PAD independently of baseline threonine. Plasma tryptophan, kynurenine/tryptophan ratio, serine and threonine might serve as early biomarkers of future PAD in subjects at a high risk of cardiovascular disease. The MedDiet supplemented with EVOO exerted a protective effect, regardless of baseline levels of threonine.

IntroductionType 2 diabetes has been linked to greater cognitive decline, but other glycemic parameters such as prediabetes, diabetes control and treatment, and HOMA-IR and HbA1c diabetes-related biomarkers have shown inconsistent results. Furthermore, there is limited research assessing these relationships in short-term studies. Thus, we aimed to examine 2-year associations between baseline diabetes/glycemic status and changes in cognitive function in older participants at high risk of cardiovascular disease.MethodsWe conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. At baseline, participants were categorized by diabetes status (no-diabetes, prediabetes, and

Abstract 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 was found. Trial registration ISRCTN35739639; registration date: 05/10/2005; recruitment start date 01/10/2003

Healthy and unhealthy lifestyles are tightly linked to general health and well-being. However, measurements of well-being have failed to include elements of health and easy to interpret information for patients seeking to improve lifestyles. Therefore, this study aimed to create an index for the assessment of general health and well-being along with two cut-off points: the lifestyle and well-being index (LWB-I). This was a cross-sectional analysis of 15,168 individuals. Internally valid multivariate linear models were constructed using key lifestyle features predicting a modified Short Form 36 questionnaire (SF-36) and used to score the LWB-I. Categorization of the LWB-I was based on self-perceived health (SPH) and analyzed using receiver operating characteristic curve analysis. Optimal cut-points identified individuals with poor and excellent SPH. Lifestyle and well-being were adequately accounted for using 12 lifestyle items. SPH groups had increasingly healthier lifestyle features and LWB-I scores; optimal cut-point for poor SPH were scores below 80 points (AUC: 0.80 (0.79, 0.82); sensitivity 75.7%, specificity 72.3%)) and above 86 points for excellent SPH (AUC: 0.67 (0.66, 0.69); sensitivity 61.4%, specificity 63.3%). Lifestyle and well-being were quantitatively scored based on their associations with a general health measure in order to create the LWB-I along with two cut points.

Obesity is associated with a higher risk of several types of cancer, grouped as obesity-related cancers (ORC). Vitamin D deficiency is more prevalent in obese subjects, and it has been suggested to play a role in the association between obesity and cancer risk. The aim of the study was to analyze the association between vitamin D intake and the subsequent risk of ORC in a prospective Spanish cohort of university graduates. The SUN Project, initiated in 1999, is a prospective dynamic multipurpose cohort. Participants answered a 556-item lifestyle baseline questionnaire that included a validated food-frequency questionnaire. We performed Cox regression models to estimate the hazard ratios (HRs) of ORC according to quartiles of energy-adjusted vitamin D intake (diet and supplements). We included 18,017 participants (mean age = 38 years, SD = 12 years), with a median follow-up of 12 years. Among 206,783 person-years of follow-up, we identified 225 cases of ORC. We found no significant associations between vitamin D intake and ORC risk after adjusting for potential confounders: HRQ2vsQ1 = 1.19 (95% CI 0.81–1.75), HRQ3vsQ1 = 1.20 (95% CI 0.81–1.78), and HRQ4vsQ1 = 1.02 (95% CI 0.69–1.51). Dietary and supplemented vitamin D do not seem to be associated with ORC prevention in the middle-aged Spanish population.

Background: Media outlets influence social attitudes toward health habits. The analysis of tweets has become a tool for health researchers.Objective: The objective of this study was to investigate the distribution of tweets about women's health and the interest generated among Twitter users.Methods: We investigated tweets posted by 25 major U.S. media outlets about pre-menopausal and post-menopausal women's health between January 2009 and December 2019 as well as the retweets generated. In addition, we measured the sentiment analysis of these tweets as well as their potential dissemination.Results: A total of 376 tweets were analyzed. Pre-menopausal women's health accounted for most of the tweets (75.3%). Contraception was the main focus of the tweets, while a very limited number were related to infertility (1.4%). With regard to medical content, the effectiveness of contraceptive methods was the most frequent topic (46.2%). However, tweets related to side effects achieved the highest retweet-to-tweet ratio (70.3). The analysis of sentiments showed negative perceptions on tubal ligation.Conclusions: The U.S. media outlets analyzed are more interested in pre-menopausal than in post-menopausal women health and focused their content on contraception, while Twitter users showed greater interest in side effects.

Resumen: Objetivo: Cuantificar el impacto de reducir el consumo de carnes rojas y procesadas sobre la mortalidad cardiovascular y la mortalidad total de la población adulta española, basado en 5 revisiones publicadas. Participantes y mediciones principales: Se define la exposición como el consumo de ≥ 3 raciones/semana de carnes rojas o procesadas, y se consideran cuatro escenarios de población expuesta (30-60%). Con datos del Instituto Nacional de Estadística, se calcula la mortalidad ponderada en población española de 40-80 años y, utilizando los riesgos relativos (RR) y los intervalos de confianza (IC) al 95% publicados en 5 revisiones (RR = 0,88; IC 95%: 0,84-0,93 para mortalidad por todas las causas y RR = 0,92; IC 95%: 0,90-0,93 para la mortalidad cardiovascular), se calculó la tasa de mortalidad en expuestos y no expuestos. Multiplicando esas tasas por el número de expuestos, se obtuvo el número de muertes atribuibles. Resultados: Asumiendo un 60% de población española de 40-80 años expuesta, el número de muertes anuales de causa cardiovascular que se podrían evitar consumiendo

Objective. The strongest locus which associated with type 2 diabetes (T2D) by the common variant rs7903146 is the transcription factor 7-like 2 gene (TCF7L2). We aimed to quantify the interaction of diet/lifestyle interventions and the genetic effect of TCF7L2 rs7903146 on glycemic traits, body weight, or waist circumference in overweight or obese adults in several randomized controlled trials (RCTs). Methods. From October 2016 to May 2018, a large collaborative analysis was performed by pooling individual-participant data from 7 RCTs. These RCTs reported changes in glycemic control and adiposity of the variant rs7903146 after dietary/lifestyle-related interventions in overweight or obese adults. Gene treatment interaction models which used the genetic effect encoded by the allele dose and common covariates were applicable to individual participant data in all studies. Results. In the joint analysis, a total of 7 eligible RCTs were included (n=4,114). Importantly, we observed a significant effect modification of diet/lifestyle-related interventions on the TCF7L2 variant rs7903146 and changes in fasting glucose. Compared with the control group, diet/lifestyle interventions were related to lower fasting glucose by -3.06 (95% CI, -5.77 to -0.36) mg/dL (test for heterogeneity and overall effect: I2=45.1%, p

This review discusses the inconsistent recommendations on alcohol consumption and its association with chronic disease, highlighting the need for an evidence-based consensus. Alcohol is an addictive substance consumed worldwide, especially in European countries. Recommendations on alcohol consumption are controversial. On one hand, many nonrandomized studies defend that moderate consumption has a beneficial cardiovascular effect or a lower risk of all-cause mortality. On the other hand, alcohol is associated with an increased risk of cancer, neurological diseases, or injuries, among others. For years, efforts have been made to answer the question regarding the safe amount of alcohol intake, but controversies remain. Observational studies advocate moderate alcohol consumption following a Mediterranean pattern (red wine with meals avoiding binge drinking) as the best option for current drinkers. However, agencies such as the IARC recommend abstention from alcohol as it is a potent carcinogen. In this context, more randomized trial with larger sample size and hard clinical endpoints should be conducted to clarify the available evidence and provide clinicians with support for their clinical practice.

Background: Visceral adipose tissue (VAT) has a hazardous influence on systemic inflammation, insulin resistance and an adverse metabolic profile, which increases the risk of developing non-alcoholic fatty liver disease (NAFLD) and chronic complications of diabetes. In our study we aimed to evaluate the association of VAT and the triglyceride glucose (TyG) as a proxy of insulin resistance surrogated with metabolic and liver risk factors among subjects diagnosed with metabolic syndrome (MetS). Methods: A cross-sectional study was performed including 326 participants with MetS (55–75 years) from the PREDIMED-Plus study. Liver-status markers, VAT and TyG were assessed. Participants were stratified by tertiles according to VAT ( n = 254) and TyG ( n = 326). A receiver operating characteristic curve was used to analyse the efficiency of TyG for VAT. Results: Subjects with greater visceral fat depots showed worse lipid profile, higher homeostatic model assessment for insulin resistance (HOMA-IR), TyG, alanine transaminase (ALT), fibroblast growth factor-21 (FGF-21), fatty liver index (FLI) and hepatic steatosis index (HSI) compared with participants in the first tertile. The multi-adjusted linear-regression analyses indicated that individuals in the third tertile of TyG (>9.1−10.7) had a positive association with HOMA-IR [ β = 3.07 (95% confidence interval (CI) 2.28−3.86; p trend

Exposure to persistent organic pollutants (POPs) may influence telomere length (TL), which is considered as a marker of biological age associated with the risk of chronic disease. We hypothesized that dietary exposure to polychlorinated biphenyls (PCBs) and dioxins could affect TL. Our aim was to evaluate the association of dietary exposure to PCBs and dioxins with TL. In this cross-sectional study of 886 subjects older than 55 y (mean age: 67.7; standard deviation (SD): 6.1; 27% women) from the “Seguimiento Universidad de Navarra” (SUN) project. TL was determined by real-time quantitative polymerase chain reaction and dietary PCBs and dioxins exposure was collected using a validated 136-item Food Frequency Questionnaire. Multivariable linear regression models were used to control for potential confounding factors. Shorter TL was associated with dietary total PCBs (SD of T/S ratio/(ng/day) = −0.30 × 10−7; 95% CI, −0.55 × 10−7 to −0.06 × 10−7), dioxin-like PCBs (DL-PCBs) (SD of T/S ratio/(pg WHO TEQ (Toxic Equivalents)/day) = −6.17 × 10−7; 95% CI, −11.30 × 10−7 to −1.03 × 10−7), and total TEQ exposure (SD of T/S ratio/(pg WHO TEQ/day) = −5.02 × 10−7; 95% CI, −9.44 × 10−7 to −0.61 × 10−7), but not with dioxins (SD of T/S ratio/(pg WHO TEQ/day) = −13.90 × 10−7; 95% CI, −37.70 × 10−7 to 9.79 × 10−7). In this sample of middle-aged and older Spanish adults, dietary exposure to total PCBs and DL-PCBs alone and together with dioxins was associated with shorter TL. Further longitudinal studies, preferably with POPs measured in biological samples, are needed to confirm this finding.

Abstract This study cross-sectionally examines in the elderly population: (a) the association of type 2 diabetes with executive function (EF); (b) the effect of BMI on both type 2 diabetes and EF; (c) the association between glycaemia control and EF in type 2 diabetes. 6823 older individuals with overweight/obesity and metabolic syndrome participating in the PREDIMED-PLUS study, were assessed with a battery of cognitive tests and a medical interview. ANOVA showed a significantly worse performance on EF in type 2 diabetes vs. non-diabetic individuals. Two complementary models were displayed: (1) in the whole sample, the presence of type 2 diabetes, depressive symptoms and BMI had a direct negative effect on EF, while apnoea had an indirect negative effect; (2) in the diabetes subsample, higher illness duration was associated with worse performance in EF. Participants with type 2 diabetes and HbA1c

BackgroundMagnesium (Mg2+) has received considerable attention with regards to its potential role in the pathophysiology of the mood disorders, but the available evidence seems inconclusive.AimsTo review and quantitatively summarise the human literature on Mg2+ intake and Mg2+ blood levels in the mood disorders and the effects of Mg2+ supplements on mood.MethodSystematic review and meta-analyses.ResultsAdherence to a Mg2+-rich diet was negatively associated with depression in cross-sectional (odds ratio = 0.66) but not in prospective studies. Mg2+ levels in bodily fluids were on average higher in patients with a mood disorder (Hedge's g = 0.19), but only in patients treated with antidepressants and/or mood stabilisers. There was no evident association between Mg2+ levels and symptom severity. Mg2+ supplementation was associated with a decline in depressive symptoms in uncontrolled (g = −1.60) but not in placebo-controlled trials (g = −0.21).ConclusionOur results provide little evidence for the involvement of Mg2+ in the mood disorders.Declaration of interestNone.

Overweight and obesity are growing worldwide and strongly associated with hypertension. The Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) index is proposed as an optimal indicator of body fatness. We aimed to investigate the association of body fat as captured by the CUN-BAE index with incident hypertension in a Mediterranean population. We assessed 15,950 participants of the SUN (Seguimiento Universidad de Navarra) prospective cohort (63.7% women) initially free of hypertension. Participants completed follow-up questionnaires biennially. A validated 136-item food-frequency questionnaire was administered at baseline. We used Cox models adjusted for multiple confounders. Among 12.3 years of median follow-up (interquartile range: 8.3, 15.0 years), 2160 participants reported having received a diagnosis of hypertension. We observed a strong direct association between progressively higher the CUN-BAE index at baseline and incident hypertension during follow-up in multivariable-adjusted models for men and women, even after further adjustment for BMI ≥ 30 kg/m2, showing a significant association also in non-obese participants. For each 2-unit increase in the CUN-BAE index, hypertension risk increased by 27% and 29% in men and women, respectively. The results remained significant when considering longitudinal repeated measures of changes in body fat assessed with the CUN-BAE index among the different biennial follow-up questionnaires. Our results emphasize the importance of reducing and maintaining a low body fat to prevent hypertension.

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. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies.

Hypertension is the strongest independent modifiable risk factor for cardiovascular disease. We aimed to investigate the association of magnesium intake with incident hypertension in a Mediterranean population, and the potential modification of this association by body mass index (BMI). We assessed 14,057 participants of the SUN (Seguimiento Universidad de Navarra) prospective cohort (67.0% women) initially free of hypertension. At baseline, a validated 136-item food frequency questionnaire was administered. We used Cox models adjusted for multiple socio-demographic, anthropometric, and lifestyle factors, and prevalent conditions present at baseline. Among a mean 9.6 years of follow-up we observed 1406 incident cases of medically diagnosed hypertension. An inverse association in multivariable-adjusted models was observed for progressively higher magnesium intake up to 500 mg/d vs. intake < 200 mg/d, which was greater among those with a BMI > 27 kg/m2. Lean participants with magnesium intake < 200 mg/d vs. >200 mg/d also had a higher risk of incident hypertension. Adherence to the Mediterranean diet did not modify these associations. In conclusion, dietary magnesium intake < 200 mg/d was independently associated with a higher risk of developing hypertension in a Mediterranean cohort, stronger for overweight/obese participants. Our results emphasize the importance of encouraging the consumption of magnesium-rich foods (vegetables, nuts, whole cereals, legumes) in order to prevent hypertension.

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 (βT3= −0.15, 95% CI; −0.28, −0.02, p-trend = 0.030), VLDL-c, (βT3= −4.21, 95% CI; −7.97, −0.46, p-trend = 0.039), total cholesterol/HDL ratio Moreover, (βT3= −0.35, 95% CI; −0.66, −0.03, p-trend = 0.241). For liver enzymes: log AST (βT3= −0.12, 95% CI; −0.22, −0.02, p-trend = 0.011, and log GGT (βT3= −0.24, 95% CI; −0.42, −0.06, p-trend = 0.002). However, there is no difference found on glucose variables between groups. To investigate the risk of elevated serum liver markers, flexible regression models indicated that total urine resveratrol metabolites were associated with a lower risk of higher ALT (169.2 to 1314.3 nmol/g creatinine), AST (599.9 to 893.8 nmol/g creatinine), and GGT levels (169.2 to 893.8 nmol/g creatinine). These results suggested that higher urinary concentrations of some resveratrol metabolites might be associated with better lipid profile and hepatic serum enzymes. Moreover, urinary resveratrol excreted showed a reduced odds ratio for higher liver enzymes, which are linked to NAFLD.

Current dietary patterns are negatively affecting both the environment and people’s health. Healthy diets are generally more environmentally friendly. However, few studies have focused on the health consequences of diets with low environmental impact. We analyzed differences in the dietary composition (types of food, macro- and micro-nutrients) of those diets with high and low environmental impact, according to greenhouse gas emission and resources use (water, land and energy) using data from a Spanish cohort (17,387 participants), collected by means of a validated food frequency questionnaire. Cox analyses were used to assess the association of dietary environmental impact with total mortality risk. At a given level of energy intake, diets with lower environmental impact contained higher amounts of plant-based foods and lower levels of animal-derived products. Less polluting diets involved higher amounts of polyunsaturated fats and dietary fiber and lower amounts of saturated fats and sodium. However, diets associated with less environmental damage also contained more added sugars, but lower levels of vitamin B12, zinc and calcium. We did not detect any association between dietary environmental impact and risk of mortality. Diets should not only produce minimal environmental impact, but the maximum overall benefits for all key dimensions encompassed in sustainable diets.

A 14-Item Mediterranean Diet Adherence Screener (MEDAS) questionnaire was developed and validated in face-to-face interviews, but not via telephone. The aims of this study were to evaluate the validity and reliability of a telephone-administered version of the MEDAS as well as to validate the Portuguese version of the MEDAS questionnaire. A convenience community-based sample of adults (n = 224) participated in a three-stage survey. First, trained researchers administered MEDAS via a telephone. Second, the Portuguese version of Food Frequency Questionnaire (FFQ), and MEDAS were administered in a semi-structured face-to-face interview. Finally, MEDAS was again administered via telephone. The telephone-administered MEDAS questionnaire was compared with the face-to-face-version using several metrics. The telephone-administered MEDAS was significantly correlated with the face-to-face-administered MEDAS [r = 0.805, p < 0.001; interclass correlation coefficient (ICC) = 0.803, p < 0.001] and showed strong agreement (k = 0.60). The MEDAS scores that were obtained in the first and second telephone interviews were significantly correlated (r = 0.661, p < 0.001; ICC = 0.639, p < 0.001). The overall agreement between the Portuguese version of MEDAS and the FFQ-derived Mediterranean diet adherence score had a Cohen’s k = 0.39. The telephone-administered version of MEDAS is a valid tool for assessing the adherence to the Mediterranean diet and acquiring data for large population-based studies.

Background: We assessed the still unclear effect of the overall alcohol-drinking pattern, beyond the amount of alcohol consumed, on the incidence of cardiovascular clinical disease (CVD). Methods: We followed 14,651 participants during up to 14 years. We built a score assessing simultaneously seven dimensions of alcohol consumption to capture the conformity to a traditional Mediterranean alcohol-drinking pattern (MADP). It positively scored moderate alcohol intake, alcohol intake spread out over the week, low spirit consumption, preference for wine, red wine consumption, wine consumed during meals and avoidance of binge drinking. Results: During 142,177 person-years of follow-up, 127 incident cases of CVD (myocardial infarction, stroke or cardiovascular mortality) were identified. Compared with the category of better conformity with the MADP, the low-adherence group exhibited a non-significantly higher risk (HR) of total CVD ((95% CI) = 1.55 (0.58–4.16)). This direct association with a departure from the traditional MADP was even stronger for cardiovascular mortality (HR (95% CI) = 3.35 (0.77–14.5)). Nevertheless, all these associations were statistically non-significant. Conclusion: Better conformity with the MADP seemed to be associated with lower cardiovascular risk in most point estimates; however, no significant results were found and more powered studies are needed to clarify the role of the MADP on CVD.

Strong observational evidence supports the association between obesity and cardiovascular events. In elderly high-risk subjects, the Mediterranean diet (MedDiet) was reported to counteract the adverse cardiovascular effects of adiposity. Whether this same attenuation is also present in younger subjects is not known. We prospectively examined the association between obesity and cardiovascular clinical events (myocardial infarction, stroke or cardiovascular death) after 10.9 years follow-up in 19,065 middle-aged men and women (average age 38 year) according to their adherence to the MedDiet (

The role of alcohol on fertility remains unclear. We aimed to investigate the association between alcohol and specific alcoholic beverages consumption and the risk of difficulty getting pregnant. We used a case-control study nested within the Seguimiento Universidad de Navarra (SUN) cohort, a prospective, dynamic and multipurpose cohort of 21,705 Spanish university graduates, followed biennially with mailed questionnaires. We identified 686 case-control pairs, matched for age and time in the cohort. Cases were women reporting difficulty getting pregnant. Controls did not consult due to difficulty conceiving and had at least one child during follow-up. After adjustment for potential confounders, we found no association between self-reported difficulty getting pregnant and the number of alcoholic beverages consumed per week, (Odds Ratio [OR] > 5 drinks/week vs. none = 1.04, 95% Confidence Interval [CI] = 0.72–1.51). No association between types of alcoholic beverage and difficulty conceiving (OR > 5 drinks of wine/week vs. none = 1.16, 95% CI = 0.72–1.88; OR > 5 drinks of beer/week vs. none = 1.06, 95% CI = 0.82–1.37; OR > 5 drinks of spirits/week vs. none = 1.24, 95% CI = 0.84–1.64) was observed. In conclusion, we found no association between alcohol intake and risk of consulting a physician due to difficulty conceiving. More studies are needed to clearly elucidate the effects of alcohol intake on women’s fertility. In the meantime, recommendations about alcohol intake to couples trying to conceive have to be given cautiously.

Previous studies have reported an association between a more pro-inflammatory diet profile and various chronic metabolic diseases. The Dietary Inflammatory Index (DII) was used to assess the inflammatory potential of nutrients and foods in the context of a dietary pattern. We prospectively examined the association between the DII and the incidence of cardiovascular disease (CVD: myocardial infarction, stroke or cardiovascular death) in the PREDIMED (Prevención con Dieta Mediterránea) study including 7216 high-risk participants. The DII was computed based on a validated 137-item food frequency questionnaire. Multivariate-adjusted hazard ratios (HR) and 95% confidence intervals of CVD risk were computed across quartiles of the DII where the lowest (most anti-inflammatory) quartile is the referent. Risk increased across the quartiles (i.e., with increasing inflammatory potential): HRquartile2 = 1.42 (95%CI = 0.97–2.09); HRquartile3 = 1.85 (1.27–2.71); and HRquartile4 = 1.73 (1.15–2.60). When fit as continuous the multiple-adjusted hazard ratio for each additional standard deviation of the DII was 1.22 (1.06–1.40). Our results provide direct prospective evidence that a pro-inflammatory diet is associated with a higher risk of cardiovascular clinical events.

BackgroundThe 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 ResultsWe designed a case‐cohort study nested within the PREDIMED (Prevention With Mediterranean Diet) trial, including 229 incident CVD cases and 751 randomly selected participants at baseline, followed up for 4.8 years. We used liquid chromatography–tandem mass spectrometry to measure, at baseline and at 1 year of follow‐up, plasma concentrations of 5 metabolites in the choline pathway: trimethylamine N‐oxide, betaine, choline, phosphocholine, and α‐glycerophosphocholine. We have calculated a choline metabolite score using a weighted sum of these 5 metabolites. We used weighted Cox regression models to estimate CVD risk. The multivariable hazard ratios (95% confidence intervals) per 1‐SD increase in choline and α‐glycerophosphocholine metabolites were 1.24 (1.05–1.46) and 1.24 (1.03–1.50), respectively. The baseline betaine/choline ratio was inversely associated with CVD. The baseline choline metabolite score was associated with a 2.21‐fold higher risk of CVD across extreme quartiles (95% confidence interval, 1.36–3.59; P

BackgroundMetabolomics is a promising tool of cardiovascular biomarker discovery. We systematically reviewed the literature on comprehensive metabolomic profiling in association with incident cardiovascular disease (CVD). Methods and ResultsWe searched MEDLINE and EMBASE from inception to January 2016. Studies were eligible if they pertained to adult humans; followed an agnostic and/or comprehensive approach; used serum or plasma (not urine or other biospecimens); conducted metabolite profiling at baseline in the context of examining prospective disease; and included myocardial infarction, stroke, and/or CVD death in the CVD outcome definition. We identified 12 original articles (9 cohort and 3 nested case‐control studies); participant numbers ranged from 67 to 7256. Mass spectrometry was the predominant analytical method. The number and chemical diversity of metabolites were very heterogeneous, ranging from 31 to >10 000 features. Four studies used untargeted profiling. Different types of metabolites were associated with CVD risk: acylcarnitines, dicarboxylacylcarnitines, and several amino acids and lipid classes. Only tiny improvements in CVD prediction beyond traditional risk factors were observed using these metabolites (C index improvement ranged from 0.006 to 0.05). ConclusionsThere are a limited number of longitudinal studies assessing associations between comprehensive metabolomic profiles and CVD risk. Quantitatively synthesizing the literature is challenging because of the widely varying analytical tools and the diversity of methodological and statistical approaches. Although some results are promising, more research is needed, notably standardization of metabolomic techniques and statistical approaches. Replication and combinations of novel and holistic methodological approaches would move the field toward the realization of its promise.

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 CVD events, the primary PREDIMED end point, were an aggregate of myocardial infarction, stroke, and cardiovascular death. Multivariate‐adjusted Cox regression was used to calculate hazard ratios for major CVD events and effect modification from the Mediterranean diet intervention across risk strata (low, moderate, high, very high). The Framingham‐REGICOR classification of PREDIMED participants was 25.1% low risk, 44.5% moderate risk, and 30.4% high or very high risk. During 6‐year follow‐up, 188 major CVD events occurred. Hazard ratios for major CVD events increased in parallel with estimated risk (2.68, 4.24, and 6.60 for moderate, high, and very high risk), particularly in men (7.60, 13.16, and 15.85, respectively, versus 2.16, 2.28, and 3.51, respectively, in women). Yet among those with low or moderate risk, 32.2% and 74.3% of major CVD events occurred in men and women, respectively. Mediterranean diet adherence was associated with CVD risk reduction regardless of risk strata (P>0.4 for interaction). Conclusions Incident CVD increased in parallel with estimated risk in the PREDIMED cohort, but most events occurred in non–high‐risk categories, particularly in women. Until predictive tools are improved, promotion of the Mediterranean diet might be useful to reduce CVD independent of baseline risk. Clinical Trial Registration URL: http://www.Controlled-trials.com. Unique identifier: ISRCTN35739639.

Living in a geographically higher altitude affects oxygen availability. The possible connection between environmental factors and the development of metabolic syndrome (MetS) feature is not fully understood, being the available epidemiological evidence still very limited. The aim of the present study was to evaluate the longitudinal association between altitude and incidence of MetS and each of its components in a prospective Spanish cohort, The Seguimiento Universidad de Navarra (SUN) project. Our study included 6860 highly educated subjects (university graduates) free from any MetS criteria at baseline. The altitude of residence was imputed with the postal code of each individual subject residence according to the data of the Spanish National Cartographic Institute and participants were categorized into tertiles. MetS was defined according to the harmonized definition. Cox proportional hazards models were used to assess the association between the altitude of residence and the risk of MetS during follow-up. After a median follow-up period of 10 years, 462 incident cases of MetS were identified. When adjusting for potential confounders, subjects in the highest category of altitude (>456 m) exhibited a significantly lower risk of developing MetS compared to those in the lowest tertile (

The Mediterranean diet is considered as the foremost dietary regimen and its adoption is associated with the prevention of degenerative diseases and an extended longevity. The preeminent features of the Mediterranean diet have been agreed upon and the consumption of olive oil stands out as the most peculiar one. Indeed, the use of olive oil as the nearly exclusive dietary fat is what mostly characterizes the Mediterranean area. Plenty of epidemiological studies have correlated that the consumption of olive oil was associated with better overall health. Indeed, extra virgin olive oil contains (poly)phenolic compounds that are being actively investigated for their purported biological and pharma-nutritional properties. On 18 and 19 May 2018, several experts convened in Jaen (Spain) to discuss the most recent research on the benefits of olive oil and its components. We reported a summary of that meeting (reviewing several topics related to olive oil, not limited to health) and concluded that substantial evidence is accruing to support the widespread opinion that extra virgin olive oil should, indeed, be the fat of choice when it comes to human health and sustainable agronomy.

Chrysohoou et al. fifteen years ago, showed in an elegant analysis nested within the ATTICAstudy [1] that a dietary score reflecting adherence to the traditional Mediterranean diet (MedDiet) wasinversely associated with plasma biomarkers of low-grade inflammation [...]

Our purpose was to study the relationship of adherence to the Mediterranean diet (MedDiet) with urinary factors that favor the formation of renal calcium and uric acid stones in overweight and obese participants who had metabolic syndrome. This cross-sectional study examined 267 participants. A well-known MedDiet score (range 0−9) was calculated for each patient, and patients were then categorized has having low (≤3), medium (4−5), or high (≥6) adherence to the MedDiet. Baseline characteristics and urinary parameters were also analyzed. High calcium salt urinary crystallization risk (CaUCR) and high uric acid urinary crystallization risk (UrUCR) were calculated from urinary parameters using pre-defined criteria. More than half of patients with MedDiet scores ≤3 had high UrUCR (55.4%) and high CaUCR (53.8%). In contrast, fewer patients with high adherence (≥6) to the MedDiet had high UrUCR (41.2%) and high CaUCR (29.4%). Relative to those with low adherence, individuals with high adherence had a prevalence ratio (PR) of 0.77 for a high UrUCR (95% CI: 0.46−1.12; p for trend: 0.069) and a PR of 0.51 for a high CaUCR (95% CI: 0.26−0.87; p for trend: 0.012) after adjusting for age, sex, body mass index, type 2 diabetes, and total energy intake. Our findings indicate that greater adherence to the MedDiet was associated with a reduced CaUCR and a reduced UrUCR. This suggests that adequate dietary management using the MedDiet patterns may prevent or reduce the incidence and recurrence of calcium salt and uric acid renal stones.

Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (≥50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56−0.64), 0.78 (95% CI 0.75−0.81) and 0.52 (95% CI 0.49−0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.

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 adequacy on the prevention of non-communicable diseases, health policies should focus on the promotion of a healthy varied diet, specifically promoting the intake of vegetables and fruit among population groups with lower DDS such as men, smokers or widow(er)s.

The aim of the study was to evaluate sleep duration and sleep variability in relation to serum uric acid (SUA) concentrations and SUA to creatinine ratio. This is a cross-sectional analysis of baseline data from 1842 elderly participants with overweight/obesity and metabolic syndrome in the (Prevención con Dieta Mediterránea) PREDIMED-Plus trial. Accelerometry-derived sleep duration and sleep variability were measured. Linear regression models were fitted to examine the aforementioned associations. A 1 hour/night increment in sleep duration was inversely associated with SUA concentrations (β = −0.07, p = 0.047). Further adjustment for leukocytes attenuated this association (p = 0.050). Each 1-hour increment in sleep duration was inversely associated with SUA to creatinine ratio (β = −0.15, p = 0.001). The findings of this study suggest that longer sleep duration is associated with lower SUA concentrations and lower SUA to creatinine ratio.

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

A moderately high-fat Mediterranean diet does not promote weight gain. This study aimed to investigate the association between dietary intake of specific types of fat and obesity and body weight. A prospective cohort study was performed using data of 6942 participants in the PREDIMED trial, with yearly repeated validated food-frequency questionnaires, and anthropometric outcomes (median follow-up: 4.8 years). The effects of replacing dietary fat subtypes for one another, proteins or carbohydrates were estimated using generalized estimating equations substitution models. Replacement of 5% energy from saturated fatty acids (SFA) with monounsaturated fatty acids (MUFA) or polyunsaturated fatty acids (PUFA) resulted in weight changes of −0.38 kg (95% Confidece Iinterval (CI): −0.69, −0.07), and −0.51 kg (95% CI: −0.81, −0.20), respectively. Replacing proteins with MUFA or PUFA decreased the odds of becoming obese. Estimates for the daily substitution of one portion of red meat with white meat, oily fish or white fish showed weight changes up to −0.87 kg. Increasing the intake of unsaturated fatty acids at the expense of SFA, proteins, and carbohydrates showed beneficial effects on body weight and obesity. It may therefore be desirable to encourage high-quality fat diets like the Mediterranean diet instead of restricting total fat intake.

Objectives: Our aim was to investigate the association between sleeping hours at night and during the siesta and the incidence of obesity in a Mediterranean cohort. Methods: After a median of 6.5 years of follow-up, we included 10,532 or 9,470 participants without chronic disease or obesity at baseline for analyzing the association between the incidence of obesity and nocturnal sleep duration or having siesta. Sleeping hours and siesta were assessed at baseline. Weight was recorded at baseline and every 2 years during the follow-up. The outcome was the incidence of obesity during follow-up among participants with initial BMI 2. Results: During follow-up we observed 446 new cases of obesity in the analysis of nocturnal sleep duration. Sleeping less than 5 h at night was associated with a higher risk of becoming obese compared to sleeping between 7 and Conclusion: Our results suggest that short nocturnal sleep duration could be a modifiable risk factor for obesity. It is possible that this association may be stronger among men and subjects who experienced previous weight gain. Additionally, siesta might be a novel and independent protective factor for obesity; however, confirmatory studies are needed.