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Background: Choline and betaine intakes have been related to cardiovascular health. Objectives: We aimed to explore the relation between 1-y changes in dietary intake of choline or betaine and 1-y changes in cardiometabolic and renal function traits within the frame of the PREDIMED (PREvención con DIeta MEDiterránea)-Plus trial. Methods: We used baseline and 1-y follow-up data from 5613 participants (48.2% female and 51.8% male; mean ± SD age: 65.01 ± 4.91 y) to assess cardiometabolic traits, and 3367 participants to assess renal function, of the Spanish PREDIMEDPlus trial. Participants met ≥3 criteria of metabolic syndrome and had overweight or obesity [BMI (in kg/m2) ≥27 and ≤40]. These criteria were similar to those of the PREDIMED parent study. Dietary intakes of choline and betaine were estimated from the FFQ. Results: The greatest 1-y increase in dietary choline or betaine intake (quartile 4) was associated with improved serum glucose concentrations (−3.39 and −2.72 mg/dL for choline and betaine, respectively) and HbA1c levels (−0.10% for quartile 4 of either choline or betaine intake increase). Other significant changes associated with the greatest increase in choline or betaine intake were reduced body weight (−2.93 and −2.78 kg, respectively), BMI (−1.05 and −0.99, respectively), waist circumference (−3.37 and −3.26 cm, respectively), total cholesterol (−4.74 and −4.52 mg/dL, respectively), and LDL cholesterol (−4.30 and −4.16 mg/dL, respectively). Urine creatinine was reduced in quartile 4 of 1-y increase in choline or betaine intake (−5.42 and −5.74 mg/dL, respectively). Conclusions: Increases in dietary choline or betaine intakes were longitudinally related to improvements in cardiometabolic parameters. Markers of renal function were also slightly improved, and they require further investigation. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870. Am J Clin Nutr 2022;116:1565–1579., Ministerio de Ciencia e Innovacion through Proyectos de I+D+i "Retos Investigacion" RTI2018-095569-B-I00 Ministerio de Ciencia e Innovacion through Programacion Conjunta Internacional PCI2018-093009, European Research Council (ERC) European Commission 20142019 340918, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473, A Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441, The Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus", Recercaixa grant 2013ACUP00194, ICREA (Catalan Institution for Research and Advanced Studies) under the ICREA Academia program SEMERGEN grant, Government of Navarra Department of Health 61/2015, Fundacio La Marato de TV3 grant 201630.10, AstraZeneca T2D 2017, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/2017/017, Balearic Islands Government 35/2011, Spanish Ministerio de Ciencia e Innovacion y Ministerio de Universidades Spanish State Research Agency Juan de la Cierva Program FJC2018-038168-I

Introduction and objectives Quantification of cardiovascular risk has been based on scores such as Framingham, Framingham-REGICOR, SCORE or Life's Simple 7 (LS7). In vitro, animal, and randomized clinical studies have shown that polyphenols may provide benefits to the vascular system and reduce the inflammatory response. However, some clinical-epidemiological studies have yielded inconsistent results. Our aim was to assess the possible association between intake of the various polyphenol classes and established cardiovascular scores. Methods This cross-sectional analysis involved 6633 PREDIMED-Plus study participants. Food polyphenol content was estimated by a semiquantitative food frequency questionnaire , adjusted for total energy intake according to the residual method. The association between polyphenol intake and cardiovascular risk was tested using linear regression analyses. Results Total polyphenol and flavonoid intake were directly and significantly associated only with the LS7 scale. Intake of lignans was directly and significantly associated with SCORE and LS7 scales, stilbene intake with SCORE, and phenolic acid intake with Framingham and Framingham-REGICOR scores. Other polyphenol classes were associated in a protective and significant manner in Framingham, SCORE and LS7 scores. In women, intake of all the polyphenol classes, except phenolic acids, showed a protective trend in the results of the Framingham, Framingham-REGICOR scores and LS7 scale. Conclusions An inverse association was found between consumption of the ‘other polyphenols’ class and, especially among women, with estimated cardiovascular risk. The results were similar to those of Framingham, Framingham-REGICOR and LS7 (after eliminating the diet component) and differed from those of SCORE, but the predictors included were limited in the latter case.

Resumen Objetivos Conocer el grado de control optimo simultaneo de la diabetes (DM), hipertension arterial (HTA) e hipercolesterolemia y determinar los factores asociados. Material y metodos Estudio descriptivo transversal en pacientes diabeticos de 18 o mas de edad, seleccionados consecutivamente en consultas de medicina de familia (MF). Los datos de los pacientes se obtuvieron mediante acceso a la historia informatizada, registrandose variables clinicas y analiticas de interes. Se considero buen control metabolico una HbA1c Resultados Se incluyo a 1.420 pacientes (55,8% varones), con una edad media (DE) de 70,6 (10,8) anos. El 75,9% eran hipertensos y el 69,1% dislipemicos. Los valores de HbA1c fueron de 6,9 (1,2) %, PA sistolica 135,0 (16,8) mmHg, PA diastolica 75,9 (10,6) mmHg y LDL-colesterol 93,7 (32,8) mg/dL. El buen control metabolico de la DM se alcanzo en el 63% (intervalo de confianza [IC] 95%: 60,4-65,5), el buen control de la HTA en el 42,6% (IC 95%: 40,0-45,2) y el buen control de colesterol LDL en el 61,1% (IC 95%: 58,4-63,7) de los pacientes. El buen control de los tres factores de riesgo cardiovascular (FRCV) simultaneamente se alcanzo en el 16,1% (IC 95%: 14,2-18,1). Se observo una asociacion positiva e independiente (p Conclusiones Los resultados de nuestro estudio indican que una proporcion pequena, menos de dos de cada 10 pacientes cumplen los objetivos de buen control recomendados por las guias de practica clinica. Encontramos diferencias importantes entre pacientes con y sin enfermedad cardiovascular.

Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and East Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions, and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Cross-tissue analyses indicated that over a third of effector genes most likely act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis, and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.

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

The aim of this study is to analyze the current evidence about the relationships between calcium/vitamin D and CRC based on case–control studies according to sex, tumor location and continental region to complement the information obtained in meta-analyses of other designs. The articles were located in three databases (PUBMED, EMBASE and SCOPUS), they should be written in English language, with a case and control design and published between 1 January 1970 and 31 October 2019. There were 37 selected studies, 32 for intake of calcium, that involved 24,353 CRC cases and 30,650 controls, and 23 for that of VIT D, with a total of 19,076 cases and 36.746 controls included. For dietary calcium intake, the overall OR was 0.94 (95% CI 0.92–0.97), suggesting a reducing effect with a 6% decrease in CRC risk for every 300 mg of calcium ingested daily. Regarding vitamin D intake a global OR of 0.96 (95% CI 0.93–0.98) was observed, what means a 4% decrease in the risk of CRC per 100 IU/day of vitamin D. Higher dietary intakes of calcium and vitamin D are associated to a decreased risk of CRC.

In this novel research a hybrid algorithm is presented, one capable of selecting a set of features that makes it possible to identify individuals who are healthy and those who suffer from prostate cancer. In this research the selection of features is carried out by means of evolutionary algorithms. In previous works, algorithms of this nature have proven their ability to find solutions for optimization problems in a wide range of fields. The present research proposes a novel hybrid algorithm based on genetic algorithms and support vector machines have been developed in order to find the best variables subset for classifying individuals. The results obtained show how well the method performs in comparison to other methodologies. Cases and controls belong to the study MCC-Spain.

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article.

Background: Non-alcoholic fatty liver disease (NAFLD) includes a spectrum of liver alterations that can result in severe disease and even death. Consumption of ultra-processed foods (UPF) has been associated with obesity and related comorbidities. However, the link between UPF and NAFLD has not been sufficiently assessed. We aimed to investigate the prospective association between UPF consumption and liver health biomarkers. Methods: We followed for 1 year 5867 older participants with overweight/obesity and metabolic syndrome (MetS) from the PREDIMED-Plus trial. A validated 143-item semi-quantitative food frequency questionnaire was used to evaluate consumption of UPF at baseline, 6, and 12 months. The degree of processing for foods and beverages (g/day) was established according to the NOVA classification system. The non-invasive fatty liver index (FLI) and hepatic steatosis index (HSI) were used to evaluate liver health at three points in time. The associations between changes in UPF consumption (percentage of total daily dietary intake (g)) and liver biomarkers were assessed using mixed-effects linear models with repeated measurements. Results: In this cohort, UPF consumption at baseline was 8.19% (SD 6.95%) of total daily dietary intake in grams. In multivariable models, each 10% daily increment in UPF consumption in 1 year was associated with significantly greater FLI ( 1.60 points, 95% CI 1.24;1.96 points) and HSI (0.43, 0.29; 0.57) scores (all p-values < 0.001). These associations persisted statistically significant after adjusting for potential dietary confounders and NAFLD risk factors. Conclusions: A higher UPF consumption was associated with higher levels of NAFLD-related biomarkers in older adults with overweight/obesity and MetS., European Research Council (ERC) European Commission 340918, Spanish National Health Institute of Health Carlos III (ISCIII), through CIBEROBN, European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206, Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018 RH-0024-2021, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/2017/017, SEMERGEN grant, Spanish Government IJC2019-042420-I, European Social Fund (ESF), Spanish National Health Institute of Health Carlos III (ISCIII) CPII20/00014 ICREA, The European Regional Development Fund PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 European Commission PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158 PI21/00465, "Fondo de Investigacion para la Salud" (FIS), European Commission PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183

Funding sponsor Funding number Acronym Balearic Islands Health Research Institute, EU-COST 35/2011, CA16112, Fondo de Investigación para la Salud, IDISBA CB12/03, CIBEROBN CB06/03, Margalida Comas DG R+D+I, Ministry of Science, Spain, European Commission 201630.10, EAT2BENICE_H2020_SFS2016, European Research Council 2013–2018, 340918, Generalitat Valenciana PROMETEO/2017/017, Instituto de Salud Carlos III, Funding sponsor Funding number Acronym Balearic Islands Health Research Institute EU-COST 35/2011, CA16112 Fondo de Investigación para la Salud IDISBA CB12/03, CIBEROBN CB06/03 Margalida Comas DG R+D+I Ministry of Science, Spain European Commission See opportunities by EC See opportunities (opens in new window) 201630.10, EAT2BENICE_H2020_SFS2016 EC European Research Council See opportunities by ERC See opportunities (opens in new window) 2013–2018, 340918 ERC Generalitat Valenciana See opportunities by GVA See opportunities (opens in new window) PROMETEO/2017/017 GVA Instituto de Salud Carlos III 2013ACUP00194, PI13/00233, PI13/00272, PI13/00462, PI13/00492, PI13/00673, PI13/00728, PI13/01056, PI13/01090, PI13/01123, PI13/02184, PI14/00618, PI14/00636, PI14/00696, PI14/00728, PI14/00853, PI14/00972, PI14/01206, PI14/01374, PI14/01471, PI14/01722, PI14/01919, PI16/00366, PI16/00381, PI16/00473, PI16/00501, PI16/00533, PI16/00662, PI16/01094, PI16/01120, PI16/01522, PI16/01873, PI17/00215, PI17/00508, PI17/00525, PI17/00532, PI17/00764, PI17/00855, PI17/00926, PI17/01183, PI17/01347, PI17/01441, PI17/01732, PI17/01827, PI19/00017, PI19/00309, PI19/00386, PI19/00576, PI19/00781, PI19/00957, PI19/01032, PI19/01226, PI19/01332, PI19/01560, PI20/00138, PI20/00339, PI20/00456, PI20/00557, PI20/00886, PI20/01158, PI20/01532, PI20/01802, Consejería de Salud y Familias, Junta de Andalucía PI0137/2018, PI0458/2013, PS0358/2016

Resumen Objetivos Conocer la prevalencia de enfermedad renal cronica (ERC) y determinar los factores asociados al deterioro de la funcion renal en poblacion asistida en atencion primaria. Pacientes y metodo Estudio transversal y multicentrico realizado en los pacientes basales del estudio IBERICAN (identificacion de la poblacion espanola de riesgo cardiovascular y renal). Se considero ERC a un filtrado glomerular estimado (FGe) Resultados Se incluyeron 7.895 pacientes (edad media 57,9 ± 14,8 anos; 54,5% mujeres). El 14,4% (IC 95%: 13,6-15,1) presentaba ERC; en hombres un 16,1% (IC 95%: 14,9-17,3) y en mujeres un 12,9% (IC 95%: 11,9-14,0). Se observo un aumento continuo de la prevalencia con la edad (24,8% ≥ 65 anos) y con la agregacion de FRCV. Las variables que mas se asociaron a la probabilidad de padecer ERC fueron hipertrofia ventricular izquierda (OR: 1,95; p Conclusiones Catorce de cada 100 pacientes incluidos en el estudio IBERICAN presenta ERC. La prevalencia de ERC afecta a la cuarta parte de pacientes ≥ 65 anos y aumenta exponencialmente con la agregacion de FRCV.

Objectives To determine the prevalence of chronic kidney disease (CKD) and the factors associated with impaired renal function in the population attended in primary care (PC). Patients and method Cross-sectional and multicentre study carried out in the baseline patients of the IBERICAN study (Identificacion de la poBlacion Espanola de RIesgo CArdiovascular y reNal). CKD was considered with an estimated glomerular filtration (eGF) Results 7895 patients were included (mean age 57.9 ± 14.8 years; 54.5% women). 14.4% (95% CI: 13.6−15.1) had CKD; 16.1% (95% CI: 14.9−17.3) in men and 12.9% (95% CI: 11.9−14.0) in women. A continuous increase of the prevalence was observed with age (24.8% in ≥ 65 years) and with CVFR aggregation. The variables that were most associated with the probability of suffering CKD were left ventricular hypertrophy (OR: 1.95; p Conclusions Fourteen out of every 100 patients included in the IBERICAN study have CKD. The prevalence of CKD affects a quarter of patients ≥ 65 years and increases exponentially with the aggregation of FRCV.

The aim of the study was to examine the association of alcohol consumption patterns (hazardous alcohol use and binge drinking) and the use of emergency services and primary care consultations in university students. An observational, descriptive, cross-sectional study was conducted at eleven Spanish universities collaborating within the uniHcos Project. University students completed an online questionnaire that assessed hazardous alcohol use and binge drinking using the AUDIT questionnaire and evaluated the use of emergency services and primary care. A descriptive analysis of the data was performed, as well as the chi-squared test and Student’s t-test and nonconditional logistic regression models to examine this association. Results: There were 10,167 participants who completed the questionnaire. The prevalence of hazardous alcohol use was 16.9% (95% CI: 16.2–17.6), while the prevalence of binge drinking was 48.8% (95% CI: 47.9–49.8). There were significant differences in the use of emergency services in those surveyed with hazardous alcohol use (p < 0.001) or binge drinking pattern (p < 0.001). However, no significant differences were observed in terms of attendance during primary care visits in individuals with hazardous alcohol use (p = 0.367) or binge drinking pattern (p = 0.755). The current study shows the association between university students with a pattern of hazardous alcohol use or binge drinking and greater use of emergency services. However, no significant association was observed between the said consumption patterns and the use of primary care services., National Drug Plan, Ministry of Health, Social Services, and Equality of Spain 2010|145 2013|034 PI16/01947

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 COUsing a cross-sectional design, the association between the adherence to an energy-reduced Mediterranean Diet (erMedDiet) score and dietary COFood 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 COMore men than women induced higher dietary levels of COThe Mediterranean diet can be environmentally protective since the higher the adherence to the Mediterranean diet, the lower total dietary CO

Background: Helping consumers to improve the nutritional quality of their diet is a key public health action to prevent cardiovascular diseases (CVDs). The modified version of the Food Standard Agency Nutrient Profiling System Dietary Index (FSAm- NPS DI) underpinning the Nutri-Score front-of-pack label has been used in public health strategies to address the deleterious consequences of poor diets. This study aimed to assess the association between the FSAm-NPS DI and some CVD risk factors including body mass index (BMI), waist circumference, plasma glucose levels, triglyceride levels, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, and diastolic and systolic blood pressure. Materials and Methods: Dietary intake was assessed at baseline and after 1 year of follow-up using a 143-item validated semi-quantitative food-frequency questionnaire. Dietary indices based on FSAm-NPS applied at an individual level were computed to characterize the diet quality of 5,921 participants aged 55–75 years with overweight/obesity and metabolic syndrome from the PREDIMED-plus cohort. Associations between the FSAm-NPS DI and CVD risk factors were assessed using linear regression models. Results: Compared to participants with a higher nutritional quality of diet (measured by a lower FSAm-NPS DI at baseline or a decrease in FSAm-NPS DI after 1 year), those participants with a lower nutritional quality of diet (higher FSAm-NPS DI or an increase in score) showed a significant increase in the levels of plasma glucose, triglycerides, diastolic blood pressure, BMI, and waist circumference (b coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90], official Spanish Institutions, European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618, The European Regional Development Fund PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508, Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus, European Research Council (ERC) European Commission 340918, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Center for Forestry Research & Experimentation (CIEF), European Commission, SEMERGEN grant, ICREA under the ICREA Academia program, Agencia de Gestio d'Ajuts Universitaris de Recerca (AGAUR FI) 2021FI_B 00145, Sara Borrell CD21/00045 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522

The following funding bodies contributed to study concept and design, research, and data collection for the PREDIMED-Plus study. The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014-2019; agreement #340918; granted to M.A.M-G.); the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacion para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), and the Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus" (J.S-S.); the Recercaixa (grant number 2013ACUP00194) (J.S-S.). Moreover, J.S-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program; the SEMERGEN grant; Department of Health of the Government of Navarra (61/2015), the Fundacio La Marato de TV (Ref. 201630.10); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (D.R.); grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant; grant of support to research groups 35/2011 (Balearic Islands Government; FEDER funds) (J.A.T.). J.K. was financially supported by the Juan de la Cierva-Incorporacion research grant (IJC2019-042420-I) of the Spanish Ministry of Economy, Industry and Competitiveness and the European Social Funds. The following funding bodies contributed to data preparation and analysis, bibliographic research, and manuscript writing. The METHYL-UP project was supported by the Spanish Ministry of Science and Innovation (RTI2018-095569-B-I00, Programa de Proyectos Orientados a los Retos de la Sociedad "Projects Toward Society Challenges Program"). R.S.-C. acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovacion y Ministerio de Universidades (FJC2018-038168-I). C.M.-P. was financially supported by a joint grant from the Community of Madrid and the European Social Fund (PEJD-2019-POST/SAL-15892). C. C.-M. was financially supported by the Formacion de Personal Investigador (FPI) grant from the Spanish Ministerio de Ciencia, Innovacion y Universidades (PRE2019-087643)., Background: Recent lifestyle changes include increased consumption of highly processed foods (HPF), which has been associated with an increased risk of non-communicable diseases (NCDs). However, nutritional information relies on the estimation of HPF consumption from food-frequency questionnaires (FFQ) that are not explicitly developed for this purpose. We aimed to develop a short screening questionnaire of HPF consumption (sQ-HPF) that integrates criteria from the existing food classification systems. Methods: Data from 4400 participants (48.1% female and 51.9% male, 64.9 ± 4.9 years) of the Spanish PREDIMED-Plus (“PREvention with MEDiterranean DIet”) trial were used for this analysis. Items from the FFQ were classified according to four main food processing-based classification systems (NOVA, IARC, IFIC and UNC). Participants were classified into tertiles of HPF consumption according to each system. Using binomial logistic regression, food groups associated with agreement in the highest tertile for at least two classification systems were chosen as items for the questionnaire. ROC analysis was used to determine cut-off points for the frequency of consumption of each item, from which a score was calculated. Internal consistency of the questionnaire was assessed through exploratory factor analysis (EFA) and Cronbach’s analysis, and agreement with the four classifications was assessed with weighted kappa coefficients. Results: Regression analysis identified 14 food groups (items) associated with high HPF consumption for at least two classification systems. EFA showed that items were representative contributors of a single underlying factor, the “HPF dietary pattern” (factor loadings around 0.2). We constructed a questionnaire asking about the frequency of consumption of those items. The threshold frequency of consumption was selected using ROC analysis. Comparison of the four classification systems and the sQ-HPF showed a fair to high agreement. Significant changes in lifestyle characteristics were detected across tertiles of the sQ-HPF score. Longitudinal changes in HPF consumption were also detected by the sQ-HPF, concordantly with existing classification systems. Conclusions: We developed a practical tool to measure HPF consumption, the sQ-HPF. This may be a valuable instrument to study its relationship with NCDs., European Research Council (ERC) European Commission 340918, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471, Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus", La Caixa Foundation 2013ACUP00194, ICREA, SEMERGEN grant, Department of Health of the Government of Navarra 61/2015, Fundacio La Marato de TV 201630.10, AstraZeneca T2D 2017, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana European Commission General Electric PROMETEO/2017/017, Balearic Islands Government 35/2011, European Commission 35/2011, Juan de la Cierva-Incorporacion research grant of the Spanish Ministry of Economy, Industry and Competitiveness and the European Social Funds IJC2019-042420-I, Spanish Ministry of Science and Innovation (Programa de Proyectos Orientados a los Retos de la Sociedad "Projects Toward Society Challenges Program") RTI2018-095569-B-I00, Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovacion y Ministerio de Universidades FJC2018-038168-I, Comunidad de Madrid, European Social Fund (ESF) PEJD-2019-POST/SAL-15892, Formacion de Personal Investigador (FPI) grant from the Spanish Ministerio de Ciencia, Innovacion y Universidades PRE2019-087643, The Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI19/00309 PI19/01560 PI19/01332, A Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781

Metabolic syndrome (MetS) is one of the most important medical problems around the world. Identification of patient´s singular characteristic could help to reduce the clinical impact and facilitate individualized management. This study aimed to categorize MetS patients using phenotypical and clinical variables habitually collected during health check-ups of individuals considered to have high cardiovascular risk. The selected markers to categorize MetS participants included anthropometric variables as well as clinical data, biochemical parameters and prescribed pharmacological treatment. An exploratory factor analysis was carried out with a subsequent hierarchical cluster analysis using the z-scores from factor analysis. The first step identified three different factors. The first was determined by hypercholesterolemia and associated treatments, the second factor exhibited glycemic disorders and accompanying treatments and the third factor was characterized by hepatic enzymes. Subsequently four clusters of patients were identified, where cluster 1 was characterized by glucose disorders and treatments, cluster 2 presented mild MetS, cluster 3 presented exacerbated levels of hepatic enzymes and cluster 4 highlighted cholesterol and its associated treatments Interestingly, the liver status related cluster was characterized by higher protein consumption and cluster 4 with low polyunsaturated fatty acid intake. This research emphasized the potential clinical relevance of hepatic impairments in addition to MetS traditional characterization for precision and personalized management of MetS patients., European Research Council (ERC) European Commission 340918, official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacio' n para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728, The Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigacio' n para la Salud (FIS) - European Regional Development Fund PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508, Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus", La Caixa Foundation 2013ACUP00194, ICREA under the ICREA Academia program, SEMERGEN grant, Department of Health of the Government of Navarra 61/ 2015, FundacioLa Maratode TV 201630.10, AstraZeneca, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Center for Forestry Research & Experimentation (CIEF), European Commission PROMETEO/ 2017/017, Balearic Islands Government 35/2011, European Commission PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158

The role of uric acid levels in the cardiovascular continuum is not clear. Our objective is to analyze the prevalence of hyperuricemia (HU) and its association with cardiovascular risk factors (CVRF), subclinical target organ damage (sTOD), and cardiovascular diseases (CVD). We evaluated the prevalence of HU in 6.927 patients included in the baseline visit of the IBERICAN study. HU was defined as uric acid levels above 6 mg/dL in women, and 7 mg/dL in men. Using adjusted logistic regression models, the odds ratios were estimated according to CVRF, sTOD, and CVD. The prevalence of HU was 16.3%. The risk of HU was higher in patients with pathological glomerular filtration rate (aOR: 2.92), heart failure (HF) (aOR: 1.91), abdominal obesity (aOR: 1.80), hypertension (HTN) (aOR: 1.65), use of thiazides (aOR: 1.54), left ventricular hypertrophy (LVH) (aOR: 1.36), atrial fibrillation (AFIB) (aOR: 1.29), and albuminuria (aOR: 1.27). On the other hand, being female (aOR: 0.82) showed a reduced risk. The prevalence of HU was higher in men, in patients presenting CVRF such as HTN and abdominal obesity, and with co-existence of LVH, atrial fibrillation (AFIB), HF, and any form of kidney injury. These associations raise the possibility that HU forms part of the early stages of the cardiovascular continuum. This may influence its management in Primary Healthcare because the presence of HU could mean an increased CV risk in the patients.

BACKGROUND: Type 2 diabetes was related with larger cognitive decline. However, other glycemic dysregulations showed inconsistent results. Our aim was to examine longitudinal associations between diabetes/glycemic status and cognitive function in older adults with metabolic syndrome. METHODS: We 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. Participants were categorized by diabetes status (no-diabetes, prediabetes, and 1c) levels were measured and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. RESULTS: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in the GCF (β=-0.11 [95%CI -0.16;-0.06]), processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in the GCF (β=-0.0094 [95%CI -0.0164;-0.0023]), but also between HbA1c levels and changes in the GCF (β=-0.0610 [95%CI -0.0889;-0.0331]), the Mini-Mental test, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. Sulfonylureas, but especially insulin use, were related to cognitive decline.CONCLUSIONS: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function at short-term in a population at high cardiovascular risk.TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 28 May 2014 - Retrospectively registered, http://www.isrctn.com/ISRCTN89898870

LThis work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (six coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014-2019; agreement #340918) granted to MAM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication., Purpose We explored the cross-sectional association between the adherence to three different provegetarian (PVG) food patterns defined as general (gPVG), healthful (hPVG) and unhealthful (uPVG), and the cardiometabolic risk in adults with metabolic syndrome (MetS) of the PREDIMED-Plus randomized intervention study. Methods We performed a cross-sectional analysis of baseline data from 6439 participants of the PREDIMED-Plus randomized intervention study. The gPVG food pattern was built by positively scoring plant foods (vegetables/fruits/legumes/ grains/potatoes/nuts/olive oil) and negatively scoring, animal foods (meat and meat products/animal fats/eggs/fish and seafood/dairy products). The hPVG and uPVG were generated from the gPVG by adding four new food groups (tea and coffee/ fruit juices/sugar-sweetened beverages/sweets and desserts), splitting grains and potatoes and scoring them differently. Multivariable-adjusted robust linear regression using MM-type estimator was used to assess the association between PVG food patterns and the standardized Metabolic Syndrome score (MetS z-score), a composed index that has been previously used to ascertain the cardiometabolic risk, adjusting for potential confounders. Results A higher adherence to the gPVG and hPVG was associated with lower cardiometabolic risk in multivariable models. The regression coefficients for 5th vs. 1st quintile were − 0.16 (95% CI: − 0.33 to 0.01) for gPVG (p trend: 0.015), and − 0.23 (95% CI: − 0.41 to − 0.05) for hPVG (p trend: 0.016). In contrast, a higher adherence to the uPVG was associated with higher cardiometabolic risk, 0.21 (95% CI: 0.04 to 0.38) (p trend: 0.019). Conclusion Higher adherence to gPVG and hPVG food patterns was generally associated with lower cardiovascular risk, whereas higher adherence to uPVG was associated to higher cardiovascular risk., official Spanish Institutions, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), European Commission PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374, The European Regional Development Fund PI14/00972 PI14/00728 PI14/01471 PI16/00473 PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215, European Commission PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, European Research Council (ERC), European Commission 340918, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana European Commission PROMETEO/2017/017, SEMERGEN grant

This study evaluates a population-based screening of asymptomatic people, using a rapid antigen diagnostic test (RADT), in areas of high transmission. To detect sources of SARS-CoV-2 infection, nasopharyngeal samples were taken and were tested using RADT. Confirmatory RT-qPCR tests were performed in both positive and negative cases. The internal validity of the RADT, the prevalence of infection, and the positive and negative predictive values (PPV and NPV) were estimated, based on the percentages of confirmed cases with 95% confidence interval.. Of the 157,920 people registered, 50,492 participated in the screening, 50,052 were negative, and 440 were positive on the RADT (0.87%). A total of 221 positive RADT samples were reanalysed using RT-qPCR and 214 were confirmed as positive (96.8%, 95% CI: 93.5–98.7%), while 657 out of 660 negative RADT samples were confirmed as RT-qPCR negative (99.5%, 95% CI 98.7–99.9%). The sensitivity obtained was 65.1% (38.4–90.2%) and the specificity was 99.97% (99.94–99.99%). The prevalence of infection was 1.30% (0.95–2.13%). The PPVs were 95.4% (85.9–98.9%) and 97.9% (93.3–99.5%), respectively, while the NPVs were 99.7% (99.4–100%) and 99.2% (98.7–100%), respectively. The high specificity found allow us to report a high screening performance in asymptomatic patients, even in areas where the prevalence of infection was less than 2%.

Background The prevalence of overweight/obesity and related manifestations such as metabolic syndrome (MetS) is increasing worldwide. High energy density diets, usually with low nutrient density, are among the main causes. Some high-quality dietary patterns like the Mediterranean diet (MedDiet) have been linked to the prevention and better control of MetS. However, it is needed to show that nutritional interventions promoting the MedDiet are able to improve nutrient intake. Objective To assess the effect of improving MedDiet adherence on nutrient density after 1 year of follow-up at the PREDIMED-Plus trial. Methods We assessed 5777 men (55-75 years) and women (60-75 years) with overweight or obesity and MetS at baseline from the PREDIMED-Plus trial. Dietary changes and MedDiet adherence were evaluated at baseline and after 1 year. The primary outcome was the change in nutrient density (measured as nutrient intake per 1000 kcal). Multivariable-adjusted linear regression models were fitted to analyse longitudinal changes in adherence to the MedDiet and concurrent changes in nutrient density. Results During 1-year follow-up, participants showed improvements in nutrient density for all micronutrients assessed. The density of carbohydrates (- 9.0%), saturated fatty acids (- 10.4%) and total energy intake (- 6.3%) decreased. These changes were more pronounced in the subset of participants with higher improvements in MedDiet adherence. Conclusions The PREDIMED-Plus dietary intervention, based on MedDiet recommendations for older adults, maybe a feasible strategy to improve nutrient density in Spanish population at high risk of cardiovascular disease with overweight or obesity.

The PREDIMED-Plus trial was supported by the European Research Council (Advanced Research grant 2014–2019; agreement #340918; granted to M.Á.M.-G.); the official Spanish institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN) and Instituto de Salud Carlos III (ISCIII) through the Fondo de Investigación para la Salud (FIS) which is co-funded by the European Regional Development Fund (coordinated FIS projects led by J.S-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332), and the Especial Action Project “Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus” (J.S.-S.); the Recercaixa (grant number 2013ACUP00194) (J.S.-S.). Moreover, J.S-S. gratefully acknowledges the financial support by ICREA under the ICREA Academia program; the SEMERGEN grant; Department of Health of the Government of Navarra (61/2015), the Fundació La Marató de TV (Ref. 201630.10); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (D.R.); grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016; PI0137/2018), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant; grant of support to research groups 35/2011 (Balearic Islands Government; FEDER funds) (J.A.T.). R.S.-C. acknowledges financial support from the Juan de la Cierva Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-038168- I). N.B.-T. acknowledges financial support from the Juan de la Cierva Formación Program Training Grants of the Spanish State Research Agency of the Spanish Ministerio de Ciencia e Innovación y Ministerio de Universidades (FJC2018-036016-I). M.R.B.-L. was supported by “Miguel Servet Type I” program (CP15/00028) from the ISCIII-Madrid (Spain), cofinanced by the Fondo Europeo de Desarrollo Regional-FEDER. S.K.N. acknowledges financial support from the Canadian Institute for Health Research, CIHR Fellowship. J.K. was supported by the ‘FOLIUM’ programme within the FUTURMed project from the Fundación Instituto de Investigación Sanitaria Illes Balears (financed by 2017 annual plan of the sustainable tourism tax and at 50% with charge to the ESF Operational Program 2014–2020 of the Balearic Islands. C.M.-P. was financially supported by a joint grant from the Community of Madrid and the European Social Fund (grant PEJD-2019- POST/SAL-15892). The METHYL-UP project was supported by the Spanish Ministry of Science and Innovation (RTI2018-095569-B-I00, Programa de Proyectos Orientados a los Retos de la Sociedad “Projects Toward Society Challenges Program”)., The association between ultra-processed food (UPF) and risk of cardiometabolic disorders is an ongoing concern. Different food processing-based classification systems have originated discrepancies in the conclusions among studies. To test whether the association between UPF consumption and cardiometabolic markers changes with the classification system, we used baseline data from 5636 participants (48.5% female and 51.5% male, mean age 65.1 4.9) of the PREDIMEDPlus (“PREvention with MEDiterranean DIet”) trial. Subjects presented with overweight or obesity and met at least three metabolic syndrome (MetS) criteria. Food consumption was classified using a 143-item food frequency questionnaire according to four food processing-based classifications: NOVA, International Agency for Research on Cancer (IARC), International Food Information Council (IFIC) and University of North Carolina (UNC). Mean changes in nutritional and cardiometabolic markers were assessed according to quintiles of UPF consumption for each system. The association between UPF consumption and cardiometabolic markers was assessed using linear regression analysis. The concordance of the different classifications was assessed with intra-class correlation coefficients (ICC3, overall = 0.51). The highest UPF consumption was obtained with the IARC classification (45.9%) and the lowest with NOVA (7.9%). Subjects with high UPF consumption showed a poor dietary profile. We detected a direct association between UPF consumption and BMI (p = 0.001) when using the NOVA system, and with systolic (p = 0.018) and diastolic (p = 0.042) blood pressure when using the UNC system. Food classification methodologies markedly influenced the association between UPF consumption and cardiometabolic risk markers., European Research Council (ERC) European Commission #340918, Centro de Investigacion Biomedica en Red-Fisiopatologia de la Obesidad y Nutricion PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441 PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471 PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332

We thank all the volunteers for the participation and personnel for the contribution in the PREDIMED-Plus trial. CIBEROBN, CIBERESP and CIBERDEM are initiatives of ISCIII, Madrid, Spain. The authors also thank the PREDIMED-Plus Biobank Network as a part of the National Biobank Platform of the ISCIII for storing and managing the PREDIMED-Plus biological samples. This work was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS), which is co-funded by the European Regional Development Fund (five coordinated FIS projects leaded by JS-S and JVi, including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926, PI19/00957, PI19/00386, PI19/00309, PI19/01032, PI19/00576, PI19/00017, PI19/01226, PI19/00781, PI19/01560, PI19/01332, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, PI20/01158); the Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus Grant to JS-S; the European Research Council (Advanced Research Grant 2014-2019; Agreement #340918) granted to MaM-G.; the Recercaixa (Number 2013ACUP00194) grant to JS-S; grants from the Consejeria de Salud de la Junta de Andalucia (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 grant from the Generalitat Valenciana; the SEMERGEN grant; funds from the European Regional Development Fund (CB06/03); International Nut & Dried Fruit Council - FESNAD (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease 2014 -2015, No. 201302) (PI: MaM-G); the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 (PI: DR); grant of support to research groups no. 35/2011 (Balearic Islands Gov.; FEDER funds) (JAT and CB); the JR17/00022 (ISCIII) grant to OC; the Boosting young talent call grant program for the development of IISPV research projects 2019-2021 (Ref.: 2019/IISPV/03 grant to AD-L); the Societat Catalana d'Endocrinologia i Nutricio (SCEN) Clinical-Research Grant 2019 (IPs: JS-S and AD-L). Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 supported by CIBEROBN entitled: Lifestyle Interventions and Chronic Kidney Disease: Inflammation, Oxidative Stress and Metabolomic Profile (LIKIDI study) grant to AD-L. IP-G receives a grant from the Spanish Ministry of Education, Culture and Sports (FPU17/01925). Jordi Salas-Salvado, the senior author of this work, gratefully acknowledges the financial support by ICREA under the ICREA Academia programme. None of the funding sources took part in the design, collection, analysis, interpretation of the data, or writing the report, or in the decision to submit the manuscript for publication., It remains unclear whether caffeinated beverages could have deleterious renal effects in elderly population with underlying comorbid conditions. We investigated the associations between coffee, tea, or caffeine intake and 1-year changes in glomerular filtration rate (eGFR) in a large Spanish cohort of overweight/obese elderly with metabolic syndrome (MetS). This prospective analysis includes 5851 overweight/obese adults (55-75 years) with MetS from the PREDIMED-Plus study. We assessed coffee, tea, and caffeine consumption from a validated food-frequency questionnaire and creatinine-based eGFR using the Chronic Kidney Disease Epidemiology Collaboration equation. Multivariate-adjusted regression models were applied to test associations between baseline coffee, tea, or caffeine intake and 1-year eGFR changes. Caffeinated coffee (> 2 cups/day) and tea (at least 1 cup/day) drinkers had 0.88 and 0.93 mL/min/1.73 m(2) greater eGFR decrease respectively, compared to those with less than 1 cup/day of coffee consumption or non-tea drinkers. Furthermore, caffeinated coffee consumption of > 2 cups/day was associated with 1.19-fold increased risk of rapid eGFR decline > 3 mL/min/1.73 m(2) (95% CI 1.01-1.41). Similarly, individuals in the highest (median, 51.2 mg/day) tertile of caffeine intake had a 0.87 mL/min/1.73 m(2) greater eGFR decrease. Decaffeinated coffee was not associated with eGFR changes. In conclusion, higher consumption of caffeinated coffee, tea, and caffeine was associated with a greater 1-year eGFR decline in overweight/obese adults with MetS., CIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/00728 PI14/01471 PI16/00473, European Research Council (ERC) European Commission 340918, La Caixa Foundation 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana European Commission PROMETEO/2017/017, European Commission CB06/03, International Nut & Dried Fruit Council - FESNAD (Long-term effects of an energy-restricted Mediterranean diet on mortality and cardiovascular disease 2014 -2015) 201302, SEMERGEN grant, AstraZeneca, Balearic Islands Gov.; FEDER funds 35/2011, (ISCIII) grant JR17/00022, Boosting young talent call grant program for the development of IISPV research projects 2019-2021 2019/IISPV/03, Societat Catalana d'Endocrinologia i Nutricio (SCEN) Clinical-Research Grant 2019, Collaborative Nutrition and/or Obesity Project for Young Researchers 2019 - CIBEROBN, Spanish Ministry of Education, Culture and Sports FPU17/01925, ICREA, the Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017 PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158, 'Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund' PI16/00662 PI16/01873 PI16/01094 PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215

Simple Summary We investigated the influence of autophagy-related variants in modulating colorectal cancer (CRC) risk through a meta-analysis of genome-wide association study (GWAS) data from four large European cohorts. We found that genetic variants within the DAPK2 and ATG5 loci were associated with CRC risk. This study also shed some light onto the functional mechanisms behind the observed associations and demonstrated the impact of DAPK2rs11631973 and ATG5rs546456 polymorphisms on the modulation of host immune responses, blood derived-cell counts and serum inflammatory protein levels, which might be involved in promoting cancer development. No effect of the DAPK2 and ATG5 polymorphisms on the autophagy flux was observed, Acknowledgments: We kindly thank all individuals who agreed to participate in the DACHS, CRCGen, CORSA and Czech Republic Colorectal Cancer studies, as well as all cooperating physicians and students. We thank Hugo Sousa for the collection of healthy donors for the autophagy in vitro studies, Data Availability Statement: The genotype data used in the present study are available from the corresponding authors upon reasonable request. Functional data used in this project have been meticulously catalogued and archived in the BBMRI-NL data infrastructure (https://hfgp.bbmri.nl/, accessed on 13 December 2019) using the MOLGENIS open-source platform for scientific data [52]. This allows flexible data querying and download, including sufficiently rich metadata and interfaces for machine processing (R statistics, REST API) and using FAIR principles to optimise findability, accessibility, interoperability and reusability [53,54]., Funding: This work was partially supported by grants from the Instituto de Salud Carlos III (Madrid, Spain; PI12/02688 and PI17/02256). CORSA was funded by the Austrian Research Promotion Agency (FFG) BRIDGE grant (no. 829675, to Andrea Gsur), the “Herzfelder’sche Familienstiftung” (grant to Andrea Gsur). Czech Republic CCS was funded by GACR grants (18–09709S, 19–10543S and 20–03997S), ProgresQ28/1.LF and UNCE/MED/006 grants. This article is based upon work from COST Action CA17118, supported by COST (European Cooperation in Science and Technology). A.K. is a recipient of a Ramalingaswami Re-Retry Faculty Fellowship (Grant; BT/RLF/Re-entry/38/2017) from the Department of Biotechnology (DBT), Government of India (GOI). V.M. received funding from the Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723, the Instituto de Salud Carlos III, co-funded by FEDER funds–a way to build Europe–grants PI14-00613, PI17-00092 and the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE. K.H. was supported by European Union Horizon 2020 grant No. 856620. We thank the CERCA Programme, Generalitat de Catalunya for institutional support., The role of genetic variation in autophagy-related genes in modulating autophagy and cancer is poorly understood. Here, we comprehensively investigated the association of autophagy-related variants with colorectal cancer (CRC) risk and provide new insights about the molecular mechanisms underlying the associations. After meta-analysis of the genome-wide association study (GWAS) data from four independent European cohorts (8006 CRC cases and 7070 controls), two loci, DAPK2 (p = 2.19 × 10−5) and ATG5 (p = 6.28 × 10−4) were associated with the risk of CRC. Mechanistically, the DAPK2rs11631973G allele was associated with IL1 β levels after the stimulation of peripheral blood mononuclear cells (PBMCs) with Staphylococcus aureus (p = 0.002), CD24 + CD38 + CD27 + IgM + B cell levels in blood (p = 0.0038) and serum levels of en-RAGE (p = 0.0068). ATG5rs546456T allele was associated with TNF α and IL1 β levels after the stimulation of PBMCs with LPS (p = 0.0088 and p = 0.0076, respectively), CD14+CD16− cell levels in blood (p = 0.0068) and serum levels of CCL19 and cortisol (p = 0.0052 and p = 0.0074, respectively). Interestingly, no association with autophagy flux was observed. These results suggested an effect of the DAPK2 and ATG5 loci in the pathogenesis of CRC, likely through the modulation of host immune responses., Instituto de Salud Carlos III (Madrid, Spain; PI12/02688 and PI17/02256), CORSA was funded by the Austrian Research Promotion Agency (FFG), BRIDGE grant (no. 829675, to Andrea Gsur), Czech Republic CCS was funded by GACR grants (18–09709S, 19–10543S and 20–03997S), ProgresQ28/1.LF and UNCE/MED/006 grants, COST Action CA17118, supported by COST (European Cooperation in Science and Technology), A.K. is a recipient of a Ramalingaswami Re-Retry Faculty Fellowship (Grant; BT/RLF/Re-entry/38/2017) from the Department of Biotechnology (DBT), Government of India (GOI), Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723, the Instituto de Salud Carlos III, co-funded by FEDER funds–a way to build Europe–grants PI14-00613, PI17-00092 and the Spanish Association Against Cancer (AECC) Scientific Foundation grant GCTRA18022MORE., European Union Horizon 2020 grant No. 856620, CERCA Programme, Generalitat de Catalunya for institutional support

This research was funded by CICYT [AGL2016-75329-R] and CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovación y Universidades, (AEI/FEDER, UE), Generalitat de Catalunya (GC) [2017SGR196]. The PREDIMED-Plus trial was supported by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated Fondo de Investigaciones Sanitarias projects lead by J.S.-S. and J.V., including the following projects: PI13/00673, PI13/00492, PI13/00272, PI13/01123, PI13/00462, PI13/00233, PI13/02184, PI13/00728, PI13/01090, PI13/01056, PI14/01722, PI14/00636, PI14/00618, PI14/00696, PI14/01206, PI14/01919, PI14/00853, PI14/01374, PI14/00972, PI14/00728, PI14/01471, PI16/00473, PI16/00662, PI16/01873, PI16/01094, PI16/00501, PI16/00533, PI16/00381, PI16/00366, PI16/01522, PI16/01120, PI17/00764, PI17/01183, PI17/00855, PI17/01347, PI17/00525, PI17/01827, PI17/00532, PI17/00215, PI17/01441, PI17/00508, PI17/01732, PI17/00926 and PI19/00781), the Especial Action Project entitled Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to J.S.-S., European Research Council (Advanced Research Grant 2014–2019, 340918) to M.Á.M.-G., the Recercaixa grant to J.S.-S. (2013ACUP00194), grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, and PI0137/2018), a grant from the Generalitat Valenciana (PROMETEO/2017/017), a SEMERGEN grant, Fundació la Marató de TV3 (PI044003), 2017 SGR 1717 from Generalitat de Catalunya, a CICYT grant provided by the Ministerio de Ciencia, Innovación y Universidades (AGL2016-75329-R), and funds from the European Regional Development Fund (CB06/03). Food companies Hojiblanca (Lucena, Spain) and Patrimonio Comunal Olivarero (Madrid, Spain) donated extra virgin olive oil, and the Almond Board of California (Modesto, CA, USA), American Pistachio Growers (Fresno, CA, USA), and Paramount Farms (Wonderful Company, LLC, Los Angeles, CA, USA) donated nuts. J.K. was supported by the “FOLIUM” program within the FUTURMed project entitled Talent for the medicine within the future from the Fundació Institut d’Investigació Sanitària Illes Balears. This call was co-financed at 50% with charge to the Operational Program FSE 2014-2020 of the Balearic Islands. This work is partially supported by ICREA under the ICREA Academia programme to J.S-S. M.M.-M. is supported by the FPU17/00513 grant, J.F.R.d.A. is supported by the FAPESP [2019/11324-8, 2013/07914-8] grants, Á.-H. is supported by the [CD17/00122] grant., We thank all the volunteers for their participation in and the personnel for their contribution to the PREDIMED-Plus trial. M.M.-M. would like to thank Dennis Helsel and Emily P. Laveriano-Santos for their valuable help and support with the statistical treatment of the data, the CCiT UB facility for the LC-MS/MS equipment support, Esperanza Muñoz-Cano for the English advice and Carlos Guimerà-Esteve for the graphical abstract design., Carotenoids are pigments contained mainly in fruit and vegetables (F&V) that have beneficial effects on cardiometabolic health. Due to their lipophilic nature, co-ingestion of fat appears to increase their bioavailability via facilitating transfer to the aqueous micellar phase during digestion. However, the extent to which high fat intake may contribute to increased carotenoid plasma concentrations is still unclear. The objective was to examine the degree to which the consumption of different amounts of both carotenoid-rich foods and fats is associated with plasma carotenoid concentrations within a Mediterranean lifestyle context (subsample from the PREDIMED-Plus study baseline) where consumption of F&V and fat is high. The study population was categorized into four groups according to their self-reported consumption of F&V and fat. Carotenoids were extracted from plasma samples and analyzed by HPLC-UV-VIS-QqQ-MS/MS. Carotenoid systemic concentrations were greater in high consumers of F&V than in low consumers of these foods (+3.04 mu mol/L (95% CI: 0.90, 5.17), p-value = 0.005), but circulating concentrations seemed to decrease when total fat intake was very high (-2.69 mu mol/L (-5.54; 0.16), p-value = 0.064). High consumption of F&V is associated with greater systemic levels of total carotenoids, in particular when fat intake is low-to-moderate rather than very high., Consejo Interinstitucional de Ciencia y Tecnologia (CICYT) European Commission AGL2016-75329-R, CIBEROBN from the Instituto de Salud Carlos III, ISCIII from the Ministerio de Ciencia, Innovacion y Universidades, (AEI/FEDER), Generalitat de Catalunya 2017SGR196, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI13/00673 PI13/00492 PI13/00272 PI13/01123 PI13/00462 PI13/00233 PI13/02184 PI13/00728 PI13/01090 PI13/01056 PI14/01722 PI14/00636 PI14/00618 PI14/00696 PI14/01206 PI14/01919 PI14/00853 PI14/01374 PI14/00972 PI14/01471 PI16/00473, Especial Action Project entitled Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, European Research Council (ERC) European Commission 340918, Recercaixa grant 2013ACUP00194, Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018, Generalitat Valenciana European Commission PROMETEO/2017/017, SEMERGEN grant, Fundacio la Marato de TV3 PI044003, Generalitat de Catalunya 2017 SGR 1717, CICYT grant by the Ministerio de Ciencia, Innovacion y Universidades AGL2016-75329-R, European Commission CB06/03, "FOLIUM" program within the FUTURMed project entitled Talent for the medicine within the future from the Fundacio Institut d'Investigacio Sanitaria Illes Balears, ICREA under the ICREA Academia programme, Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) 2019/11324-8 2013/07914-8, the Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) - European Regional Development Fund PI16/00501 PI16/00533 PI16/00381 PI16/00366 PI16/01522 PI16/01120 PI17/00764 PI17/01183 PI17/00855 PI17/01347 PI17/00525 PI17/01827 PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00781 PI14/00728 PI16/00662 PI16/01873 PI16/01094 FPU17/00513 CD17/00122

Background In the last years, evidence that dietary vitamin K could have a role in the cognitive domain has increased. However, data from large trials are limited. The objective of this study was to assess the association of 2 year changes in the dietary intake of vitamin K with cognitive function measured through neuropsychological performance tests. Methods In 5,533 participants of the multicentre PREDIMED-Plus study (48.1% women, age 65.1 ± 4.9 years with overweight/obesity and metabolic syndrome), we assessed the adjusted odds ratios of cognitive function decline according to 2 year changes in vitamin K intake. Participants answered a battery of cognitive function tests and Food Frequency Questionnaires (FFQs) in order to estimate the vitamin K dietary intake. Results After adjusting for potential cofounders, the highest tertile of change of dietary vitamin K intake (median [IQR]; 194.4 μg/d [120.9, 373.1]) was inversely associated with a Mini-Mental State Examination (MMSE) score ≤24 (OR [95% CI]; 0.53 [0.35, 0.79] P for trend = 0.002) compared with a decrease in the intake of vitamin K (median [IQR]; −97.8 μg/d [−292.8, −51.5]). A significant positive association between changes in dietary vitamin K intake and the semantic verbal fluency test scores (OR [95% CI]; 0.69 [0.51, 0.94] P for trend = 0.019) was found. Conclusions An increase of the intake of dietary vitamin K was associated with better cognitive function scores, independently of recognised risk factors for cognitive decline, in an older adult Mediterranean population with high cardiovascular risk.