Morbid liver manifestations are intrinsically bound to metabolic syndrome and nutrient intake based on a machine-learning cluster analysis

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 340918official Spanish institutions for funding scientific biomedical researchCIBER 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 PI14/00728The 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 PI17/00508Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus"La Caixa Foundation 2013ACUP00194ICREA under the ICREA Academia programSEMERGEN grantDepartment of Health of the Government of Navarra 61/ 2015FundacioLa Maratode TV 201630.10AstraZenecaJunta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018Center for Forestry Research & Experimentation (CIEF)European Commission PROMETEO/ 2017/017Balearic Islands Government 35/2011European 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 PI20/0115

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

The aim of the study was to evaluate sleep duration and sleep variability in relation to serum uric acid (SUA) concentrations and SUA to creatinine ratio. This is a cross-sectional analysis of baseline data from 1842 elderly participants with overweight/obesity and metabolic syndrome in the (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.The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (three coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, 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, 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), the Especial Action Project entitled: Implementación y evaluación de una intervención intensives obre la actividad física Cohorte PREDIMED-PLUS grant to Jordi Salas-Salvadó, the European Research Council (Advanced Research Grant 2013–2018; 340918) grant to Miguel Ángel Martínez-Gonzalez, the Recercaixa grant to Jordi Salas-Salvadó (2013ACUP00194), the grant from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016), 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, and FEDER funds (CB06/03). Olga Castaner was granted by the JR17/00022, ISCIII. Christopher Papandreou is supported by a postdoctoral fellowship granted by the Autonomous Government of Catalonia (PERIS 2016–2020 Incorporació de Científics I Tecnòlegs, SLT002/0016/00428). José C. Fernández-García is supported by a research contract from Servicio Andaluz de Salud (SAS) (B-0003-2017). None of the funding sources took part in the design, collection, analysis, or interpretation of the data, or in the decision to submit the manuscript for publication. The corresponding authors had full access to all the data in the study and had final responsibility forsubmitting for publication

Does Consumption of Ultra-Processed Foods Matter for Liver Health? Prospective Analysis among Older Adults with Metabolic Syndrome

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 340918Spanish National Health Institute of Health Carlos III (ISCIII), through CIBEROBNEuropean 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 PI14/01206Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grantLa Caixa Foundation 2013ACUP00194Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018 RH-0024-2021Center for Forestry Research & Experimentation (CIEF)European Commission PROMETEO/2017/017SEMERGEN grantSpanish Government IJC2019-042420-IEuropean Social Fund (ESF)Spanish National Health Institute of Health Carlos III (ISCIII) CPII20/00014 ICREAThe 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 PI17/0118

Circulating carotenoids are associated with favorable lipid and fatty acid profiles in an older population at high cardiovascular risk

Carotenoid intake has been reported to be associated with improved cardiovascular health, but there is little information on actual plasma concentrations of these compounds as biomarkers of cardiometabolic risk. The objective was to investigate the association between circulating plasma carotenoids and different cardiometabolic risk factors and the plasma fatty acid profile. This is a cross-sectional evaluation of baseline data conducted in a subcohort (106 women and 124 men) of an ongoing multi-factorial lifestyle trial for primary cardiovascular prevention. Plasma concentrations of carotenoids were quantified by liquid chromatography coupled to mass spectrometry. The associations between carotenoid concentrations and cardiometabolic risk factors were assessed using regression models adapted for interval-censored variables. Carotenoid concentrations were cross-sectionally inversely associated with serum triglyceride concentrations [-2.79 mg/dl (95% CI: -4.25, -1.34) and -5.15 mg/dl (95% CI: -7.38, -2.93), p-values = 0.0002 and <0.00001 in women and men, respectively], lower levels of plasma saturated fatty acids [-0.09% (95% CI: -0.14, -0.03) and -0.15 % (95% CI: -0.23, -0.08), p-values = 0.001 and 0.0001 in women and men, respectively], and higher levels of plasma polyunsaturated fatty acids [(0.12 % (95% CI: -0.01, 0.25) and 0.39 % (95% CI: 0.19, 0.59), p-values = 0.065 and 0.0001 in women and men, respectively] in the whole population. Plasma carotenoid concentrations were also associated with higher plasma HDL-cholesterol in women [0.47 mg/dl (95% CI: 0.23, 0.72), p-value: 0.0002], and lower fasting plasma glucose in men [-1.35 mg/dl (95% CI: -2.12, -0.59), p-value: 0.001].(AGL2016-75329-R and PID2020- 114022RB-I0) Instituto de Salud Carlos III,Ministerio de Ciencia, Innovación y Universidades, (AEI/FEDER 10.13039/501100011033, UE)Generalitat de Catalunya (GC) (2017SGR196, 2017SGR622)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, PI20/01158European Research Council (Advanced Research Grant 2014–2019; agreement #340918)Recercaixa (number 2013ACUP00194)Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018)PROMETEO/2017/017 grant from the Generalitat ValencianaSEMERGEN grantICREAFPU17/0051

How Did the COVID-19 Lockdown Pandemic Affect the Depression Symptomatology in Mediterranean Older Adults with Metabolic Syndrome?

Background and Aims. To control the COVID-19 spread, in March 2020, a forced home lockdown was established in Spain. In the present study, we aimed to assess the effect of mobility and social COVID-19-established restrictions on depressive symptomatology in older adults with metabolic syndrome. We hypothesize that severe restrictions might have resulted in detrimental changes in depressive symptomatology. Methods. 2,312 PREDIMED-Plus study participants (%; mean years) who completed a COVID-19 lockdown questionnaire to assess the severity of restrictions/lockdown and the validated Spanish version of the Beck Depression Inventory-II (BDI-II) during the three established phases concerning the COVID-19 lockdown in Spain (prelockdown, lockdown, and postlockdown) were included in this longitudinal analysis. Participants were categorized according to high or low lockdown severity. Analyses of covariance were performed to assess changes in depressive symptomatology across lockdown phases. Results. No significant differences in participant depression symptomatology changes were observed between lockdown severity categories (low/high) at the studied phases. During the lockdown phase, participants showed a decrease in BDI-II score compared to the prelockdown phase (mean (95% CI), -0.48 (-0.24, -0.72), ); a nonsignificantly larger decrease was observed in participants allocated in the low-lockdown category (low: -0.59 (-0.95, -0.23), high: -0.43 (-0.67, -0.19)). Similar decreases in depression symptomatology were found for the physical environment dimension. The post- and prelockdown phase BDI-II scores were roughly similar. Conclusions. The COVID-19 pandemic lockdown was associated with a decrease in depressive symptomatology that returned to prelockdown levels after the lockdown. The degree of lockdown was not associated with depressive symptomatology. The potential preventive role of the physical environment and social interactions on mental disorders during forced home lockdown should be further studied. This trial is registered with ISRCTN89898870. Retrospectively registered on 24 July 2014.European Union (EU) 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 PI14/01471European Research Council (ERC) 340918La Caixa Foundation 2013ACUP00194Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018 MFE-171207Department of Health of the Junta de AndaluciaICREACIBER Fisiopatologia de la Obesidad y Nutricion (CIBEROBN)MICIN/AEI/FEDER, UEInstituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion para la Salud (FIS) SLT006/17/00246Especial Action Project entitled: Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus CEX2021-001234-MGeneralitat de CatalunyaFundacion Francisco Soria Melguiz

Integrative development of a short screening questionnaire of highly processed food consumption (sQ-HPF)

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 340918CIBER 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 PI14/01471Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus"La Caixa Foundation 2013ACUP00194ICREASEMERGEN grantDepartment of Health of the Government of Navarra 61/2015Fundacio La Marato de TV 201630.10AstraZeneca T2D 2017Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018Generalitat Valenciana European Commission General Electric PROMETEO/2017/017Balearic Islands Government 35/2011European Commission 35/2011Juan de la Cierva-Incorporacion research grant of the Spanish Ministry of Economy, Industry and Competitiveness and the European Social Funds IJC2019-042420-ISpanish Ministry of Science and Innovation (Programa de Proyectos Orientados a los Retos de la Sociedad "Projects Toward Society Challenges Program") RTI2018-095569-B-I00Juan 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-IComunidad de MadridEuropean Social Fund (ESF) PEJD-2019-POST/SAL-15892Formacion de Personal Investigador (FPI) grant from the Spanish Ministerio de Ciencia, Innovacion y Universidades PRE2019-087643The 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 PI19/01332A 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 PI19/0078

Role of NAFLD on the Health Related QoL Response to Lifestyle in Patients With Metabolic Syndrome: The PREDIMED Plus Cohort

Objective: To evaluate the effect of Non-alcoholic fatty liver disease (NAFLD) status in the impact of lifestyle over Health-related quality of life (HRQoL) in patients with metabolic syndrome (MetS). Methods: Baseline and 1 year follow up data from the PREDIMED-plus cohort (men and women, 55-75 years old with overweight/obesity and MetS) were studied. Adherence to an energy-restricted Mediterranean Diet (er-MeDiet) and Physical Activity (PA) were assessed with a validated screeners. Hepatic steatosis index (HSI) was implemented to evaluate NAFLD while the SF-36 questionnaire provided HRQoL evaluation. Statistical analyses were performed to evaluate the influence of baseline NAFLD on HRQoL as affected by lifestyle during 1 year of follow up. Results: Data from 5205 patients with mean age of 65 years and a 48% of female participants. Adjusted linear multivariate mixed regression models showed that patients with lower probability of NAFLD (HSI < 36 points) were more responsive to er-MeDiet (b 0.64 vs b 0.05 per er-MeDiet adherence point, p< 0.01) and PA (b 0.05 vs b 0.01 per MET-h/week, p = 0.001) than those with high probability for NAFLD in terms Physical SF- 36 summary in the 1 year follow up. 10 points of er-MeDiet adherence and 50 MET-h/ week were thresholds for a beneficial effect of lifestyle on HRQoL physical domain in patients with lower probability of NAFLD. Conclusion: The evaluation of NAFLD by the HSI index in patients with MetS might identify subjects with different prospective sensitivity to lifestyle changes in terms of physical HRQoL (http://www.isrctn.com/ISRCTN89898870).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 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 PI20/01158Special Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus"La Caixa Foundation 2013ACUP00194Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018SEMERGEN grantDepartment of Health of the Government of Navarra 61/201Fundacio La Marato de TV 201630.10European Research Council (ERC) European Commission 340918Ministerio de Ciencia e Investigacion RTI2018-095569-B-I00 PCI2018-093009 35/201

One-year longitudinal association between changes in dietary choline or betaine intake and cardiometabolic variables in the PREvención con DIeta MEDiterránea-Plus (PREDIMED-Plus) trial

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 PCI2018-093009European Research Council (ERC) European Commission 20142019 340918CIBER 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 PI16/00473A 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 PI17/01441The 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 PI20/01158Especial Action Project "Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus"Recercaixa grant 2013ACUP00194ICREA (Catalan Institution for Research and Advanced Studies) under the ICREA Academia program SEMERGEN grantGovernment of Navarra Department of Health 61/2015Fundacio La Marato de TV3 grant 201630.10AstraZeneca T2D 2017Junta de Andalucia PI0458/2013 PS0358/2016 PI0137/2018Center for Forestry Research & Experimentation (CIEF)European Commission PROMETEO/2017/017Balearic Islands Government 35/2011Spanish Ministerio de Ciencia e Innovacion y Ministerio de Universidades Spanish State Research Agency Juan de la Cierva Program FJC2018-038168-

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

Background: Nut consumption has been associated with improved nutrient adequacy and diet quality in healthy adult populations but this association has never been explored in individuals at high cardiovascular risk. Objective: to assess the associations between consumption of nuts and nutrient adequacy and diet quality in a Mediterranean population at high cardiovascular risk. Design: baseline assessment of nutritional adequacy in participants (n = 6060, men and women, with ages 55–75 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.The PREDIMED-Plus trial was supported by the official funding agency for biomedical research of the Spanish government, ISCIII through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund (four coordinated FIS projects led by Jordi Salas-Salvadó and Josep Vidal, 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, 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), the Especial Action Project entitled: Implementación y evaluación de una intervención intensive sobre la actividad física Cohorte PREDIMED-PLUS grant to Jordi Salas-Salvadó, the European Research Council (Advanced Research Grant 2013–2018; 340918) grant to Miguel Ángel Martínez–Gonzalez, the Recercaixa grant to Jordi Salas–Salvadó (2013ACUP00194), the grant from the Consejería de Salud de la Junta de Andalucía (PI0458/2013; PS0358/2016), the PROMETEO/2017/017 grant from the Generalitat Valenciana, the SEMERGEN grant, and CIBEROBN and FEDER funds (CB06/03), ISCIII. Josep A. Tur, Maria del Mar Bibiloni, Alicia Julibert and Cristina Bouzas are granted by Grant of support to research groups no. 35/2011 (Balearic Islands Gov.; FEDER funds) and EU-COST ACTION CA16112. None of the funding sources took part in the design, collection, analysis or interpretation of the data, or in the decision to submit the manuscript for publication

[Fertility in Spain, 1996-2006: foreign versus Spanish women].

OBJECTIVES: To determine fertility trends in Spain and whether women's specific fertility rates differ by age and nationality during the period 1996-2006. METHODS: We performed a population-based, cross-sectional study. Direct standardization was used to compare fertility rates by nationality. Foreign versus Spanish women's fertility rates by age and the period under review were compared by a generalized linear model. The trend by nationality was described by time plots and was analyzed by simple linear regression models. RESULTS: Foreign women had more children (total fertility rate: 2 versus 1.2) and at younger age. The upward trend observed in the fertility of Spanish women (p<0.001) was primarily due to increased fertility in older mothers (35 years and older). The fertility of foreign women aged < or =19 was six times higher than that of Spanish women (rate ratio: 6.00, 95% CI: 2.60-13.86). CONCLUSIONS: The fertility pattern of foreign women differs from that of Spanish women and is mainly characterized by higher fertility, especially in younger women (< or =19 years). This pattern may be associated with social and cultural differences. Prevention and sexual educational policies should be reformulated to take into account the specific sociocultural characteristics of this group and to adapt prevention messages to their cultural context