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The aim of our cross-sectional and longitudinal study is to assess the relationship between daytime and night-time sleep duration and health-related quality of life (HRQoL) in adults with metabolic syndrome after a 1-year healthy lifestyle intervention. Analysis of the data from 2119 Spanish adults aged 55-75 years from the PREDIMED-Plus study was performed. Sleep duration was assessed using a wrist-worn accelerometer. HRQoL was measured using the SF-36 questionnaire. Linear regression models adjusted for socioeconomic and lifestyle factors and morbidity were developed. In cross-sectional analyses, participants with extreme night-time sleep duration categories showed lower physical component summary scores in Models 1 and 2 [β-coefficient (95% confidence interval) <6 h vs. 7-9 h: -2, 3 (-3.8 to -0.8); p = 0.002. >9 h vs. 7-9 h: -1.1 (-2.0 to -0.3); p = 0.01]. Participants who sleep less than 7 h a night and take a nap are associated with higher mental component summary scores [β-coefficient (95% confidence interval) 6.3 (1.3 to 11.3); p = 0.01]. No differences between night-time sleep categories and 12-month changes in HRQoL were observed. In conclusion, in cross-sectional analyses, extremes in nocturnal sleep duration are related to lower physical component summary scores and napping is associated with higher mental component summary scores in older adults who sleep less than 7 h a night.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m 2 , harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (βadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Background: The COVID-19 lockdown represented an immense impact on human health, which was characterized by lifestyle and dietary changes, social distancing and isolation at home. Some evidence suggests that these consequences mainly affected women and altered relevant ongoing clinical trials. The aim of this study was to evaluate the status and changes in diet, physical activity (PA), sleep and self-reported health status (SRH) as perceived by older adult men and women with metabolic syndrome during the COVID-19 lockdown., Methods: We analyzed data from 4681 Spanish adults with metabolic syndrome. We carried out a telephone survey during May and June 2020 to collect information on demographics, dietary habits, PA, sleep, SRH and anthropometric data., Results: The mean age of participants was 64.9 years at recruitment, and 52% of participants were men. Most participants (64.1%) perceived a decrease in their PA during confinement. Regarding gender-specific differences, a higher proportion of women than men perceived a decrease in their PA (67.5% vs. 61.1%), Mediterranean diet adherence (20.9% vs. 16.8%), sleep hours (30.3% vs. 19.1%), sleep quality (31.6% vs. 18.2%) and SRH (25.9% vs. 11.9%) (all p < 0.001)., Conclusions: The COVID-19 lockdown affected women more negatively, particularly their self-reported diet, PA, sleep and health status.

Background : Lifestyles influence atrial fibrillation (AF) risk. Determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods : We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m 2 . Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results : At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5). Conclusions : Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.

Background: Excessive alcohol consumption has been associated with increased risk of atrial fibrillation, although the underlying mechanisms remain unclear. An enlarged left atrium and impaired left atrial function may lead to atrial fibrillation. The association of alcohol consumption with structural and functional left atrial measures, however, has received limited attention., Methods and Results: We studied 503 participants from the PREDIMED-Plus (Prevención con Dieta Mediterránea) trial, a randomized trial testing intensive weight loss intervention with an energy-reduced Mediterranean diet and physical activity promotion in preventing cardiovascular disease in adults with metabolic syndrome. Participants underwent transthoracic echocardiography at baseline, year 3, and year 5 of the study. Outcomes of interest included volume index and reservoir, conduit, and contractile strains of the left atrium. Alcohol consumption was calculated through food frequency questionnaires and presented as drinks consumed per day. Multiple linear regression and mixed models estimated the association of alcohol consumption with left atrial measurements at baseline and through follow-up. Cross-sectionally, higher alcohol consumption (per 1 drink/day increases) was associated with larger left atrial volume (0.65 mL/m 2 [95% CI, 0.18-1.11]) and lower left atrial reservoir and contractile strain (-0.44% [95% CI, -0.87 to -0.01]; and -0.44% [95% CI, -0.75 to -0.14]). Baseline alcohol consumption was not associated with changes in left atrial measurements, but increases in alcohol consumption (per 1 drink/day increase) during follow-up were associated with left atrial enlargement (0.71 mL/m 2 [95% CI, 0.17-1.26])., Conclusions: In a population at high cardiovascular risk, increased alcohol consumption was associated with left atrial enlargement and worsening atrial function., Registration: URL: http://www.controlled-trials.com; Unique identifier: ISRCTN89898870.

Background: Endocrine disruptors (EDs) have emerged as potential contributors to the development of type-2 diabetes. Perfluorooctane sulfonate (PFOS), is one of these EDs linked with chronic diseases and gathered attention due to its widespread in food., Objective: To assess at baseline and after 1-year of follow-up associations between estimated dietary intake (DI) of PFOS, and glucose homeostasis parameters and body-mass-index (BMI) in a senior population of 4600 non-diabetic participants from the PREDIMED-plus study., Methods: Multivariable linear regression models were conducted to assess associations between baseline PFOS-DI at lower bound (LB) and upper bound (UB) established by the EFSA, glucose homeostasis parameters and BMI., Results: Compared to those in the lowest tertile, participants in the highest tertile of baseline PFOS-DI in LB and UB showed higher levels of HbA1c [β-coefficient(CI)] [0.01 %(0.002 to 0.026), and [0.06 mg/dL(0.026 to 0.087), both p-trend ≤ 0.001], and fasting plasma glucose in the LB PFOS-DI [1.05 mg/dL(0.050 to 2.046),p-trend = 0.022]. Prospectively, a positive association between LB of PFOS-DI and BMI [0.06 kg/m 2 (0.014 to 0.106) per 1-SD increment of energy-adjusted PFOS-DI was shown. Participants in the top tertile showed an increase in HOMA-IR [0.06(0.016 to 0.097), p-trend = 0.005] compared to participants in the reference tertile after 1-year of follow-up., Discussion: This is the first study to explore the association between DI of PFOS and glucose homeostasis. In this study, a high baseline DI of PFOS was associated with a higher levels of fasting plasma glucose and HbA1c and with an increase in HOMA-IR and BMI after 1-year of follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: To evaluate the effect of an intensive lifestyle intervention (ILI) on the structural and functional cardiac substrate of atrial fibrillation (AF) in overweight or obese people with metabolic syndrome (Mets)., Methods and Results: Participants of the PREvención con DIeta MEDiterranea-Plus trial (n = 6874) were randomized 1:1 to an ILI programme based on an energy-reduced Mediterranean diet, increased physical activity, and cognitive-behavioural weight management or to a control intervention of low-intensity dietary advice. A core echocardiography lab evaluated left atrial (LA) strain, function, and volumes in 534 participants at baseline, 3-year, and 5-year follow-ups. Mixed models were used to evaluate the effect of the ILI on LA structure and function. In the subsample, the baseline mean age was 65 years [standard deviation (SD) 5 years], and 40% of the participants were women. The mean weight change after 5 years was -3.9 kg (SD 5.3 kg) in the ILI group and -0.3 kg (SD 5.1 kg) in the control group. Over the 5-year period, both groups experienced a worsening of LA structure and function, with increases in LA volumes and stiffness index and decreases in LA longitudinal strain, LA function index, and LA emptying fraction over time. Changes in the ILI and control groups were not significantly different for any of the primary outcomes {LA emptying fraction: -0.95% [95% confidence interval (CI) -0.93, -0.98] in the control group, -0.97% [95% CI -0.94, -1.00] in the ILI group, Pbetween groups = 0.80; LA longitudinal strain: 0.82% [95% CI 0.79, 0.85] in the control group, 0.85% [95% CI 0.82, 0.89] in the ILI group, Pbetween groups = 0.24} or any of the secondary outcomes., Conclusion: In overweight or obese people with Mets, an ILI had no impact on the underlying structural and functional LA substrate measurements associated with AF risk., Competing Interests: Conflict of interest: Dr Salas-Salvadó reported receiving personal fees from Instituto Danone Spain as a member of the advisory board, fees or travel expenses for meeting attendant from Danone Institute International and International Nut and Dried Fruit Foundation; and grants from the International Nut and Dried Fruit Foundation grant to his institution and is an unpaid member of the advisory board outside the submitted work., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The coronavirus disease 2019 (COVID-19) has serious physiological and psychological consequences. The long-term (>12 weeks post-infection) impact of COVID-19 on mental health, specifically in older adults, is unclear. We longitudinally assessed the association of COVID-19 with depression symptomatology in community-dwelling older adults with metabolic syndrome within the framework of the PREDIMED-Plus cohort., Methods: Participants ( n = 5486) aged 55-75 years were included in this longitudinal cohort. COVID-19 status (positive/negative) determined by tests (e.g. polymerase chain reaction severe acute respiratory syndrome coronavirus 2, IgG) was confirmed via event adjudication (410 cases). Pre- and post-COVID-19 depressive symptomatology was ascertained from annual assessments conducted using a validated 21-item Spanish Beck Depression Inventory-II (BDI-II). Multivariable linear and logistic regression models assessed the association between COVID-19 and depression symptomatology., Results: COVID-19 in older adults was associated with higher post-COVID-19 BDI-II scores measured at a median (interquartile range) of 29 (15-40) weeks post-infection [fully adjusted β = 0.65 points, 95% confidence interval (CI) 0.15-1.15; p = 0.011]. This association was particularly prominent in women ( β = 1.38 points, 95% CI 0.44-2.33, p = 0.004). COVID-19 was associated with 62% increased odds of elevated depression risk (BDI-II ≥ 14) post-COVID-19 when adjusted for confounders (odds ratio; 95% CI 1.13-2.30, p = 0.008)., Conclusions: COVID-19 was associated with long-term depression risk in older adults with overweight/obesity and metabolic syndrome, particularly in women. Thus, long-term evaluations of the impact of COVID-19 on mental health and preventive public health initiatives are warranted in older adults.

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

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

Background: Cross-sectionally, older age and obesity are associated with increased coronavirus disease-2019 (COVID-19) risk. We assessed the longitudinal associations of baseline and changes in adiposity parameters with COVID-19 incidence in older adults at high cardiovascular risk., Methods: This analysis included 6874 men and women (aged 55-75 years) with overweight/obesity and metabolic syndrome in the PREDIMED-Plus lifestyle intervention trial for cardiovascular risk reduction. Body weight, body-mass-index (BMI), waist circumference, waist-to-height ratio (WHtR), and a body shape index (ABSI) were measured at baseline and annual follow-up visits. COVID-19 was ascertained by an independent Event Committee until 31 December 2021. Cox regression models were fitted to evaluate the risk of COVID-19 incidence based on baseline adiposity parameters measured 5-6 years before the pandemic and their changes at the visit prior to censoring., Results: At the time of censoring, 653 incident COVID-19 cases occurred. Higher baseline body weight, BMI, waist circumference, and WHtR were associated with increased COVID-19 risk. During the follow-up, every unit increase in body weight (HR adj (95%CI): 1.01 (1.00, 1.03)) and BMI (HR adj : 1.04 (1.003, 1.08)) was associated with increased COVID-19 risk., Conclusions: In older adults with overweight/obesity, clinically significant weight loss may protect against COVID-19., Trial Registration: This study is registered at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870 )., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Evidence supports associations of lifestyle (including diet and physical activity) and weight with cognitive functioning, but the pathways responsible for these associations have not been fully elucidated. Because healthier lifestyles have been associated with better left atrial structure and function, which in turn is associated with better cognitive functioning, we tested the hypothesis that left atrial structure and function is a potential mediator of the association between lifestyle and cognition. We included 476 participants classed as overweight or obese with metabolic syndrome from three centers in Spain. These participants underwent lifestyle assessments and transthoracic echocardiography at baseline and repeated measurements of the Trail Making A test, a measure of executive function, taken at baseline and at the two-year follow-up. We conducted mediation analyses to test if measures of left atrial structure and function mediated associations between adherence to the Mediterranean diet scores, physical activity, and weight at baseline, as well as a two-year change in Trail Making A scores. The analysis did not find an association between these factors and Trail Making A scores, and no indirect effects appeared to be mediated by echocardiographic measurements. The modest sample size in this analysis is a limitation, and larger studies should be conducted to determine potential cardiovascular factors mediating the association between lifestyle and cognition.

Background: Dietary patterns can produce an environmental impact. Changes in people's diet, such as the increased consumption of ultra-processed food (UPF) can not only influence human health but also environment sustainability., Objectives: Assessment of the impact of 2-year changes in UPF consumption on greenhouse gas emissions and water, energy and land use., Design: A 2-year longitudinal study after a dietary intervention including 5879 participants from a Southern European population between the ages of 55-75 years with metabolic syndrome., Methods: Food intake was assessed using a validated 143-item food frequency questionnaire, which allowed classifying foods according to the NOVA system. In addition, sociodemographic data, Mediterranean diet adherence, and physical activity were obtained from validated questionnaires. Greenhouse gas emissions, water, energy and land use were calculated by means of the Agribalyse® 3.0.1 database of environmental impact indicators for food items. Changes in UPF consumption during a 2-year period were analyzed. Statistical analyses were conducted using computed General Linear Models., Results: Participants with major reductions in their UPF consumption reduced their impact by -0.6 kg of CO 2 eq and -5.3 MJ of energy. Water use was the only factor that increased as the percentage of UPF was reduced., Conclusions: Low consumption of ultra-processed foods may contribute to environmental sustainability. The processing level of the consumed food should be considered not only for nutritional advice on health but also for environmental protection., Trial Registration: ISRCTN, ISRCTN89898870. Registered 05 September 2013, http://www.isrctn.com/ISRCTN89898870., Competing Interests: Declaration of competing interest This work 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 (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: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to JS-S; the European Research Council (Advanced Research Grant 2014–2019; agreement #340918) granted to MÁM-G.; the Recercaixa (number 2013ACUP00194) grant to JS-S; grants from the Consejería de Salud de la Junta de Andalucía (PI0458/2013, PS0358/2016, PI0137/2018); the PROMETEO/2017/017 and the AICO/2021/347 grants from the Generalitat Valenciana; the SEMERGEN grant. J.S-S is partially supported by ICREA under the ICREA Academia programme. C.B. was granted by Juan de la Cierva grant. P.M.G. was granted by the Specialist Postdoctoral program of the Consejería de Salud y Familias, Junta de Andalucía (Spain). 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. J.S.-S. reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Eroski Foundation and Instituto Danone, receiving nonfinancial support from Hojiblanca, Patrimonio Comunal Olivarero, the California Almond Board of California, Pistachio Growers and Borges S.A; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and personal fees from Instituto Danone Spain; Serving in the Board of Danone Institute International. D.C. reported receiving grants from Instituto de Salud Carlos III. R.E. reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Meditarránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. The rest of the authors have declared that no competing interests exist. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Tree nuts and peanuts (henceforth, nuts) are nutrient-dense foods rich in neuroprotective components; thus, their consumption could benefit cognitive health. However, evidence to date is limited and inconsistent regarding the potential benefits of nuts for cognitive function., Objective: To prospectively evaluate the association between nut consumption and 2-y changes in cognitive performance in older adults at cognitive decline risk., Methods: A total of 6,630 participants aged 55 to 75 y (mean age 65.0±4.9 y, 48.4% women) with overweight/obesity and metabolic syndrome completed a validated semi-quantitative food frequency questionnaire and a comprehensive battery of neuropsychological tests at baseline and a 2-y follow-up. Composite cognitive scores were used to assess global, general, attention, and executive function domains. Nut consumption was categorized as <1, ≥1 to <3, ≥3 to <7, and ≥7 servings/wk (1 serving=30 g). Multivariable-adjusted linear regression models were fitted to assess associations between baseline nut consumption and 2-y cognitive changes., Results: Nut consumption was positively associated with 2-y changes in general cognitive function (P-trend <0.001). Compared with participants consuming <1 serving/wk of nuts, those categorized as consuming ≥3 to <7 and ≥7 servings/wk showed more favorable changes in general cognitive performance (β z-score [95% CI] = 0.06 [0.00,0.12] and 0.13 [0.06,0.20], respectively). No significant changes were observed in the multivariable-adjusted models for other cognitive domains assessed., Conclusion: Frequent nut consumption was associated with a smaller decline in general cognitive performance over 2 y in older adults at risk of cognitive decline. Randomized clinical trials to verify our findings are warranted., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: A major barrier to a healthy diet may be the higher price of healthy foods compared to low-quality foods., Objectives: This study aimed to assess the association between the monetary cost of food and diet quality in Spanish older adults at high risk of cardiovascular disease., Methods: Cross-sectional analysis was carried out in Spanish older adults ( n = 6,838; 48.6% female). A validated food frequency questionnaire was used to assess dietary intake. Metabolic syndrome severity, adherence to the Mediterranean diet (MedDiet), adherence to a provegetarian dietary pattern, and dietary inflammatory index were assessed. The economic cost of the foods was obtained from the Spanish Ministry of Agriculture Fisheries and Food database (2015-2017, the period of time when the participants were recruited). The total cost of diet adjusted per 1,000 kcal was computed., Results: The healthier dietary pattern was associated with a higher cost of the diet. Higher adherence to the MedDiet, anti-inflammatory diet, and the healthy version of the provegetarian dietary pattern were related to higher costs of the diet., Conclusion: Higher diet quality was associated with a higher dietary cost of the diet per 1,000 kcal/day. Food prices can be an important component of interventions and policies aimed at improving people's diets and preventing diet-related chronic diseases., Clinical Trial Registry Number: The trial was registered in 2014 at the International Standard Randomized Controlled Trial (ISRCT; http://www.isrctn.com/ISRCTN89898870) with the number 89898870., Competing Interests: JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from Patrimonio Comunal Olivarero, Spain and Borges SA, Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation, Instituto Danone, Spain, and Abbot Laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer MM-A declared a shared affiliation with the author BR-G to the handling editor at the time of review., (Copyright © 2023 Bouzas, Pastor, García, Monserrat-Mesquida, Martínez-González, Salas-Salvadó, Corella, Schröder, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, Lopez-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Riquelme-Gallego, Romero-Secin, Pintó, Gaforio, Matía, Vidal, Zapatero, Daimiel, Ros, García-Arellano, Babio, Gonzalez-Monje, Castañer, Abete, Tojal-Sierra, Benavente-Marín, Signes-Pastor, Konieczna, García-Ríos, Castro-Barquero, Fernández-García, Santos-Lozano, Bes-Rastrollo, Mestres, Guillem-Saiz, Goday, Goicolea-Güemez, Puig-Aguiló, Ruiz-Canela, Palau-Galindo, Fitó and Tur.)

Background and Aims: The association between changes in ultra-processed food (UPF) consumption and cardiometabolic risk (CMR) factors remains understudied. We evaluated the association between changes in UPF consumption over 12 months of follow-up and changes in CMR factors in adults diagnosed with metabolic syndrome., Methods: We analysed data from 5373 adults (aged 55-75 years) participating in the PREDIMED-Plus trial. Diet was evaluated at baseline, 6- and 12-month visits using a validated food frequency questionnaire, and UPF consumption (in grams/day and percentage of total daily dietary intake in grams) was categorized based on NOVA classification. We used mixed-effects linear models with repeated measurements at baseline, 6 and 12 months of follow-up to assess the associations between changes in UPF consumption and changes in CMR factors adjusting for sociodemographic and lifestyles variables., Results: In multivariable-adjusted models, when comparing the highest versus the lowest quartile of UPF consumption, positive associations were found for several CMR factors: weight (kg, β = 1.09; 95% confidence interval 0.91 to 1.26); BMI (kg/m 2 , β = 0.39; 0.33 to 0.46); waist circumference (cm, β = 1.03; 0.81 to 1.26); diastolic blood pressure (mm Hg, β = 0.67; 0.29 to 1.06); fasting blood glucose (mg/dl, β = 1.66; 0.61 to 2.70); HbA1c (%, β = 0.04; 0.01 to 0.07); triglycerides (mg/dl, β = 6.79; 3.66 to 9.91) and triglycerides and glucose index (β = 0.06; 0.04 to 0.08)., Conclusions: Higher UPF consumption was associated with adverse evolution in objectively measured CMR factors after 12 months of follow-up in adults with metabolic syndrome. Further research is needed to explore whether these changes persist for longer periods., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The principal source of exposure to Polychlorinated dibenzo-p-dioxins and polychlorinated dibenzo-p-furans (PCDD/Fs) in humans comes from food intake. PCDD/Fs, are a family of potential endocrine disruptors and have been associated with different chronic diseases such as diabetes and hypertension. However, studies assessing the relationship between dietary exposure to PCDD/Fs and adiposity or obesity status in a middle-aged population are limited., Objective: To assess cross-sectionally and longitudinally the associations between estimated dietary intake (DI) of PCDD/Fs and body mass index (BMI), waist circumference, and the prevalence/incidence of obesity and abdominal obesity in a middle-aged population., Methods: In 5899 participants aged 55-75 years (48% women) living with overweight/obesity from the PREDIMED-plus cohort, PCDD/Fs DI was estimated using a 143-item validated food-frequency questionnaire, and the levels of food PCDD/F expressed as Toxic Equivalents (TEQ). Consequently, cross-sectional and prospective associations between baseline PCDD/Fs DI (in pgTEQ/week) and adiposity or obesity status were assessed at baseline and after 1-year follow-up using multivariable cox, logistic or linear regression models., Results: Compared to participants in the first PCDD/F DI tertile, those in the highest tertile presented a higher BMI (β-coefficient [confidence interval]) (0.43kg/m2 [0.22; 0.64]; P-trend <0.001), a higher waist circumference (1.11 cm [0.55; 1.66]; P-trend <0.001), and a higher prevalence of obesity and abdominal obesity (1.05 [1.01; 1.09] and 1.02 [1.00; 1.03]; P-trend = 0.09 and 0.027, respectively). In the prospective analysis, participants in the top PCDD/F DI baseline tertile showed an increase in waist circumference compared with those in the first tertile after 1-year of follow-up (β-coefficient 0.37 cm [0.06; 0.70]; P-trend = 0.015)., Conclusion: Higher DI of PCDD/Fs was positively associated with adiposity parameters and obesity status at baseline and with changes in waist circumference after 1-year of follow-up in subjects living with overweight/obesity. Further large prospective studies using a different population with longer follow-up periods are warranted in the future to strengthen our results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To assess the comparative effects of glucagon-like peptide-1 receptor agonists (GLP-1RA), 4-dipeptidyl peptidase inhibitors (DPP-4I), and metformin treatment during one year on metabolic syndrome (MetS) components and severity in MetS patients., Methods: Prospective study (n = 6165 adults) within the frame of PREDIMED-Plus trial. The major end-point was changes on MetS components and severity after one- year treatment of GLP-1RA, DPP-4I, and metformin. Anthropometric measurements (weight, height and waist circumference), body mass index (BM), and blood pressure were registered. Blood samples were collected after overnight fasting. Plasma glucose, glycosylated hemoglobin (HbA1c), plasma triglycerides and cholesterol were measured. Dietary intakes as well as physical activity were assessed through validated questionnaires., Results: MetS parameters improved through time. The treated groups improved glycaemia compared with untreated (glycaemia ∆ untreated: -1.7 mg/dL(± 13.5); ∆ metformin: - 2.5(± 23.9) mg/dL; ∆ DPP-4I: - 4.5(± 42.6); mg/dL ∆ GLP-1RA: - 4.3(± 50.9) mg/dL; and HbA1c: ∆ untreated: 0.0(± 0.3) %; ∆ metformin: - 0.1(± 0.7) %; ∆ DPP-4I: - 0.1(± 1.0) %; ∆ GLP-1RA: - 0.2(± 1.2) %. Participants decreased BMI and waist circumference. GLP-1RA and DPP-4I participants registered the lowest decrease in BMI (∆ untreated: -0.8(± 1.6) kg/m 2 ; ∆ metformin: - 0.8(± 1.5) kg/m 2 ; ∆ DPP-4I: - 0.6(± 1.3) kg/m 2 ; ∆ GLP-1RA: - 0.5(± 1.2) kg/m 2 . and their waist circumference (∆ untreated: -2.8(± 5.2) cm; ∆ metformin: - 2.6(± 15.2) cm; ∆ DPP-4I: - 2.1(± 4.8) cm; ∆ GLP-1RA: - 2.4(± 4.1) cm., Conclusion: In patients with MetS and healthy lifestyle intervention, those treated with GLP-1RA and DPP-4I obtained better glycemic profile. Anthropometric improvements were modest., Competing Interests: Conflict of interest statement JS-S reports serving on the board of and receiving grant support through his institution from the International Nut and Dried Fruit Council, and Eroski Foundation. Reports serving in the Executive Committee of the Instituto Danone Spain and on the Scientific Committee of the Danone International Institute. He has received research support from Patrimonio Comunal Olivarero, Spain; and Borges S.A., Spain. Reports receiving consulting fees or travel expenses from Danone; Eroski Foundation, Instituto Danone - Spain, and Abbot Laboratories., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: The COVID-19 pandemic has affected the implementation of most ongoing clinical trials worldwide including the PREDIMED-Plus study. The PREDIMED-Plus is an ongoing, multicenter, controlled intervention trial, aimed at weight-loss and cardiovascular disease prevention, in which participants were randomized (1:1 ratio) to an intervention group (energy-reduced Mediterranean diet, promotion of physical activity, and behavioral support) or to a control group (Mediterranean diet with usual care advice). When the pandemic began, the trial was in the midst of the planned intervention. The objective of this report was to examine the effects of the pandemic on the delivery of the intervention and to describe the strategies established to mitigate the possible adverse effects of the pandemic lockdown on data collection and adiposity., Methods: We assessed the integrity of the PREDIMED-Plus trial during 5 identified periods of the COVID-19 pandemic determined according to restrictions dictated by the Spanish government authorities. A standardized questionnaire was delivered to each of the 23 PREDIMED-Plus recruiting centers to collected data regarding the trial integrity. The effect of the restrictions on intervention components (diet, physical activity) was evaluated with data obtained in the three identified lockdown phases: pre lockdown, lockdown proper, and post lockdown., Results: During the lockdown (March/2020-June/2021), 4,612 participants (48% women, mean age 65y) attended pre-specified yearly follow-up visits to receive lifestyle recommendations and obtain adiposity measures. The overall mean (SD) of the proportions reported by each center showed that 40.4% (25.4) participants had in-person visits, 39.8% (18.2) participants were contacted by telephone and 35% (26.3) by electronic means. Participants' follow-up and data collection rates increased across lockdown periods (from ≈10% at onset to ≈80% at the end). Compared to pre-lockdown, waist circumference increased during (0.75 cm [95% CI: 0.60-0.91]) and after (0.72 cm [95% CI: 0.56-0.89]) lockdown. Body weight did not change during lockdown (0.01 kg [95% CI: -0.10 to 0.13) and decreased after lockdown (-0.17 kg [95% CI: -0.30 to -0.04])., Conclusion: Mitigating strategies to enforce the intervention and patient's follow-up during lockdown have been successful in preserving the integrity of the trial and ensuring its continuation, with minor effects on adiposity., Clinical Trial Registration: https://doi.org/10.1186/ISRCTN89898870, identifier ISRCTN89898870., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Paz-Graniel, Fitó, Ros, Buil-Cosiales, Corella, Babio, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Vázquez, Daimiel, García-Gavilán, Toledo, Nishi, Sorlí, Castañer, García-Ríos, García de la Hera, Barón-López, Ruiz-Canela, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Fernández-García, Vázquez-Ruiz, Fernández-Carrión, Goday, Peña-Orihuela, Compañ-Gabucio, Schröder, Martínez-Gonzalez and Salas-Salvadó.)

Background: It has been proposed that physical activity (PA) could prevent cognitive decline., Objective: To evaluate the association between changes in PA and changes in cognitive function in a cohort of adults with metabolic syndrome., Methods: Longitudinal observational study including 5,500 adults (mean age 65 years, SD = 5; women = 49.3% ) with metabolic syndrome. Participants underwent physical activity measurements and cognitive evaluation at baseline and at two-years of follow-up. PA was quantified using the Minnesota questionnaire-shortened version. Cognitive function was evaluated using a battery of tests: Mini-Mental Test Examination, Clock Drawing Test, Trail Making Test A and B, Verbal Fluency Test, and Digit Span. The primary outcome was two-year change in cognition, measured through the Global Composite Score (GCS) of all neuropsychological tests. Multivariable-adjusted linear regression models were fitted with baseline PA and their changes as the main exposures and changes in cognitive function as the outcome., Results: No significant association was found between PA levels (or their changes) in the GCS of cognitive function. A greater increase in PA levels was associated with a more favorable two-year change in the Trail Making Test A (Q4 versus Q1: b = - 2.24s, 95% CI -4.36 to -0.12s; p-trend = 0.020). No significant association was found for other neuropsychological test., Conclusion: Our results do not support an association between increases in PA and the evolution of the global cognitive function at two-year in an intervention trial which included PA promotion in one of its two randomized arms, but they suggested a possible beneficial effect of PA on attentional function in older adults.

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 PREDIMED-Plus 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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Atrial fibrillation has been associated with cognitive impairment. Whether subclinical abnormalities in atrial function and substrate predisposing to atrial fibrillation impact cognitive function has received limited attention. We tested associations of echocardiographic markers of atrial structure and function with cognitive function and decrease in 510 participants with obesity and metabolic syndrome (mean age SD of 64.4 [5.2] years in men and 66.5 [3.9] years in women). Left atrial (LA) markers (volume index, emptying fraction, strain, function index, and stiffness index) were estimated based on transthoracic echocardiography. General cognitive functioning (Mini-mental state examination), verbal ability (verbal fluency test), memory and attention (Digit Span Tests), and processing speed and executive function (Trail-Making Tests A and B) were assessed at baseline and at 2-year follow-up. Multiple linear regression was used to test associations of atrial markers (modeled in SD units) with baseline and 2-year changes in cognitive scores adjusted for demographic and health covariates. LA structure and function were not associated with cognitive function at baseline. Larger LA volume index (standardized β [95% confidence interval] -0.13 [-0.22 to -0.03]), lower peak longitudinal strain (-0.11 [-0.20 to -0.01]), and higher stiffness index (-0.18 [-0.28 to -0.08]) were associated with 2-year worsening in Trail-Making Test A. Strain measurements were also associated with a 2-year change in the Controlled Oral Word Association Test. In conclusion, overall, adverse markers of LA structure and function were associated with 2-year detrimental executive function-related cognitive changes in a sample of participants at high risk for cardiovascular disease, highlighting LA substrate as a potential risk factor for cognitive decrease and dementia., Competing Interests: Disclosures Drs. Ines Gonzalez Casanova and Alvaro Alonso declare financial support from National Heart Lung and Blood Institute. The remaining authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background Dietary polyphenol intake has been associated with a decreased risk of hyperuricemia, but most of this knowledge comes from preclinical studies. The aim of the present study was to assess the association of the intake of different classes of polyphenols with serum uric acid and hyperuricemia. Methods and Results This cross-sectional analysis involved baseline data of 6332 participants. Food polyphenol content was estimated by a validated semiquantitative food frequency questionnaire and from the Phenol-Explorer database. Multivariable-adjusted linear regression models with serum uric acid (milligrams per deciliter) as the outcome and polyphenol intake (quintiles) as the main independent variable were fitted. Cox regression models with constant follow-up time (t=1) were performed to estimate the prevalence ratios (PRs) of hyperuricemia (≥7 mg/dL in men and ≥6 mg/dL in women). An inverse association between the intake of the phenolic acid class (β coefficient, -0.17 mg/dL for quintile 5 versus quintile 1 [95% CI, -0.27 to -0.06]) and hydroxycinnamic acids (β coefficient, -0.19 [95% CI, -0.3 to -0.09]), alkylmethoxyphenols (β coefficient, -0.2 [95% CI, -0.31 to -0.1]), and methoxyphenols (β coefficient, -0.24 [95% CI, -0.34 to -0.13]) subclasses with serum uric acid levels and hyperuricemia (PR, 0.82 [95% CI, 0.71-0.95]; PR, 0.82 [95% CI, 0.71-0.95]; PR, 0.80 [95% CI, 0.70-0.92]; and PR, 0.79 [95% CI, 0.69-0.91]; respectively) was found. The intake of hydroxybenzoic acids was directly and significantly associated with mean serum uric acid levels (β coefficient, 0.14 for quintile 5 versus quintile 1 [95% CI, 0.02-0.26]) but not with hyperuricemia. Conclusions In individuals with metabolic syndrome, a higher intake of some polyphenol subclasses (hydroxycinnamic acids, alkylmethoxyphenol, and methoxyphenol) was inversely associated with serum uric acid levels and hyperuricemia. Nevertheless, our findings warrant further research.

Background and Aims: Previous studies have shown beneficial associations between fruit and vegetable (FV) consumption and cardiometabolic risk factors. However, variety in FV, which may play an important role on cardiovascular health due to the different nutrient and phytochemical content among the different groups and subgroups of FV has been poorly investigated. We longitudinally investigated associations between 1-year changes in variety and quantity of FV and concurrent changes in cardiometabolic risk factors in elderly subjects with overweight/obesity and metabolic syndrome., Methods: a one-year data longitudinal analysis of 6647 PREDIMED-plus study participants (48% women) was conducted. Data were collected at baseline, six months and 1-year of follow-up. Variety and quantity of FV were estimated using a food frequency questionnaire and continuous scores for variety were created based on items/month of FV. Linear mixed-models adjusted for potential confounders were performed to estimate associations (β-coefficients and 95% confidence interval) between 1-year changes in FV variety and/or quantity and concurrent changes in cardiometabolic risk factors., Results: Two points increment in the FV variety score over one year was associated with a concurrent decrease in glucose (-0.33 mg/dL (0.58, -0.07)), body weight (-0.07 kg (-0.13, -0.02)) and waist circumference (WC) (-0.08 cm (-0.16, -10.01)). An increment of 100 g/d of FV over one year was associated with a concurrent decrease in triglycerides (-0.50 mg/dL (-0.93, -0.08)), glucose (-0.21 mg/dL (-0.32, -0.11)), body weight (-0.11 kg (-0.15, -0.07)) and WC (-0.10 cm (-0.14, -0.06)) over 1-year. Changes in FV consumption which led to higher quantity and variety over one year were associated with downward changes in glucose (-1.26 mg/dL (-2.09, -0.43)), body weight (-0.40 kg (-0.58, -0.23)) and WC (-0.50 cm (-0.73, -0.28))., Conclusion: Greater variety, in combination with higher quantity of FV was significantly associated with a decrease in several cardiometabolic risk factors among elderly subjects at high cardiovascular risk., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Diets high in acid load may contribute to kidney function impairment. This study aimed to investigate the association between dietary acid load and 1-year changes in glomerular filtration rate (eGFR) and urine albumin/creatinine ratio (UACR)., Methods: Older adults with overweight/obesity and metabolic syndrome (mean age 65 ± 5 years, 48% women) from the PREDIMED-Plus study who had available data on eGFR ( n = 5,874) or UACR ( n = 3,639) at baseline and after 1 year of follow-up were included in this prospective analysis. Dietary acid load was estimated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) at baseline from a food frequency questionnaire. Linear and logistic regression models were fitted to evaluate the associations between baseline tertiles of dietary acid load and kidney function outcomes. One year-changes in eGFR and UACR were set as the primary outcomes. We secondarily assessed ≥ 10% eGFR decline or ≥10% UACR increase., Results: After multiple adjustments, individuals in the highest tertile of PRAL or NEAP showed higher one-year changes in eGFR (PRAL, β: -0.64 ml/min/1.73 m 2 ; 95% CI: -1.21 to -0.08 and NEAP, β: -0.56 ml/min/1.73 m 2 ; 95% CI: -1.13 to 0.01) compared to those in the lowest category. No associations with changes in UACR were found. Participants with higher levels of PRAL and NEAP had significantly higher odds of developing ≥10% eGFR decline (PRAL, OR: 1.28; 95% CI: 1.07-1.54 and NEAP, OR: 1.24; 95% CI: 1.03-1.50) and ≥10 % UACR increase (PRAL, OR: 1.23; 95% CI: 1.04-1.46) compared to individuals with lower dietary acid load., Conclusions: Higher PRAL and NEAP were associated with worse kidney function after 1 year of follow-up as measured by eGFR and UACR markers in an older Spanish population with overweight/obesity and metabolic syndrome., Competing Interests: Author JS-S reported receiving research support from the Instituto de Salud Carlos III (ISCIII), Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the California Walnut Commission, Patrimonio Comunal Olivarero, La Morella Nuts, and Borges S.A; receiving consulting fees or travel expenses from California Walnut Commission, Eroski Foundation, Instituto Danone, Abbott Laboratories and Mundifarma, receiving non-financial support from Hojiblanca, Patrimonio Comunal Olivarero, and Almond Board of California; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and grants and personal fees from Instituto Danone. Author ER reported receiving grants, personal fees, and non-financial support from the California Walnut Commission during the conduct of the study and grants, personal fees, non-financial support from Alexion; personal fees from Amarin; and non-financial support from the International Nut Council outside the submitted work. Author RE reported receiving grants from Instituto de Salud Carlos III and olive oil for the trial from Fundacion Patrimonio Comunal Olivarero/during the conduct of the study and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes, Pernaud Richar, Fundación Dieta Mediterránea, Wine and Culinary International Forum; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories outside the submitted work. Author XP reported receiving grants from ISCIII during the conduct of the study; receiving consulting fees from Sanofi Aventis, Amgen, and Abbott laboratories; receiving lecture personal fees from Esteve, Lacer and Rubio laboratories. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Valle-Hita, Becerra-Tomás, Díaz-López, Vázquez-Ruiz, Megías, Corella, Goday, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Gaforio, Matía-Martín, Vidal, Amengual-Galbarte, Daimiel, Ros, García-Arellano, Barragán, Fitó, Peña-Orihuela, Asencio-Aznar, Gómez-Gracia, Martinez-Urbistondo, Morey, Casas, Garrido-Garrido, Tojal-Sierra, Damas-Fuentes, Goñi, Ortega-Azorín, Castañer, Garcia-Rios, Gisbert-Sellés, Sayón-Orea, Schröder, Salas-Salvadó and Babio.)

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]., Competing Interests: JS-S reported receiving research support from the Instituto de Salud Carlos III, Ministerio de Educación y Ciencia, Departament de Salut Pública de la Generalitat de Catalunya, the European Commission, the USA National Institutes of Health; receiving consulting fees or travel expenses from Eroski Foundation, Instituto Danone, Mundipharma, receiving non-financial support from Hojiblanca, Patrimonio Comunal Olivarero, the Almond Board of California, Pistachio Growers and Borges S.A.; serving on the board of and receiving grant support through his institution from the International Nut and Dried Foundation and the Eroski Foundation; and personal fees from Instituto Danone; Serving in the Scientific Board of Danone Institute International. DC reported receiving grants from Instituto de Salud Carlos III. RE reported receiving grants from Instituto de Salud Carlos III, Fundación Dieta Mediterránea and Cerveza y Salud and olive oil for the trial from Fundación Patrimonio Comunal Olivarero and personal fees from Brewers of Europe, Fundación Cerveza y Salud, Interprofesional del Aceite de Oliva, Instituto Cervantes in Albuquerque, Milano and Tokyo, Pernod Ricard, Fundación Dieta Mediterránea (Spain), Wine and Culinary International Forum and Lilly Laboratories; non-financial support from Sociedad Española de Nutrición and Fundación Bosch y Gimpera; and grants from Uriach Laboratories. ER reports grants, personal fees, non-financial support, and other from California Walnut Commission, during the conduct of the study; grants, personal fees, non-financial support, and other from Alexion; personal fees and other from Amarin, outside the submitted work. RL-R reports personal fees from Cerveceros de España, personal fees and other from Adventia, other from Ecoveritas, S.A., outside the submitted work. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Marhuenda-Muñoz, Domínguez-López, Langohr, Tresserra-Rimbau, Martínez González, Salas-Salvadó, Corella, Zomeño, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, López-Miranda, Estruch, Tinahones, Lapetra, Serra-Majem, Bueno-Cavanillas, Tur, Martín-Sánchez, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Daimiel, Ros, Toledo, Fernández de la Puente Cervera, Barragán, Fitó, Tojal-Sierra, Gómez-Gracia, Zazo, Morey, García-Ríos, Casas, Gómez-Pérez, Santos-Lozano, Vázquez-Ruiz, Atzeni, Asensio, Gili-Riu, Bullon, Moreno-Rodriguez, Lecea, Babio, Peñas Lopez, Gómez Melis and Lamuela-Raventós.)

The burden of depression is increasing worldwide, specifically in older adults. Unhealthy dietary patterns may partly explain this phenomenon. In the Spanish PREDIMED-Plus study, we explored (1) the cross-sectional association between the adherence to the Prime Diet Quality Score (PDQS), an a priori-defined high-quality food pattern, and the prevalence of depressive symptoms at baseline (cross-sectional analysis) and (2) the prospective association of baseline PDQS with changes in depressive symptomatology after 2 years of follow-up. After exclusions, we assessed 6612 participants in the cross-sectional analysis and 5523 participants in the prospective analysis. An energy-adjusted high-quality dietary score (PDQS) was assessed using a validated FFQ. The cross-sectional association between PDQS and the prevalence of depression or presence of depressive symptoms and the prospective changes in depressive symptoms were evaluated through multivariable regression models (logistic and linear models and mixed linear-effects models). PDQS was inversely associated with depressive status in the cross-sectional analysis. Participants in the highest quintile of PDQS (Q5) showed a significantly reduced odds of depression prevalence as compared to participants in the lowest quartile of PDQS (Q1) (OR (95 %) CI = 0·82 (0·68, 0·98))). The baseline prevalence of depression decreased across PDQS quintiles ( P for trend = 0·015). A statistically significant association between PDQS and changes in depressive symptoms after 2-years follow-up was found ( β (95 %) CI = -0·67 z-score (-1·17, -0·18). A higher PDQS was cross-sectionally related to a lower depressive status. Nevertheless, the null finding in our prospective analysis raises the possibility of reverse causality. Further prospective investigation is required to ascertain the association between PDQS and changes in depressive symptoms along time.

Aims: To describe the natural history of SARS-CoV-2 infection in patients with hypertrophic cardiomyopathy (HCM) compared with a control group and to identify predictors of adverse events., Methods and Results: Three hundred and five patients [age 56.6 ± 16.9 years old, 191 (62.6%) male patients] with HCM and SARS-Cov-2 infection were enrolled. The control group consisted of 91 131 infected individuals. Endpoints were (i) SARS-CoV-2 related mortality and (ii) severe clinical course [death or intensive care unit (ICU) admission]. New onset of atrial fibrillation, ventricular arrhythmias, shock, stroke, and cardiac arrest were also recorded. Sixty-nine (22.9%) HCM patients were hospitalized for non-ICU level care, and 21 (7.0%) required ICU care. Seventeen (5.6%) died: eight (2.6%) of respiratory failure, four (1.3%) of heart failure, two (0.7%) suddenly, and three (1.0%) due to other SARS-CoV-2-related complications. Covariates associated with mortality in the multivariable were age {odds ratio (OR) per 10 year increase 2.25 [95% confidence interval (CI): 1.12-4.51], P = 0.0229}, baseline New York Heart Association class [OR per one-unit increase 4.01 (95%CI: 1.75-9.20), P = 0.0011], presence of left ventricular outflow tract obstruction [OR 5.59 (95%CI: 1.16-26.92), P = 0.0317], and left ventricular systolic impairment [OR 7.72 (95%CI: 1.20-49.79), P = 0.0316]. Controlling for age and sex and comparing HCM patients with a community-based SARS-CoV-2 cohort, the presence of HCM was associated with a borderline significant increased risk of mortality OR 1.70 (95%CI: 0.98-2.91, P = 0.0600)., Conclusions: Over one-fourth of HCM patients infected with SARS-Cov-2 required hospitalization, including 6% in an ICU setting. Age and cardiac features related to HCM, including baseline functional class, left ventricular outflow tract obstruction, and systolic impairment, conveyed increased risk of mortality., (© 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: To examine the cross-sectional and longitudinal (2-year follow-up) associations between dietary diversity (DD) and depressive symptoms., Design: An energy-adjusted dietary diversity score (DDS) was assessed using a validated FFQ and was categorised into quartiles (Q). The variety in each food group was classified into four categories of diversity (C). Depressive symptoms were assessed with Beck Depression Inventory-II (Beck II) questionnaire and depression cases defined as physician-diagnosed or Beck II >= 18. Linear and logistic regression models were used., Setting: Spanish older adults with metabolic syndrome (MetS)., Participants: A total of 6625 adults aged 55-75 years from the PREDIMED-Plus study with overweight or obesity and MetS., Results: Total DDS was inversely and statistically significantly associated with depression in the cross-sectional analysis conducted; OR Q4 v . Q1 = 0·76 (95 % CI (0·64, 0·90)). This was driven by high diversity compared to low diversity (C3 v . C1) of vegetables (OR = 0·75, 95 % CI (0·57, 0·93)), cereals (OR = 0·72 (95 % CI (0·56, 0·94)) and proteins (OR = 0·27, 95 % CI (0·11, 0·62)). In the longitudinal analysis, there was no significant association between the baseline DDS and changes in depressive symptoms after 2 years of follow-up, except for DD in vegetables C4 v . C1 = ( β = 0·70, 95 % CI (0·05, 1·35))., Conclusions: According to our results, DD is inversely associated with depressive symptoms, but eating more diverse does not seem to reduce the risk of future depression. Additional longitudinal studies (with longer follow-up) are needed to confirm these findings.

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 (β coefficient [95% confidence interval]; P for trend) (1.67 [0.43, 2.90]; <0.001; 6.27 [2.46, 10.09]; <0.001; 0.56 [0.08, 1.05]; 0.001; 0.51 [0.41, 0.60]; <0.001; 1.19 [0.89, 1.50]; <0.001, respectively). No significant associations in relation to changes in HDL and LDL-cholesterol nor with systolic blood pressure were shown., Conclusion: This prospective cohort study suggests that the consumption of food items with a higher FSAm-NPS DI is associated with increased levels of several major risk factors for CVD including adiposity, fasting plasma glucose, triglycerides, and diastolic blood pressure. However, results must be cautiously interpreted because no significant prospective associations were identified for critical CVD risk factors, such as HDL and LDL-cholesterol, and systolic blood pressure., Competing Interests: JSS served on the board of the International Nut and Dried Fruit Council and receives grant support through this institution. He also served in the Executive Committee of the Instituto Danone, Spain, and on the Scientific Committee of the Danone International Institute. He received research support from the Patrimonio Comunal Olivarero, Spain, and Borges S.A., Spain. He received consulting fees or travel expenses from Eroski Foundation, the Instituto Danone, Spain, Mundipharma and Abbot Laboratories. ER reports grants, personal fees, non-financial support, and others from California Walnut Commission and Alexion, personal fees, non-financial support, and others from Ferrer International and Danone, and personal fees from Amarin, other than the submitted study. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khoury, Gómez-Donoso, Martínez, Martínez-González, Corella, Fitó, Martínez, Alonso-Gómez, Wärnberg, Vioque, Romaguera, León-Acuña, Tinahones, Santos-Lozano, Serra-Majem, Massó Guijarro, Tur, Martín Sánchez, Pintó, Delgado-Rodríguez, Matía-Martín, Vidal, Vázquez, Daimiel, Ros, Bes-Rastrollo, Barragan, Castañer, Torres-Peña, Notario-Barandiaran, Muñoz-Bravo, Abete, Prohens, Cano-Ibáñez, Tojal Sierra, Fernández-García, Sayon-Orea, Pascual, Sorli, Zomeño, Peña-Orihuela, Signes-Pastor, Basterra-Gortari, Schröeder, Salas Salvadó and Babio.)

Background: The metabolic syndrome (MetS) is associated with increased cardiovascular morbidity and mortality. Characterization of cardiac structural and functional abnormalities due to the MetS can help recognize individuals who would benefit the most from preventive interventions. Transthoracic echocardiography (TTE) provides an opportunity to identify those abnormalities in a reproducible and cost-efficient manner. In research settings, implementation of protocols for the acquisition and analysis of TTE images are key to ensure validity and reproducibility, thus facilitating answering relevant questions about the association of the MetS with cardiac alterations., Methods and Results: The Palma Echo Platform (PEP) is a coordinated network that is built up to evaluate the underlying structural and functional cardiac substrate of participants with MetS. Repeated TTE will be used to evaluate 5-year changes in the cardiac structure and function in a group of 565 individuals participating in a randomized trial of a lifestyle intervention for the primary prevention of cardiovascular disease. The echocardiographic studies will be performed at three study sites, and will be centrally evaluated at the PEP core laboratory. Planned analyses will involve evaluating the effect of the lifestyle intervention on cardiac structure and function, and the association of the MetS and its components with changes in cardiac structure and function. Particular emphasis will be placed on evaluating parameters of left atrial structure and function, which have received more limited attention in past investigations. This PEP will be available for future studies addressing comparable questions., Conclusion: In this article we describe the protocol of a central echocardiography laboratory for the study of functional and structural alterations of the MetS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 López, Rossello, Romaguera, Alonso-Gómez, Toledo, Fortuny, Noris, Mas-Lladó, Fiol, Ramallal, Tojal-Sierra, Alonso and Fernandez-Palomeque.)

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., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: Long-term nutrition trials may fail to respond to their original hypotheses if participants do not comply with the intended dietary intervention. We aimed to identify baseline factors associated with successful dietary changes towards an energy-reduced Mediterranean diet (MedDiet) in the PREDIMED-Plus randomized trial., Methods: Longitudinal analysis of 2985 participants (Spanish overweight/obese older adults with metabolic syndrome) randomized to the active intervention arm of the PREDIMED-Plus trial. Dietary changes were assessed with a 17-item energy-reduced MedDiet questionnaire after 6 and 12 months of follow-up. Successful compliance was defined as dietary changes from baseline of ≥ 5 points for participants with baseline scores < 13 points or any increase if baseline score was ≥ 13 points. We conducted crude and adjusted multivariable logistic regression models to identify baseline factors related to compliance., Results: Consistent factors independently associated with successful dietary change at both 6 and 12 months were high baseline perceived self-efficacy in modifying diet (OR 6-month : 1.51, 95% CI 1.25-1.83; OR 12-month : 1.66, 95% CI 1.37-2.01), higher baseline fiber intake (OR 6-month : 1.62, 95% CI 1.07-2.46; OR 12-month : 1.62, 95% CI 1.07-2.45), having > 3 chronic conditions (OR 6-month : 0.65, 95% CI 0.53-0.79; OR 12-month : 0.76, 95% CI 0.62-0.93), and suffering depression (OR 6-month : 0.80, 95% CI 0.64-0.99; OR 12-month : 0.71, 95% CI 0.57-0.88)., Conclusion: Our results suggested that recruitment of individuals with high perceived self-efficacy to dietary change, and those who initially follow diets relatively richer in fiber may lead to greater changes in nutritional recommendations. Participants with multiple chronic conditions, specifically depression, should receive specific tailored interventions., Trial Registration: ISRCTN registry 89898870, 24th July 2014 retrospectively registered http://www.isrctn.com/ISRCTN89898870 ., (© 2021. The Author(s).)

Previous studies suggested that dietary polyphenols could reduce the incidence and complications of type-2 diabetes (T2D); although the evidence is still limited and inconsistent. This work analyzes whether changing to a diet with a higher polyphenolic content is associated with an improved glucose profile. At baseline, and at 1 year of follow-up visits, 5921 participants (mean age 65.0 ± 4.9, 48.2% women) who had overweight/obesity and metabolic syndrome filled out a validated 143-item semi-quantitative food frequency questionnaire (FFQ), from which polyphenol intakes were calculated. Energy-adjusted total polyphenols and subclasses were categorized in tertiles of changes. Linear mixed-effect models with random intercepts (the recruitment centers) were used to assess associations between changes in polyphenol subclasses intake and 1-year plasma glucose or glycosylated hemoglobin (HbA1c) levels. Increments in total polyphenol intake and some classes were inversely associated with better glucose levels and HbA1c after one year of follow-up. These associations were modified when the analyses were run considering diabetes status separately. To our knowledge, this is the first study to assess the relationship between changes in the intake of all polyphenolic groups and T2D-related parameters in a senior population with T2D or at high-risk of developing T2D.