Search

Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. The PREDIMED-Plus trial was supported by the European Research Council (advanced research grant 2014-2019, 340918 to MAM-G as PI) and by the official Spanish Institutions for funding scientific biomedical research, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn) and Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion en Salud (FIS), which is cofunded by the European Regional Development Fund coordinated 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, PI20/01802, PI20/00138, PI20/01532, PI20/00456, PI20/00339, PI20/00557, PI20/00886, and PI20/01158); the Especial Action Project entitled Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, the Recercaixa grant (2013ACUP00194), Grants from the Consejeria de Salud de la Junta de Andalucia, a grant from the Generalitat Valenciana, a SEMERGEN grant, and funds from the European Regional Development Fund (CB06/03; CB12/03), The International Nut & Dried Fruit; and the AstraZeneca Young Investigators Award in Category of Obesity and T2D 2017 to DR. J.S.-S. is partially supported by ICREA under the ICREA Academia programme. 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., 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 (OR6-month: 1.51, 95% CI 1.25-1.83; OR12-month: 1.66, 95% CI 1.37-2.01), higher baseline fiber intake (OR6-month: 1.62, 95% CI 1.07-2.46; OR12-month: 1.62, 95% CI 1.07-2.45), having > 3 chronic conditions (OR6-month: 0.65, 95% CI 0.53-0.79; OR12-month: 0.76, 95% CI 0.62-0.93), and suffering depression (OR6-month: 0.80, 95% CI 0.64-0.99; OR12-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., CRUE-CSIC, Springer Nature, European Research Council (ERC), European Commission 340918, CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion en 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, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion en Salud (FIS) - the European Regional Development Fund 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, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion en Salud (FIS) - 'European Regional Development Fund' PI17/00532 PI17/00215 PI17/01441 PI17/00508 PI17/01732 PI17/00926 PI19/00957 PI19/00386 PI19/00309 PI19/01032 PI19/00576 PI19/00017, Especial Action Project entitled Implementacion y evaluacion de una intervencion intensiva sobre la actividad fisica Cohorte PREDIMED-Plus grant, Recercaixa grant 2013ACUP00194, Junta de Andalucia, Generalitat Valenciana, European Commission, General Electric, SEMERGEN grant, International Nut Dried Fruit, AstraZeneca, ICREA under the ICREA Academia programme, European Commission CB06/03 CB12/03, Instituto de Salud Carlos III (ISCIII), through the Fondo de Investigacion en Salud (FIS) - the 'European Regional Development Fund' PI19/01226 PI19/00781 PI19/01560 PI19/01332 PI20/01802 PI20/00138 PI20/01532 PI20/00456 PI20/00339 PI20/00557 PI20/00886 PI20/01158 T2D 2017

Background & aims: Some cognitive profiles might facilitate successful weight loss and its maintenance. Also, weight reductions may result in cognitive benefits. However, little work to date has examined the interactions between cognition and weight changes in the context of interventions with the Mediterranean diet (MedDiet). We studied the within-subject longitudinal relationships between cognition, body mass index (BMI), physical activity (PA), and quality of life (QoL), in older adults following a MedDiet. Methods: The PREDIMED-Plus is a primary prevention trial testing the effect of a lifestyle intervention program with an energy-restricted MedDiet (er-MedDiet), weight-loss goals and PA promotion on cardiovascular disease. The PREDIMED-Plus-Cognition sub-study included 487 participants (50% women, mean age 65.2 ± 4.7 years), with overweight/obesity, metabolic syndrome and normal cognitive performance at baseline. A comprehensive neurocognitive test battery was administered at baseline and after 1 and 3 years. Results: Baseline higher performance in verbal memory (OR = 1.5; 95%CI 1.0, 2.1), visuoconstructive praxis and attention (OR = 1.5; 95%CI 0.9, 2.3), and inhibition (OR = 1.3; 95%CI 0.9, 1.9) were associated with a higher odd of achieving at least 8% weight loss after 3 years follow-up in participants randomized to the intervention group. There were moderate improvements in specific tests of memory and executive functions during follow-up. Higher adherence to the er-MedDiet was associated with greater improvements in memory. Women exhibited lower rates of change in global cognition, PA and QoL. Moreover, improvements in memory correlated with reductions in BMI after 1 year (βSTD = -0.14) and with improvements in PA after 3 years (βSTD = 0.13). Finally, participants who experienced greater improvements in executive functions and global cognition also experienced greater improvements in their QoL. Conclusions: This study refines the understanding of the determinants and mutual interrelationships between longitudinally-assessed cognitive performance and weight loss, adding further evidence to the cognitive benefits associated with better adherence to a MedDiet. Our results also suggest that weight loss interventions tailored to the cognitive profile and gender of participants are promising avenues for future studies. Study resulting from the following grants: SLT006/17/00246, SLT002/16/00045 and SLT006/17/00077 funded by the Department of Health of the Generalitat de Catalunya by the calls “Acció instrumental de programes de recerca orientats en l'àmbit de la recerca i la innovació en salut” and "Pla estratègic de recerca i innovació en salut (PERIS)". We thank CERCA Programme / Generalitat de Catalunya for institutional support. This project was funded by Instituto de Salud Carlos III (ISCIII), the Spanish Government Official Agency for funding biomedical research - with competitive grants leaded by Jordi Salas-Salvadó and Josep Vidal for the periods 2014-2016, 2015-2017, 2017-2019 and 2018-2020, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund, ERDF, a way to build Europe) [grants: PI13/00233, PI13/00728, PI13/01123, PI13/00462, PI16/00533, PI16/00366, PI16/01094, PI16/00501, PI17/01167, PI19/00017, PI19/00781, PI19/01032, PI19/00576]; the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to Jordi Salas-Salvadó; the European Research Council [Advanced Research Grant 2014-2019; agreement #340918] granted to Miguel Ángel Martínez-González; the Recercaixa (number 2013ACUP00194) grant to Jordi SalasSalvadó. This research was also partially funded by EU-H2020 Grants (Eat2beNICE/ H2020-SFS-2016-2; Ref 728018; and PRIME/ H2020-SC1-BHC-2018-2020; Ref: 847879), Grant PROMETEO/2017/017 (Generalitat Valenciana) and Grant FEA/SEA 2017 for Primary Care Research. This work is also partially supported by ICREA under the ICREA Academia programme. This work was supported by grants from DIUE de la Generalitat de Catalunya 2017 SGR 138 from the Departament d‟Economia i Coneixement de la Generalitat de Catalunya (Spain). CVA are supported by a predoctoral Grant of the Ministerio de Educación, Cultura y Deporte (FPU16/01453). JFG-G has received the Contratos Predoctorales de Formación en Investigación en Salud (PFIS FI17/00255) of the Acción Estratégica en Salud program (AES) from the Carlos III Health Institute (ISCIII), Spanish Ministry of Health. The Physiopathology of Obesity and Nutrition Networking Biomedical Research Center (CIBEROBN) is an initiative of ISCIII. None of these funding sources plays any role in the design, collection, analysis, or interpretation of the data or in the decision to submit manuscripts for publication. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. Conflict of interest Dr. Salas-Salvadó reports non-financial support from Nut and Dried Fruit Foundation, personal fees

ResumenAntecedentes y objetivosEste estudio post hoc analizó la percepción de la importancia de la enfermedad renal crónica (ERC) en el cribado de la dislipidemia y en la elección del tratamiento con estatinas entre médicos de Atención Primaria (MAP) y otras especialidades mediante cuestionario Delphi.MétodosEl cuestionario incluyó 4bloques de preguntas alrededor del paciente dislipémico con alteración del metabolismo hidrocarbonado. Aquí se presentan los resultados relacionados con la consideración de la ERC en el cribado y la elección de la estatina.ResultadosDe los 497 expertos incluidos, el 58% eran MAP y el 42%, especialistas (35, el 7%, nefrólogos). Hubo consenso en realizar un cribado de la dislipidemia en los pacientes con ERC, sin diferencias entre MAP y especialistas; y también en realizar el cribado en la práctica clínica habitual. Sin embargo, no se alcanzó el consenso en considerar el filtrado glomerular estimado (aunque sí entre MAP y nefrólogos) o la albuminuria en la elección de la estatina, ni en su determinación durante el seguimiento después de instaurar un tratamiento con estatinas (aunque hubo consenso entre nefrólogos).ConclusionesEl consenso en analizar el perfil lipídico en los pacientes con ERC indica el reconocimiento del alto riesgo cardiovascular de esta enfermedad. La ausencia de acuerdo en considerar la función renal o la albuminuria, tanto en la elección de la estatina como durante el seguimiento, indica un conocimiento limitado de las diferencias entre estatinas en relación con la ERC, por lo que sería deseable disponer de una guía/documento de consenso sobre uso de estatinas en la ERC.AbstractBackground and objectivesThis post hoc study analysed the perception of the relevance of chronic kidney disease (CKD) in dyslipidaemia screening and the choice of statin among primary care physicians (PCPs) and other specialists through a Delphi questionnaire.MethodsThe questionnaire included 4blocks of questions concerning dyslipidaemic patients with impaired carbohydrate metabolism. This study presents the results of the impact of CKD on screening and the choice of statin.ResultsOf the 497 experts included, 58% were PCPs and 42% were specialists (35, 7% were nephrologists). There was consensus by both PCPs and specialists, with no difference between PCPs and specialists, that CKD patients should undergo a dyslipidaemia screening and that the screening should be part of routine clinical practice. However, there was no consensus in considering the estimated glomerular filtration rate (eGFR) (although there was consensus among PCPs and nephrologists), or considering albuminuria when selecting a statin, or in determining albuminuria during follow-up after having initiated treatment with statins (although there was consensus among the nephrologists).ConclusionsThe consensus to analyse the lipid profile in CKD patients suggests acknowledgment of the high cardiovascular risk of this condition. However, the lack of consensus in considering renal function or albuminuria, both when selecting a statin and during follow-up, suggests a limited knowledge of the differences between statins in relation to CKD. Thus, it would be advisable to develop a guideline/consensus document on the use of statins in CKD.

BACKGROUND: Eggs are a major source of dietary cholesterol and their consumption has been sometimes discouraged. A relationship between egg consumption and the incidence of cardiovascular disease (CVD) has been suggested to be present exclusively among patients with type2 diabetes. AIMS: To assess the association between egg consumption and CVD in a large Mediterranean cohort where approximately 50% of participants had type 2 diabetes. METHODS: We prospectively followed 7216 participants (55-80 years old) at high cardiovascular risk from the PREDIMED (PREvención con DIeta MEDiterránea) study for a mean of 5.8 years. All participants were initially free of CVD. Yearly repeated measurements of dietary information with a validated 137-item food-frequency questionnaire were used to assess egg consumption and other dietary exposures. The endpoint was the rate of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes). RESULTS: A major cardiovascular event occurred in 342 participants. Baseline egg consumption was not significantly associated with cardiovascular events in the total population. Non-diabetic participants who ate on average >4 eggs/week had a hazard ratio (HR) of 0.96 (95% confidence interval, 0.33-2.76) in the fully adjusted multivariable model when compared with non-diabetic participants who reported the lowest egg consumption (

Introduction The therapeutic response to statins has a high interindividual variability with respect to reductions in plasma LDL-cholesterol (c-LDL) and increases in HDL cholesterol (c-HDL). Many studies suggest that there is a relationship between the rs20455 KIF6 gene variant (c.2155T> C, Trp719Arg) and a lower risk of cardiovascular disease in patients being treated with statins. Aim The aim of this study was to investigate whether or not the c.2155T> C KIF6 gene variant modulates the hypercholesteremic effects of treatment with simvastatin, atorvastatin, or rosuvastatin. Materials and methods This was a prospective, observational and multicenter study. Three hundred and forty-four patients who had not undergone prior lipid-lowering treatment were recruited. Simvastatin, atorvastatin or rosuvastatin were administered. Lipid profiles and multiple clinical and biochemical variables were assessed before and after treatment. Results The c.2155T> C variant of the KIF6 gene was shown to influence physiological responses to treatment with simvastatin and atorvastatin. Patients who were homozygous for the c.2155T> C variant (CC genotype, ArgArg) had a 7.0% smaller reduction of LDL cholesterol levels (p = 0.015) in response to hypolipidemic treatment compared to patients with the TT (TrpTrp) or CT (TrpArg) genotype. After pharmacological treatment with rosuvastatin, patients carrying the genetic variant had an increase in c-HDL that was 21.9% lower compared to patients who did not carry the variant (p = 0.008). Conclusion Being a carrier of the c.2155T> C variant of the KIF6 gene negatively impacts patient responses to simvastatin, atorvastatin or rosuvastatin in terms of lipid lowering effect. Increasing the intensity of hypolipidemic therapy may be advisable for patients who are positive for the c.2155T> C variant.

Background: Although the Fat Mass and Obesity (FTO) and Melanocortin-4 Receptor (MC4R) genes have been consistently associated with obesity risk, the association between the obesity-risk alleles with type 2 diabetes is still controversial. In some recent meta-analyses in which significant results have been reported, the associations disappeared after adjustment for body mass index (BMI). However gene-diet interactions with dietary patterns have not been investigated. Our main aim was to analyze whether these associations are modulated by the level of adherence to the Mediterranean Diet (MedDiet). Methods: Case-control study in 7,052 high cardiovascular risk subjects (3,430 type 2 diabetes cases and 3,622 non-diabetic subjects) with no differences in BMI. Diet was assessed by validated questionnaires. FTO-rs9939609 and MC4R-rs17782313 were determined. An aggregate genetic score was calculated to test additive effects. Gene-diet interactions were analyzed. Results: Neither of the polymorphisms was associated with type 2 diabetes in the whole population. However, we found consistent gene-diet interactions with adherence to the MedDiet both for the FTO-rs9939609 (P-interaction=0.039), the MC4R-rs17782313 (P-interaction=0.009) and for their aggregate score (P-interaction=0.006). When adherence to the MedDiet was low, carriers of the variant alleles had higher type 2 diabetes risk (OR=1.21, 95%CI: 1.03-1.40; P=0.019 for FTO-rs9939609 and OR=1.17, 95%CI:1.01-1.36; P=0.035 for MC4R-rs17782313) than wild-type subjects. However, when adherence to the MedDiet was high, these associations disappeared (OR=0.97, 95%CI: 0.85-1.16; P=0.673 for FTO-rs9939609 and OR=0.89, 95%CI:0.78-1.02; P=0.097 for MC4R-rs17782313). These gene-diet interactions remained significant even after adjustment for BMI. As MedDiet is rich in folate, we also specifically examined folate intake and detected statistically significant interaction effects on fasting plasma glucose concentrations in non-diabetic subjects. However these findings should be interpreted with caution because folate intake may simply reflect a healthy dietary pattern. Conclusions: These novel results suggest that the association of the FTO-rs9939609 and the MC4R-rs17782313 polymorphisms with type 2 diabetes depends on diet and that a high adherence to the MedDiet counteracts the genetic predisposition., This study has been supported by The Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministry of Economy and Innovation, Spain and Fondo Europeo de Desarrollo Regional (projects PI051839, PI070240, PI1001407, G03/140, CIBER 06/03, RD06/0045 PI07-0954, CNIC-06, PI11/02505, SAF2009-12304 and AGL2010-22319-C03-03), by contracts 53-K06-5-10 and 58-1950-9-001 from the US Department of Agriculture Research, USA and by the Generalitat Valenciana, Spain (AP111/10, AP-042/11, BEST11-263, BEST/2011/261, GVACOMP2011-151, ACOMP/2011/145 and ACOMP/2012/190).

Abstract The genetic and biochemical basis of fish-eye disease (FED) was investigated in a 63-year-old female proband with low plasma HDL cholesterol. Analyses of corneal and plasma lipids of the proband were consistent with impaired lecithin:cholesterol acyltransferase (LCAT) activity. Free cholesterol and phospholipid levels were elevated relative to control values, whereas cholesteryl ester levels were greatly reduced. Fatty acid compositions of corneal lipids from the proband and control subjects differ from the respective fatty acid compositions of their plasma lipids. This suggests that the metabolic pathways and acyl chain specificities for phospholipid, cholesteryl ester, and triglyceride metabolism within the cornea are distinct from those of plasma. Sequencing of the LCAT gene from the proband revealed a novel mutation at nucleotide 399, corresponding to an Arg 99 →Cys substitution. Secretion of LCAT (Arg 99 →Cys) by transfected COS-6 cells was ≈50% of that of the wild type, but its specific activity against reassembled HDL was 93% lower than that of wild-type LCAT. The specific activities of wild-type and LCAT (Arg 99 →Cys) against LDL were reduced similarly, suggesting that the appearance of the FED phenotype does not require enhanced activity against LDL. Our data support the hypothesis that FED is a partial LCAT deficiency in which poor esterification in specific types of HDL particles may contribute to the appearance of the corneal opacities.

The dietary inflammatory index (DII) is a new tool to assess the inflammatory potential of the diet. In the present study, we aimed to determine the association between the DII and BMI, waist circumference and waist:height ratio (WHtR). We conducted a cross-sectional study of 7236 participants recruited into the PREvención con DIeta MEDiterránea trial. Information from a validated 137-item FFQ was used to calculate energy, food and nutrient intakes. A fourteen-item dietary screener was used to assess adherence to the Mediterranean diet (MeDiet). Sex-specific multivariable linear regression models were fitted to estimate differences (and 95 % CI) in BMI, waist circumference and WHtR across the quintiles of the DII. All nutrient intakes, healthy foods and adherence to the MeDiet were higher in the quintile with the lowest DII score (more anti-inflammatory values) except for intakes of animal protein, saturated fat and monounsaturated fat. Although an inverse association between the DII and total energy was apparent, the DII was associated with higher average BMI, waist circumference and WHtR after adjusting for known risk factors. The adjusted difference in the WHtR for women and men between the highest and lowest quintiles of the DII was 1·60 % (95 % CI 0·87, 2·33) and 1·04 % (95 % CI 0·35, 1·74), respectively. Pro-inflammatory scores remained associated with obesity after controlling for the effect that adherence to a MeDiet had on inflammation. In conclusion, the present study shows a direct association between the DII and indices of obesity, and supports the hypothesis that diet may have a role in the development of obesity through inflammatory modulation mechanisms. The PREDIMED trial was supported by the official funding agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III (ISCIII), through grants provided to research networks specifically developed for the trial: RTIC G03/140 (Coordinator: R Estruch, MD, PhD), CIBERobn, and RTIC RD 06/0045 (Coordinator: MA Martínez-González, MD, PhD). We also acknowledge grants from Centro Nacional de Investigaciones Cardiovasculares CNIC 06/2007, Fondo de Investigación Sanitaria - Fondo Europeo de Desarrollo Regional (PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI11/01647), Ministerio de Ciencia e Innovación (AGL-2009-13906-C02, AGL2010-22319-C03), Fundación Mapfre 2010, Public Health Division of the Department of Health of the Autonomous Government of Catalonia and Generalitat Valenciana (ACOMP06109, GVACOMP2010-181, GVACOMP2011-151, CS2010-AP-111 and CS2011-AP-042), and a joint contract (CES09/030) with the Instituto de Salud Carlos III and the Health Department of the Catalan Government (Generalitat de Catalunya).

Background: Fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) and are relevant genes associated with obesity. This could be through food intake, but results are contradictory. Modulation by diet or other lifestyle factors is also not well understood. Objective: To investigate whether MC4R and FTO associations with body-weight are modulated by diet and physical activity (PA), and to study their association with alcohol and food intake. Methods: Adherence to Mediterranean diet (AdMedDiet) and physical activity (PA) were assessed by validated questionnaires in 7,052 high cardiovascular risk subjects. MC4R rs17782313 and FTO rs9939609 were determined. Independent and joint associations (aggregate genetic score) as well as statistical and biological gene-lifestyle interactions were analyzed. Results: FTO rs9939609 was associated with higher bodymass index (BMI), waist circumference (WC) and obesity (P < 0.05 for all). A similar, but not significant trend was found for MC4R rs17782313. Their additive effects (aggregate score) were significant and we observed a 7% per-allele increase of being obese (OR = 1.07; 95% CI 1.01-1.13). We found relevant statistical interactions (P, 0.05) with PA. So, in active individuals, the associations with higher BMI, WC or obesity were not detected. A biological (non-statistical) interaction between AdMedDiet and rs9939609 and the aggregate score was found. Greater AdMedDiet in individuals carrying 4 or 3-risk alleles counterbalanced their genetic predisposition, exhibiting similar BMI (P = 0.502) than individuals with no risk alleles and lower AdMedDiet. They also had lower BMI (P = 0.021) than their counterparts with low AdMedDiet. We did not find any consistent association with energy or macronutrients, but found a novel association between these polymorphisms and lower alcohol consumption in variant-allele carriers (B+/-SE: -0.57+/-0.16 g/d per-score-allele; P = 0.001). Conclusion: Statistical and biological interactions with PA and diet modulate the effects of FTO and MC4R polymorphisms on obesity. The novel association with alcohol consumption seems independent of their effects on BMI., The Official funding agency for Biomedical Research of the Spanish Government, Instituto de Salud Carlos III (ISCIII) and Fondo Europeo de Desarrollo Regional (FEDER), provided the grants for his study: RTIC G03/140, CIBERobn, RD 06/0045, PI04-2239, PI 05/2584, CP06/00100, PI07/0240, PI07/1138, PI07/0954, PI 07/0473, PI10/01407, PI11/02505 PI11/01647 CNIC-06 and AGL2010-22319-C03-03. The Generalitat Valenciana provided grants AP-042/11 and BEST11-263. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Background: Interventions promoting weight loss can reduce the incidence of type 2 diabetes mellitus. Whether dietary changes without calorie restriction also protect from diabetes has not been evaluated. Objective: To assess the efficacy of Mediterranean diets for the primary prevention of diabetes in the Prevención con Dieta Mediterránea trial, from October 2003 to December 2010 (median follow-up, 4.1 years). Design: Subgroup analysis of a multicenter, randomized trial. (Current Controlled Trials: ISRCTN35739639) Setting: Primary care centers in Spain. Participants: Men and women without diabetes (3541 patients aged 55 to 80 years) at high cardiovascular risk. Intervention: Participants were randomly assigned and stratified by site, sex, and age but not diabetes status to receive 1 of 3 diets: Mediterranean diet supplemented with extra-virgin olive oil (EVOO), Mediterranean diet supplemented with nuts, or a control diet (advice on a low-fat diet). No intervention to increase physical activity or lose weight was included. Measurements: Incidence of new-onset type 2 diabetes mellitus (prespecified secondary outcome). Results: During follow-up, 80, 92, and 101 new-onset cases of diabetes occurred in the Mediterranean diet supplemented with EVOO, Mediterranean diet supplemented with mixed nuts, and control diet groups, respectively, corresponding to rates of 16.0, 18.7, and 23.6 cases per 1000 person-years. Multivariate-adjusted hazard ratios were 0.60 (95% CI, 0.43 to 0.85) for the Mediterranean diet supplemented with EVOO and 0.82 (CI, 0.61 to 1.10) for the Mediterranean diet supplemented with nuts compared with the control diet. Limitations: Randomization was not stratified by diabetes status. Withdrawals were greater in the control group. Conclusion: A Mediterranean diet enriched with EVOO but without energy restrictions reduced diabetes risk among persons with high cardiovascular risk. © 2014 American College of Physicians.

BACKGROUND & AIMS: There is little evidence on post hoc-derived dietary patterns (DP) and all-cause mortality in Southern-European populations. Furthermore, the potential effect modification of a DP by a nutritional intervention has not been sufficiently assessed. We assessed the association between a posteriori defined baseline major DP and total mortality or cardiovascular events within each of the three arms of a large primary prevention trial (PREDIMED) where participants were randomized to two active interventions with Mediterranean-type diets or to a control group (allocated to a low-fat diet). DESIGN: We followed-up 7216 participants for a median of 4.3 years. A validated 137-item food-frequency questionnaire was administered. Baseline DP were ascertained through factor analysis based on 34 predefined groups. Cox regression models were used to estimate multivariable-adjusted hazard ratios (HR) for cardiovascular disease (CVD) or mortality across quartiles of DP within each of the three arms of the trial. RESULTS: We identified two major baseline DP: the first DP was rich in red and processed meats, alcohol, refined grains and whole dairy products and was labeled Western dietary pattern (WDP). The second DP corresponded to a 'Mediterranean-type' dietary pattern (MDP). During follow-up, 328 participants died. After controlling for potential confounders, higher baseline adherence to the MDP was associated with lower risk of CVD (adjusted HR for fourth vs. first quartile: 0.52; 95% CI (Confidence Interval): 0.36, 0.74; p-trend

[Background] It is unknown whether individuals at high cardiovascular risk sustain a benefit in cardiovascular disease from increased olive oil consumption. The aim was to assess the association between total olive oil intake, its varieties (extra virgin and common olive oil) and the risk of cardiovascular disease and mortality in a Mediterranean population at high cardiovascular risk., [Methods] We included 7,216 men and women at high cardiovascular risk, aged 55 to 80 years, from the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter, randomized, controlled, clinical trial. Participants were randomized to one of three interventions: Mediterranean Diets supplemented with nuts or extra-virgin olive oil, or a control low-fat diet. The present analysis was conducted as an observational prospective cohort study. The median follow-up was 4.8 years. Cardiovascular disease (stroke, myocardial infarction and cardiovascular death) and mortality were ascertained by medical records and National Death Index. Olive oil consumption was evaluated with validated food frequency questionnaires. Multivariate Cox proportional hazards and generalized estimating equations were used to assess the association between baseline and yearly repeated measurements of olive oil intake, cardiovascular disease and mortality., [Results] During follow-up, 277 cardiovascular events and 323 deaths occurred. Participants in the highest energy-adjusted tertile of baseline total olive oil and extra-virgin olive oil consumption had 35% (HR: 0.65; 95% CI: 0.47 to 0.89) and 39% (HR: 0.61; 95% CI: 0.44 to 0.85) cardiovascular disease risk reduction, respectively, compared to the reference. Higher baseline total olive oil consumption was associated with 48% (HR: 0.52; 95% CI: 0.29 to 0.93) reduced risk of cardiovascular mortality. For each 10 g/d increase in extra-virgin olive oil consumption, cardiovascular disease and mortality risk decreased by 10% and 7%, respectively. No significant associations were found for cancer and all-cause mortality. The associations between cardiovascular events and extra virgin olive oil intake were significant in the Mediterranean diet intervention groups and not in the control group., [Conclusions] Olive oil consumption, specifically the extra-virgin variety, is associated with reduced risks of cardiovascular disease and mortality in individuals at high cardiovascular risk.Trial registration: This study was registered at controlled-trials.com (http://www.controlled-trials.com/ISRCTN35739639). International Standard Randomized Controlled Trial Number (ISRCTN): 35739639. Registration date: 5 October 2005. © 2014 Guasch-Ferré et al.; licensee BioMed Central Ltd., We thank all the participants in the PREDIMED study. This study was funded, in part, by the Spanish Ministry of Health (ISCIII), PI1001407, Thematic Network G03/140, RD06/0045, FEDER (Fondo Europeo de Desarrollo Regional), and the Centre Català de la Nutrició de l’Institut d’Estudis Catalans. The Fundación Patrimonio Comunal Olivarero and Hojiblanca SA (Málaga, Spain), California Walnut Commission (Sacramento, CA), Borges SA (Reus, Spain), and Morella Nuts SA (Reus, Spain) donated the olive oil, walnuts, almonds and hazelnuts, respectively, used in the study.

Background: Excess sodium intake is associated with high blood pressure, a major risk factor for cardiovascular disease (CVD). It is unknown whether decreasing sodium intake to ,2300 mg/d has an effect on CVD or all-cause mortality. Objective: The objective was to assess whether reductions in sodium intake to ,2300 mg/d were associated with either an increased or a decreased risk of fatal and nonfatal CVD and all-cause mortality. Design: This observational prospective study of the PREvencicon DIeta MEDiterr� (PREDIMED) trial included 3982 participants at high CVD risk. Sodium intake was evaluated with a validated food- frequency questionnaire and categorized as low (,1500 mg/d), in- termediate ($1500 to #2300 mg/d), high (.2300 to #3400 mg/d), or very high (.3400 mg/d). Subsequently, 1-y and 3-y changes in sodium intake were calculated. Multivariate relative risks were as- sessed by using Cox proportional hazards ratios. Marginal structural models with inverse probability weighting were used to test the effect of changes in sodium intake and the Mediterranean diet (MedDiet). Results: We documented 125 CVD events and 131 deaths after a 4.8-y median follow-up. Sodium intake ,2300 mg/d was associated with a lower risk of all-cause mortality: 48% (HR: 0.52; 95% CI: 0.30, 0.91; P = 0.02) and 49% (HR: 0.51; 95% CI: 0.26, 0.98; P = 0.04) after 1 and 3 y, respectively. Increasing sodium intake after 1 y was associated with a 72% (HR: 1.72; 95% CI: 1.01, 2.91; P = 0.04) higher risk of CVD events. The incidence rate of CVD was reduced for those who reduced their sodium intake and were randomly assigned to MedDiet interven- tions (4.1/10,000 (95% CI: 3.1, 8.0) compared with 4.4/10,000 (95% CI: 2.7, 12.4) person-years; P =0 .002). Conclusions: Decreasing sodium intake to ,2300 mg/d was asso- ciated with a reduced risk of all-cause mortality, whereas increasing the intake to .2300 mg/d was associated with a higher risk of CVD. Our observational data suggest that sodium intake ,2300 mg/d was associated with an enhanced beneficial effect of the MedDiet on CVD. These results should be interpreted with caution, and other confirma- tory studies are necessary. This study was registered at controlled-trials. com as 35739639. Am J Clin Nutr 2015;101:440-8.

Background Oxidatively induced DNA damage, an important factor in cancer etiology, is repaired by oxyguanine glycosylase 1 (OGG1). The lower repair capacity genotype (homozygote Cys326Cys) in the OGG1-rs1052133 (Ser326Cys) polymorphism has been associated with cancer risk. However, no information is available in relation to cancer mortality, other causes of death, and modulation by diet. Objective Our aim was to evaluate the association of the OGG1-rs1052133 with total, cancer, and cardiovascular disease (CVD) mortality and to analyze its modulation by the Mediterranean diet, focusing especially on total vegetable intake as one of the main characteristics of this diet. Design Secondary analysis in the PREDIMED (Prevención con Dieta Mediterránea) trial is a randomized, controlled trial conducted in Spain from 2003 to 2010. Participants/setting Study participants (n=7,170) were at high risk for CVD and were aged 55 to 80 years. Intervention Participants were randomly allocated to two groups with a Mediterranean diet intervention or a control diet. Vegetable intake was measured at baseline. Main outcome measures Main outcomes were all-cause, cancer, and CVD mortality after a median follow-up of 4.8 years. Statistical analyses Multivariable-adjusted Cox regression models were fitted. Results Three hundred eighteen deaths were detected (cancer, n=127; CVD, n=81; and other, n=110). Cys326Cys individuals (prevalence 4.2%) presented higher total mortality rates than Ser326-carriers (P=0.009). The multivariable-adjusted hazard ratio for Cys326Cys vs Ser326-carriers was 1.69 (95% CI 1.09 to 2.62; P=0.018). This association was greater for CVD mortality (P=0.001). No relationship was detected for cancer mortality in the whole population (hazard ratio 1.07; 95% CI 0.47 to 2.45; P=0.867), but a significant age interaction (P=0.048) was observed, as Cys326Cys was associated with cancer mortality in participants

Objective: To evaluate prescribing patterns of lipid-lowering drugs used in management of patients at risk of coronary heart disease (CHD) in usual clinical practice in Spain and to assess low-density lipoprotein cholesterol (LDL-C) goal attainment among CHD and CHD equivalent patients (30% to attain goal. In a logistic regression model for goal attainment, CHD/CHD equivalent patients (odds ratio [OR] 0.47; 95% confidence interval [CI] 0.31, 0.72) and patients with baseline LDL-C >190 mg/dL (OR 0.53; 95% CI 0.35, 0.80) were least likely to reach cholesterol goal when compared with patients having baseline LDL-C >100 mg/dL and

© 2014 The Authors. Epidemiological and clinical studies have reported that olive oil reduces the incidence of cardiovascular disease. However, the mechanisms involved in this beneficial effect have not been delineated. The endothelium plays an important role in blood pressure regulation through the release of potent vasodilator and vasoconstrictor agents such as nitric oxide (NO) and endothelin-1 (ET-1), respectively, events that are disrupted in type 2 diabetes. Extra virgin olive oil contains polyphenols, compounds that exert a biological action on endothelial function. This study analyzes the effects of olive oil polyphenols on endothelial dysfunction using an in vitro model that simulates the conditions of type 2 diabetes. Our findings show that high glucose and linoleic and oleic acids decrease endothelial NO synthase phosphorylation, and consequently intracellular NO levels, and increase ET-1 synthesis by ECV304 cells. These effects may be related to the stimulation of reactive oxygen species production in these experimental conditions. Hydroxytyrosol and the polyphenol extract from extra virgin olive oil partially reversed the above events. Moreover, we observed that high glucose and free fatty acids reduced NO and increased ET-1 levels induced by acetylcholine through the modulation of intracellular calcium concentrations and endothelial NO synthase phosphorylation, events also reverted by hydroxytyrosol and polyphenol extract. Thus, our results suggest a protective effect of olive oil polyphenols on endothelial dysfunction induced by hyperglycemia and free fatty acids., This study was partly supported by the Spanish Ministry of Health (Instituto de Salud Carlos III) (RD06/0045), Fondo Europeo de Desarrollo Regional (FEDER), the Spanish Ministry of Science (BFU2007-61727/BFI) and the Generalitat de Catalunya (2009SGR00438)

Excerpt To the editor: In the August issue, Kraus and Massey (1) report the association of Bell's palsy and acute myocardial infarction in three patients without finding an etiopathogenic explanati...

To the Editor.— We have read with interest the article by Gomez et al 1 about the relationship between lipid metabolism abnormalities and xanthelasma. In their study, the lipoprotein profile found in subjects with xanthelasma does not explain their predisposition to the dermal lipid deposits, and, curiously, lower levels of the atherogenic apoprotein B were observed with respect to a control group. We have actually studied lipid metabolism in 96 subjects with xanthelasma (age, 52.3 ± 11.4 years; 25 male, 71 female) and in 104 healthy control subjects (age, 50.7 ± 10.6 years; 56 male, 48 female). The design of our study differs mainly in the selection of control subjects that were included on the basis of the absence of xanthelasma, but not of plasma lipid values as stated by Gomez. As can be seen in the Table, subjects with xanthelasma of both sexes had total and low-density lipoprotein cholesterol and