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Objective: To investigate the association between the Trp64Arg beta3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. DESIGN AND SUBJECT: Cross-sectional study in 1063 (476 men and 587 women) randomly selected from this population (aged: 18-68 years).Measurements: Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism.Results: Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042-0.060). We found gender-specific associations between the Trp64Arg mutation and obesity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 +/- 3.81 vs. 26.34 +/- 3.57 kg m-2, P=0.049) and total cholesterol (5.85 +/- 1.45 vs. 5.28 +/- 1.06 mmol L-1; P=0.011) compared with wild-type individuals. Logistic regression analysis, revealed that the risk of overweight was two times higher in male carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fasting glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables. For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men and women. However, after adjustment for covariates, these associations only remained statistically significant (P < 0.02) in women. Moreover, in women, a statistically significant interaction (P=0.026) between the LPL and the ADRB3 gene loci in determining BMI was found. Thus, the Arg64 allele was associated with a higher BMI only in H+/H+ women.Conclusions: The Trp64Arg mutation was associated with BMI and lipids in men. In women, an additional gene-gene interaction with the LPL-HindIII polymorphism may explain the results. [ABSTRACT FROM AUTHOR]

Abstract. Corella D, Guillén M, Portolés O, Sorlí JV, Alonso V, Folch J, Sáiz C (School of Medicine, University of Valencia, Valencia, Spain). Gender specific associations of the Trp64Arg mutation in the β3-adrenergic receptor gene with obesity-related phenotypes in a Mediterranean population: interaction with a common lipoprotein lipase gene variation. J Intern Med 2001; 250: 348–360. Objective. To investigate the association between the Trp64Arg β3-adrenergic receptor (ADRB3) mutation and obesity-related phenotypes in a Mediterranean Spanish population considering the effect of other genetic and environmental factors. Design and subject. Cross-sectional study in 1063 (476 men and 587 women) randomly selected from this population (aged: 18–68 years). Measurements. Anthropometric (weight, height and waist-to-hip ratio), blood pressure, biochemical (lipids, fasting glucose, and uric acid), life-style variables, and the Trp64Arg, HindIII-Lipoprotein lipase (LPL) and apolipoprotein E polymorphism. Results. Frequency of the Arg64 allele was low (0.051; 95% CI: 0.042–0.060). We found gender-specific associations between the Trp64Arg mutation and obesity related phenotypes. In men, carriers of the Arg64 variant had higher body mass index (BMI) (27.63 ± 3.81 vs. 26.34 ± 3.57 kg m-2, P=0.049) and total cholesterol (5.85 ± 1.45 vs. 5.28 ± 1.06 mmol L-1; P=0.011) compared with wild-type individuals. Logistic regression analysis, revealed that the risk of overweight was two times higher in male carriers of the Arg64 allele. In women, the Arg64 variant was only associated with higher fasting glucose (P=0.031). These genotype effects persisted after adjustment for age, genetic and life-style variables. For the LPL polymorphism, the H-/H- genotype was associated with lower BMI and with lower risk of overweight (OR: 0.49; 95% CI: 0.30-0.81) in both men and women.... [ABSTRACT FROM AUTHOR]

Background: High saturated fat consumption, mostly from red meat and sausage meat has been associated with an increase in cardiovascular risk (CVR) in contrast to the effect of high fish consumption. Objective: To get to know the frequency of meat and fish consumption in an elderly high Mediterranean population, their correlations with adherence to the Mediterranean diet (MD) and their association with intermediate CVR phenotypes. Methods: A cross-sectional study was carried out on 945 people (67.4 ± 6.2 years old) with high CVR recruited in primary care centres of Valencia, and participating in the PREDIMED study. The frequency of meat and fish consumption was determined through a validated questionnaire. We analyzed clinical, biochemical and anthropometric variables using standard methods. Results: Mean red meat consumption was high (7.4 ± 4.7 times/week), being higher in men than in women (P = 0.031) and was associated with greater weight (P = 0.001) and prevalence of obesity (P = 0.025). Fish consumption was also high (4.5 ± 2.6 time/week) and was associated with lower concentrations of fasting plasma glucose (P = 0.016) as well as with lower prevalence of diabetes (P = 0.017). Conclusion: Red meat consumption in this high CVR population is very high and far from the recommendations of MD, needing, therefore, to be reduced. Fish consumption is closer to the recommendations and should be maintained. [ABSTRACT FROM AUTHOR]

Introduction: Coffee and tea consumption recommendations for a healthy diet have been changing in recent years as it has increased the level of evidence on their benefits has increased. Objective: To know the frequency of coffee and tea consumption of in a high cardiovascular risk Mediterranean population (CVR) and to analyze whether there are differences between the consumption of these drinks by cardiovascular risk factors Methods: A cross-sectional study was carried out on 945 people (340 males, 605 females) (67.4 ± 6.2 years old) with high CVR recruited in primary care centres of Valencia, included in the PREDIMED study. Coffee and tea consumption has been determined through a validated questionnaire. We analyzed biochemical, clinical and anthropometric variables by standard methods. Results: Tea consumption is very low in this Mediterranean population (0,4 ± 1,6 cups/weeks). By contrast, coffee consumption averaged nearly one cup per day (6,5 ± 5,2 cups/weeks). Hypertensive patients showed a lower overall consumption of coffee than in non-hypertensive patients (6,6 ± 5,1 vs 7,3 ± 5,9; P = 0,023 respectively). These differences were greatest when caffeinated coffee consumption is analyzed (2.9 ± 4.5 vs 4 3 ± 5.3, P < 0001). Moreover, diabetics consumed significantly less coffee and tea than non-diabetics (P = 0,015 and P = 0,022 respectively), these differences being greater for caffeinated coffee (P < 0,025). Conclusions: In conclusion, in this high cardiovascular risk Mediterranean population a coffee consumption pattern, based on traditional recommendations, is observed, that as a result of new scientific evidence should be update. [ABSTRACT FROM AUTHOR]

BACKGROUND Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. METHODS In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. RESULTS A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol. CONCLUSIONS In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639.). [ABSTRACT FROM AUTHOR]

Background: High saturated fat consumption, mostly from red meat and sausage meat has been associated with an increase in cardiovascular risk (CVR) in contrast to the effect of high fish consumption.Objective: To get to know the frequency of meat and fish consumption in an elderly high Mediterranean population, their correlations with adherence to the Mediterranean diet (MD) and their association with intermediate CVR phenotypes.Methods: A cross-sectional study was carried out on 945 people (67.4±6.2 years old) with high CVR recruited in primary care centres of Valencia, and participating in the PREDIMED study. The frequency of meat and fish consumption was determined through a validated questionnaire. We analyzed clinical, biochemical and anthropometric variables using standard methods.Results: Mean red meat consumption was high (7.4±4.7 times/week), being higher in men than in women (P=0.031) and was associated with greater weight (P=0.001) and prevalence of obesity (P=0.025). Fish consumption was also high (4.5±2.6 time/week) and was associated with lower concentrations of fasting plasma glucose (P=0.016) as well as with lower prevalence of diabetes (P=0.017).Conclusion: Red meat consumption in this high CVR population is very high and far from the recommendations of MD, needing, therefore, to be reduced. Fish consumption is closer to the recommendations and should be maintained. [ABSTRACT FROM AUTHOR]

Introduction and Objectives: Metabolic syndrome (MetS) is a combination of various cardiovascular risk factors with a major impact on morbidity and premature mortality. However, the impact of MetS on self-reported health-related quality of life (HRQoL) is unknown. This study evaluated the HRQoL in a Spanish adult population aged 55 years and older with MetS., Method: A cross-sectional analysis was performed with baseline data from the PREDIMED-Plus multicentre randomized trial. The participants were 6430 men and women aged 55-75 years with overweight/obesity (body mass index ≥27 and ≤40kg/m 2 ) and MetS. The SF-36 questionnaire was used as a tool to measure HRQoL. Scores were calculated on each scale of the SF-36 by gender and age., Results: Participants showed higher scores in the social function (mean 85.9, 95% CI; 85.4-86.4) and emotional role scales (mean 86.8, 95% CI; 86.0-87.5). By contrast, the worst scores were obtained in the aggregated physical dimensions. In addition, men obtained higher scores than women on all scales. Among men, the worst score was obtained in general health (mean 65.6, 95% CI; 65.0-66.2), and among women, in body pain (mean 54.3, 95%CI; 53.4-55.2). A significant decrease was found in the aggregated physical dimensions score among participants 70-75 years old, but an increased one in the aggregated mental dimensions, compared to younger participants., Conclusions: Our results reflect that the MetS may negatively affect HRQoL in the aggregated physical dimensions, body pain in women, and general health in men. However, this adverse association was absent for the psychological dimensions of HRQoL, which were less affected., (Copyright © 2020 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background & Aims: Little is known about the impact of specific dietary patterns on the development of obesity phenotypes. We aimed to determine the association of longitudinal changes in adherence to the traditional Mediterranean diet (MedDiet) with the transition between different obesity phenotypes., Methods: Data of 5801 older men and women at high cardiovascular risk from PREDIMED trial were used. Adherence to MedDiet was measured with the validated 14p-Mediterranean Diet Adherence Screener (MEDAS). Using the simultaneous combination of metabolic health- and body size-related parameters participants were categorized into one of four phenotypes: metabolically healthy and abnormal obese (MHO and MAO), metabolically healthy and abnormal non-obese (MHNO and MANO). Cox regression models with yearly repeated measures during 5-year of follow-up were built with use of Markov chain assumption., Results: Each 2-point increase in MEDAS was associated with the following transitions: in MAO participants, with a 16% (95% CI 3-31%) greater likelihood of becoming MHO; in MHO participants with a 14% (3-23%) lower risk of becoming MAO; in MHNO participants with a 18% (5-30%) lower risk of becoming MHO. In MANO women, but not in men, MEDAS was associated with 20% (5-38%) greater likely of becoming MHNO (p for interaction by gender 0.014). No other significant associations were observed., Conclusions: Better adherence to the traditional MedDiet is associated with transitions to healthier phenotypes, promoting metabolic health improvement in MAO, MANO (only in women), and MHO, as well as protecting against obesity incidence in MHNO subjects., (Copyright © 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Background and Aim: We tested the hypothesis that an intervention with a Mediterranean diet (MeDiet) could mitigate the well-known harmful effects of abdominal obesity on cardiovascular health., Methods and Results: We assessed the relationship between baseline waist-to-height ratio (WHtR) and major cardiovascular events during a median follow-up of 4.8 years in the Prevention with Mediterranean Diet (PREDIMED) randomized primary prevention trial, which tested a MeDiet against a control diet (advice on a low-fat diet). We also examined whether the MeDiet intervention was able to counteract the detrimental cardiovascular effects of an increased WHtR. The trial included 7447 participants (55-80 years old, 57% women) at high cardiovascular risk but free of cardiovascular disease (CVD) at enrollment. An increased risk of CVD events (myocardial infarction, stroke, or cardiovascular death) was apparent for the highest versus the lowest quartile of WHtR (multivariable-adjusted hazard ratio: 1.98) (95% confidence interval: 1.10-3.57; linear trend: p = 0.019) only in the control-diet group, but not in the two groups allocated to intervention with MeDiet (p for interaction = 0.034). This apparent interaction suggesting that the intervention counterbalanced the detrimental cardiovascular effects of adiposity was also significant for body mass index (BMI) (p = 0.01) and waist circumference (p = 0.043)., Conclusions: The MeDiet may counteract the harmful effects of increased adiposity on the risk of CVD., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Aims: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study., Methods and Results: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02)., Conclusion: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: To define whether the rs9939609 FTO (fat mass and obesity associated) single nucleotide polymorphism (SNP) is associated with anthropometric measurements and its modulation by educational level in a Mediterranean population., Methods: We studied 3 independent adult samples: a random sample (n = 1580) from the general population (GP), obese hospital patients (OHP) (n = 203) and elderly subjects (n = 1027) with high cardiovascular risk (HCR). Weight and height were directly measured. Education and physical activity (PA) were measured using questionnaires., Results: The rs9939609 presented heterogeneous associations with BMI. In the GP, the minor A-allele was significantly associated with greater BMI, following a co-dominant pattern (P = 0.009), whereas in the OHP this association was recessive (P = 0.004). Conversely, we did not find a significant association with BMI in the HCR group (P < 0.596). In the GP we found a significant interaction between the FTO SNP and education (P = 0.048). In the stratified analysis, no association of the FTO SNP with greater BMI in university subjects was detected (P = 0.786), whereas the association was observed in non-university subjects (P = 0.001). The FTO × education interaction (P = 0.020) was also observed in determining obesity risk in the GP. A-allele carriers had a greater risk of being obese only if they had no university education (OR: 1.56; 95%CI: 1.09-2.23 for TA and OR: 2.01; 95%CI: 1.27-3.26 for AA subjects). The interaction of the FTO with education remained significant even after adjustment for PA., Conclusions: The association of the FTO SNP with greater BMI and obesity risk in the GP was strongly modulated by education., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Neuropeptide Y (NPY) is a neurotransmitter widely distributed in the central nervous system. Several studies have demonstrated that increases of NPY are associated with reduced alcohol intake and anxiety manifestations. The Leu7Pro polymorphism in the NPY has been associated with alcohol consumption, but evidence is scarce. In the Spanish Mediterranean population, this variant is not polymorphic. Thus, our aim is to identify novel functional variants in the NPY and to investigate the impact of these markers and others previously described on alcohol consumption in this population. A total of 911 subjects (321 men and 590 women) from the Spanish Mediterranean population were recruited. Alcohol consumption, and demographic and lifestyle variables were measured. Nucleotide sequence determination and SNP analyses were carried out. Only one exonic SNP was detected by direct sequencing (1258 G>A or rs9785023; allele frequency 0.47). From the intronic markers chosen (483 A>G or rs13235938, 2517 A>G or rs4722342, and 7065 A>G or rs4722343), only the two latter ones were polymorphic (allele frequencies 0.46 and 0.04, respectively), and none of them were associated with alcohol consumption. However, the 1258 G>A SNP was associated (recessive pattern) with higher alcohol intake. This association was particularly relevant in men with high alcohol intake (59.1±5.0 g/day in AA as opposed to 40.6±7.5 in the G carriers, P=.022) and women with moderate alcohol intake (7.3±5.5 g/day in AA as opposed to 4.6±3.9g/day in G carriers, P=.048). The 1258 G>A polymorphism in the NPY is associated with higher alcohol consumption in the Mediterranean population., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction: Coffee and tea consumption recommendations for a healthy diet have been changing in recent years as it has increased the level of evidence on their benefits has increased., Objective: To know the frequency of coffee and tea consumption of in a high cardiovascular risk Mediterranean population (CVR) and to analyze whether there are differences between the consumption of these drinks by cardiovascular risk factors., Methods: A cross-sectional study was carried out on 945 people (340 males, 605 females) (67.4+/-6.2 years old) with high CVR recruited in primary care centres of Valencia, included in the PREDIMED study. Coffee and tea consumption has been determined through a validated questionnaire. We analyzed biochemical, clinical and anthropometric variables by standard methods., Results: Tea consumption is very low in this Mediterranean population (0.4+/-1.6 cups/weeks). By contrast, coffee consumption averaged nearly one cup per day (6.5+/-5.2 cups/weeks). Hypertensive patients showed a lower overall consumption of coffee than in non-hypertensive patients (6.6+/-5.1 vs 7.3+/-5.9; P=0.023 respectively). These differences were greatest when caffeinated coffee consumption is analyzed (2.9+/-4.5 vs 4.3+/-5.3, P<0001). Moreover, diabetics consumed significantly less coffee and tea than non-diabetics (P=0.015 and P=0.022 respectively), these differences being greater for caffeinated coffee (P<0.025)., Conclusions: In conclusion, in this high cardiovascular risk Mediterranean population a coffee consumption pattern, based on traditional recommendations, is observed, that as a result of new scientific evidence should be update.

Background: Peroxisome Proliferator-Activated Receptors (PPARs) and its co-activators are regulatory elements of the cellular lipid homeostasis and have been associated with feeding behavior modulation. Animal models suggest that these genes may be involved in alcohol consumption regulation. However, no studies in humans exist. Our aim is to estimate the possible association between polymorphisms in the PPAR-alpha, PPAR-gamma and PPAR-gamma co-activator 1A (PGC-1A) genes and alcohol consumption in humans., Methods: We have conducted a cross-sectional study between the PPAR-alpha L162V, PPAR-gamma P12A and PGC-1A G482S polymorphisms, and alcohol consumption in a general Mediterranean Spanish population (303 men and 443 women)., Results: We have found an association between the L162V polymorphism and alcohol consumption in which, carriers of the V allele were more prevalent among alcohol consumers (19.4% vs. 9.8%; OR 2.69; 95% CI: 1.31-5.54, p=0.007). The G482S polymorphism showed a significantly higher frequency in the group of high alcohol drinkers than in non-high alcohol drinkers (33.4% vs. 20.6%; OR 2.28; 95% CI: 1.07-4.88, p=0.034). Mean alcohol consumption was higher as the number of G alleles increased (GG 8.6+/-12.8 g/day, GS 6.6+/-9.2 g/day, SS 5.6+/-7.8 g/day, p=0.003). These results remained statistically significant after covariate adjustment., Conclusions: PPAR-alpha L162V and PGC-1A G482S polymorphisms are associated with alcohol consumption in the Mediterranean population.