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Tresserra-Rimbau A.,University of Barcelona | Tresserra-Rimbau A.,CIBER ISCIII | Rimm E.B.,Harvard University | Medina-Remon A.,University of Barcelona | And 39 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2014

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. Clinical trial registry: International Standard Randomized Controlled Trial Number (ISRCTN of London, England) 35739639. © 2014 Elsevier B.V.


Mayneris-Perxachs J.,CIBER ISCIII | Guerendiain M.,University of Barcelona | Castellote A.I.,CIBER ISCIII | Castellote A.I.,University of Barcelona | And 16 more authors.
Clinical Nutrition | Year: 2014

Background & aims: The metabolic syndrome (MetS) is a clustering of various metabolic abnormalities which is associated with increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus. Due to its increasing prevalence, it has become an important public health concern. Altered fatty acid (FA) composition and desaturase activities have been associated with several metabolic diseases, including MetS. The aim of the present study was to evaluate the relationship of the plasma FA profile and desaturase activities with the MetS in a Mediterranean population at high risk of CVD. Methods: Baseline data from 427 participants aged 55-80 years who took part in the interventional PREDIMED study were obtained. Individual FA was determined in plasma and desaturase activities were estimated from product/precursor ratios. Odds ratios (OR) and partial correlation coefficients were used to examine these relations with MetS and its components, respectively. Results: We found higher levels of C14:0, C16:0, C16:1n-7, estimated δ9- or stearoyl-CoA desaturase (SCD), and estimated δ6 desaturase (D6D), and lower levels of C18:2n-6 in people with MetS compared to those without it. After adjustment for several confounders, only higher quartiles of C14:0, C16:0, C16:1n-7, and D6D were found to be associated with an increasing prevalence of MetS, while higher quartiles of C18:2n-6 were inversely associated with MetS. High proportions of C14:0, C16:0, C16:1n-7, C20:3n-6, SCD, and D6D, and decreased proportions of C18:2n-6 and estimated δ5-desaturase (D5D) were associated with adverse profiles of several metabolic risk factors. Women showed more unhealthy FA pattern and lipid profiles than men, but only among those with MetS. Conclusion: A FA composition and estimated desaturase activities consisting in high levels of SFA, SCD and D6D, and low levels of PUFA and D5D are associated with increased MetS probability and are characteristic of people presenting MetS, especially women. These findings support those observed in non-Mediterranean populations in which an altered FA profile and estimated desaturase activities are associated with MetS. © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.


Corella D.,University of Valencia | Corella D.,CIBER ISCIII | Carrasco P.,University of Valencia | Carrasco P.,CIBER ISCIII | And 41 more authors.
Diabetes Care | Year: 2013

Objective - Transcription factor 7-like 2 (TCF7L2) polymorphisms are strongly associated with type 2 diabetes, but controversially with plasma lipids and cardiovascular disease. Interactions of theMediterranean diet (MedDiet) on these associations are unknown. We investigated whether the TCF7L2-rs7903146 (C>T) polymorphism associations with type 2 diabetes, glucose, lipids, and cardiovascular disease incidence were modulated by MedDiet. Research Design and Methods - A randomized trial (twoMedDiet intervention groups and a control group) with 7,018 participants in the PREvención con DIetaMEDiterránea study was undertaken and major cardiovascular events assessed. Data were analyzed at baseline and after a median follow-up of 4.8 years. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) for cardiovascular events. Results - The TCF7L2-rs7903146 polymorphismwas associated with type 2 diabetes (odds ratio 1.87 [95% CI 1.62-2.17] for TT compared with CC). MedDiet interacted significantly with rs7903146 on fasting glucose at baseline (P interaction = 0.004).When adherence to theMedDiet was low, TT had higher fasting glucose concentrations (132.3 ± 3.5 mg/dL) than CC+CT (127.3 ± 3.2 mg/dL) individuals (P = 0.001). Nevertheless, when adherence was high, this increase was not observed (P = 0.605). This modulation was also detected for total cholesterol, LDL cholesterol, and triglycerides (P interaction < 0.05 for all). Likewise, in the randomized trial, TT subjects had a higher stroke incidence in the control group (adjusted HR 2.91 [95%CI 1.36- 6.19]; P = 0.006 compared with CC), whereas dietary intervention with MedDiet reduced stroke incidence in TT homozygotes (adjustedHR 0.96 [95%CI 0.49-1.87]; P = 0.892 for TT compared with CC). Conclusions - Our novel results suggest that MedDiet may not only reduce increased fasting glucose and lipids in TT individuals, but also stroke incidence. © 2013 by the American Diabetes Association.


Tresserra-Rimbau A.,University of Barcelona | Tresserra-Rimbau A.,CIBER ISCIII | Tresserra-Rimbau A.,Institute Salud Carlos III | Medina-Remon A.,University of Barcelona | And 38 more authors.
Nutrition, Metabolism and Cardiovascular Diseases | Year: 2013

Background and aims: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. Methods and results: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55-80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820±323mg day-1 (443±218mg day-1 of flavonoids and 304±156mg day-1 of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. Conclusion: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil. Clinical trial registry: International Standard Randomised Controlled Trial Number (ISRCTN of London, England) 35739639. © 2012 Elsevier B.V.


Corella D.,University of Valencia | Corella D.,CIBER ISCIII | Carrasco P.,University of Valencia | Carrasco P.,CIBER ISCIII | And 23 more authors.
Journal of Lipid Research | Year: 2010

Genome-wide association studies show that cholesteryl ester transfer protein (CETP) single nucleotide polymorphisms (SNPs) are more strongly associated with HDL cholesterol (HDL-C) concentrations than any other loci across the genome. However, gene-environment interactions for clinical applications are still largely unknown. We studied gene-environment interactions between CETP SNPs and dietary fat intake, adherence to the Mediterranean diet, alcohol consumption, smoking, obesity, and diabetes on HDL-C in 4,210 high cardiovascular risk subjects from a Mediterranean population. We focused on the -4,502C>T and the TaqIB SNPs in partial linkage disequilibrium (D = 0.88; P < 0.001). They were independently associated with higher HDL-C ( P < 0.001); this clinically relevant association was greater when their diplotype was considered (14% higher in TT/B2B2 vs. CC/B1B1). No gene-gene interaction was observed. We also analyzed the association of these SNPs with blood pressure, and no clinically relevant associations were detected. No statistically signifi cant interactions of these SNPs with obesity, diabetes, and smoking in determining HDL-C concentrations were found. Likewise, alcohol, dietary fat, and adherence to the Mediterranean diet did not statistically interact with the CETP variants (independently or as diplotype) in determining HDL-C. In conclusion, the strong association of the CETP SNPs and HDL-C was not statistically modified by diet or by the other environmental factors. Copyright © 2010 by the American Society for Biochemistry and Molecular Biology, Inc.


Tresserra-Rimbau A.,INSA Nutrition and Food Safety Research Institute | Tresserra-Rimbau A.,CIBER ISCIII | Guasch-Ferre M.,CIBER ISCIII | Guasch-Ferre M.,Rovira i Virgili University | And 37 more authors.
Journal of Nutrition | Year: 2016

Background: Higher consumption of some polyphenols has been associated with a reduced risk of diabetes. However, no studies have evaluated the relation between all polyphenol subclasses and the incidence of diabetes. Objective: We aimed to prospectively examine the associations between the intake of total polyphenols and different groups of polyphenols (flavonoids, phenolic acids, stilbenes, lignans, and others) on the risk of incident diabetes in the PREDIMED (Prevención con Dieta Mediterránea) trial. Methods: This was an observational cohort analysis of the nondiabetic participants in the PREDIMED trial. This study was a multicenter, controlled, randomized, parallel-group feeding trial to assess the effects of either a Mediterranean diet that was supplemented with extra-virgin olive oil or nuts or advice to adhere to a low-fat control diet on cardiovascular outcomes in elderly men and women at high cardiovascular disease risk. From the 7447 randomly assigned participants, 3430 were selected because they were free of diabetes at baseline and filled out the food-frequency questionnaires (FFQs). Polyphenol intake was calculated by matching food consumption data from repeated FFQs with the Phenol- Explorer database on the polyphenol content of each reported food. HRs and 95% CIs for diabetes according to tertiles of polyphenol intake were estimated with the use of time-dependent Cox proportional hazards models. Results: Over a mean of 5.51 y of follow-up (18,900 person-years), there were 314 new cases of diabetes. After multivariable adjustment, we observed a 28% reduction in new-onset diabetes in the highest compared with the lowest tertile of total polyphenol intake (HR: 0.72; 95% CI: 0.52, 0.99; P-trend = 0.05). The intake of subclasses of polyphenols also was inversely associated with diabetes risk, including for total flavonoids (HR: 0.67; 95% CI: 0.48, 0.93; P-trend = 0.02), stilbenes (HR: 0.57; 95% CI: 0.38, 0.84; P-trend = 0.003), dihydroflavonols (HR: 0.59; 95% CI: 0.40, 0.88; P-trend = 0.003), and flavanones (HR: 0.69; 95% CI: 0.49, 0.97; P-trend = 0.03). Conclusions: A high intake of total polyphenols, total flavonoids (specifically flavanones and dihydroflavonols), and stilbenes is associated with a reduced risk of diabetes in elderly persons at high risk of cardiovascular disease. © 2016 American Society for Nutrition.


Corella D.,University of Valencia | Corella D.,CIBER ISCIII | Sorli J.V.,University of Valencia | Sorli J.V.,CIBER ISCIII | And 39 more authors.
American Journal of Clinical Nutrition | Year: 2014

Background: MicroRNAs have emerged as important epigenetic regulators in cardiovascular diseases (CVDs). Using an observational meta-analysis design, we previously characterized a gain-of-function microRNA-410 target site polymorphism (rs13702T>C) in the 3'untranslated region of the lipoprotein lipase (LPL) gene. The C allele was associated with lower triglycerides, and this association was modulated by fat intake. Objectives: We aimed to extend our findings by assessing the interaction between the rs13702 polymorphism and fat intake on triglycerides at baseline and longitudinally by using a dietary intervention design. We also examined as a primary outcome the association of this variant with CVD incidence and its modulation by the Mediterranean diet (MedDiet). Design: We studied 7187 participants in the PREDIMED (Prevención con Dieta Mediterránea) randomized trial that tested a MedDiet intervention compared with a control diet, with a median 4.8-y follow-up. LPL polymorphisms and triglycerides were determined and CVD assessed. Gene-diet interactions for triglycerides were analyzed at baseline (n = 6880) and after a 3-y intervention (n = 4131). Oxidative stress parameters were investigated in a subsample. Results: The rs13702T>C polymorphism was strongly associated with lower triglycerides in C allele carriers and interacted synergistically with dietary monounsaturated (P = 0.038) and unsaturated fat intake (P = 0.037), decreasing triglycerides at baseline. By 3 y, we observed a gene-diet interaction (P = 0.025) in which the C allele was associated with a greater reduction in triglycerides after intervention with MedDiet, high in unsaturated fat. Although the polymorphism was associated with lower stroke risk (HR: 0.74; 95% CI: 0.57, 0.97; P = 0.029 per C allele), this association reached statistical significance only in the MedDiet intervention (HR: 0.58; 95% CI: 0.37, 0.91; P = 0.019 in C compared with TT carriers), not in the control group (HR: 0.94; 95% CI: 0.55, 1.59; P = 0.805). Conclusion: We report a novel association between a microRNA target site variant and stroke incidence, which is modulated by diet in terms of decreasing triglycerides and possibly stroke risk in rs13702 C allele carriers after a high-unsaturated fat MedDiet intervention. This trial was registered at controlled-trials.com as ISRCTN35739639. © 2014 American Society for Nutrition.

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