Nuestros investigadores

Cristina Razquin Burillo

Publicaciones científicas más recientes (desde 2010)

Autores: Papandreou, C.; Sala-Vila, A.; Galie, S.; et al.
ISSN 1079-5642  Vol. 39  Nº 4  2019  págs. 819 - 825
Objective- To examine the associations between baseline levels of fatty acids in blood cell membranes and their 1-year changes with the incidence of coronary heart disease (CHD) in older adults at high cardiovascular disease risk. Approach and Results- This is a case-control study nested in the PREDIMED trial (Prevencion con Dieta Mediterranea), with 136 CHD cases and 272 controls (matched on age, sex, body mass index, intervention group, and time of permanence in the study to the time event). We used gas chromatography to measure the proportion of 22 fatty acids in blood cell membranes at baseline and after 1 year. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% CIs. After adjustment for classical CHD risk factors and multiple testing, 1 SD increase in baseline levels of C22:0, C24:0 and the sum of individual very long chain saturated fatty acids was associated with 56% (OR, 0.44 [95% CI, 0.28-0.69]), 59% (OR, 0.41 [95% CI, 0.25-0.65]), and 55% (OR, 0.45 [95% CI, 0.29-0.70]) a decreased odds of developing CHD, respectively. Baseline C20:1n9 was associated with higher odds of CHD (OR, 1.58 [95% CI, 1.25-2.00]). Conclusions- Higher levels of C22:0 and C24:0 were associated with a lower CHD incidence, whereas higher levels of C20:1n9 were associated with a higher risk. This study adds to the growing body of evidence suggesting potential differences in the cardiovascular disease effects of different types of circulating saturated fatty acids.
Autores: Munoz-Garcia, M.; Razquin, Cristina; et al.
ISSN 0213-9111  Vol. 33  Nº 5  2019  págs. 415 - 420
Objective: To compare the Spanish version of the modified Telephone Interview of Cognitive Status (STICS-m) with the Mini-Mental State Examination (MMSE) and predict its ability to detect the development of dementia. Method: 106 participants in a dietary intervention trial underwent face-to-face evaluation with the MMSE, and phone interview with the STICS-m. The correlation between STICS-m and MMSE was assessed with the intraclass correlation coefficient (ICC) of consistency. Secondly, 932 participants over 55 years old from the "Seguimiento Universidad de Navarra" cohort were evaluated with the STICS-m and data on dementia diagnosis were gathered (median follow-up time of 6.5 years). A logistic regression model evaluated the association between STICS-m score or 2-year changes in STICS-m score and risk of developing dementia, adjusting for ApoE, age and years of university education. Results: The ICC between the MMSE and the STICS-m was 0.31 (95% confidence interval [95%CI]: 0.13-0.48). The adjusted odds ratio (OR) for the development of dementia for each additional point in the baseline STICS-m score was 0.85 (95%Cl: 0.72-1.02; p =0.084). When considering the 2-year change in the STICS-m score as exposure, the OR for the development of dementia was 0.79 (95%CI: 0.67-0.93; p = 0.006). Conclusions: The weak correlation between the STICS-m and the MMSE reflects moderate-low concurrent validity. Even so, the STICS-m can be regarded as an useful tool in the epidemiological setting since increasing scores appear to be able to predict a lower risk of developing dementia. (C) 2018 SESPAS. Published by Elsevier Espana, S.L.U. This is an open access article under the CC BY-NC-ND license (
Autores: Abete, Itziar; Konieczna, J.; Zulet, María de los Ángeles, (Autor de correspondencia); et al.
ISSN 2190-5991  Vol. 10  Nº 5  2019  págs. 974 - 984
Background Sarcopenia is a progressive age-related skeletal muscle disorder associated with increased likelihood of adverse outcomes. Muscle wasting is often accompanied by an increase in body fat, leading to 'sarcopenic obesity'. The aim of the present study was to analyse the association of lifestyle variables such as diet, dietary components, physical activity (PA), body composition, and inflammatory markers, with the risk of sarcopenic obesity. Methods A cross-sectional analysis based on baseline data from the PREDIMED-Plus study was performed. A total of 1535 participants (48% women) with overweight/obesity (body mass index: 32.5 +/- 3.3 kg/m(2); age: 65.2 +/- 4.9 years old) and metabolic syndrome were categorized according to sex-specific tertiles (T) of the sarcopenic index (SI) as assessed by dual-energy X-ray absorptiometry scanning. Anthropometrical measurements, biochemical markers, dietary intake, and PA information were collected. Linear regression analyses were carried out to evaluate the association between variables. Results Subjects in the first SI tertile were older, less physically active, showed higher frequency of abdominal obesity and diabetes, and consumed higher saturated fat and less vitamin C than subjects from the other two tertiles (all P < 0.05). Multiple adjusted linear regression models evidenced significant positive associations across tertiles of SI with adherence to the Mediterranean dietary score (P-trend < 0.05), PA (P-trend < 0.0001), and the 30 s chair stand test (P-trend < 0.0001), whereas significant negative associations were found with an inadequate vitamin C consumption (P-trend < 0.05), visceral fat and leucocyte count (all P-trend < 0.0001), and some white cell subtypes (neutrophils and monocytes), neutrophil-to-lymphocyte ratio, and platelet count (all P-trend < 0.05). When models were additionally adjusted by potential mediators (inflammatory markers, diabetes, and waist circumference), no relevant changes were observed, only dietary variables lost significance. Conclusions Diet and PA are important regulatory mediators of systemic inflammation, which is directly involved in the sarcopenic process. A healthy dietary pattern combined with exercise is a promising strategy to limit age-related sarcopenia.
Autores: Papandreu, C.; Li, J.; Bullo, M., (Autor de correspondencia); et al.
ISSN 2045-2322  Vol. 9  2019  págs. 2892
Studies examining associations between purine metabolites and type 2 diabetes (T2D) are limited. We prospectively examined associations between plasma levels of purine metabolites with T2D risk and the modifying effects of transcription factor-7-like-2 (TCF7L2) rs7903146 polymorphism on these associations. This is a case-cohort design study within the PREDIMED study, with 251 incident T2D cases and a random sample of 694 participants (641 non-cases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 years). Metabolites were semi-quantitatively profiled with LC-MS/MS. Cox regression analysis revealed that high plasma allantoin levels, including allantoin-to-uric acid ratio and high xanthine-to-hypoxanthine ratio were inversely and positively associated with T2D risk, respectively, independently of classical risk factors. Elevated plasma xanthine and inosine levels were associated with a higher T2D risk in homozygous carriers of the TCF7L2-rs7903146 T-allele. The potential mechanisms linking the aforementioned purine metabolites and T2D risk must be also further investigated.
Autores: Chaffin, M. D.; Cao, L.; Deik, A. A.; et al.
ISSN 1535-3893  Vol. 18  Nº 3  2019  págs. 1446 - 1450
High-throughput metabolomics using liquid chromatography and mass spectrometry (LC/MS) provides a useful method to identify biomarkers of disease and explore biological systems. However, the majority of metabolic features detected from untargeted metabolomics experiments have unknown ion signatures, making it critical that data should be thoroughly quality controlled to avoid analyzing false signals. Here, we present a postalignment method relying on intermittent pooled study samples to separate genuine metabolic features from potential measurement artifacts. We apply the method to lipid metabolite data from the PREDIMED (PREvencion con Dleta MEDi-terranea) study to demonstrate clear removal of measurement artifacts. The method is publicly available as the R package MetProc, available on CRAN under the GPL-v2 license.
Autores: Muralidharan, J.; Papandreou, C.; Sala-Vila, A.; et al.
ISSN 2072-6643  Vol. 11  Nº 3  2019  págs. 576
There is limited evidence from epidemiological studies for the inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes. Therefore, this study examined associations between baseline (n = 282) and 1-year (n = 143) changes in the levels of fatty acids in blood cell membranes with circulating inflammatory markers in older adults at high cardiovascular risk. The data for this cross-sectional analysis was obtained from a case-control study within the PREDIMED study. Linear regression with elastic net penalty was applied to test associations between measured fatty acids and inflammatory markers. Several fatty acids were associated with interferon-gamma (IFN gamma) and interleukins (ILs) IL-6, IL-8, and IL-10 at baseline and additionally also with IL-1b at 1 year. Omega-6 fatty acids were consistently positively associated with pro-inflammatory IL-6 and IL-8 at baseline. Omega-3 fatty acids including C20:5n3 and C18:3n3 were negatively associated with IFN-gamma at 1 year. It is interesting to note that the cis and trans forms of C16:1n7 at 1 year were oppositely associated with the inflammatory markers. C16:1n7trans was negatively associated with IFN-gamma, IL-6, IL-8, IL-10, and IL-1b, whereas C16:1n7cis was positively associated with IL-1b. This study adds to the growing body of evidence suggesting potential differences in inflammatory or anti-inflammatory properties of fatty acids in blood cell membranes.
Autores: Liu, X. R.; Zheng, Y.; Guasch-Ferre, M.; et al.
ISSN 0939-4753  Vol. 29  Nº 10  2019  págs. 1040 - 1049
Background and aims: Glutamate, glutamine are involved in energy metabolism, and have been related to cardiometabolic disorders. However, their roles in the development of type-2 diabetes (T2D) remain unclear. The aim of this study was to examine the effects of Mediterranean diet on associations between glutamine, glutamate, glutamine-to-glutamate ratio, and risk of new-onset T2D in a Spanish population at high risk for cardiovascular disease (CVD). Methods and results: The present study was built within the PREDIMED trial using a case-cohort design including 892 participants with 251 incident T2D cases and 641 non-cases. Participants (mean age 66.3 years; female 62.8%) were non diabetic and at high risk for CVD at baseline. Plasma levels of glutamine and glutamate were measured at baseline and after 1-year of intervention. Higher glutamate levels at baseline were associated with increased risk of T2D with a hazard ratio (HR) of 2.78 (95%CI, 1.43-5.41, P for trend = 0.0002). In contrast, baseline levels of glutamine (HR: 0.64, 95% CI, 0.36-1.12; P for trend = 0.04) and glutamine-to-glutamate ratio (HR: 0.31, 95% CI, 0.16-0.57; P for trend = 0.0001) were inversely associated with T2D risk when comparing extreme quartiles. The two Mediterranean diets (MedDiet + EVOO and MedDiet + mixed nuts) did not alter levels of glutamine and glutamate after intervention for 1 year. However, MedDiet mitigated the positive association between higher baseline plasma glutamate and T2D risk (P for interaction = 0.01). Conclusion: Higher levels of glutamate and lower levels of glutamine were associated with increased risk of T2D in a Spanish population at high risk for CVD. Mediterranean diet might mitigate the association between the imbalance of glutamine and glutamate and T2D risk. This trial is registered at, ISRCTN35739639. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
Autores: Yu, E.; Ruiz-Canela, Miguel; Razquin, Cristina; et al.
ISSN 1462-8902  Vol. 21  Nº 2  2019  págs. 397 - 401
The associations between arginine-based metabolites and incident type 2 diabetes (T2D) are unknown. We employed a case-cohort design, nested within the PREDIMED trial, to examine six plasma metabolites (arginine, citrulline, ornithine, asymmetric dimethylarginine [ADMA], symmetric dimethylarginine [SDMA] and N-monomethyl-l-arginine [NMMA]) among 892 individuals (251 cases) for associations with incident T2D and insulin resistance. Weighted Cox models with robust variance were used. The 1-year changes in arginine (adjusted hazard ratio [HR] per SD 0.68, 95% confidence interval [CI] 0.49, 0.95; Q4 vs. Q1 0.46, 95% CI 0.21, 1.04; P trend = 0.02) and arginine/ADMA ratio (adjusted HR per SD 0.73, 95% CI 0.51, 1.04; Q4 vs. Q1 0.52, 95% CI 0.22, 1.25; P trend = 0.04) were associated with a lower risk of T2D. Positive changes of citrulline and ornithine, and negative changes in SDMA and arginine/(ornithine + citrulline) were associated with concurrent 1-year changes in homeostatic model assessment of insulin resistance. Individuals in the low-fat-diet group had a higher risk of T2D for 1-year changes in NMMA than individuals in Mediterranean-diet groups (P interaction = 0.02). We conclude that arginine bioavailability is important in T2D pathophysiology.
Autores: Papandreou, C.; Hernandez-Alonso, P.; Bullo, M., (Autor de correspondencia); et al.
ISSN 2072-6643  Vol. 11  Nº 5  2019  págs. E1032
Few studies have examined the association of a wide range of metabolites with total and subtypes of coffee consumption. The aim of this study was to investigate associations of plasma metabolites with total, caffeinated, and decaffeinated coffee consumption. We also assessed the ability of metabolites to discriminate between coffee consumption categories. This is a cross-sectional analysis of 1664 participants from the PREDIMED study. Metabolites were semiquantitatively profiled using a multiplatform approach. Consumption of total coffee, caffeinated coffee and decaffeinated coffee was assessed by using a validated food frequency questionnaire. We assessed associations between 387 metabolite levels with total, caffeinated, or decaffeinated coffee consumption (50 mL coffee/day) using elastic net regression analysis. Ten-fold cross-validation analyses were used to estimate the discriminative accuracy of metabolites for total and subtypes of coffee. We identified different sets of metabolites associated with total coffee, caffeinated and decaffeinated coffee consumption. These metabolites consisted of lipid species (e.g., sphingomyelin, phosphatidylethanolamine, and phosphatidylcholine) or were derived from glycolysis (alpha-glycerophosphate) and polyphenol metabolism (hippurate). Other metabolites included caffeine, 5-acetylamino-6-amino-3-methyluracil, cotinine, kynurenic acid, glycocholate, lactate, and allantoin. The area under the curve (AUC) was 0.60 (95% CI 0.56-0.64), 0.78 (95% CI 0.75-0.81) and 0.52 (95% CI 0.49-0.55), in the multimetabolite model, for total, caffeinated, and decaffeinated coffee consumption, respectively. Our comprehensive metabolic analysis did not result in a new, reliable potential set of metabolites for coffee consumption.
Autores: Papandreou, C.; Bullo, M., (Autor de correspondencia); Ruiz-Canela, Miguel; et al.
ISSN 0002-9165  Vol. 109  Nº 3  2019  págs. 626 - 634
Background: Insulin resistance is a complex metabolic disorder and is often associated with type 2 diabetes (T2D). Objectives: The aim of this study was to test whether baseline metabolites can additionally improve the prediction of insulin resistance beyond classical risk factors. Furthermore, we examined whether a multimetabolite model predicting insulin resistance in nondiabetics can also predict incident T2D. Methods: We used a case-cohort study nested within the Prevencion con Dieta Mediterranea (PREDIMED) trial in subsets of 700, 500, and 256 participants without T2D at baseline and 1 and 3 y. Fasting plasma metabolites were semiquantitatively profiled with liquid chromatography-tandem mass spectrometry. We assessed associations between metabolite concentrations and the homeostasis model of insulin resistance (HOMA-IR) through the use of elastic net regression analysis. We subsequently examined associations between the baseline HOMA-IR-related multimetabolite model and T2D incidence through the use of weighted Cox proportional hazard models. Results: We identified a set of baseline metabolites associated with HOMA-IR. One-year changes in metabolites were also significantly associated with HOMA-IR. The area under the curve was significantly greater for the model containing the classical risk factors and metabolites together compared with classical risk factors alone at baseline [0.81 (95% CI: 0.79, 0.84) compared with 0.69 (95% CI: 0.66, 0.73)] and during a 1-y period [0.69 (95% CI: 0.66, 0.72) compared with 0.57 (95% CI: 0.53, 0.62)]. The variance in HOMA-IR explained by the combination of metabolites and classical risk factors was also higher in all time periods. The estimated HRs for incident T2D in the multimetabolite score (model 3) predicting high HOMA-IR (median value or higher) or HOMA-IR (continuous) at baseline were 2.00 (95% CI: 1.58, 2.55) and 2.24 (95% CI: 1.72, 2.90), respectively, after adjustment for T2D risk factors. Conclusions: The multimetabolite model identified in our study notably improved the predictive ability for HOMA-IR beyond classical risk factors and significantly predicted the risk of T2D.
Autores: Ruiz-Canela, Miguel, (Autor de correspondencia); Guasch-Ferre, M. ; Toledo, Estefanía Ainhoa; et al.
ISSN 0012-186X  Vol. 61  Nº 7  2018  págs. 1560 - 1571
Aims/hypothesis Branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with type 2 diabetes. However, repeated measurements of BCAA/AAA and their interactions with dietary interventions have not been evaluated. We investigated the associations between baseline and changes at 1 year in BCAA/AAA with type 2 diabetes in the context of a Mediterranean diet (MedDiet) trial. Methods We included 251 participants with incident type 2 diabetes and a random sample of 694 participants (641 participants without type 2 diabetes and 53 overlapping cases) in a case-cohort study nested within the PREvencin con DIeta MEDiterranea (PREDIMED) trial. Participants were randomised to a MedDiet+extra-virgin olive oil (n = 273), a MedDiet+nuts (n = 324) or a control diet (n = 295). We used LC-MS/MS to measure plasma levels of amino acids. Type 2 diabetes was a pre-specified secondary outcome of the PREDIMED trial. Results Elevated plasma levels of individual BCAAs/AAAs were associated with higher type 2 diabetes risk after a median follow-up of 3.8 years: multivariable HR for the highest vs lowest quartile ranged from 1.32 for phenylalanine ([95% CI 0.90, 1.92], p for trend = 0.015) to 3.29 for leucine ([95% CI 2.03, 5.34], p for trend<0.001). Increases in BCAA score at 1 year were associated with higher type 2 diabetes risk in the control group with HR per SD = 1.61 (95% CI 1.02, 2.54), but not in the MedDiet groups (p for interaction <0.001). The MedDiet+extra-virgin olive oil significantly reduced BCAA levels after 1 year of intervention (p = 0.005 vs the control group). Conclusions/interpretation Our results support that higher baseline BCAAs and their increases at 1 year were associated with higher type 2 diabetes risk. A Mediterranean diet rich in extra-virgin olive oil significantly reduced the levels of BCAA and attenuated the positive association between plasma BCAA levels and type 2 diabetes incidence.
Autores: Razquin, Cristina; Liang, L. M.; Toledo, Estefanía Ainhoa; et al.
ISSN 0167-5273  Vol. 253  2018  págs. 126 - 132
Background: The study of the plasma lipidome may help to better characterize molecular mechanisms underlying cardiovascular disease. The identification of new lipid biomarkers could provide future targets for prevention and innovative therapeutic approaches. In the frame of the PREDIMED trial, our aim was to examine the associations of baseline lipidome patterns or their changes with the risk of clinical CVD events. Methods: We included 983 participants in our case-cohort study. The end-point was the incidence of major CVD during 4.8 years of median follow-up. We repeatedly measured 202 plasma known lipid metabolites at baseline and after 1-year of intervention. Principal component analysis was used to identify lipidome factors. Among the 15 identified factors, 7 were significantly associated with CVD. Considering common patterns among factors, lipids were grouped (summed) into scores. Results: After adjustment for traditional CVD risk factors, scores of baseline polyunsaturated phosphatidylcholines (PC)/lysoPC/PC-plasmalogens and polyunsaturated cholesterol esters (CE) showed inverse associations with CVD (p = 0,036 and 0.012, respectively); whereas scores of monoacylglycerols (MAGs)/diacylglycerols (DAGs) and short triacylglycerols (TAGs) showed a direct association with CVD (p = 0,026 and 0.037, respectively). Baseline phosphatidylethanolamines (PEs) and their 1-y changes tended to be associated with higher CVD risk (p = 0.066 and 0.081, respectively). We did not find a significant effect of the intervention with the Mediterranean Diet on these scores. Conclusions: Our study suggests that polyunsaturated PCs and CEs may confer protection against CVD. In contrast, MAGs, DAGs, TAGs and PEs appeared to be associated with higher CVD risk. (c) 2017 Elsevier B.V. All rights reserved.
Autores: Papandreou, C. ; Bullo, M., (Autor de correspondencia); Zheng, Y. ; et al.
ISSN 0002-9165  Vol. 108  Nº 1  2018  págs. 163 - 173
Background: The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective: The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design: This is a case-cohort design study within the Prevencion con Dieta Mediterranea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, a-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results: After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and a-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16: 0 LPC, C18: 1 LPC, C18: 0 LPC, C20: 4 LPC, C22: 6 LPC, C18: 1 LPC plasmalogen, and C16: 0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion: Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated.
Autores: Yu, E.; Papandreou, C.; Ruiz-Canela, Miguel; et al.
ISSN 0009-9147  Vol. 64  Nº 8  2018  págs. 1211 - 1220
BACKGROUND: Metabolites of the tryptophan-kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case-cohort design nested in the Prevencion con Dieta Mediterranea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS: Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS: Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04-1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09-1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS: Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity. (C) 2018 American Association for Clinical Chemistry
Autores: Razquin, Cristina; Rojo-Bustamante, E.; et al.
ISSN 0197-4580  Vol. 66  2018  págs. 177.e7 - 177.e10
The main genetic risk factors for progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are located at chromosome 17q21.31. The identification of risk H1 subhaplotypes suggests that disease-specific variants can be identified by resequencing the 17q21.31 region (1.4 Mb) in carriers of risk H1 subhaplotypes. We hypothesized that PSP/CBD H1 subhaplotype carriers could have undergone a mutational event absent among unaffected carriers leading to the disease risk. We performed this strategy in definite PSP subjects, definite CBD subjects, and healthy controls and tried to replicate the findings in a larger PSP/CBD case-control series. In the resequencing process, 40 candidate variants were identified, but an association between PSP and rs76970862 was replicated only using an unadjusted model. Gene expression association analysis of this variant suggested no potential functional effect. Although our results failed to identify disease-associated variants, it is still possible that the risk of PSP/CBD at chromosome 17 is driven by rare variants, even in PSP/CBD H1 cases or variants located outside the capture regions. (C) 2018 Elsevier Inc. All rights reserved.
Autores: de la Fuente-Arrillaga, Carmen; Bes-Rastrollo, Maira; et al.
ISSN 0212-1611  Vol. 35  Nº 1  2018  págs. 153 - 161
Introduction and objectives: Our aim was to prospectively evaluate the association between egg consumption and dyslipidemia in a Mediterranean cohort. Methods: We followed-up 13,104 Spanish university graduates for a mean period of 8 years. Dietary habits at baseline were assessed using a validated semi-quantitative 136-item food-frequency questionnaire. Self-reported blood concentrations of total cholesterol, high-density lipoproteins cholesterol (HDL-c) and triglycerides were evaluated according to categories of egg consumption after 6 and 8 years of follow-up. We also assessed the association between baseline egg consumption and the incidence of hypercholesterolemia, low HDL-c concentrations and hypertriglyceridemia during follow-up. Results: We observed a significant inverse association for intermediate levels of egg consumption (2 to 4 eggs/week vs. less than 1 egg/week) and hypertriglyceridemia with OR = 0.71 (95% confidence interval [CI]: 0.54 to 0.93, p < 0.05) in the multivariable-adjusted model. Using HDL-c values after 8-year follow-up, we found an association between higher egg consumption and lower HDL-c levels (p for trend = 0.02) with an adjusted difference of -4.01 mg/dl (-7.42 to -0.61) for > 4 vs. < 1 egg/week. Lower means of triglycerides were found in each of the three upper categories of egg consumption compared to the lowest category (< 1 egg/week) with significant results for some of these categories both after 6 and 8 year follow-up. Conclusions: Our data do not support that higher egg consumption was associated with abnormal blood levels of total cholesterol or triglycerides; an inverse association with HDL-c as a quantitative variable was found only in one of our analyses.
Autores: Razquin, Cristina; Toledo, Estefanía Ainhoa; Clish, C. B.; et al.
ISSN 0149-5992  Vol. 41  Nº 12  2018  págs. 2617 - 2624
OBJECTIVE Specific lipid molecular changes leading to type 2 diabetes (T2D) are largely unknown. We assessed lipidome factors associated with future occurrence of T2D in a population at high cardiovascular risk. RESEARCH DESIGN AND METHODS We conducted a case-cohort study nested within the PREDIMED trial, with 250 incident T2D cases diagnosed during 3.8 years of median follow-up, and a random sample of 692 participants (639 noncases and 53 overlapping cases) without T2D at baseline. We repeatedly measured 207 plasma known lipid metabolites at baseline and after 1 year of follow-up. We built combined factors of lipid species using principal component analysis and assessed the association between these lipid factors (or their 1-year changes) and T2D incidence. RESULTS Baseline lysophosphatidylcholines and lysophosphatidylethanolamines (lysophospholipids [LPs]), phosphatidylcholine-plasmalogens (PC-PLs), sphingomyelins (SMs), and cholesterol esters (CEs) were inversely associated with risk of T2D (multivariable-adjusted P for linear trend <0.001 for all). Baseline triacylglycerols (TAGs), diacylglycerols (DAGs), and phosphatidylethanolamines (PEs) were positively associated with T2D risk (multivariable-adjusted P for linear trend <0.001 for all). One-year changes in these lipids showed associations in similar directions but were not significant after adjustment for baseline levels. TAGs with odd-chain fatty acids showed inverse associations with T2D after adjusting for total TAGs. CONCLUSIONS Two plasma lipid profiles made up of different lipid classes were found to be associated with T2D in participants at high cardiovascular risk. A profile including LPs, PC-PLs, SMs, and CEs was associated with lower T2D risk. Another profile composed of TAGs, DAGs, and PEs was associated with higher T2D risk.
Autores: Ruiz-Canela, Miguel; Guasch-Ferre, M.; Toledo, Estefanía Ainhoa; et al.
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 173
Autores: Razquin, Cristina; Toledo, Estefanía Ainhoa; Clish, C.; et al.
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 179
Autores: Martínez, Miguel Ángel; Carlos, Silvia; de la Fuente-Arrillaga, Carmen; et al.
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 178
Autores: Papandreou, C.; Bullo, M. ; Zheng, Y. ; et al.
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 176
Autores: Perez, V. P. ; Romaguera, D.; Konieczna, J.; et al.
ISSN 0014-2972  Vol. 48  Nº Supl. 1  2018  págs. 171 - 171
Autores: Toledo, Estefanía Ainhoa; Wang, D. D.; Ruiz-Canela, Miguel; et al.
ISSN 0002-9165  Vol. 106  Nº 4  2017  págs. 973 - 983
Background: Lipid metabolites may partially explain the inverse association between the Mediterranean diet (MedDiet) and cardiovascular disease (CVD). Objective: We evaluated the associations between 1) lipid species and the risk of CVD (myocardial infarction, stroke, or cardiovascular death); 2) a MedDiet intervention [supplemented with extra virgin olive oil (EVOO) or nuts] and 1-y changes in these molecules; and 3) 1-y changes in lipid species and subsequent CVD. Design: With the use of a case-cohort design, we profiled 202 lipid species at baseline and after 1 y of intervention in the PREDIMED (PREvencion con DIeta MEDiterranea) trial in 983 participants [230 cases and a random subcohort of 790 participants (37 overlapping cases)]. Results: Baseline concentrations of cholesterol esters (CEs) were inversely associated with CVD. A shorter chain length and higher saturation of some lipids were directly associated with CVD. After adjusting for multiple testing, direct associations remained significant for 20 lipids, and inverse associations remained significant for 6 lipids. When lipid species were weighted by the number of carbon atoms and double bonds, the strongest inverse association was found for CEs [HR: 0.39 (95% CI: 0.22, 0.68)] between extreme quintiles (P-trend = 0.002). Participants in the MedDiet + EVOO and MedDiet + nut groups experienced significant (P < 0.05) 1-y changes in 20 and 17 lipids, respectively, compared with the control group. Of these changes, only those in CE(20:3) in the MedDiet + nuts group remained significant after correcting for multiple testing. None of the 1-y changes was significantly associated with CVD risk after correcting for multiple comparisons. Conclusions: Although the MedDiet interventions induced some significant 1-y changes in the lipidome, they were not significantly associated with subsequent CVD risk. Lipid metabolites with a longer acyl chain and higher number of double bonds at baseline were significantly and inversely associated with the risk of CVD.
Autores: Wang, D. D.; Toledo, Estefanía Ainhoa; Hruby, A.; et al.
ISSN 0009-7322  Vol. 135  Nº 21  2017  págs. 2028 - 2040
BACKGROUND: Although in vitro studies and investigations in animal models and small clinical populations have suggested that ceramides may represent an intermediate link between overnutrition and certain pathological mechanisms underlying cardiovascular disease (CVD), no prospective studies have investigated the association between plasma ceramides and risk of CVD. METHODS: The study population consisted of 980 participants from the PREDIMED trial (Prevencion con Dieta Mediterranea), including 230 incident cases of CVD and 787 randomly selected participants at baseline ( including 37 overlapping cases) followed for <= 7.4 years. Participants were randomized to a Mediterranean diet supplemented with extra virgin olive oil, a Mediterranean diet supplemented with nuts, or a control diet. Plasma ceramide concentrations were measured on a liquid chromatography tandem mass spectrometry metabolomics platform. The primary outcome was a composite of nonfatal acute myocardial infarction, nonfatal stroke, or cardiovascular death. Hazard ratios were estimated with weighted Cox regression models using Barlow weights to account for the case-cohort design. RESULTS: The multivariable hazard ratios (HR) and 95% confidence intervals (Cls) comparing the extreme quartiles of plasma concentrations of C16:0, C22:0, C24:0, and C24: 1 ceramides were 2.39 (1.49-3.83, P-trend < 0.001), 1.91 (1.21-3.01, P-trend = 0.003), 1.97 (1.21-3.20, P-trend = 0.004), and 1.73 (1.09-2.74, P-trend = 0.011), respectively. The ceramide score, calculated as a weighted sum of concentrations of four ceramides, was associated with a 2.18-fold higher risk of CVD across extreme quartiles (HR, 2.18; 95% Cl, 1.36-3.49; P-trend < 0.001). The association between baseline ceramide score and incident CVD varied significantly by treatment groups (P-interaction = 0.010). Participants with a higher ceramide score and assigned to either of the 2 active intervention arms of the trial showed similar CVD risk to those with a lower ceramide score, whereas participants with a higher ceramide score and assigned to the control arm presented significantly higher CVD risk. Changes in ceramide concentration were not significantly different between Mediterranean diet and control groups during the first year of follow-up. CONCLUSIONS: Our study documented a novel positive association between baseline plasma ceramide concentrations and incident CVD. In addition, a Mediterranean dietary intervention may mitigate potential deleterious effects of elevated plasma ceramide concentrations on CVD.
Autores: Razquin, Cristina; Sánchez Tainta, Ana; Salas-Salvado, J. ; et al.
ISSN 0963-7486  Vol. 68  Nº 7  2017  págs. 865 - 872
The association of dietary energy density (ED) and overweight is not clear in the literature. Our aim was to study in 4259 of the PREDIMED trial whether an increase in dietary ED based on a higher adherence to a Mediterranean dietary pattern was associated with 3-year weight gain.A validated 137-item food-frequency questionnaire was administered. Multivariable-adjusted models were used to analyze the association between 3-year ED change and the subsequent 3-year body weight change.The most important weight reduction after 3-year follow-up was observed in the two lowest quintiles and the highest quintile of ED change. The highest ED increase was characterized by an increased intake of extra virgin olive oil (EVOO) and nuts and a decreased intake of other oils, vegetable and fruit consumption (p<.001).In conclusion, increased 3-year ED in the PREDIMED study, associated with a higher EVOO and nuts consumption, was not associated with weight gain.
Autores: Arpón, A.; Riezu-Boj, José Ignacio; Milagro FI; et al.
ISSN 1138-7548  Vol. 73  Nº 3  2017  págs. 445 - 455
Epigenetic processes, including DNA methylation, might be modulated by environmental factors such as the diet, which in turn have been associated with the onset of several diseases such as obesity or cardiovascular events. Meanwhile, Mediterranean diet (MedDiet) has demonstrated favourable effects on cardiovascular risk, blood pressure, inflammation and other complications related to excessive adiposity. Some of these effects could be mediated by epigenetic modifications. Therefore, the objective of this study was to investigate whether the adherence to MedDiet is associated with changes in the methylation status from peripheral blood cells. A subset of 36 individuals was selected within the Prevencion con Dieta Mediterranea (PREDIMED)-Navarra study, a randomised, controlled, parallel trial with three groups of intervention in high cardiovascular risk volunteers, two with a MedDiet and one low-fat control group. Changes in methylation between baseline and 5 years were studied. DNA methylation arrays were analysed by several robust statistical tests and functional classifications. Eight genes related to inflammation and immunocompetence (EEF2, COL18A1, IL4I1, LEPR, PLAGL1, IFRD1, MAPKAPK2, PPARGC1B) were finally selected as changes in their methylation levels correlated with adherence to MedDiet and because they presented sensitivity related to a high variability in methylation changes. Additionally, EEF2 methylation levels positively correlated with concentrations of TNF-alph
Autores: Dols-Icardo, O.; Iborra, O.; Valdivia, J.; et al.
ISSN 0197-4580  Vol. 38   Nº 1  2016  págs. 215.e13 - 215.e14
The tubulin alpha 4a (TUBA4A) gene has been recently associated with amyotrophic lateral sclerosis. Interestingly, some of the mutation carriers were also diagnosed with frontotemporal degeneration (FTD) or mild cognitive impairment. With the aim to investigate the role of TUBA4A in FTD, we screened TUBA4A in a series of 814 FTD patients from Spain. Our data did not disclose any nonsense or missense variant in the cohort, thus suggesting that TUBA4A mutations are not associated with FTD.
Autores: Martínez, Miguel Ángel; Razquin, Cristina; et al.
ISSN 0261-5614  Vol. 35  Nº 6  2016  págs. 1399 - 1405
Background & aims A healthy lifestyle has been associated with longer telomeres, but whether Mediterranean Diet (MeDiet) affect telomere length (TL) has not been fully elucidated yet. Our aim was to assess the relationship between MeDiet and TL in high cardiovascular risk subjects in the context of a randomized nutritional intervention trial. Methods We assessed 520 participants (55¿80 years, 55% women) from the PREDIMED-NAVARRA trial. Leukocyte TL was measured by qPCR at baseline and after 5 years of a dietary intervention program where subjects were randomly assigned to a low-fat control diet or to two MeDiets, one supplemented with extra virgin olive oil (MeDiet-EVOO) and the other with mixed nuts (MeDiet-nuts). A validated 14-item questionnaire was used to appraise baseline adherence of participants to the MeDiet. Results Better adherence to MeDiet (as appraised by the 14-item score) was associated with longer basal telomeres in women in the baseline cross-sectional analysis, whereas the opposite was observed in men (P interaction = 0.036). Female subjects who scored 10 points had longer basal telomeres (0.27, 95% CI: 0.03¿0.52) than women scoring ¿6 points at the beginning of the study (¿0.46, 95% CI: ¿0.85 to ¿0.7) (P = 0.003). However, allocation to the MeDiet-nuts group (¿0.24, 95% CI: ¿0.38 to ¿0.01) was associated with a higher risk of telomere shortening after 5 years of intervention, whereas no differences were found for the MeDiet-EVOO group (0.14, 95% CI: 0.02¿0.27), in comparison with the Control group (0.07, 95% CI: ¿0.08 to 0.23) (P = 0.003 and P = 0.537, respectively). Conclusion A greater baseline adherence to a Mediterranean dietary pattern was associated with longer telomeres only in women. No beneficial effect of the intervention with the MeDiet for the prevention of telomere shortening in comparison with a low-fat diet was observed.
Autores: Ajona, Daniel; Razquin, Cristina; Pastor, M. D.; et al.
Revista: PLOS ONE
ISSN 1932-6203  Vol. 10  Nº 3  2015  págs. e0119878
Molecular markers in bronchial fluids may contribute to the diagnosis of lung cancer. We previously observed a significant increase of C4d-containing complement degradation fragments in bronchoalveolar lavage (BAL) supernatants from lung cancer patients in a cohort of 50 cases and 22 controls (CUN cohort). The present study was designed to determine the diagnostic performance of these complement fragments (hereinafter jointly referred as C4d) in bronchial fluids. C4d levels were determined in BAL supernatants from two independent cohorts: the CU cohort (25 cases and 26 controls) and the HUVR cohort (60 cases and 98 controls). A series of spontaneous sputum samples from 68 patients with lung cancer and 10 controls was also used (LCCCIO cohort). Total protein content, complement C4, complement C5a, and CYFRA 21-1 were also measured in all cohorts. C4d levels were significantly increased in BAL samples from lung cancer patients. The area under the ROC curve was 0.82 (95%CI = 0.71-0.94) and 0.67 (95%CI = 0.58-0.76) for the CU and HUVR cohorts, respectively. In addition, unlike the other markers, C4d levels in BAL samples were highly consistent across the CUN, CU and HUVR cohorts. Interestingly, C4d test markedly increased the sensitivity of bronchoscopy in the two cohorts in which cytological data were available (CUN and HUVR cohorts). Finally, in the LCCCIO cohort, C4d levels were higher in sputum supernatants from patients with lung cancer (area under the ROC curve: 0.7; 95%CI
Autores: Martínez, Miguel Ángel; Razquin, Cristina; et al.
ISSN 1942-325X  Vol. 8  Nº 1  2015  págs. 91 - 99
García-Calzón S, Martinez-González MA, Razquin C, Corella D, Salas-Salvadó J, Martinez JA, Zalba G, Marti A. Background: The gene variant Pro/Ala (rs1801282) in the PPAR¿2 has been associated with lower cardiovascular risk and greater benefit from lifestyle interventions. This polymorphism also seems to be associated with longer lifespan, but no information on telomere length (TL) is available. Our aim was to study the association between the Ala allele and changes in TL in high cardiovascular risk subjects, and the potential interaction with a Mediterranean Diet (MeDiet) pattern. Methods and Results: A total of 521 subjects (55-80 years) participating in the Prevención con Dieta Mediterránea (PREDIMED) randomized trial were genotyped. Changes in TL, measured by quantitative real-time PCR, were assessed over 5 years of a nutritional intervention which promoted adherence to the MeDiet. Interestingly, Ala carriers showed lower telomere shortening after 5 years, compared with the Pro/Pro genotype (P=0.031). This association was modulated by MeDiet since those Ala carriers who reported better conformity to the MeDiet exhibited increased TL (P<0.001). Moreover, a reduction in carbohydrate intake (¿9.5 g/d) resulted in increased TL among Ala carriers. Notably, an apparent gene-diet interaction was found through the observed changes in the MUFA+PUFA/Carbohydrates ratio: as this ratio increased, TL lengthening was detected to a greater extent in the Ala carriers compared with the Pro/Pro subjects (P for interaction <0.001). Conclusions: The Pro12Ala polymorphism is associated with TL homeostasis after 5 years follow-up in subjects at high cardiovascular risk. In addition, a higher adherence to the MeDiet
Autores: Mathias Thelen; Razquin, Cristina; Isabel Hernandez; et al.
ISSN 0197-4580  Vol. 35  Nº 11  2014  págs. 2657.e13-e19
Frontotemporal dementia (FTD) is a clinically and genetically heterogeneous disorder. Rare TREM2 variants have been recently identified in families affected by FTD-like phenotype. However, genetic studies of the role of rare TREM2 variants in FTD have generated conflicting results possibly because of difficulties on diagnostic accuracy. The aim of the present study was to investigate associations between rare TREM2 variants and specific FTD subtypes (FTD-S). The entire coding sequence of TREM2 was sequenced in FTD-S patients of Spanish (n = 539) and German (n = 63) origin. Genetic association was calculated using Fisher exact test. The minor allele frequency for controls was derived from in-house genotyping data and publicly available databases. Seven previously reported rare coding variants (p.A28V, p.W44X, p.R47H, p.R62H, p.T66M, p.T96K, and p.L211P) and 1 novel missense variant (p.A105T) were identified. The p.R47H variant was found in 4 patients with FTD-S. Two of these patients showed cerebrospinal fluid pattern of amyloid beta, tau, and phosphorylated-tau suggesting underlying Alzheimer's disease (AD) pathology. No association was found between p.R47H and FTD-S. A genetic association was found between p.T96K and FTD-S (p = 0.013, odds ratio = 4.23, 95% Confidence Interval [1.17¿14.77]). All 6 p.T96K patients also carried the TREM2 variant p.L211P, suggesting linkage disequilibrium. The remaining TREM2 variants were found in 1 patient, respectively, and were absent in controls. The present findings provide evidence that p.T96K is associated with FTD-S and that p.L211P may contribute to its pathogenic effect. The data also suggest that p.R47H is associated with an FTD phenotype that is characterized by the presence of underlying AD pathology.
Autores: A. Gea; Razquin, Cristina; et al.
ISSN 0307-0565  Vol. 38  2014  págs. 177 - 182
Background:Telomeres are nucleoprotein structures that protect the ends of eukaryote chromosomes. Shorter telomere length (TL) is associated with some age-related human disorders, but its relationship with obesity or adiposity parameters remains unclear.Objective:The aim of this study was to assess the relationship between TL and changes in adiposity indices after a 5-year nutritional intervention.Design and subjects:TL was measured by quantitative real-time PCR in 521 subjects (55-80 years, 55% women). Participants were randomly selected from the PREDIMED-NAVARRA centre after they completed a 5-year intervention programme. Anthropometric parameters were directly measured by trained personnel at baseline and on a yearly basis thereafter. TL at baseline and changes in TL after a 5-year intervention were assessed.Results:Higher baseline TL significantly predicted a greater decrease in body weight (B=-1.09¿kg, 95% confidence interval (CI): -2.01 to -0.16), body mass index (BMI) (B=-0.47¿kg¿m(-2), 95% CI: -0.83 to -0.11), waist circumference (B=-1.15¿cm, 95% CI: -2.28 to -0.01) and waist to height ratio (B=-0.008, 95% CI: -0.010 to -0.001) in multiple-adjusted models. In addition, changes in TL during the 5-year intervention were inversely associated with changes in the four anthropometric variables. The reduction in adiposity indices during the intervention, associated with increasing TL, was even higher among subjects with the longest telomeres at baseline. Logistic regression analysis showed that the risk of remaining obese after 5 years was lower in those participants who initially had the longest telomeres and increased their TL after intervention (odds ratio=0.27, 95% CI: 0.03-2.03).Conclusions:Our research suggests that TL is inversely associated with changes in obesity parameters. The assessment of TL can provide further insights for biological pathways leading to adiposity. We show for the first time an improvement of obesity indices when an increase in TL is observed after a 5-year Mediterranean diet intervention.
Autores: Luis, Elkin ; Ortega-Cubero, S.; Lamet, María Isabel; et al.
ISSN 0197-4580  Vol. 35  Nº 12  2014  págs. 2681-90
A rare heterozygous TREM2 variant p.R47H (rs75932628) has been associated with an increased risk for Alzheimer's disease (AD). We aimed to investigate the clinical presentation, neuropsychological profile, and regional pattern of gray matter and white matter loss associated with the TREM2 variant p.R47H, and to establish which regions best differentiate p.R47H carriers from noncarriers in 2 sample sets (Spanish and Alzheimer's Disease Neuroimaging Initiative, ADNI1). This was a cross-sectional study including a total number of 16 TREM2 p.R47H carriers diagnosed with AD or mild cognitive impairment, 75 AD p.R47H noncarriers and 75 cognitively intact TREM2 p.R47H noncarriers. Spanish AD TREM2 p.R47H carriers showed apraxia (9 of 9) and psychiatric symptoms such as personality changes, anxiety, paranoia, or fears more frequently than in AD noncarriers (corrected p = 0.039). For gray matter and white matter volumetric brain magnetic resonance imaging voxelwise analyses, we used statistical parametric mapping (SPM8) based on the General Linear Model. We used 3 different design matrices with a full factorial design. Voxel-based morphometry analyses were performed separately in the 2 sample sets. The absence of interset statistical differences allowed us to perform joint and conjunction analyses. Independent voxel-based morphometry analysis of the Spanish set as well as conjunction and joint analyses revealed substantial gray matter loss in orbitofrontal cortex and anterior cingulate cortex with relative preservation of parietal lobes in AD and/or mild cognitive impairment TREM2 p.R47H carriers, suggesting that TREM2 p.R47H variant is associated with certain clinical and neuroimaging AD features in addition to the increased TREM2 p.R47H atrophy in temporal lobes as described previously. The high frequency of pathologic behavioral symptoms, combined with a preferential frontobasal gray matter cortical loss, suggests that frontobasal and temporal regions could be more susceptible to the deleterious biological effects of the TREM2 variant p.R47H.
Autores: Martínez, Miguel Ángel; Zazpe I; Razquin, Cristina; et al.
ISSN 0261-5614  Vol. 34  Nº 5  2014  págs. 859 - 867
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 <0.001) and all-cause mortality (adjusted HR: 0.53; 95% CI: 0.38, 0.75; p-trend <0.001), regardless of the allocated arm of the trial. An increasing mortality rate was found across increasing quartiles of the WDP in the control group (allocated to a low-fat diet), though the linear trend was not statistically significant (p = 0.098). Conclusions: Higher adherence to an empirically-derived MDP at baseline was associated with a reduced risk of CVD and mortality in the PREDIMED trial regardless of the allocated arm. The WDP was not associated with higher risk of mortality or cardiovascular events.
Autores: Razquin, Cristina; Marti A; Martínez, JA;
ISSN 1613-4125  Vol. 55  Nº 1  2011  págs. 136 - 149
Obesity is a complex disease that results from the interaction between lifestyle (dietary patterns and sedentary habits) and genetic factors. The recognition of a genetic basis for human obesity has driven to identify putative causal genes to understand the pathways that control body mass and fat deposition in humans as well as to provide personalized treatments and prevention strategies to fight against obesity. More than 120 candidate genes have been associated with obesity-related traits. Genome-wide association study has so far identified over 20 novel loci convincingly associated with adiposity. This review is specifically focused on the study of the effects of melanocortin 4 receptor, Peroxisome proliferator-activated receptor ¿ and fat mass and obesity associated (FTO) gene variants and their interactions with dietary intake, physical activity or drug administration on body weight control. The advances in this field are expected to open new ways in genome-customized diets for obesity prevention and therapy following personalized approaches.
Autores: Sánchez, María Almudena; Galbete, Cecilia; Martínez, Miguel Ángel; et al.
ISSN 1028-415X  Vol. 14  Nº 5  2011  págs. 195 - 201
There are no human studies assessing the effect of nutritional interventions on plasma brain-derived neurotrophic factor (BDNF) concentrations.Tthis study assesses the role of a nutritional intervention based on a Mediterranean diet on plasma BDNF levels.
Autores: Razquin, Cristina; Martínez, JA; Martínez, Miguel Ángel; et al.
ISSN 0307-0565  Vol. 34  Nº 2  2010  págs. 266 - 272
Autores: Razquin, Cristina; Martínez, JA; Martínez, Miguel Ángel; et al.
ISSN 1436-6207  Vol. 49  Nº 5  2010  págs. 311 - 319
Purpose: Adiponectin gene variations have been associated with obesity. There are few interventional studies analyzing this association. The aim of this study was to analyze the effects of a nutritional intervention with Mediterranean-style diet and three (-4034A/C, +45T/G, and +276 G/T) adiponectin gene variants on 3-year body weight changes in high cardiovascular risk patients. Subjects and methods: A total of 737 participants, aged 55-80 at high cardiovascular risk were assigned to a low-fat diet or to a Mediterranean-style diet (MD) groups, one with high intake of virgin olive oil (VOO) and the other with high intake of nuts. Anthropometric parameters were taken at baseline and after 3-year follow-up, and the genotyping of the -4034A/C, +45T/G, and +276 G/T polymorphisms was done. Results: GG genotype of the +45T/G polymorphism was associated with 3-year higher body weight gain (B = 1.399; B = 0.043). TT genotype of the +276G/T polymorphism was linked to the highest 3-year body weight gain in men. Both Mediterranean diets appeared to reverse this effect (p for interaction = 0.053). Conclusion: Adiponectin gene variation appeared to be associated with 3-year body weight changes in a high cardiovascular risk population. This association may be modulated by a nutritional intervention with a Mediterranean-style diet.
Autores: Razquin, Cristina; Martínez, JA; Martínez, Miguel Ángel; et al.
ISSN 1613-4125  Vol. 54  Nº 1  2010  págs. S75 - S82
Only a few studies have analyzed the effects of the potential interaction between the -174G/C polymorphism of IL6 gene and the adherence to the Mediterranean diet (MD) on adiposity indexes. Our aim was to investigate the interplay between the -174G/C polymorphism of the IL6 gene and a Mediterranean-style diet on body weight changes after 3 years of nutritional intervention in a high cardiovascular risk population. A total of 737 participants, aged 55-80 years were assigned to a low-fat diet or to a Mediterranean-style diet group with high intake of virgin olive oil (VOO) or nuts. Anthropometric measurements were taken at baseline and after 3-year follow-up. The -174G/C polymorphism of the IL6 gene was genotyped. Minor allele frequency (C) was 0.39. At baseline, the CC genotype was associated with higher measures of adiposity. After 3 years, a significant interaction (p = 0.028) was found between the polymorphism (GG+GC versus CC) and the nutritional intervention: CC subjects following the MD+VOO had the lowest body weight gain. In conclusion, at baseline, CC subjects for the -174G/C polymorphism of IL6 had the highest body weight and BMI. However, after 3 years of nutritional intervention with MD+VOO, these subjects were predicted to have the greatest reduction in body weight.