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Background: Lifestyles influence atrial fibrillation (AF) risk. Blood biomarkers can characterize the atrial substrate that facilitates the development of AF. Therefore, determining the effect of lifestyle interventions on blood concentrations of biomarkers of AF-related pathways could help understand AF pathophysiology and contribute to AF prevention. Methods: The PREDIMED-PLUS study is a Spanish multicenter randomized trial in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m 2 . Participants were randomized 1:1 to an intensive lifestyle intervention (ILI) program, emphasizing physical activity, weight loss, and adherence to the Mediterranean diet, or a control intervention. In a sub-sample, serum biomarkers including carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), N-terminal propeptide of B-type natriuretic peptide (NT-proBNP), and 3-nitrotyrosine (3-NT) were measured at baseline and years 3 and 5 after randomization. Mixed models were used to evaluate the effect of ILI on changes in biomarkers through years 3 and 5. Follow-up time was modeled as a categorical and continuous variable. Results: Of 481 participants (65 mean age, 40% female, 49% assigned to ILI), 453 (94%) and 442 (92%) had available samples at years 3 and 5. After 5 years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.25 (NT-proBNP). Participants in the ILI group experienced greater decreases in hsCRP or smaller increases in 3-NT, NT-proBNP, and in hsTnT to a lesser extent, as compared to the control group (Table). The ILI did not affect PICP concentrations. Results were consistent when modeling follow-up time as a continuous variable. Conclusion: Over five years, an ILI favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, and of hs-TnT to a lesser degree, pointing to specific mechanisms in the pathways linking lifestyles and AF.

Introduction: Higher consumption of coffee and caffeine has been linked to less weight gain and lower body mass index in prospective cohort studies, usually with exposure assessment limited to baseline values. As BMI is a proxy for adiposity but does not capture fat tissue or its metabolically relevant distribution, precise measurements of distinct adipose tissues are needed, so the cardiometabolic impact of an anti-obesity effect can be assessed. Hypothesis: We assessed the hypothesis that an increase in coffee consumption is associated with a reduction in body fat, in particular with trunk fat and visceral adipose tissue (VAT). Methods: In the setting of a large, randomized trial of Mediterranean diet and physical activity intervention, we evaluated 1483 participants with metabolic syndrome. Changes in the consumption of caffeinated and decaffeinated coffee were derived from validated food frequency questionnaires at baseline, 6 months and yearly during follow-up. Fat tissue was measured with dual x-ray absorptiometry at baseline and after 6, 12 months and three years. Linear multilevel mixed effect models were used to investigate the relationship between changes in coffee consumption and corresponding concurrent changes in fat tissue over three years. Results: After adjustment for intervention group, and other potential confounders, an increase in caffeinated coffee consumption from no or infrequent consumption (≤ 3 cups/ month) to moderate consumption (1-7 cups/week) was associated with reductions in total body fat (Δ z-score: -0.06; 95 % CI: -0.11 to -0.02), trunk fat (Δ z-score: -0.07; 95 % CI: -0.12 to -0.02), and VAT (Δ z-score: -0.07; 95 % CI: -0.13 to -0.01). However, changes to even higher levels (> 1 cup/day) showed no significant association. Conclusions: Moderate consumption of caffeinated coffee, but not high consumption, was associated with reductions in total body fat, trunk fat and VAT in a Mediterranean cohort with metabolic syndrome. Decaffeinated coffee was not linked to adiposity indicators. In conclusion, moderate consumption of caffeinated coffee may be part of a weight management strategy.

Background: Metabolomics technologies can efficiently profile a large number of structurally diverse lipids, e.g., glycerophospholipids, sphingolipids, and glycerolipids, that may play differential roles in pathogenesis of cardiovascular disease (CVD). However, existing studies were focused more on discovering individual lipid metabolites for CVD risk prediction than inferring perturbed pathways responsible for the pathological processes. Hypothesis: We hypothesized that different lipid metabolic pathways, captured by network analysis, were divergently associated with CVD risk; the associations could be modified by the Mediterranean diet (MedDiet) intervention. Methods: We conducted this study in the PREDIMED trial with participants randomized to three intervention diets: MedDiet with extra-virgin olive oil, MedDiet with nuts, or a low-fat control diet. This study comprises a subcohort of 788 participants randomly selected from the PREDIMED cohort and 230 cases. The outcome was a composite endpoint of non-fatal acute myocardial infarction, non-fatal stroke and cardiovascular death. We performed network analysis using Gaussian graphic model among 200 targeted lipid metabolites and subsequent dimensionality reduction using Greedy Modularity Optimization to detect subnetworks. We calculated the subnetwork scores by summing up the products of the topological connectivity weight (representing network structure) and metabolite level and included the scores into Cox proportional hazards model with simultaneous adjustment for other subnetwork scores and covariates. The Benjamini-Hochberg procedure was applied to detect smaller subnetworks of specific interest for further investigation. Results: We detected 4 major subnetworks of lipid metabolic pathway. Most lipid metabolites with larger numbers of carbon atom and double bond clustered within a same subnetwork (subnetwork 2), while those with smaller numbers of carbon atom and double bond clustered within other 3 subnetworks (subnetworks 1, 3 and 4). The hazard ratio (HR) of CVD across quartiles of the subnetwork score 2 was 0.56 (95% CI, 0.35, 0.91, P trend =0.008) after multivariable adjustment. The HRs of CVD comparing extreme quartiles of subnetwork scores 3 and 4 were 1.85 (95% CI, 1.15, 2.97, P trend =0.02) and 1.93 (95% CI, 1.19, 3.14, P trend =0.01), respectively. The MedDiet appeared to enhance the inverse association between subnetwork score 2 and CVD ( P interaction =0.03). We detected several smaller subnetworks with functional interpretation related to CVD pathogenesis such as the ceramide pathway and the pathway including phospholipids with high unsaturation. Conclusions: Based on topological structure of lipid metabolic pathways, we detected biologically meaningful pathways. We found divergent associations between subnetworks and CVD and smaller subnetworks with functional interpretation.

Objectives: To assess the association between potato consumption, blood pressure changes and the risk of hypertension in two Mediterranean populations. Design: Separate analyses were performed in the PREDIMED (PREvención con DIeta MEDiterránea), a multicenter nutrition intervention trial, and the SUN (“Seguimiento Universidad de Navarra”) project, an open, prospective cohort, both in Spain. Participants: The PREDIMED trial included 6,940 participants aged 55-80 years at high risk for cardiovascular disease. The SUN project included 13,837 middle-aged participants who were university graduates. Main outcome measures: In PREDIMED, generalized estimating equations adjusted for lifestyle and dietary characteristics were used to assess changes in blood pressure across quintiles of total potato consumption during a 4-year follow-up. Controlled blood pressure levels during follow-up were also assessed. For SUN, multivariable-adjusted hazard ratios (HR) for incident hypertension during an average 6.7-year follow-up were calculated. Results: In PREDIMED, the mean (SD) total potato intake was 81.9 (40.6) g/day. No overall significant differences in blood pressure changes were detected based on consumption of potatoes. For total potatoes, the mean change in systolic BP after multivariate adjustment was quintile 5 (Q5) vs. quintile 1 (Q1): -0.90, 95% CI: (-2.56 to 0.76) mmHg, p for trend=0.14 and for diastolic BP it was Q5 vs. Q1: -0.02, 95% CI: (-0.93 to 0.89) mmHg, p for trend=0.81. In SUN, the mean (SD) total potato consumption was 52.7 (33.6) g/day and no significant association between potato consumption and hypertension incidence was observed: HR: for total potato consumption, Q5 vs. Q1: 0.98, 95% CI: (0.80 to 1.19), p for trend=0.84. Conclusions: Potato consumption is not associated with changes in blood pressure or risk of hypertension in Mediterranean populations and this might be explained by relatively low consumption of potatoes and characteristics of the traditional Mediterranean diet, particularly the custom of accompanying potatoes with vegetables or legumes and dressing them with olive oil.

Background - The PREDIMED (Prevención con Dieta Mediterránea) randomized primary prevention trial showed that a Mediterranean diet enriched with either extravirgin olive oil or mixed nuts reduces the incidence of stroke, myocardial infarction, and cardiovascular mortality. We assessed the effect of these diets on the incidence of atrial fibrillation in the PREDIMED trial. Methods and Results - Participants were randomly assigned to 1 of 3 diets: Mediterranean diet supplemented with extravirgin olive oil, Mediterranean diet supplemented with mixed nuts, or advice to follow a low-fat diet (control group). Incident atrial fibrillation was adjudicated during follow-up by an events committee blinded to dietary group allocation. Among 6705 participants without prevalent atrial fibrillation at randomization, we observed 72 new cases of atrial fibrillation in the Mediterranean diet with extravirgin olive oil group, 82 in the Mediterranean diet with mixed nuts group, and 92 in the control group after median follow-up of 4.7 years. The Mediterranean diet with extravirgin olive oil significantly reduced the risk of atrial fibrillation (hazard ratio, 0.62; 95% confidence interval, 0.45-0.85 compared with the control group). No effect was found for the Mediterranean diet with nuts (hazard ratio, 0.89; 95% confidence interval, 0.65-1.20). Conclusions - In the absence of proven interventions for the primary prevention of atrial fibrillation, this post hoc analysis of the PREDIMED trial suggests that extravirgin olive oil in the context of a Mediterranean dietary pattern may reduce the risk of atrial fibrillation. © 2014 American Heart Association, Inc., The PREDIMED trial was supported by the Official funding agency for Biomedical Research of the Spanish Government (Spanish analogous institution to the NIH: Instituto de Salud Carlos III, through grants provided to research networks specifically developed for the trial: RTIC G03/140 (Coordinator: R Estruch, MD, PhD), and RTIC RD 06/0045 (Coordinatos: MA Martínez-González, MD, PhD). All investigator of the PREDIMED t rial belong to Centro de Investigación Biomédica en Red (CIBER), an initiative of Instituto de Salud Carlos III. We also acknowledge the grants from NIH 1R01HL118264-01, Fondo de Investigación Sanitaria - Fondo Europeo de Desarrollo Regional (PI04/0233, PI05/0976, PI07/0240 , PI10/01407, PI10/02658 and PI11/00049) and Consejería de Salud de la Junta de Andalucía (PI0105/2007).