RESUMEN
Background: Lifestyles influence atrial fibrillation (AF) risk. 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: We studied 532 participants enrolled in the PREDIMED-Plus trial, a Spanish randomized trial conducted in adults (55-75 years) with metabolic syndrome and body mass index between 27-40 kg/m2. Eligible participants were randomized 1:1 to an intensive lifestyle intervention, emphasizing physical activity, weight loss, and adherence to an energy-reduced Mediterranean diet or to a control group. Serum biomarkers [carboxy-terminal propeptide of procollagen type I (PICP), high-sensitivity troponin T (hsTnT), high-sensitivity C reactive protein (hsCRP), 3-nitrotyrosine (3-NT), and N-terminal propeptide of B-type natriuretic peptide (NT-proBNP)] were measured at baseline, 3 and 5 years after randomization. Mixed models were used to evaluate the effect of intervention on changes in biomarkers through year 5. Mediation analysis was performed to examine the proportion mediated by each component of the intervention. Results: At baseline, participants' mean age was 65, 40% were female, and 50% were assigned to the intervention. After five years, mean changes in log-transformed biomarkers were -0.01 (PICP), 0.20 (hsTnT), -0.17 (hsCRP), 0.12 (3-NT), and 0.27 (NT-proBNP). Compared to the control group, participants in the intervention group experienced greater decreases in hsCRP (-14%, 95% confidence interval (CI) -26%, 0%) or smaller increases in 3-NT (-16%, 95% CI -25%, -5%) and NT-proBNP (-12%, 95% CI -23%, 1%). The intervention had minimal impact on hsTnT (-3%, 95% CI -7%, 2%) or PICP concentrations (-2%, 95% CI -9%, 6%). The effect of the intervention on hsCRP was primarily mediated by weight loss (89% at year 5). Conclusions: Over five years, a dietary and lifestyle intervention for weight-loss favorably affected concentrations of hsCRP, 3-NT, and NT-proBNP, pointing to specific mechanisms in pathways linking lifestyles and AF.
RESUMEN
BACKGROUND: Legume consumption has been linked to a reduced risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), while the potential association between plasma metabolites associated with legume consumption and the risk of cardiometabolic diseases has never been explored. Therefore, we aimed to identify a metabolite signature of legume consumption, and subsequently investigate its potential association with the incidence of T2D and CVD. METHODS: The current cross-sectional and longitudinal analysis was conducted in 1833 PREDIMED study participants (mean age 67 years, 57.6% women) with available baseline metabolomic data. A subset of these participants with 1-year follow-up metabolomics data (n = 1522) was used for internal validation. Plasma metabolites were assessed through liquid chromatography-tandem mass spectrometry. Cross-sectional associations between 382 different known metabolites and legume consumption were performed using elastic net regression. Associations between the identified metabolite profile and incident T2D and CVD were estimated using multivariable Cox regression models. RESULTS: Specific metabolic signatures of legume consumption were identified, these included amino acids, cortisol, and various classes of lipid metabolites including diacylglycerols, triacylglycerols, plasmalogens, sphingomyelins and other metabolites. Among these identified metabolites, 22 were negatively and 18 were positively associated with legume consumption. After adjustment for recognized risk factors and legume consumption, the identified legume metabolite profile was inversely associated with T2D incidence (hazard ratio (HR) per 1 SD: 0.75, 95% CI 0.61-0.94; p = 0.017), but not with CVD incidence risk (1.01, 95% CI 0.86-1.19; p = 0.817) over the follow-up period. CONCLUSIONS: This study identified a set of 40 metabolites associated with legume consumption and with a reduced risk of T2D development in a Mediterranean population at high risk of cardiovascular disease. TRIAL REGISTRATION: ISRCTN35739639.