Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk: Two Case-Control Studies in the PREDIMED Trial

OBJECTIVES: To prospectively analyze the associations between urea cycle metabolites and incident atrial fibrillation (AF) or heart failure (HF), and to evaluate the effect of a Mediterranean diet (MD) intervention on such associations. METHODS: We designed two nested case-control studies within the PREDIMED trial, a randomized controlled trial aimed to evaluate the effect of two MD interventions, supplemented with either extra virgin olive oil (EVOO) or nuts, on cardiovascular disease (CVD). Fasting blood samples were collected at baseline and urea cycle metabolites (arginine, citrulline, and ornithine) and methylarginines (asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA…