BACKGROUND
Arginine-derived metabolites are involved in oxidative and inflammatory processes related with endothelial function and cardiovascular risk.
OBJECTIVE
To prospectively examine the associations of arginine catabolism metabolites with the risk of atrial fibrillation (AF) or heart failure (HF), and to evaluate the potential modification of these associations through Mediterranean diet (MedDiet) interventions in a large primary prevention trial.
METHODS
Two nested matched case-control studies were designed within the PREDIMED trial. Five hundred and nine incident cases and 547 matched controls for the AF case-control study, and 326 cases and 402 matched controls for the HF case-control study participants were selected using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using liquid chromatography tandem mass spectrometry. Multivariable conditional logistic regression models were applied to test the associations between the metabolites and incident AF or HF. Interactions between metabolites and intervention groups (MedDiet groups vs control group) were analyzed with the likelihood ratio test.
RESULTS
Inverse associations with incident AF were observed for arginine [OR per 1 SD (95% CI): 0.83 (0.73, 0.94)]) and homoarginine [0.87 (0.76, 0.98)], whereas positive associations were found for the asymmetric dimethylarginine/symmetric dimethylarginine ratio (ADMA/SDMA) [1.15 (1.01, 1.31)] and citrulline [1.19 (1.01, 1.39)]. For HF, inverse associations were found for arginine [0.82 (0.69, 0.97)] and homoarginine [0.81 (0.68, 0.96)], and positive associations for the ADMA/SDMA ratio [1.19 (1.02, 1.41)], N1-acetylspermidine [1.34 (1.12, 1.60)], and diacetylspermine [1.20 (1.02, 1.41)]. In the stratified analysis according to the dietary intervention, the lower HF risk associated with arginine was restricted to participants in the MedDiet groups (p for interaction 0.044).
CONCLUSIONS
Our results suggest that arginine catabolism metabolites could be involved in AF and HF. Interventions with the MedDiet may contribute to strengthen the inverse association between arginine and the risk of HF.This trial was registered at controlled-trials.com as ISRCTN35739639.