TY - JOUR
T1 - Arginine catabolism metabolites and atrial fibrillation or heart failure risk
T2 - 2 case-control studies within the Prevención con Dieta Mediterránea (PREDIMED) trial
AU - Goni, Leticia
AU - Razquin, Cristina
AU - Toledo, Estefanía
AU - Guasch-Ferré, Marta
AU - Clish, Clary B
AU - Babio, Nancy
AU - Wittenbecher, Clemens
AU - Atzeni, Alessandro
AU - Li, Jun
AU - Liang, Liming
AU - Dennis, Courtney
AU - Alonso-Gómez, Ángel
AU - Fitó, Montserrat
AU - Corella, Dolores
AU - Gómez-Gracia, Enrique
AU - Estruch, Ramón
AU - Fiol, Miquel
AU - Lapetra, Jose
AU - Serra-Majem, Lluis
AU - Ros, Emilio
AU - Arós, Fernando
AU - Salas-Salvadó, Jordi
AU - Hu, Frank B
AU - Martínez-González, Miguel A
AU - Ruiz-Canela, Miguel
N1 - © The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.
PY - 2022
Y1 - 2022
N2 - BACKGROUND: Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks.OBJECTIVES: We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications 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 Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 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 using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. 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 compared with control group) were analyzed with the likelihood ratio test.RESULTS: Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73-0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13-2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69-0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68-0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02-1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12-1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 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-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.
AB - BACKGROUND: Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks.OBJECTIVES: We prospectively examined the associations of arginine catabolism metabolites with the risks of atrial fibrillation (AF) or heart failure (HF), and evaluated the potential modifications 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 Prevención con Dieta Mediterránea (PREDIMED) trial. We selected 509 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 using incidence density sampling. Fasting blood samples were collected at baseline and arginine catabolism metabolites were measured using LC-tandem MS. 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 compared with control group) were analyzed with the likelihood ratio test.RESULTS: Inverse association with incident AF was observed for arginine (OR per 1 SD, 0.83; 95% CI: 0.73-0.94), whereas a positive association was found for N1-acetylspermidine (OR for Q4 compared with Q1 1.58; 95% CI: 1.13-2.25). For HF, inverse associations were found for arginine (OR per 1 SD, 0.82; 95% CI: 0.69-0.97) and homoarginine (OR per 1 SD, 0.81; 95% CI: 0.68-0.96), and positive associations were found for the asymmetric dimethylarginine (ADMA) and symmetric dimethlyarginine (SDMA) ratio (OR per 1 SD, 1.19; 95% CI: 1.02-1.41), N1-acetylspermidine (OR per 1 SD, 1.34; 95% CI: 1.12-1.60), and diacetylspermine (OR per 1 SD, 1.20; 95% CI: 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-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.
KW - Arginine
KW - Atrial Fibrillation/prevention & control
KW - Cardiovascular Diseases/prevention & control
KW - Case-Control Studies
KW - Diet, Mediterranean
KW - Heart Failure/prevention & control
KW - Humans
KW - Mediterranea
KW - Risk Factors
U2 - 10.1093/ajcn/nqac139
DO - 10.1093/ajcn/nqac139
M3 - Journal article
C2 - 35575609
VL - 116
SP - 653
EP - 662
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
SN - 0002-9165
IS - 3
ER -