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 -