TY - JOUR

T1 - Urea Cycle Metabolites and Atrial Fibrillation or Heart Failure Risk:

T2 - wo Case-Control Studies in the PREDIMED Trial

AU - Goni, L

AU - Razquin, C

AU - Toledo, E

AU - Guasch-Ferre, M

AU - Clish, C

AU - Hernández-Alonso, P

AU - Li, J

AU - Liang, L

AU - Wittenbecher, C

AU - Dennis, C

AU - Alonso-Gomez, A

AU - Fitó, M

AU - Corella, D

AU - Ruiz-Canela, M

PY - 2021

Y1 - 2021

N2 - ObjectivesTo 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.MethodsWe 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/SDMA ratio)) were determined using liquid chromatography tandem mass spectrometry. We used conditional logistic regression models, adjusted for potential confounders, to analyze the associations between the metabolites and incident AF or HF. Potential interactions between metabolites and intervention (MD groups vs control group) were tested with the likelihood ratio test.ResultsThe study population comprised a total of 1241 participants (509 cases) for AF case-control and 824 participants (326 cases) for HF case-control. Arginine was inversely associated with incident AF (OR per SD 0.83, 95% CI 0.73; 0.94) and HF (OR per SD 0.82, 95% CI 0.69; 0.97). Whereas ADMA/SDMA ratio was positively associated with AF (OR per SD 1.19, 95% CI 1.02; 1.41) but not with HF risk. A statistically significant interaction (P = 0.044) was found between arginine and intervention on HF risk. The lower risk of HF associated with arginine was only observed in participants of the MD groups (EVOO + nuts).ConclusionsThe results of the present study suggest that urea cycle metabolites, arginine and ADMA/SDMA ratio specifically, could be involved in AF and HF pathophysiology. Moreover, the dietary intervention may modify the association between arginine and HF.

AB - ObjectivesTo 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.MethodsWe 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/SDMA ratio)) were determined using liquid chromatography tandem mass spectrometry. We used conditional logistic regression models, adjusted for potential confounders, to analyze the associations between the metabolites and incident AF or HF. Potential interactions between metabolites and intervention (MD groups vs control group) were tested with the likelihood ratio test.ResultsThe study population comprised a total of 1241 participants (509 cases) for AF case-control and 824 participants (326 cases) for HF case-control. Arginine was inversely associated with incident AF (OR per SD 0.83, 95% CI 0.73; 0.94) and HF (OR per SD 0.82, 95% CI 0.69; 0.97). Whereas ADMA/SDMA ratio was positively associated with AF (OR per SD 1.19, 95% CI 1.02; 1.41) but not with HF risk. A statistically significant interaction (P = 0.044) was found between arginine and intervention on HF risk. The lower risk of HF associated with arginine was only observed in participants of the MD groups (EVOO + nuts).ConclusionsThe results of the present study suggest that urea cycle metabolites, arginine and ADMA/SDMA ratio specifically, could be involved in AF and HF pathophysiology. Moreover, the dietary intervention may modify the association between arginine and HF.

UR - http://europepmc.org/abstract/PMC/PMC8265681

M3 - Journal article

C2 - PMC8265681

VL - 5

SP - 18

JO - Current Developments in Nutrition

JF - Current Developments in Nutrition

SN - 2475-2991

IS - Supplement 2

ER -