Plasma arginine/asymmetric dimethylarginine ratio and incidence of cardiovascular events: A case-cohort study
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Plasma arginine/asymmetric dimethylarginine ratio and incidence of cardiovascular events : A case-cohort study. / Yu, Edward; Ruiz-Canela, Miguel; Hu, Frank B.; Clish, Clary B.; Corella, Dolores; Salas-Salvadó, Jordi; Hruby, Adela; Fitó, Montserrat; Liang, Liming; Toledo, Estefana; Ros, Emilio; Estruch, Ramon; Gómez-Gracia, Enrique; Lapetra, Jose; Arós, Fernando; Romaguera, Dora; Serra-Majem, Llus; Guasch-Ferre, Marta; Wang, Dong D.; Martnez-González, Miguel A.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 102, No. 6, 2017, p. 1879-1888.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma arginine/asymmetric dimethylarginine ratio and incidence of cardiovascular events
T2 - A case-cohort study
AU - Yu, Edward
AU - Ruiz-Canela, Miguel
AU - Hu, Frank B.
AU - Clish, Clary B.
AU - Corella, Dolores
AU - Salas-Salvadó, Jordi
AU - Hruby, Adela
AU - Fitó, Montserrat
AU - Liang, Liming
AU - Toledo, Estefana
AU - Ros, Emilio
AU - Estruch, Ramon
AU - Gómez-Gracia, Enrique
AU - Lapetra, Jose
AU - Arós, Fernando
AU - Romaguera, Dora
AU - Serra-Majem, Llus
AU - Guasch-Ferre, Marta
AU - Wang, Dong D.
AU - Martnez-González, Miguel A.
N1 - Publisher Copyright: Copyright © 2017 Endocrine Society.
PY - 2017
Y1 - 2017
N2 - Context: Arginine, its methylated metabolites, and other metabolites related to the urea cycle have been independently associated with cardiovascular risk, but the potential causal meaning of these associations (positive for some metabolites and negative for others) remains elusive due to a lack of studies measuring metabolite changes over time. Objective: To examine the association between baseline and 1-year concentrations of urea cycle metabolites and cardiovascular disease (CVD) in a case-cohort setting. Design: Acase-cohort studywas nestedwithin the Prevenció n conDietaMediterránea trial.We used liquid chromatography-tandem mass spectrometry to assess metabolite levels at baseline and after 1-year follow-up. The primary CVD outcome was a composite of myocardial infarction, stroke and cardiovascular death. We used weighted Cox regression models (Barlow weights) to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Setting: Multicenter randomized trial in Spain. Participants: Participants were 984 participants accruing 231 events over 4.7 years' median follow-up. Main Outcome Measure: Incident CVD. Results: Baseline arginine/asymmetric dimethylarginine ratio [HR per standard deviation (SD) = 0.80; 95% CI, 0.67 to 0.96] and global arginine availability [arginine / (ornithine + citrulline)] (HR per SD = 0.83; 95% CI, 0.69 to 1.00) were significantly associated with lower risk of CVD. We observed no significant association for 1-year changes in these ratios or any effect modification by the Mediterranean diet (MD) intervention. Conclusions: A higher baseline arginine/asymmetric dimethylarginine ratio was associated with lower CVD incidence in a high cardiovascular risk population. The intervention with the MD did not change 1-year levels of these metabolites.
AB - Context: Arginine, its methylated metabolites, and other metabolites related to the urea cycle have been independently associated with cardiovascular risk, but the potential causal meaning of these associations (positive for some metabolites and negative for others) remains elusive due to a lack of studies measuring metabolite changes over time. Objective: To examine the association between baseline and 1-year concentrations of urea cycle metabolites and cardiovascular disease (CVD) in a case-cohort setting. Design: Acase-cohort studywas nestedwithin the Prevenció n conDietaMediterránea trial.We used liquid chromatography-tandem mass spectrometry to assess metabolite levels at baseline and after 1-year follow-up. The primary CVD outcome was a composite of myocardial infarction, stroke and cardiovascular death. We used weighted Cox regression models (Barlow weights) to estimate multivariable-adjusted hazard ratios (HRs) and their 95% confidence intervals (CIs). Setting: Multicenter randomized trial in Spain. Participants: Participants were 984 participants accruing 231 events over 4.7 years' median follow-up. Main Outcome Measure: Incident CVD. Results: Baseline arginine/asymmetric dimethylarginine ratio [HR per standard deviation (SD) = 0.80; 95% CI, 0.67 to 0.96] and global arginine availability [arginine / (ornithine + citrulline)] (HR per SD = 0.83; 95% CI, 0.69 to 1.00) were significantly associated with lower risk of CVD. We observed no significant association for 1-year changes in these ratios or any effect modification by the Mediterranean diet (MD) intervention. Conclusions: A higher baseline arginine/asymmetric dimethylarginine ratio was associated with lower CVD incidence in a high cardiovascular risk population. The intervention with the MD did not change 1-year levels of these metabolites.
U2 - 10.1210/jc.2016-3569
DO - 10.1210/jc.2016-3569
M3 - Journal article
C2 - 28323949
AN - SCOPUS:85020407381
VL - 102
SP - 1879
EP - 1888
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 6
ER -
ID: 358111147