Yu Edward, Ruiz-Canela Miguel, Hu Frank B, Clish Clary B, Corella Dolores, Salas-Salvadó Jordi, Hruby Adela, Fitó Montserrat, Liang Liming, Toledo Estefanía, Ros Emilio, Estruch Ramón, Gómez-Gracia Enrique, Lapetra José, Arós Fernando, Romaguera Dora, Serra-Majem Lluís, Guasch-Ferré Marta, Wang Dong D, Martínez-González Miguel A
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts 02115.
Department of Preventive Medicine and Public Health, University of Navarra, and Instituto de Investigacion Sanitaria de Navarra (IdiSNA), University of Navarra, 31008 Pamplona, Spain.
J Clin Endocrinol Metab. 2017 Jun 1;102(6):1879-1888. doi: 10.1210/jc.2016-3569.
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.
To examine the association between baseline and 1-year concentrations of urea cycle metabolites and cardiovascular disease (CVD) in a case-cohort setting.
A case-cohort study was nested within the Prevención con Dieta Mediterránea 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).
Multicenter randomized trial in Spain.
Participants were 984 participants accruing 231 events over 4.7 years' median follow-up.
Incident CVD.
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.
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.
精氨酸、其甲基化代谢产物以及其他与尿素循环相关的代谢产物已分别与心血管风险相关，但由于缺乏对代谢产物随时间变化的测量研究，这些关联（某些代谢产物为正相关，其他代谢产物为负相关）的潜在因果意义仍不明确。
在病例队列研究中，检验尿素循环代谢产物的基线浓度与1年浓度和心血管疾病（CVD）之间的关联。
一项病例队列研究嵌套于地中海饮食预防试验中。我们使用液相色谱 - 串联质谱法评估基线和1年随访后的代谢产物水平。主要CVD结局是心肌梗死、中风和心血管死亡的复合结局。我们使用加权Cox回归模型（Barlow权重）来估计多变量调整后的风险比（HRs）及其95%置信区间（CIs）。
西班牙的多中心随机试验。
984名参与者在4.7年的中位随访期内发生了231起事件。
新发CVD。
基线精氨酸/不对称二甲基精氨酸比值[每标准差（SD）的HR = 0.80；95%CI，0.67至0.96]和总体精氨酸可用性[精氨酸/（鸟氨酸 + 瓜氨酸）]（每SD的HR = 0.83；95%CI，0.69至1.00）与较低的CVD风险显著相关。我们未观察到这些比值的1年变化有显著关联，也未观察到地中海饮食（MD）干预有任何效应修饰作用。
在心血管风险较高的人群中，较高的基线精氨酸/不对称二甲基精氨酸比值与较低的CVD发病率相关。MD干预并未改变这些代谢产物的1年水平。
