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Abstract：
Arginine-derived metabolites are involved in oxidative and inflammatory processes related to endothelial functions and cardiovascular risks.
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.
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.
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).
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.
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.
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.
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).
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.
摘要：
精氨酸衍生的代谢物参与与内皮功能和心血管风险相关的氧化和炎症过程。
我们前瞻性地检查了精氨酸分解代谢代谢物与房颤（AF）或心力衰竭（HF）风险的关系。并评估了通过地中海饮食（MedDiet）干预对这些关联的潜在修改，初级预防试验。
两个嵌套，匹配，病例对照研究是在PrevenciónconDietaMediterránea(PREDIMED)试验中设计的.我们选择了509例事件病例和547个匹配的对照进行AF病例对照研究，选择了326例病例和402个匹配的对照进行HF病例对照研究。在基线时收集空腹血样，并使用LC串联MS测量精氨酸分解代谢代谢物。应用多变量条件逻辑回归模型来测试代谢物与房颤或HF之间的关联。用似然比检验分析代谢物与干预组（MedDiet组与对照组相比）之间的相互作用。
观察到精氨酸与发生房颤的反向关联（OR每1SD，0.83；95%CI：0.73-0.94），而N1-乙酰亚精胺呈正相关(Q4的OR与Q11.58比较;95%CI:1.13-2.25).对于HF，发现精氨酸的逆相关(OR每1SD，0.82；95%CI：0.69-0.97）和高精氨酸（OR/1SD，0.81；95%CI：0.68-0.96），发现非对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）比率呈正相关（OR/1SD，1.19；95%CI：1.02-1.41），N1-乙酰亚精胺（OR每1SD，1.34；95%CI：1.12-1.60），和二乙酰精胺(OR每1SD，1.20；95%CI：1.02-1.41）。在分层分析中，根据饮食干预，与精氨酸相关的较低HF风险仅限于MedDiet组参与者(P-交互作用=0.044).
我们的结果表明，精氨酸分解代谢代谢产物可能参与AF和HF。使用MedDiet进行干预可能有助于加强精氨酸与HF风险之间的负相关。该试验在controlled-trials.com注册为ISRCTN35739639。
我们前瞻性地检查了精氨酸分解代谢代谢物与房颤（AF）或心力衰竭（HF）风险的关系。
两个嵌套，
观察到精氨酸与发生房颤的反向关联（OR每1SD，
我们的结果表明，精氨酸分解代谢代谢产物可能参与AF和HF。
