Department of Preventive Medicine and Public Health, University of Navarra, Pamplona, Spain.
IdiSNA (Instituto de Investigación Sanitaria de Navarra), Pamplona, Spain.
Am J Clin Nutr. 2022 Sep 2;116(3):653-662. doi: 10.1093/ajcn/nqac139.
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.
精氨酸衍生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。
我们前瞻性地研究了精氨酸分解代谢物与心房颤动（AF）或心力衰竭（HF）风险的关联，并在一项大型一级预防试验中，通过地中海饮食（MedDiet）干预评估了这些关联的潜在变化。
在 Prevención con Dieta Mediterránea（PREDIMED）试验中设计了两个嵌套、匹配的病例对照研究。我们使用密度抽样法选择了 509 例新发病例和 547 例匹配对照进行 AF 病例对照研究，以及 326 例病例和 402 例匹配对照进行 HF 病例对照研究。在基线时采集空腹血样，并使用 LC-串联 MS 测量精氨酸分解代谢物。应用多变量条件逻辑回归模型检验代谢物与新发 AF 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）之间的交互作用。
与 AF 发生呈负相关的是精氨酸（每 1 SD 的 OR，0.83；95%CI：0.73-0.94），而 N1-乙酰精脒（Q4 与 Q1 相比 OR 为 1.58；95%CI：1.13-2.25）则呈正相关。HF 呈负相关的是精氨酸（每 1 SD 的 OR，0.82；95%CI：0.69-0.97）和同型精氨酸（每 1 SD 的 OR，0.81；95%CI：0.68-0.96），而正相关的是不对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）比值（每 1 SD 的 OR，1.19；95%CI：1.02-1.41）、N1-乙酰精脒（每 1 SD 的 OR，1.34；95%CI：1.12-1.60）和二乙酰精脒（每 1 SD 的 OR，1.20；95%CI：1.02-1.41）。根据饮食干预的分层分析，精氨酸与 HF 风险呈负相关，这与 MedDiet 组参与者有关（P 交互作用=0.044）。
我们的研究结果表明，精氨酸分解代谢物可能与 AF 和 HF 有关。地中海饮食的干预可能有助于加强精氨酸与 HF 风险之间的负相关关系。本试验在 controlled-trials.com 上注册为 ISRCTN35739639。
