Hov Gunhild Garmo, Aasarød Knut Ivar, Sagen Erling, Åsberg Arne
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Medical Biochemistry, St. Olavs Hospital, Trondheim University Hospital, Norway.
Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway.
Clin Biochem. 2015 Jul;48(10-11):646-51. doi: 10.1016/j.clinbiochem.2015.03.012. Epub 2015 Mar 28.
Arginine, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), arginine/ADMA ratio and homoarginine could potentially affect nitric oxide production and have been studied in relation to cardiovascular risk (CVR) in various clinical populations. Prospective studies on the CVR associated with arginine/ADMA ratio and homoarginine in patients with moderate chronic kidney disease (CKD) are still scarce. We have studied how arginine, homoarginine and dimethylated arginine can predict cardiovascular events in such a population.
We measured plasma concentrations of arginine (P-arginine), ADMA (P-ADMA), SDMA (P-SDMA), homoarginine (P-homoarginine) and other covariates in 160 patients with predialytic CKD (mean age 57 years and mean eGFR 43 mL/min/1.73 m(2)) and followed them for 58 months in median. The risks of fatal and non-fatal cardiovascular events associated with the predictors were evaluated with multivariable Cox proportional hazard analysis.
There were 31 cardiovascular events during the observation period. In a multivariable model adjusted for age, sex, previous cardiovascular disease, P-cystatin C and P-homoarginine, the hazard ratio (HR) associated with an increase in arginine/ADMA ratio by 10 was 0.83 (P=0.03). The HR of a 1 μmol/L increase in P-homoarginine in the same model was 1.78 (P=0.01). A statistically significant interaction between P-homoarginine and P-cystatin C was found in an extended multivariable model. P-SDMA was not associated with increased CVR after adjustment for basic covariates.
This study demonstrates a negative association between arginine/ADMA ratio and CVR in CKD patients and a positive association between P-homoarginine and CVR. The latter is in contrast to what has been demonstrated by others.
精氨酸、不对称二甲基精氨酸（ADMA）、对称二甲基精氨酸（SDMA）、精氨酸/ADMA比值和高精氨酸可能会影响一氧化氮的生成，并且在不同临床人群中已针对其与心血管风险（CVR）的关系展开研究。关于中度慢性肾脏病（CKD）患者中精氨酸/ADMA比值和高精氨酸与CVR相关性的前瞻性研究仍然较少。我们研究了精氨酸、高精氨酸和二甲基化精氨酸如何预测此类人群的心血管事件。
我们测量了160例透析前CKD患者（平均年龄57岁，平均估算肾小球滤过率[eGFR]为43 mL/min/1.73 m²）的血浆精氨酸（P-精氨酸）、ADMA（P-ADMA）、SDMA（P-SDMA）、高精氨酸（P-高精氨酸）浓度及其他协变量，并对他们进行了为期58个月的中位随访。通过多变量Cox比例风险分析评估与预测因子相关的致命和非致命心血管事件风险。
观察期内发生了31例心血管事件。在调整了年龄、性别、既往心血管疾病、P-胱抑素C和P-高精氨酸的多变量模型中，精氨酸/ADMA比值增加10时的风险比（HR）为0.83（P=0.03）。在同一模型中，P-高精氨酸每增加1 μmol/L的HR为1.78（P=0.01）。在扩展的多变量模型中发现P-高精氨酸和P-胱抑素C之间存在统计学显著的交互作用。调整基本协变量后，P-SDMA与CVR增加无关。
本研究表明CKD患者中精氨酸/ADMA比值与CVR呈负相关，P-高精氨酸与CVR呈正相关。后者与其他人的研究结果相反。
