Institute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany; DZHK (Deutsches Zentrum für Herz-Kreislauf-Forschung e.V.), partner site Hamburg/Kiel/Lübeck, Germany.
Department of Neurology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, 20246 Hamburg, Germany.
J Neurol Sci. 2019 Feb 15;397:156-161. doi: 10.1016/j.jns.2018.12.037. Epub 2018 Dec 31.
Guanidino compounds, including l-homoarginine (l-hArg), symmetric dimethylarginine (SDMA), asymmetric dimethylarginine (ADMA) and l-arginine (l-Arg) are associated with mortality, fatal strokes, stroke incidence, and atherosclerosis.
We aimed to study the association of guanidino compounds (l-hArg/ADMA and l-hArg/SDMA) with stroke etiology, internal carotid artery (ICA) stenosis and CHADS-VASc score in patients with cerebrovascular disease.
We analyzed l-hArg, SDMA, ADMA, l-Arg, and compound molar ratios, i.e. l-hArg/ADMA and l-hArg/SDMA, in 272 patients with cerebrovascular disease in a cross-sectional discovery cohort and two cross-sectional validation cohorts of acute stroke patients from Germany (n = 137) and UK (n = 394). The guanidino compound levels were compared with clinical, imaging, and ultrasound parameters.
Low l-hArg/ADMA and l-hArg/SDMA molar ratios predicted territorial infarcts (OR 1.74; 95% CI 1.34-2.26 and OR 1.64; 95% CI 1.26-2.15, respectively) and were associated with stroke subtypes due to large vessel disease or cardio-embolism (OR 1.52; 95% CI 1.12-2.06 and OR 2.01; 95% CI 1.35-3.00, respectively) in meta-analysis of the discovery and validation cohort data. In line with these results, a low l-hArg/ADMA and l-hArg/SDMA molar ratio was found in patients with ICA stenosis (OR 0.73; 95% CI 0.55-0.97 and OR 0.69; 95% CI 0.50-0.94, respectively) in the discovery and validation cohort. Furthermore, guanidino compound ratios (i.e. l-hArg/ADMA and l-hArg/SDMA) were strongly correlated with CHADS-VASC score (p < .001) in all three cohorts.
The results from these three cross-sectional studies reveal that guanidino compound ratios (i.e. l-hArg/ADMA and l-hArg/SDMA) can discriminate stroke etiologies, predict ICA stenosis and estimate risk prediction in patients with cerebrovascular disease.
胍基化合物，包括 l-同型精氨酸（l-hArg）、对称二甲基精氨酸（SDMA）、非对称二甲基精氨酸（ADMA）和 l-精氨酸（l-Arg）与死亡率、致命性中风、中风发病率和动脉粥样硬化有关。
我们旨在研究胍基化合物（l-hArg/ADMA 和 l-hArg/SDMA）与脑血管疾病患者中风病因、颈内动脉（ICA）狭窄和 CHADS-VASc 评分的关系。
我们在一个横断面发现队列和来自德国（n=137）和英国（n=394）的急性中风患者的两个横断面验证队列中分析了 272 名脑血管疾病患者的 l-hArg、SDMA、ADMA、l-Arg 和化合物摩尔比，即 l-hArg/ADMA 和 l-hArg/SDMA。比较了胍基化合物水平与临床、影像学和超声参数。
低 l-hArg/ADMA 和 l-hArg/SDMA 摩尔比预测区域性梗死（OR 1.74；95%CI 1.34-2.26 和 OR 1.64；95%CI 1.26-2.15），并与大血管疾病或心源性栓塞引起的中风亚型相关（OR 1.52；95%CI 1.12-2.06 和 OR 2.01；95%CI 1.35-3.00）meta 分析发现，发现和验证队列数据。与这些结果一致的是，在发现和验证队列中，ICA 狭窄患者的 l-hArg/ADMA 和 l-hArg/SDMA 摩尔比较低（OR 0.73；95%CI 0.55-0.97 和 OR 0.69；95%CI 0.50-0.94）。此外，胍基化合物比值（即 l-hArg/ADMA 和 l-hArg/SDMA）与 CHADS-VASC 评分密切相关（p<0.001）在所有三个队列中。
这三项横断面研究的结果表明，胍基化合物比值（即 l-hArg/ADMA 和 l-hArg/SDMA）可区分中风病因，预测 ICA 狭窄，并估计脑血管疾病患者的风险预测。
