The Association Of Asymmetric Dimethylarginine With Coronary Artery Disease And Its Prognosis

BackgroundEndothelial dysfunction, dyslipidemia and inflammation play critical roles in the process of coronary atherosclerosis. Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of endothelial nitric oxide synthase and an important cause of endothelial dysfunction. Its elevated plasma concentration is associated with a variety of traditional cardiovascular risk factors, and may mediate their effects on vascular endothelium dysfunction. Many studies have implicated ADMA is an independent predictor of coronary artery disease, but rare studies focus on the association between ADMA level and the prognosis of coronary artery disease in Chinese.Objectives1. Establish the high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the analysis of asymmetric dimethylarginine relevant items (including ADMA, SDMA, Arginine, Citrulline and Ornithine) in human plasma.2. Determine the ADMA level of plasma sample from patients in the group of control, stable angina pectoris (SAP) and acute coronary syndrome (ACS) by means of HPLC-MS/MS, and investigate the relationship between ADMA and coronary artery disease and its prognosis.Method1. Build the HPLC-MS/MS method for the analysis of asymmetric dimethylarginine relevant items, and examine its specificity, sensitivity and intra-and inter-batch accuracy and precision.2. Consecutive patients referred to the ward of cardiology department, cardiac care unit and emergency of PUMC for percutaneous coronary intervention from February2007to June2009are enrolled in this study, and their plasma samples and clinical information are collected after informed consent. They are followed up prospectively for2years and the major adverse cardiac events are considered as terminal event. The ADMA levels are determined by HPLC-MS/MS.Results1. Established the HPLC-MS/MS method for the analysis of asymmetric dimethylarginine relevant items successfully and it passed methodology examination.2. A total of170cases are selected, including20cases in control group,45patients in SAP group,105cases in the ACS group, and received follow-up results from155patients.3. The statistics result indicates that significant difference of ADMA relevant items exists among the groups; ADMA concentration correlates with total cholesterol, left ventricle ejection fraction, brain natriuretic peptide and other clinical and biochemical parameters; ADMA concentration is associated with the extent and severity of coronary lesion; ADMA relevant ratios are independent risk factors of coronary disease and independent predict its prognosis.Conclusion1. Establish the HPLC-MS/MS method for the analysis of asymmetric dimethylarginine relevant items.2. ADMA relevant items are independent risk factors of coronary disease, and are closely related to its prognosis.