Böger Rainer H
Clinical Pharmacology Unit, University Hospital Hamburg-Eppendorf, Germany.
Vasc Med. 2005 Jul;10 Suppl 1:S19-25. doi: 10.1177/1358836X0501000104.
Evidence has accumulated that asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase. ADMA inhibits vascular NO production at concentrations found in pathophysiological conditions; it also causes local vasoconstriction when infused intra-arterially. ADMA is increased in the plasma of humans with hypercholesterolemia, atherosclerosis, hypertension, chronic renal failure, chronic heart failure, and other clinical conditions. Increased ADMA levels are associated with reduced NO synthesis as assessed by impaired endothelium-dependent vasodilation or reduced NO metabolite levels. In several prospective and cross-sectional studies, ADMA has evolved as a marker of cardiovascular risk. Moreover, prospective clinical studies have suggested that it may play a role as a novel cardiovascular risk factor. Zoccali and coworkers were the first to show that elevated ADMA is associated with a three-fold increased risk of future severe cardiovascular events and mortality in patients undergoing hemodialysis. Valkonen and coworkers demonstrated in a nested case-control study that elevated ADMA was associated with a four-fold increased risk for acute coronary events in clinically healthy, nonsmoking men. In patients with stable angina pectoris, preinterventional ADMA indicates the risk of developing restenosis or severe clinical events after coronary intervention. Furthermore, in humans with no underlying cardiovascular disease who are undergoing intensive care unit treatment, ADMA is a marker of the mortality risk. A number of additional prospective clinical trials are currently under way in diverse patient populations, among them individuals with congestive heart failure, cardiac transplantation patients, and patients with pulmonary hypertension. In summary, an increasing number of prospective clinical trials have shown that the association between elevated ADMA levels and major cardiovascular events and total mortality is robust and extends to diverse patient populations. However, we need to define more clearly in the future who will profit from ADMA determination, in order to use this novel risk marker as a more specific diagnostic tool.
越来越多的证据表明，不对称二甲基精氨酸（ADMA）是一氧化氮（NO）合酶的内源性竞争性抑制剂。在病理生理条件下发现的浓度下，ADMA会抑制血管中NO的生成；动脉内注入时，它还会引起局部血管收缩。在患有高胆固醇血症、动脉粥样硬化、高血压、慢性肾衰竭、慢性心力衰竭和其他临床病症的人类血浆中，ADMA水平会升高。通过内皮依赖性血管舒张受损或NO代谢物水平降低评估，ADMA水平升高与NO合成减少有关。在一些前瞻性和横断面研究中，ADMA已成为心血管风险的标志物。此外，前瞻性临床研究表明，它可能作为一种新的心血管危险因素发挥作用。佐卡利及其同事率先表明，在接受血液透析的患者中，ADMA升高与未来发生严重心血管事件和死亡的风险增加三倍有关。瓦尔科宁及其同事在一项巢式病例对照研究中证明，在临床健康的非吸烟男性中，ADMA升高与急性冠状动脉事件的风险增加四倍有关。在稳定型心绞痛患者中，介入治疗前的ADMA可表明冠状动脉介入治疗后发生再狭窄或严重临床事件的风险。此外，在接受重症监护病房治疗且无潜在心血管疾病的人群中，ADMA是死亡风险的标志物。目前正在不同患者群体中进行多项额外的前瞻性临床试验，其中包括充血性心力衰竭患者、心脏移植患者和肺动脉高压患者。总之，越来越多的前瞻性临床试验表明，ADMA水平升高与主要心血管事件和总死亡率之间的关联是密切的，并且适用于不同的患者群体。然而，我们未来需要更明确地界定谁将从ADMA检测中获益，以便将这一新的风险标志物用作更具特异性的诊断工具。
