Zeller Marianne, Korandji Claudia, Guilland Jean-Claude, Sicard Pierre, Vergely Catherine, Lorgis Luc, Beer Jean-Claude, Duvillard Laurence, Lagrost Anne-Cécile, Moreau Daniel, Gambert Philippe, Cottin Yves, Rochette Luc
Laboratory of Experimental Cardiovascular Pathophysiology and Pharmacology, Faculty of Medicine, University of Burgundy, Dijon Cedex, France.
Arterioscler Thromb Vasc Biol. 2008 May;28(5):954-60. doi: 10.1161/ATVBAHA.108.162768. Epub 2008 Feb 14.
Asymmetrical dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthases. From a prospective cohort of patients with acute myocardial infarction (MI), we aimed to analyze the predictive value of circulating ADMA concentrations on prognosis.
Blood samples from 249 consecutive patients hospitalized for acute MI <24 hours were taken on admission. Serum levels of ADMA and its stereoisomer, symmetrical dimethylarginine (SDMA), were determined using high-performance liquid chromatography. The independent predictors of ADMA were glomerular filtration rate, female sex, and SDMA (R(2)=0. 25). Baseline ADMA levels were higher in patients who had died than in patients who were alive at 1 year follow-up (1.23 [0.98 to 1.56] versus 0.95 [0.77 to 1.20] micromol/L, P<0.001). By Cox multivariate analysis, the higher tertile of ADMA (median [interquartile range]: 1.45 [1.24 to 1.70] micromol/L) was a predictor for mortality (Hazard Ratio [95% CI], 4.83 [1.59 to 14.71]), when compared to lower tertiles, even when adjusted for potential confounders, such as acute therapy, biological, and clinical factors.
Our study suggests that the baseline ADMA level has a strong prognostic value for mortality after MI, beyond traditional risk factors and biomarkers.
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。在一个急性心肌梗死(MI)患者的前瞻性队列中,我们旨在分析循环ADMA浓度对预后的预测价值。
对249例急性MI发病<24小时入院的连续患者入院时采集血样。采用高效液相色谱法测定ADMA及其立体异构体对称二甲基精氨酸(SDMA)的血清水平。ADMA的独立预测因素为肾小球滤过率、女性性别和SDMA(R² = 0.25)。在1年随访时死亡患者的基线ADMA水平高于存活患者(1.23 [0.98至1.56] 对0.95 [0.77至1.20] μmol/L,P<0.001)。通过Cox多变量分析,与较低三分位数相比,ADMA较高三分位数(中位数[四分位间距]:1.45 [1.24至1.70] μmol/L)是死亡率的预测因素(风险比[95%CI],4.83 [1.59至14.71]),即使在调整潜在混杂因素(如急性治疗、生物学和临床因素)后也是如此。
我们的研究表明,除传统危险因素和生物标志物外,基线ADMA水平对MI后死亡率具有很强的预后价值。