Baldus Stephan, Heeschen Christopher, Meinertz Thomas, Zeiher Andreas M, Eiserich Jason P, Münzel Thomas, Simoons Maarten L, Hamm Christian W
University of Hamburg, Department of Cardiology, Martinistrasse 52, 20246 Hamburg, Germany.
Circulation. 2003 Sep 23;108(12):1440-5. doi: 10.1161/01.CIR.0000090690.67322.51. Epub 2003 Sep 2.
Polymorphonuclear neutrophils (PMNs) have gained attention as critical mediators of acute coronary syndromes (ACS). Myeloperoxidase (MPO), a hemoprotein abundantly expressed by PMNs and secreted during activation, possesses potent proinflammatory properties and may contribute directly to tissue injury. However, whether MPO also provides prognostic information in patients with ACS remains unknown.
MPO serum levels were assessed in 1090 patients with ACS. We recorded death and myocardial infarctions during 6 months of follow-up. MPO levels did not correlate with troponin T, soluble CD40 ligand, or C-reactive protein levels or with ST-segment changes. However, patients with elevated MPO levels (>350 microg/L; 31.3%) experienced a markedly increased cardiac risk (adjusted hazard ratio [HR] 2.25 [1.32 to 3.82]; P=0.003). In particular, MPO serum levels identified patients at risk who had troponin T levels below 0.01 microg/L (adjusted HR 7.48 [95% CI 1.98 to 28.29]; P=0.001). In a multivariate model that included other biochemical markers, troponin T (HR 1.99; P=0.023), C-reactive protein (1.25; P=0.044), vascular endothelial growth factor (HR 1.87; P=0.041), soluble CD40 ligand (HR 2.78; P<0.001), and MPO (HR 2.11; P=0.008) were all independent predictors of the patient's 6-month outcome.
In patients with ACS, MPO serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers. Given its proinflammatory properties, MPO may serve as both a marker and mediator of vascular inflammation and further points toward the significance of PMN activation in the pathophysiology of ACS.
多形核中性粒细胞（PMNs）作为急性冠状动脉综合征（ACS）的关键介质已受到关注。髓过氧化物酶（MPO）是一种由PMNs大量表达并在激活时分泌的血红素蛋白，具有强大的促炎特性，可能直接导致组织损伤。然而，MPO是否也能为ACS患者提供预后信息仍不清楚。
对1090例ACS患者的MPO血清水平进行了评估。我们记录了随访6个月期间的死亡和心肌梗死情况。MPO水平与肌钙蛋白T、可溶性CD40配体、C反应蛋白水平或ST段变化均无相关性。然而，MPO水平升高（>350μg/L；31.3%）的患者心脏风险显著增加（校正风险比[HR]2.25[1.32至3.82]；P = 0.003）。特别是，MPO血清水平可识别出肌钙蛋白T水平低于0.01μg/L的高危患者（校正HR 7.48[95%CI 1.98至28.29]；P = 0.001）。在包含其他生化标志物的多变量模型中，肌钙蛋白T（HR 1.99；P = 0.023）、C反应蛋白（1.25；P = 0.044）、血管内皮生长因子（HR 1.87；P = 0.041）可溶性CD40配体（HR 2.78；P < 0.001）和MPO（HR 2.11；P = 0.008）均为患者6个月预后的独立预测因素。
在ACS患者中，MPO血清水平有力地预测了随后心血管事件风险的增加，并扩展了从传统生化标志物获得的预后信息。鉴于其促炎特性，MPO可能既是血管炎症的标志物又是介质，进一步表明PMN激活在ACS病理生理学中的重要性。
