Cosin-Sales Juan, Christiansen Michael, Kaminski Paul, Oxvig Claus, Overgaard Michael T, Cole Della, Holt David W, Kaski Juan Carlos
Department of Cardiac and Vascular Sciences, St George's Hospital Medical School, London, UK.
Circulation. 2004 Apr 13;109(14):1724-8. doi: 10.1161/01.CIR.0000124716.67921.D2. Epub 2004 Mar 15.
The metalloproteinase pregnancy-associated plasma protein-A (PAPP-A) has been implicated in coronary plaque disruption. Its endogenous inhibitor, the proform of eosinophil major basic protein (proMBP), may also play a role in this process. Atheromatous plaque disruption often presents as complex angiographic lesions. We sought to assess whether PAPP-A, proMBP, and PAPP-A/ProMBP ratio are markers of angiographic plaque complexity in patients with chronic stable angina.
We studied 396 stable angina patients (age 63+/-10 years, 230 men) of whom 289 had angiographically documented coronary artery disease (> or =75% stenosis). All coronary stenoses > or =30% diameter reduction (n =531 in 322 patients) were assessed and classified as complex (n =228) or smooth (n =303) by previously validated criteria. PAPP-A, proMBP, and C-reactive protein (hs-CRP) serum levels were measured by ELISA. Patients with complex coronary stenoses had a significantly (P<0.001) higher PAPP-A/proMBP ratio (3.1+/-1.2 versus 2.7+/-0.8x10(-3)) and PAPP-A levels (5.9+/-1.6 versus 5.1+/-1.4 mIU/L) than those without. On univariate analysis, male gender (P<0.001), age (P<0.001), previous history of myocardial infarction (P=0.013), reduced ejection fraction (P<0.001), severe coronary artery disease (P<0.001), aspirin treatment (P<0.001), PAPP-A levels (P<0.001), and PAPP-A/proMBP ratio (P<0.001) were correlated with the number of complex stenoses. Multiple regression analysis showed that male gender, age, severe coronary artery disease, and PAPP-A/proMBP ratio were independent predictors of the number of angiographically complex stenoses.
In patients with stable angina, PAPP-A and PAPP-A/proMBP ratio are associated with angiographic plaque complexity.
金属蛋白酶妊娠相关血浆蛋白-A（PAPP-A）与冠状动脉斑块破裂有关。其内源性抑制剂，即嗜酸性粒细胞主要碱性蛋白的前体形式（proMBP），可能也在此过程中发挥作用。动脉粥样硬化斑块破裂常表现为复杂的血管造影病变。我们试图评估PAPP-A、proMBP以及PAPP-A/ProMBP比值是否为慢性稳定型心绞痛患者血管造影斑块复杂性的标志物。
我们研究了396例稳定型心绞痛患者（年龄63±10岁，男性230例），其中289例有血管造影记录的冠状动脉疾病（狭窄≥75%）。对所有直径减少≥30%的冠状动脉狭窄（322例患者共531处）进行评估，并根据先前验证的标准分为复杂型（n = 228）或光滑型（n = 303）。通过酶联免疫吸附测定法（ELISA）测量PAPP-A、proMBP和C反应蛋白（hs-CRP）的血清水平。冠状动脉狭窄复杂的患者的PAPP-A/proMBP比值（3.1±1.2对2.7±0.8×10⁻³）和PAPP-A水平（5.9±1.6对5.1±1.4 mIU/L）显著高于无复杂狭窄的患者（P<0.001）。单因素分析显示，男性（P<0.001）、年龄（P<0.001）、既往心肌梗死病史（P = 0.013）、射血分数降低（P<0.001）、严重冠状动脉疾病（P<0.001）、阿司匹林治疗（P<0.001）、PAPP-A水平（P<0.001）以及PAPP-A/proMBP比值（P<0.001）与复杂狭窄的数量相关。多元回归分析表明，男性、年龄、严重冠状动脉疾病以及PAPP-A/proMBP比值是血管造影复杂狭窄数量的独立预测因素。
在稳定型心绞痛患者中，PAPP-A和PAPP-A/proMBP比值与血管造影斑块复杂性相关。
