Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria.
Clin Chem Lab Med. 2010 Apr;48(4):537-42. doi: 10.1515/CCLM.2010.103.
Pregnancy-associated plasma protein-A (PAPP-A) has been associated with peripheral artery disease (PAD). The aim of this study was to evaluate the utility of PAPP-A as a marker for long-term mortality in patients with atherosclerotic PAD.
PAPP-A serum concentrations were measured using an enzymatically amplified two-step sandwich-type immunoassay in 487 consecutive patients admitted to a tertiary care hospital with symptomatic PAD. The main outcome measure was all-cause mortality at 5 years.
During follow-up, 114 patients died and 373 survived. The median PAPP-A concentration was higher among decedents compared with survivors (0.96 vs. 0.78 mU/L, p=0.024). The area under the receiver operating characteristic curve for the prediction of 5-year mortality by PAPP-A was 0.57 [95% confidence interval (CI), 0.53-0.61; p=0.026]. Survival probability was not significantly associated with PAPP-A concentrations using Kaplan-Meier curve analysis. However, univariate Cox proportional-hazards regression analysis revealed that PAPP-A was associated with 5-year mortality [risk ratio 1.25; 95% CI, 1.05-1.50; p=0.013 per one standard deviation (SD) increase in log transformed values]. In the multivariate model using a bootstrapping method, the predictive value of PAPP-A remained significant (risk ratio 1.31; 95% CI, 1.01-1.73; p=0.024 per 1 SD increase in log transformed values), even after adjustment for clinical confounders and other biomarkers, such as high-sensitivity C-reactive protein and amino terminal pro-B-type natriuretic peptide.
In this study, PAPP-A was an independent predictor of 5-year all-cause mortality in patients with symptomatic PAD. However, based on the weak association between PAPP-A and outcome in our cohort, we consider PAPP-A measurements to not be useful in clinical practice for prognostic purposes in patients with PAD.
妊娠相关血浆蛋白 A（PAPP-A）与外周动脉疾病（PAD）有关。本研究旨在评估 PAPP-A 作为动脉粥样硬化性 PAD 患者长期死亡率标志物的效用。
采用酶放大两步夹心型免疫分析法检测 487 例因有症状 PAD 而入住三级护理医院的连续患者的 PAPP-A 血清浓度。主要转归指标为 5 年全因死亡率。
随访期间，114 例患者死亡，373 例存活。与幸存者相比，死者的中位数 PAPP-A 浓度更高（0.96 与 0.78 mU/L，p=0.024）。PAPP-A 预测 5 年死亡率的受试者工作特征曲线下面积为 0.57 [95%置信区间（CI），0.53-0.61；p=0.026]。Kaplan-Meier 曲线分析并未显示生存概率与 PAPP-A 浓度显著相关。然而，单变量 Cox 比例风险回归分析显示，PAPP-A 与 5 年死亡率相关[风险比 1.25；95%CI，1.05-1.50；p=0.013，每增加一个标准差（SD）log 转换值]。在使用 bootstrap 方法的多变量模型中，PAPP-A 的预测值仍然显著（风险比 1.31；95%CI，1.01-1.73；p=0.024，每增加一个 SD 的 log 转换值），即使在校正临床混杂因素和其他生物标志物（如高敏 C 反应蛋白和氨基末端 pro-B 型利钠肽）后也是如此。
在本研究中，PAPP-A 是有症状 PAD 患者 5 年全因死亡率的独立预测因子。然而，基于我们队列中 PAPP-A 与结局之间的弱关联，我们认为 PAPP-A 测量值对于 PAD 患者的预后目的在临床上没有用处。
