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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

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Volume 48, Issue 4 (Apr 2010)


Pregnancy-associated plasma protein-A as a marker for long-term mortality in patients with peripheral atherosclerosis: inconclusive findings from the Linz Peripheral Arterial Disease (LIPAD) study

Thomas Mueller / Benjamin Dieplinger / Thomas Forstner / Werner Poelz / Meinhard Haltmayer
  • Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria
  • Paracelsus Private Medical University, Salzburg, Austria
  • Other articles by this author:
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Published Online: 2010-02-12 | DOI: https://doi.org/10.1515/CCLM.2010.103


Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Clin Chem Lab Med 2010;48:537–42.

Keywords: metalloproteinases; natriuretic peptides; outcome; peripheral artery disease; prognosis

About the article

Corresponding author: Thomas Mueller, MD, Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Seilerstaette 2–4, 4020 Linz, Austria Phone: +43-732-7677-3621, Fax: +43-732-7677-3799,

Received: 2009-08-22

Accepted: 2009-12-06

Published Online: 2010-02-12

Published in Print: 2010-04-01

Citation Information: Clinical Chemistry and Laboratory Medicine, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2010.103.

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©2010 by Walter de Gruyter Berlin New York. Copyright Clearance Center

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