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
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Thomas Mueller
Abstract
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.
©2010 by Walter de Gruyter Berlin New York
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- Editorials
- Molecular biology and genetics in clinical chemistry and laboratory medicine
- Improving the post-analytical phase
- Reviews
- State of the art in therapeutic drug monitoring
- Decision criteria for rational selection of homogeneous genotyping platforms for pharmacogenomics testing in clinical diagnostics
- Reference Values and Biological Variations
- Assessment of critical values policies in Italian institutions: comparison with the US situation
- Genetics and Molecular Diagnostics
- Performance evaluation of the Abbott RealTime HCV Genotype II for hepatitis C virus genotyping
- Genotyping mitochondrial DNA single nucleotide polymorphisms by PCR ligase detection reactions
- FOXL2 mutations in Taiwanese patients with blepharophimosis, ptosis, epicanthus inversus syndrome
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