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.
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.
Department of Laboratory Medicine, Konventhospital Barmherzige Brueder, Linz, Austria. thomas.mueller@bs-lab.at
Thomas
T
Mueller
Benjamin
B
Dieplinger
Thomas
T
Forstner
Werner
W
Poelz
Meinhard
M
Haltmayer
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000175:diagnosis / Q000401:mortality*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016491:Peripheral Vascular Diseases / Q000175:diagnosis / Q000401:mortality*; D011247:Pregnancy; D011266:Pregnancy-Associated Plasma Protein-A / Q000032:analysis*; D012372:ROC Curve
D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A