Increased Pregnancy-Associated Plasma Protein-A as a Marker for Peripheral Atherosclerosis: Results from the Linz Peripheral Arterial Disease Study

Abstract

The aim of the present investigation was to test the hypothesis that pregnancy-associated plasma protein-A (PAPP-A), a zinc-binding metalloproteinase implicated in acute coronary syndrome, is associated with atherosclerotic peripheral arterial disease (PAD). The study comprised 433 patients with symptomatic atherosclerotic PAD (i.e., chronic limb ischemia) and 433 controls matched to the patients with PAD in a 1:1 design by sex, age (+/-2 years), and diabetes mellitus status. Serum PAPP-A concentrations were measured with an enzymatically amplified 2-step sandwich-type immunoassay. The entire study sample included 612 male and 254 female patients with a median age of 68 years. The median PAPP-A value was higher in the patients with PAD than in the referents (0.81 vs 0.64 mU/L; P <0.001). After we adjusted for several possible confounding variables with multivariable logistic regression, odds ratios for PAD were 1.59 (95% confidence interval, 1.00-2.52; P = 0.049), 2.28 (1.45-3.61; P <0.001), and 2.86 (1.78-4.59; P <0.001) in the 2nd, 3rd, and 4th quartiles of serum PAPP-A concentrations compared with the first quartile. In the present study, PAPP-A added to the predictive value of other markers commonly in use. PAPP-A was associated with atherosclerotic PAD in the elderly sample studied. Because atherosclerotic PAD is considered an indicator of systemic atherosclerotic disease in elderly patients, the present results indicate that circulating PAPP-A may be a marker for systemic atherosclerotic disease.