Is Serum Pregnancy-Associated Plasma Protein A Really a Potential Marker of Atherosclerotic Carotid Plaque Stability?

Abstract

Objectives The search for markers predicting risk of plaque rupture in carotid atherosclerosis is still ongoing. Previous findings showed that pregnancy-associated plasma protein-A (PAPP-A) levels correlate with an adverse plaque morphology. However, the role of PAPP-A in plaque destabilisation is still uncertain. Material and methods Patients with carotid artery stenosis involved in the study were asymptomatic ( n = 29) and symptomatic ( n = 37). Carotid plaques were characterised by histology ( n = 33). Immunohistochemistry ( n = 17) was used to determine expression of PAPP-A and CD68 within the plaques. Serum levels of PAPP-A were measured by the enzyme-linked immunosorbent assay (ELISA). Results Circulating PAPP-A levels were significantly higher in patients with unstable versus stable plaques (0.10 ± 0.06 vs. 0.07 ± 0.04 μg ml −1, p = 0.047) and interestingly, in asymptomatic versus symptomatic patients (0.11 ± 0.05 vs. 0.069 ± 0.09 μg ml −1, p = 0.025). These differences remained statistically significant after adjustment for age, gender and degree of stenosis ( p = 0.050). PAPP-A expression in plaques correlated significantly with CD68 positive macrophages, cap-thickness and its serological values ( r = +0.291, p < 0.001, r = −0.639, p < 0.001 and r = 0.618, p < 0.008, respectively). Furthermore, PAPP-A serum values demonstrated a significant positive predictive value of 68.8% for unstable plaques. Conclusion Our present data confirmed the close relationship between expression of PAPP-A and plaque instability and furthermore correlated significantly with cap thickness. However, the question whether PAPP-A is a useful predictive marker of plaque instability remains unresolved.