Is serum pregnancy-associated plasma protein A really a potential marker of atherosclerotic carotid plaque stability?

Abstract

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. 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). Circulating PAPP-A levels were significantly higher in patients with unstable versus stable plaques (0.10+/-0.06 vs. 0.07+/-0.04 microg ml(-1), p=0.047) and interestingly, in asymptomatic versus symptomatic patients (0.11+/-0.05 vs. 0.069+/-0.09 microg 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. 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.