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

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 mu g ml(-1), p = 0.047) and interestingly, in asymptomatic versus symptomatic patients (0.11 +/- 0.05 vs. 0.069 +/- 0.09 mu g 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. (C) 2010 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.