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

Eur J Vasc Endovasc Surg. 2010 Jun;39(6):668-75. doi: 10.1016/j.ejvs.2010.03.012. Epub 2010 Apr 15.

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 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.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Atherosclerosis / blood*
  • Atherosclerosis / complications
  • Atherosclerosis / pathology
  • Biomarkers / blood*
  • Carotid Stenosis / blood*
  • Carotid Stenosis / etiology
  • Carotid Stenosis / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follow-Up Studies
  • Humans
  • Immunohistochemistry
  • Male
  • Pregnancy-Associated Plasma Protein-A / biosynthesis*
  • Prognosis
  • Prospective Studies
  • Severity of Illness Index

Substances

  • Biomarkers
  • Pregnancy-Associated Plasma Protein-A