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


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.


CONCLUSIONS
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.
Heider
P
P
Vascular and Endovascular Surgery, Isar Medical Center, Sonnenstr. 24-26, D-80331 Munich, Germany. heiderpeter@t-online.de
Pfäffle
N
N
Pelisek
J
J
Wildgruber
M
M
Poppert
H
H
Rudelius
M
M
Eckstein
H-H
HH
D000368:Aged; D050197:Atherosclerosis / Q000097:blood* / Q000150:complications / Q000473:pathology; D015415:Biomarkers / Q000097:blood*; D016893:Carotid Stenosis / Q000097:blood* / Q000209:etiology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011266:Pregnancy-Associated Plasma Protein-A / Q000096:biosynthesis*; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index
D015415:Biomarkers; D011266:Pregnancy-Associated Plasma Protein-A