Multiple biological predictors for vulnerable carotid lesions.
BACKGROUND
In this study a multiscore analysis of various biomarkers including matrix metalloproteinases (MMPs), inflammatory factors and other clinical parameters was performed to establish a set of reliable biomarkers for improved detection of plaque instability in patients with advanced carotid stenosis.


METHODS
Study patients (n = 101) were classified as histologically stable (n = 37) or unstable (n = 64). Serum levels of MMP-1, -2, -3, -7, -8, -9, MMP inhibitors TIMP-1, -2, and inflammatory factors such as tumor necrosis factor (TNF-alpha), interleukin (IL)-1beta, -6, -8, -10, and -12 were measured by ELISA assays. Multiscore analysis was performed using multiple receiver operating characteristics analysis and determination of appropriate cutoff values.


RESULTS
Circulating levels of MMP-1, -7, TIMP-1, TNF-alpha, and IL-8 were significantly enhanced in patients with unstable plaques compared to individuals with stable lesions, mean differences being 1.2 (p = 0.032), 2.5 (p = 0.004), 30.0 (p = 0.014), 1.3 (p = 0.047), and 2.2 (p = 0.033), respectively. The combination of MMP-1, -7, TIMP-1 and IL-8 demonstrated the highest positive predictive value of 89.4% and negative predictive value of 60.1% for patients correctly classified as individuals with unstable and stable carotid lesions by means of blood sample analysis.


CONCLUSIONS
Multiple relevant biomarkers that play a decisive role in plaque instability can improve the correct determination of vulnerable carotid plaques in patients with advanced carotid artery stenosis.
Department of Vascular Surgery, Klinikum rechts der Isar der Technischen Universitat Munchen, Ismaninger Strasse 22, Munich, Germany. pelisek@gmx.de
Jaroslav
J
Pelisek
Martina
M
Rudelius
Peter
P
Zepper
Holger
H
Poppert
Christian
C
Reeps
Tibor
T
Schuster
Hans-Henning
HH
Eckstein
D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D016893:Carotid Stenosis / Q000097:blood / Q000150:complications*; D005260:Female; D006801:Humans; D007378:Interleukins / Q000097:blood; D008297:Male; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012372:ROC Curve; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D007378:Interleukins; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D020782:Matrix Metalloproteinases