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.
Pelisek
Jaroslav
J
Department of Vascular Surgery, Klinikum rechts der Isar der Technischen Universitat Munchen, Ismaninger Strasse 22, Munich, Germany. pelisek@gmx.de
Rudelius
Martina
M
Zepper
Peter
P
Poppert
Holger
H
Reeps
Christian
C
Schuster
Tibor
T
Eckstein
Hans-Henning
HH
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