An increase of C-reactive protein is associated with enhanced activation of endogenous fibrinolysis at baseline but an impaired endothelial fibrinolytic response after venous occlusion.
OBJECTIVE
The goal of this study was to determine whether chronic inflammation of the vascular wall may be associated with an impaired activation of the fibrinolytic system.


BACKGROUND
Inflammation plays an important role in the initiation and progression of atherosclerosis, and the fibrinolytic system may prevent local thrombus formation.


METHODS
We included 50 patients six months after their first myocardial infarction. Plasma levels of the inflammatory marker C-reactive protein (CRP) were determined at basal conditions, and the fibrinolytic parameters tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1) were measured at basal conditions and after a standardized venous occlusion (VO) of the forearm.


RESULTS
Patients with high CRP levels (> or =3 mg/l) showed a significantly higher t-PA activity at baseline compared with patients with medium (1 to 2.9 mg/l) and low (<1 mg/l) CRP levels (p <0.005). In contrast, patients with low CRP levels showed a higher increase of t-PA activity (p <0.05) and a higher reduction of PAI-1 activity during VO (p <0.05) compared with patients with medium and high CRP levels. A multivariate analysis that included cardiovascular risk factors and medical treatment showed that CRP is an independent predictor of the t-PA response after a standardized VO.


CONCLUSIONS
Chronic low-grade inflammation is associated with enhanced activation of endogenous fibrinolysis at baseline but a reduced fibrinolytic response to VO. This impaired endogenous fibrinolytic capacity might be an important contributor to the increased coronary event rate associated with elevated CRP levels.
Speidl
Walter Stefan
WS
Department of Internal Medicine II, Medical University of Vienna and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria.
Zeiner
Andrea
A
Nikfardjam
Mariam
M
Geppert
Alexander
A
Jordanova
Nelli
N
Niessner
Alexander
A
Zorn
Gerlinde
G
Maurer
Gerald
G
Schreiber
Wolfgang
W
Wojta
Johann
J
Huber
Kurt
K
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D003324:Coronary Artery Disease / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005342:Fibrinolysis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000097:blood*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood
D017395:Plasminogen Activator Inhibitor 1; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator