CLINICAL RESEARCH: ATHEROTHROMBOSIS
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
Walter Stefan Speidl, MD*,
Andrea Zeiner, MD ,
Mariam Nikfardjam, MD*,
Alexander Geppert, MD ,
Nelli Jordanova, MD,
Alexander Niessner, MD*,
Gerlinde Zorn, BSc*,
Gerald Maurer, MD, FACC*,
Wolfgang Schreiber, MD,
Johann Wojta, PhD* and
Kurt Huber, MD, FACC,*
* Department of Internal Medicine II, Medical University of Vienna and the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria
Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria
3rd Department of Medicine (Cardiology and Emergency Medicine), Wilhelminenspital, Vienna, Austria
Manuscript received May 25, 2004;
revised manuscript received September 20, 2004,
accepted September 21, 2004.
* Reprint requests and correspondence: Dr. Kurt Huber, 3rd Department of Medicine, Wilhelminenspital, Montlearstr. 37, A-1171 Wien, Austria
(Email: kurt.huber{at}meduniwien.ac.at).
OBJECTIVES: 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 ( 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.
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Abbreviations and Acronyms
| | CRP = C-reactive protein | | F1+2 = prothrombin fragment F1+2 | | PAI-1 = plasminogen activator inhibitor type-1 | | sICAM-1 = soluble intercellular cell adhesion molecule-1 | | STEMI = ST-segment elevation myocardial infarction | | TNF = tumor necrosis factor | | t-PA = tissue-type plasminogen activator | | VO = venous occlusion |
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