Aims: Von Willebrand factor (VWF), a key player in hemostasis and thrombosis, is released from endothelial cells during inflammation. Upon release, VWF is processed by ADAMTS13 into an inactive conformation. The aim of our study was to investigate whether plasma levels of active VWF, total VWF, ADAMTS13, osteoprotegerin (OPG) and the ratios between VWF and ADAMTS13 are risk factors for first ST-segment elevation myocardial infarction (STEMI). Methods and results: We assessed 1026 patients with confirmed first STEMI and 652 control subjects from China, Italy and Scotland, within six hours after their cardiovascular event. Median plasma levels of total VWF, active VWF, OPG and ratios VWF/ADAMTS13 were increased, while plasma levels of ADAMTS13 were decreased in patients compared to controls. The odds ratio (OR) of STEMI in patients with high plasma levels of active VWF was 2.3 (interquartile range (IQR): 1.8–2.9), total VWF was 1.8 (1.4–2.3), ADAMTS13 was 0.6 (05–0.8), OPG was 1.6 (1.2–2.0) and high VWF/ADAMTS13 ratios was 1.5 (1.2–2.0). The OR for total VWF, active VWF and ratios VWF/ADAMTS13 remained significant after adjustment for established risk factors, medical treatment, C-reactive protein, total VWF, ADAMTS13 and OPG. When we adjusted for levels of active VWF, the significance of the OR for VWF and ratios VWF/ADAMTS13 disappeared while the OR for active VWF remained significant. Conclusions: We found evidence that plasma levels of active VWF are an independent risk factor for first STEMI in patients from three different ethnic groups. Our findings confirm the presence of VWF abnormalities in patients with STEMI and may be used to develop new therapeutic approaches.
Abstract Unstable coronary artery disease is a term encompassing both unstable angina and non‐Q‐wave (non‐ST‐segment elevation) myocardial infarction. Patients with these conditions are at risk of early progression to acute myocardial infarction and death. Thus, management of these conditions must aim to reduce long‐term mortality and morbidity. Risk stratification is crucial for the identification of patients whose risk of early progression is high; they may require coronary angiography and (if suitable) either percutaneous transluminal coronary angioplasty or coronary artery bypass surgery. No single variable can accurately predict risk, but considerable data are emerging to show that biochemical markers of myocardial injury, such as troponin‐T and troponin‐I, are valuable in combination with electrocardiographic findings and clinical features. Routine early invasive procedures (coronary angiography with or without revascularization) have not yet been shown to have any significant advantage over conservative regimens for the majority of patients. Antiplatelet, anticoagulant, and anti‐ischemic agents remain the mainstay of treatment in the acute phase. New agents, such as glycoprotein IIb/IIIa receptor inhibitors and low‐molecular‐weight heparins, as well as antithrombins and Factor Xa inhibitors add to the treatments currently available. Thrombolytic agents are contraindicated in the absence of ST‐segment elevation. After clinical stabilization, ongoing assessment should include exercise testing for all patients who are able; other imaging techniques should be used for patients unable to exercise. A profile indicating a high risk of future events is an indication for elective angiography and consideration for revascularization.
INTRODUCTION Thrombin plays a pivotal role in platelet-mediated thrombosis associated with atheromatous plaque rupture in patients with acute coronary syndromes. Thrombin inhibition is, therefore, a basic therapeutic goal in this setting, together with thrombolysis and platelet inhibition.
Serum C-reactive protein (CRP) and creatine kinase (CK) MB levels were measured prospectively in patients with definite myocardial infarction, patients with spontaneous or exercise-induced angina, subjects undergoing coronary arteriography, and patients with non-cardiac chest pain. All individuals with infarction developed raised CRP levels and there was a significant correlation between the peak CRP and CK MB values. The CRP, however, peaked around 50 hours after the onset of pain at a time when the CK MB, which peaked after about 15 hours, had already returned to normal. In 20 patients who recovered uneventfully, CRP levels fell, returning to normal about seven days after infarction in four cases who were followed to this point. In eight complicated cases, including four who died within the first 10 days, the CRP level remained high. Angina alone or coronary arteriography did not cause a rise in the CRP or CK MB concentrations. Increased CRP production is a non-specific response to tissue injury and raised CRP levels in cases of chest pain with a normal CK MB indicated a pathological process other than myocardial infarction. Regular monitoring of CRP levels may also assist in early recognition of intercurrent complications occurring after myocardial infarction.
The end-product of coagulation is a clot with a fibrin meshwork. Fibrin, however, is not a permanent structure, but stimulates a biochemical pathway that leads to its lysis pathway and fragmentation of the clot. Essential components of this, as a consequence, are the plasminogen activators (PAs). PAs convert the zymogen plasminogen to the ultimate fibrinolytic enzyme plasmin (Fig. 1). At least two types of PAs have been identified in plasma: one produced and secreted by endothelial cells (first isolated in urine), called tissue-type PA (t-PA), and another called urinary-type PA or urokinase (UK). UK was later also identified in plasma, mainly as a proenzyme known as pro-urokinase (pro-UK). t-PA and pro-UK both activate plasminogen, preferentially in the presence of fibrin, but by different mechanisms (for review, see [5]).
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