Fibrinolytic and Endothelial Markers in Cardiovascular Disease and Diabetes Mellitus

Medicine

Rumley, Ann

University:University of Glasgow

关键词: Medicine;   

Others  :  http://theses.gla.ac.uk/76107/1/13818904.pdf

来源: University of Glasgow

【 摘 要 】

Plasminogen activator inhibitor (PAI) activity, tissue plasminogen activator (tPA) antigen and von Willebrand factor (VWF) antigen are endothelial products with roles in fibrinolysis and platelet function respectively. Fibrin D-dimer antigen (D-dimer) is a marker of cross-linked fibrin formation and lysis. Plasma levels of these four haemostatic variables (as well as the acute phase reactants, fibrinogen and red cell aggregation) were studied with regard to variability, associations with ischaemic heart disease (IHD) and its risk factors, and associations with diabetes mellitus (including microalbuminuria and response to insulin and exercise). Laboratory, biological and total variability were defined and appeared satisfactory for clinical studies. In a population sample (North Glasgow MONICA study) distributions and independent associations were defined. PAI was related to time of day, serum triglyceride, alcohol intake, diabetes and interleukin-6. tPA was related to PAI, age, male sex, time of day, cigarette smoking, triglyceride and alcohol use. VWF was related to age, smoking and diabetes. D-dimer was related to age, VWF, fibrinogen and red cell aggregation. In a case control study, survivors of premature myocardial infarction had higher levels of PAI, VWF, D-dimer, fibrinogen and red cell aggregation (which were independent of standard risk factors); and of tPA (which was not independent). In a prospective population study (Caerphilly Heart Study), D-dimer and VWF were independent predictors of IHD events, while PAI and tPA were not. In a prospective study of patients with peripheral arterial disease (Edinburgh Claudication Study), D-dimer was an independent predictor of IHD events and progression of arterial disease; while fibrinogen was an independent predictor of mortality. Non-insulin-dependent diabetic patients with microalbuminuria (a predictor of IHD) had higher levels of tPA and VWF than diabetic or non-diabetic controls without microalbuminuria. Compared to nondiabetic controls, insulin-dependent diabetic patients had lower increments in tPA in response to insulin induced hypoglycaemia or exercise, suggesting an endothelial defect. The results of these studies are consistent with potential roles of disturbed fibrinolysis, endothelial and platelet function, and fibrin turnover in the pathogenesis of ischaemic heart disease and of diabetic vascular complications.