Circulating levels of plasminogen activator inhibitor type-1, tissue plasminogen activator, and thrombomodulin in hemodialysis patients: biochemical correlations and role as independent predictors of coronary artery stenosis.
This study investigated the relationship between the circulating levels of the endothelial cell glycoproteins plasminogen activator inhibitor type 1 (PAI-1), tissue plasminogen activator (TPA), and thrombomodulin (TM) and the major vascular risk factors described in dialysis patients. In addition, the role of these endothelial cell products as independent predictors of coronary artery disease (CAD) was analyzed. Levels of TM, TPA antigen (Ag), TPA activity, PAI-1 Ag, PAI-1 activity, TPA/PAI complexes, thrombin-antithrombin complexes, fibrinopeptide A, C-reactive protein (CRP), interleukin-1beta and tumor necrosis factor-alpha, lipids, apoproteins A1 and B, and albumin were measured in a group of 200 nondiabetic dialysis patients and 100 healthy matched volunteers. When compared with healthy controls, dialysis patients showed increased levels of CRP, TM, TPA, and PAI-1 and evidence of increased thrombin-dependent fibrin formation. Increased levels of active PAI-1 were associated to a great extent with major classic vascular risk factors and to a lesser extent with CRP and serum triglycerides. Forty-six patients (23%) had evidence of CAD. Variables associated with CAD in the univariate analysis included age, time on dialysis, male gender, number of packs of cigarettes per year, high BP, fibrinogen, apolipoprotein B, albumin, PAI-1 activity, CRP, thrombin-antithrombin complexes, and fibrinopeptide A. Logistic regression analysis found age, high-density lipoprotein cholesterol, gender, high BP, CRP, time on dialysis, and PAI-1 activity to be independent predictors of CAD. This model classified correctly 85% of patients as having CAD and showed adequate goodness of fit for all risk categories. Our data support a pathogenic link among activated inflammatory response, endothelial injury, and CAD in hemodialysis patients and suggest that assessment of circulating PAI-1 levels could be an additional tool to identify dialysis patients who are at risk for developing atheromatous cardiovascular disease.
Segarra
Alfons
A
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Chacón
Pilar
P
Bioquímica, Hospital Valle Hebrón, Barcelona, Spain.
Martinez-Eyarre
Cristina
C
CDR Monolab, Hospital Sant Gervasi, Barcelona, Spain.
Argelaguer
Xavier
X
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Vila
Josefa
J
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Ruiz
Pilar
P
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Fort
Joan
J
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Bartolomé
Jorge
J
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Camps
Joaquin
J
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Moliner
Ernesto
E
Unidad de Hemodiálisis, Hospital Sant Gervasi, Barcelona, Spain.
Pelegrí
Antoni
A
Centro de Nefrología, Virgen de Montserrat, Barcelona, Spain.
Marco
Fernando
F
Centro de Diálisis Nephros, Barcelona, Spain.
Olmos
Antonio
A
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
Piera
Lluis
L
Servicios de Nefrología, Hospital Valle Hebrón, Barcelona, Spain.
D016022:Case-Control Studies; D016009:Chi-Square Distribution; D003327:Coronary Disease / Q000097:blood / Q000209:etiology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000628:therapy; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011237:Predictive Value of Tests; D012044:Regression Analysis; D006435:Renal Dialysis; D012307:Risk Factors; D018180:Thrombomodulin / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood*
D017395:Plasminogen Activator Inhibitor 1; D018180:Thrombomodulin; D010959:Tissue Plasminogen Activator