Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study.
OBJECTIVE
To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects.


METHODS
Nested case-control study. Follow-up periods 7-15 years.


METHODS
Included in the study were 133 cases with coronary heart disease and 258 controls.


METHODS
None.


METHODS
Subjects with ischaemic heart disease identified in 1991 by the Danish National Hospital Register. Protein concentration of C-reactive protein (CRP) and tissue-type plasminogen activator (t-PA) were measured with ELISA methods in stored serum samples.


RESULTS
CRP and t-PA concentrations were both significantly higher in cases than in controls (P < 0.001 and P < 0. 001). This difference between cases and controls for CRP and t-PA was present in both men (CRP: P = 0.022; t-PA: P = 0.001) and women (CRP: P = 0.013; t-PA: P = 0.005) and it was present in both the 7-9 years follow-up cohort (CRP: P = 0.014; t-PA: P = 0.001) and the 15 years follow-up cohort (CRP: P = 0.027; t-PA: P = 0.012). The best predictor of CRP was t-PA, whilst the best predictor of t-PA was triglycerides. In a logistic regression analysis model, t-PA still came out as independent predictor of coronary heart disease, whilst such a significance disappeared for CRP. With the use of ROC curves we determined that AUC for t-PA was 0.62, and for CRP 0.59, indicating that none of these two analytes has a high prognostic power in predicting future coronary events in an initially healthy population.


CONCLUSIONS
We conclude that moderate increases in serum concentrations of CRP and t-PA are present for up to 15 years before the presence of clinical overt coronary heart disease; that a low-grade inflammation is determined by other risk factors and that t-PA is an independent risk factor for evolution of coronary heart disease.
Gram
J
J
Department of Clinical Biochemistry, Ribe County Hospital, South Jutland University Centre, Esbjerg, Denmark. JGR@ribeamt.DK
Bladbjerg
E M
EM
Møller
L
L
Sjøl
A
A
Jespersen
J
J
D000208:Acute Disease; D002097:C-Reactive Protein / Q000378:metabolism*; D016022:Case-Control Studies; D003327:Coronary Disease / Q000097:blood*; D003718:Denmark; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D012372:ROC Curve; D010959:Tissue Plasminogen Activator / Q000097:blood*
D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator