Tissue-type plasminogen activator and C-reactive protein in acute coronary heart disease. A nested case-control study.

Objectives: To study the importance of inflammation and fibrinolysis for evolution of ischaemic heart disease in a cohort of initially healthy subjects.

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

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

Interventions: None.

Main Outcome Measures: 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.

Conclusion: 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.