Low grade inflammation, fibrinolysis, and evolution of future coronary heart disease in initially healthy men and women

Recent large scale prospective studies have reported that low grade inflammation and an unbalanced fibrinolysis determine the risk for evolution of coronary heart disease. In a nested case-control study including 133 cases with coronary heart disease and 258 controls comparable for sex and age, we have studied the occasion and the role of C-reactive protein (CRP) and tissue plasminogen activator (t-PA) in the evolution of future coronary heart disease. We measured protein concentration of CRP and t-PA with the use of highly sensitive methods in stored serum samples, and the cohorts were followed from 7 to 16 years. CRP and t-PA concentrations were both significantly higher in cases than in controls (p < 0.001 and p < 0.000). 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-year follow-up cohort (CRP: p < 0.014;t-PA:p< 0.001)andthe 16-year follow-up cohort (CRP: p < 0.027; t-PA: p < 0.012). Both CRP and t-PA correlated significantly with a number of other cardiovascular risk factors. The best predictor of CRP was t-PA, while the best predictor of t-PA was triglycérides. In a logistic regression analysis model t-PA still came out as independent predictor of coronary heart disease, while such a significance disappeared for CRP. With use of ROC curves we determined that AUC for t-PA was 0.62 and for CRP 0.59, indicating that none of the two analytes has a high prognostic power to predict future coronary events in an initially healthy population. We conclude that moderate increases in serum concentrations of CRP and t-PA are present in up to 16 years before the presence of clinical overt coronary heart disease; that CRP is not an independent risk factor and that t-PA is an independent risk factor for evolution of coronary heart disease; and that neither t-PA nor CRP has a high power to predict evolution of future coronary heart disease.