Plasma urokinase antigen and C-reactive protein predict angina recurrence after coronary angioplasty

Inflammation is a recognized key component of acute coronary syndromes. Such pathogenetic achievement has led to the use of inflammatory cells and proteins as prognostic markers in these syndromes. A number of markers have been proposed, including proinflammatory cytokines such as interleukin-6, interleukin-1RA, and tumor necrosis factor-alpha, adhesion molecules such as intracellular adhesion molecule-1 and vascular adhesion molecule-1 and markers of cell activation. Although all are of scientific interest, the clinical use of these markers is limited by their high cost, low availability, and unfavorable biological profile. Conversely, common markers of inflammation such as C-reactive protein (CRP), the prototypic acute phase protein, and to a lesser extent fibrinogen, have been proven to be reliable and important markers of risk in ischemic heart disease. CRP, in particular, has been found to be associated with short- and long-term prognosis in acute coronary syndromes, including ST-elevation myocardial infarction, and in stable angina, and to predict the risk of restenosis and major events, including death, after revascularization procedures. CRP has been consistently found to be independent from other risk factors and to have an incremental value beyond the common risk factors and biochemical markers of risk, including troponin. Whether CRP also should be used as a guide to therapy is still a matter of discussion that deserves further, properly designed studies.

Although C-reactive protein (CRP) has been proposed as a useful biomarker for predicting atherothrombosis, the association between CRP and stent thrombosis after drug-eluting stent implantation has not been defined. We prospectively evaluated 2691 patients treated with drug-eluting stents who had a baseline CRP measurement. The primary outcome was stent thrombosis; secondary outcomes were death, myocardial infarction (MI), death or MI, and target vessel revascularization. During follow-up (median, 3.9 years), 32 patients had definite or probable stent thrombosis, 137 patients died, 227 had an MI, and 195 underwent target vessel revascularization. In multivariable Cox proportional-hazards models, elevated levels of CRP were significantly associated with increased risk of stent thrombosis (hazard ratio, 3.86; 95% confidence interval, 1.82 to 8.18; P<0.001). Elevated CRP levels also significantly predicted the risks of death (hazard ratio, 1.61; 95% confidence interval, 1.13 to 2.28; P=0.008), MI (hazard ratio, 1.63; 95% confidence interval, 1.25 to 2.12; P=0.001), and death or MI (hazard ratio, 1.61; 95% confidence interval, 1.29 to 2.00; P<0.001) but not target vessel revascularization (hazard ratio, 1.20; 95% confidence interval, 0.90 to 1.61; P=0.21). The incorporation of CRP into a model with patient, lesion, and procedural factors resulted in a significant increase in the C statistic for the prediction of stent thrombosis, MI, and the composite of death or MI. Elevated CRP levels were significantly associated with increased risks of stent thrombosis, death, and MI in patients receiving drug-eluting stents, suggesting the usefulness of inflammatory risk assessment with CRP. Given the relatively infrequent occurrence of stent thrombosis, death, and MI, larger studies with longer-term follow-up are required to confirm the novel relationship.