EVIDENCE FOR TIME-DEPENDENT ACTIVATION OF MONOCYTES IN THE SYSTEMIC CIRCULATION IN UNSTABLE ANGINA BUT NOT IN ACUTE MYOCARDIAL-INFARCTION OR IN STABLE ANGINA

Background Platelet activation plays a pivotal role in the pathogenesi s of acute coronary disease. Monocytes are involved in the progression of atherosclerosis and are potent activators of blood coagulation thr ough their ability to synthesize tissue factor (TF). The aim of this s tudy was to compare markers of monocyte and coagulation activation in the systemic blood of patients with unstable angina, acute myocardial infarction, or stable angina. Methods and Results We studied 26 patien ts with unstable angina (10 +/- 5 hours after the onset of the last ep isode of pain), 18 patients with acute myocardial infarction (5 +/- 4 hours after the onset of pain), and 34 patients with stable angina. We measured levels of TF expression in peripheral blood mononuclear cell s (isolated by gradient centrifugation and incubated for 16 hours, wit h or without endotoxin stimulation), levels of plasma prothrombin frag ment 1 + 2 (F1 + 2), and levels of fibrinogen in peripheral blood. In patients with unstable angina, both stimulated and unstimulated cells exhibited higher levels of TF expression than in patients with stable angina (P = .0001). In patients with acute myocardial infarction, mono cyte TF activity did not differ from that in patients with stable angi na. Mean levels of F1 + 2 and of fibrinogen did not differ significant ly between groups. Only in the unstable angina group, a modest correla tion was found between fibrinogen (r = .72, P = .005) and F1 + 2 level s (r = .54, P = .001) levels and the degree of monocyte TF expression. In patients with unstable angina, monocyte TF expression (both stimul ated and unstimulated, assessed by biological activity and by antigen techniques) and fibrinogen levels were correlated with the time elapse d from the beginning of the most recent episode of pain (.61 < r < .72 , .02 < P < .0001). By contrast, there was no correlation between thes e variables and the time from onset of pain in patients with acute myo cardial infarction. Conclusions A time-dependent activation of systemi c monocytes and a time-dependent increase in fibrinogen levels occurs in unstable angina but not in myocardial infarction. These findings pr ovide further evidence that a specific inflammatory process occurs in unstable angina. Further studies are required to determine whether mon ocyte activation is a cause or a consequence of plaque instability in patients with unstable angina and to clarify the interrelations betwee n platelet and monocyte activation in these circumstances.