Previous studies have shown that overall fibrinolytic activity in blood follows a diurnal rhythm with a peak in the morning and a trough in the evening. The purpose of this study was to determine which fibrinolytic factor(s) was responsible for this diurnal rhythm. Resting and postvenous occlusion tissue-type plasminogen activator (t-PA) activity, resting t-PA antigen, and resting plasminogen activator inhibitor 1 (PAI-1) activity were measured in the morning and evening in 33 healthy men (mean age, 31 years) and in 15 patients (mean age, 57 years) with previous myocardial infarction or unstable angina. PAI-1 activity and t-PA antigen were significantly higher (p <0.01) in the morning compared with the evening in controls and patients. In contrast, resting t-PA activity was significantly lower in the morning (p <0.01) in both groups and was inversely correlated with PAI-1 activity (r= -0.57, p < 0.0001). Postvenous occlusion t-PA activity and t-PA capacity were not significantly different between morning and evening in either group. Because t-PA antigen levels and PAI-1 activity were highest in the morning, the variation in t-PA activity was probably not due to decreased secretion of t-PA but instead to changes in the secretion of PAI-1. Our findings indicate that diurnal variations in PAI-1 activity may reduce fibrinolytic activity in the morning in healthy individuals and in patients with coronary artery disease. (Circulation 1989;79:101-106) I ncidence of acute myocardial infarction follows a circadian rhythm with a peak in the morning and a trough in the evening. Muller et all found a threefold increase in the frequency of myocardial infarction at 9 AM compared with 11 PM. A similar diurnal variation in the time of onset has been found for a number of other disorders associated with arterial thrombosis, including sudden cardiac death, angina at rest, and stroke.2-4A number of different factors may play a role in the circadian variation of arterial thrombosis. Heart rate, arterial blood pressure, and catecholamine levels have been shown to peak in the morning hours, indicating that coronary vasoconstriction may be increased in the morning as well.5-7Another approach has been to study factors that may increase the risk of initiating thrombus formation. Platelet aggregability has been found to increase in the morning after arising.8,9 A concurrent increase in From plasma epinephrine and norepinephrine were also found. These studies have concentrated on factors that may increase the risk of vasoconstriction or thrombus initiation. Another possible explanation would be alterations in blood components that depress the rate of thrombus removal. In vivo, newly forming thrombi are removed by the fibrinolytic system. Fibrinolysis is initiated by tissue-type plasminogen activator (t-PA), an enzyme secreted by endothelial cells that, in the presence of fibrin, converts the proenzyme plasminogen into its active form, plasmin.10 In turn, plasmin proteolytically degrades the fibrin that holds the thrombus together. Th...

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