Circadian activity of the endogenous fibrinolytic system in stable coronary artery disease: Effects of beta-adrenoreceptor blockers and angiotensin-converting enzyme inhibitors

Objectives. To examine circadian changes in the sympathovagal balance, the activity of the renin-angiotensin system and hemostatic variables in patien ts with stable coronary artery disease, and the effects of beta-adrenocepto r blockade and angiotensin-converting enzyme inhibition. Background. Sympathovagal balance and key components of the fibrinolytic sy stem show circadian variability. The effects of beta-adrenergic blocking ag ents and angiotensin converting enzyme inhibitors on these autonomic and he mostatic rhythms are not well defined. Methods. Twenty patients with coronary artery disease underwent 24-h Holter monitoring for heart rate variability and blood sampling (6 hourly for 24 hours) after three consecutive treatment phases, (firstly with placebo, the n bisoprolol, and finally quinapril). The effects on sympathovagal balance, hemostatic variables and the renin-angiotensin system activity were measur ed. Results. The fibrinolytic capacity shelved marked circadian variation at th e end of the placebo phase (p = 0.002), plasminogen activator inhibitor-1 ( PAI-1) activity peaking at 06.00 AM when tissue plasminogen activator (tPA) activity was at its nadir. Sympathovagal balance showed a sharp increase a t approximately the same time but plasma renin activity did not rise until later in the day. Inspection of the 24-h profiles suggested that bisoprolol reduced sympathovagal balance and the morning peak of PAI-1 activity and a ntigen, with a small increase in tPA activity, although these changes were not significant. Quinapril produced a substantial rise in renin (p = 0.01) but did not significantly affect either PAI-1 or tPA. Sympathovagal balance was unaffected by quinapril. Conclusions. In patients with stable coronary artery disease, angiotensin-c onverting enzyme inhibition with quinapril does not affect either sympathov agal balance or the endogenous fibrinolytic system. Our data suggest that t he sympathoadrenal system may modify fibrinolytic activity, judged by the r esponse to beta-adrenoreceptor blockade with bisoprolol. (J Am Coll Cardiol 1998;32:1962-8) (C) 1998 by the American College of Cardiology.