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CLINICAL STUDIES

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

^a Department of Cardiology, Royal Hospitals Trust, Environmental Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom
^b Department of Haematology, Royal Hospitals Trust, Environmental Epidemiology Unit, London School of Hygiene and Tropical Medicine, London, United Kingdom

Manuscript received October 28, 1997; revised manuscript received July 30, 1998, accepted August 20, 1998.

Address for correspondence: Dr. Adam D. Timmis, Royal Hospitals Trust (London Chest Hospital), Bonner Road, London, United Kingdom E2 9JX
adam{at}timmis-lch.demon.co.uk

Objectives. To examine circadian changes in the sympathovagal balance, the activity of the renin-angiotensin system and hemostatic variables in patients with stable coronary artery disease, and the effects of beta-adrenoceptor blockade and angiotensin-converting enzyme inhibition.

Background. Sympathovagal balance and key components of the fibrinolytic system show circadian variability. The effects of beta-adrenergic blocking agents and angiotensin-converting enzyme inhibitors on these autonomic and hemostatic 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, then bisoprolol, and finally quinapril). The effects on sympathovagal balance, hemostatic variables and the renin-angiotensin system activity were measured.

Results. The fibrinolytic capacity showed marked circadian variation at the 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 at 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 antigen, 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-converting enzyme inhibition with quinapril does not affect either sympathovagal balance or the endogenous fibrinolytic system. Our data suggest that the sympathoadrenal system may modify fibrinolytic activity, judged by the response to beta-adrenoreceptor blockade with bisoprolol.

Abbreviations and Acronyms   ßTG = beta-thromboglobulin   PAI-1 = plasminogen activator inhibitor-1   PF4 = platelet factor 4   RAS = renin-angiotensin system   tPA = tissue plasminogen activator   vWF = von Willebrand factor

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