The incidence of most adverse cardiovascular events appears to follow a circadian pattern, reaching a peak in the morning shortly after wakening and arising. The activities of many physiologic parameters, including hemodynamic, hematologic and humoral factors, also fluctuate in a cyclical manner over the 24 h. It has been suggested that, during the post-awakening hours, the phases of these cycles synchronize to create an environment that predisposes to atherosclerotic plaque rupture and thrombosis in susceptible individuals, thereby accounting for the heightened cardiovascular risk at this time of day. Blood pressure and heart rate are part of this physiologic process, following a clear circadian rhythm characterized by a fall during sleep and a sharp rise upon awakening. This so-called ‘morning surge’ in blood pressure may act as a trigger for cardiovascular events, including myocardial infarction and stroke. The clinical implication of these observations is that antihypertensive therapy should provide blood pressure control over the entire interval between doses. For agents taken once daily in the morning, the time of trough plasma drug level (and lowest pharmacodynamic effect) will often coincide with the early morning surge in blood pressure and heart rate. For these reasons, chronotherapeutic formulations of drugs and intrinsically long-acting antihypertensive agents provide the most logical approach to the treatment of hypertensive patients since they provide 24 h blood pressure control from a single daily dose as well as attenuating the early morning rise in blood pressure (and in some instances heart rate).
Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
Correspondence and requests for reprints to William B. White, MD, Professor and Chief, Section of Hypertension and Clinical Pharmacology, University of Connecticut School of Medicine, 263 Farmington Avenue, Farmington, CT 06030-3940, USA. Tel: +1 860 679-2104; fax: +1 860 679-1250; e-mail: firstname.lastname@example.org
Received 1 March 2001
Accepted 7 March 2001
Sponsorship: Financial support for this week was provided by the Patrick and Catherine Weldon Donaglive Medical Research Foundation, Hertford, Connecticut, USA, and Boehringer Ingelheim GmbH, Ingelheim am Rhein, Germany.