"Circadian" variation in cardiovascular events and implications for therapy?

For many years, it was thought that acute cardiovascular events occurred in a random fashion. However, over the past 13 years or so, a significant amount of research, both retrospective and prospective, has shown that there is an excess of ischaemic activity, arrhythmic activity and acute cardiovascular events in the first few hours after waking and commencing activity. This excess may well be at least partly linked to the known physiological changes which occur after waking, including a surge in heart rate, blood pressure and catecholamine release, activation of the renin-angiotensin system, an increase in platelet aggregability on assuming the upright posture, and the final trough in the fibrinolytic system. Because of the relatively short half-life and duration of the therapeutic effect (<24 h) of many anti-ischaemic and anti-arrhythmic agents, it is likely that single day agents taken in the morning will have reached subtherapeutic levels at the time of waking and commencing activity the following morning. As many patients do not take their daily (morning) medication immediately on rising, and allowing for time for adsorption, it is likely that, despite our knowledge of "circadian variations" in both physiological responses and pathophysiological events in the morning waking hours, patients are in fact at least protection at this particular high-risk time of the 24 h day. With our knowledge about when events are more likely to happen, we should consider carefully the timing of administration of medications, having factored in the likely length of therapeutic effect in each instance. It is likely that the almost universal inability to demonstrate prognostic benefit with many anti-ischaemic and anti-arrhythmic agents to date relates at least in part to a lack of appropriate "protection" at the time of apparent greatest risk in the patient with cardiovascular disease. Intelligent prescribing might indeed improve outcome, and even in the absence of proof on this regard, it would seem appropriate that we at least strive to achieve such an outcome.