The circadian pattern of blood pressure: cardiovascular risk and therapeutic opportunities

It has been known for many years that humans possess internal time clocks that regulate multiple physiologic factors (chronobiology). Epidemiologic studies have demonstrated that the peak incidence of many diseases, including respiratory disease (asthma, allergy), cardiovascular disease (hypotension, angina, myocardial infarction, stroke), as well as several others, tends to occur in a circadian pattern. In particular, studies utilizing ambulatory blood pressure monitoring have demonstrated that blood pressure has a very definite and reproducible circadian pattern over a 24-h period. Blood pressure is highest during the day; lowest during sleep, and then rapidly increases during the period 0400 h to 1200 h. Because recent data have demonstrated a possible cause-effect relationship between increases in blood pressure and angina, effective antihypertensive control in the early morning is desirable. Some once-a-day drugs taken in the morning may lose efficacy in the last few hours of the dosing interval, resulting in increases in blood pressure during the early morning period. In an attempt to ensure peak plasma levels during the early morning period, novel, controlled-onset, extended release-delivery systems have been developed. Studies using these delivery systems have demonstrated that, when dosed at night, these formulations provide maximal plasma levels during the period 0600 h to 1200 h, when blood pressure is physiologically rising at its greatest rate. The use of drugs designed to have peak efficacy at certain desirable times in the circadian pattern is referred to as chronotherapeutics.