Circadian variation of blood pressure: clinical relevance and implications for cardiovascular chronotherapeutics.

Changes in hemodynamics, caused by the inherent variability of the activity and awake-sleep cycle, may influence the outcome of various cardiovascular diseases. Recent data suggest that increased variability of blood pressure may promote excessive hypertensive target-organ disease. Several epidemiologic studies have demonstrated that myocardial ischemia, myocardial infarction, and sudden cardiac death have an excess incidence in the first several hours after awakening. In addition, surveys of the incidence of stroke (both ischemic and hemorrhagic) have shown an excess for the hours between 0800 a.m. and noon. The pathophysiologic bases for the increased number of cardiac and cerebrovascular events in the early-morning hours may be both hemodynamic and rheologic in nature. Over the past several years, therapeutic studies have evaluated the effects of antihypertensive and anti-ischemic therapies during the morning surge of blood pressure and heart rate. Generally, the few studies that have evaluated night-time dosing of conventional antihypertensive therapies have been statistically underpowered to demonstrate differences of morning versus evening dosing on early-morning blood pressure. One future direction of antihypertensive and anti-ischemic therapy is the delivery of the agents according to inherent variability that changes with time. The clinical impact of cardiovascular chronotherapy is that drug delivery is greatest when disease activity is enhanced (for example, during the early-morning hours) and least when disease activity is reduced.