Chronobiology and chronotherapeutics. Applications to cardiovascular medicine

The concept of homeostasis, ie, constancy of the milieu interne, has dominated the teaching, research, and practice of medicine during the 20th century. According to this theory, biologic functions and processes are maintained in relative constancy over time. The emerging concepts of chronobiology, the scientific discipline of biologic rhythm study, and the findings from research in this field challenge the construct of homeostasis. Epidemiology studies document that the occurrence and exacerbation of many human diseases vary predictably in time over 24 h, the menstrual cycle, and year due to underlying rhythms of corresponding period. Advances in the chronobiology of cardiovascular disease have proceeded rapidly during the past decade and have influenced the manner in which diagnostic procedures are conducted and interpreted. Twenty-four-hour ambulatory blood pressure (BP) monitoring and Holter monitoring reveal the marked circadian (24-h) rhythms in BP in hypertensive patients and electrocardiographic events in patients with ischemic heart disease. Homeostatically devised pharmacotherapies, ie, medications designed to ensure constant drug levels over time, may be inadequate to optimally control diseases whose courses vary in risk or severity during the 24-h period. Chronotherapies--medications formulated to deliver varying amounts of drug at different times during the 24 h period to correlate with biologic need--theoretically could offer improved efficacy. A chronotherapy for cardiovascular disease already exists in the form of the evening administration for lipid-lowering medications. The chronotherapy for hypertension and of ischemic heart disease is forthcoming.