Munger M A, Kenney J K
Department of Pharmacy Practice, University of Utah, Salt Lake City 84112-5820, USA.
Ann Pharmacother. 2000 Nov;34(11):1313-9. doi: 10.1345/aph.19234.
To review the chronobiology of hypertension and coronary artery disease and the application of chronotherapeutics to their treatment and prevention.
Clinical trials and review articles (English-language) on the topic of chronotherapy and cardiovascular disease were identified via a MEDLINE search from 1990 to March 2000, using the search terms chronotherapy, circadian rhythm, cardiovascular disease, hypertension, and angina.
Search and evaluation focused on published clinical trials and review articles of circadian variation associated with pharmacotherapy for cardiovascular disease.
The existence of circadian rhythm in cardiovascular disease is well established. Heart rate and blood pressure peak during the morning hours and reach a nadir at bedtime. The incidence of myocardial infarction, stroke, sudden cardiac death, and myocardial ischemia also increases during the early-morning hours. Based on these relationships, researchers have begun to apply the science of chronotherapeutics, or timing of drug effect with biologic need, to improve cardiovascular outcomes. This includes administering traditional agents at specific times throughout the day and developing new agents--chronotherapeutic formulations with special release mechanisms--targeted at inducing the greatest effect during the morning surges. Chronotherapeutic agents are specifically designed to provide peak plasma concentrations during the early-morning hours, when effect appears most needed; lowest concentrations occur at night, when heart rate and blood pressure are lowest and, consequently, cardiovascular events are least likely to occur.
Whether chronotherapy of cardiovascular disease offers an advantage in long-term outcomes over traditional therapy must be studied in clinical trials.
综述高血压和冠状动脉疾病的时间生物学以及时间治疗学在其治疗和预防中的应用。
通过1990年至2000年3月的MEDLINE检索，使用时间治疗学、昼夜节律、心血管疾病、高血压和心绞痛等检索词，确定了关于时间治疗学和心血管疾病主题的临床试验和综述文章（英文）。
检索和评估聚焦于已发表的与心血管疾病药物治疗相关的昼夜变化的临床试验和综述文章。
心血管疾病中昼夜节律的存在已得到充分证实。心率和血压在上午时段达到峰值，在就寝时降至最低点。心肌梗死、中风、心源性猝死和心肌缺血的发病率在清晨时段也会增加。基于这些关系，研究人员已开始应用时间治疗学，即根据生物需求安排药物作用时间，以改善心血管疾病的治疗效果。这包括在一天中的特定时间给予传统药物，并开发新的药物——具有特殊释放机制的时间治疗制剂——旨在在上午高峰期产生最大效果。时间治疗药物经过专门设计，可在清晨时段（此时似乎最需要药物作用）提供血浆浓度峰值；夜间浓度最低，此时心率和血压最低，因此心血管事件发生的可能性最小。
心血管疾病的时间治疗在长期治疗效果上是否优于传统治疗，必须通过临床试验进行研究。
