Bioengineering and Chronobiology Laboratories, University of Vigo, Campus Universitario, Vigo, Pontevedra, Spain.
Chronobiol Int. 2013 Mar;30(1-2):280-314. doi: 10.3109/07420528.2012.709448. Epub 2012 Oct 19.
Specific features of the 24-h blood pressure (BP) pattern are linked to progressive injury of target tissues and risk of cardiovascular disease (CVD) events. Several studies have consistently shown an association between blunted asleep BP decline and risk of fatal and nonfatal CVD events. Thus, there is growing focus on ways to properly control BP during nighttime sleep as well as during daytime activity. One strategy, termed chronotherapy, entails the timing of hypertension medications to endogenous circadian rhythm determinants of the 24-h BP pattern. Significant and clinically meaningful treatment-time differences in the beneficial and/or adverse effects of at least six different classes of hypertension medications, and their combinations, are now known. Generally, calcium channel blockers (CCBs) are more effective with bedtime than morning dosing, and for dihydropyridine derivatives bedtime dosing significantly reduces risk of peripheral edema. The renin-angiotensin-aldosterone system is highly circadian rhythmic and activates during nighttime sleep. Accordingly, evening/bedtime ingestion of the angiotensin-converting enzyme inhibitors (ACEIs) benazepril, captopril, enalapril, lisinopril, perindopril, quinapril, ramipril, spirapril, trandolapril, and zofenopril exerts more marked effect on the asleep than awake systolic (SBP) and diastolic (DBP) BP means. Likewise, the bedtime, in comparison with morning, ingestion schedule of the angiotensin-II receptor blockers (ARBs irbesartan, olmesartan, telmisartan, and valsartan exerts greater therapeutic effect on asleep BP, plus significant increase in the sleep-time relative BP decline, with the additional benefit, independent of drug terminal half-life, of converting the 24-h BP profile into a more normal dipping pattern. This is the case also for the bedtime versus upon-awakening regimen of combination ARB-CCB, ACEI-CCB, and ARB-diuretic medications. The chronotherapy of conventional hypertension medications constitutes a new and cost-effective strategy for enhancing the control of daytime and nighttime SBP and DBP levels, normalizing the dipping status of their 24-h patterning, and potentially reducing the risk of CVD events and end-organ injury, for example, of the blood vessels and tissues of the heart, brain, kidney, and retina.
24 小时血压（BP）模式的特定特征与靶组织的进行性损伤和心血管疾病（CVD）事件的风险相关。多项研究一致表明，睡眠时 BP 下降减弱与致命和非致命性 CVD 事件的风险相关。因此，人们越来越关注如何在夜间睡眠期间以及白天活动期间正确控制 BP。一种策略称为时间治疗学，它涉及将高血压药物的时间安排与 24 小时 BP 模式的内源性昼夜节律决定因素相匹配。现在已经知道，至少六种不同类别的高血压药物及其组合在有益和/或不良影响方面存在显著且具有临床意义的治疗时间差异。一般来说，钙通道阻滞剂（CCB）在睡前给药比早晨给药更有效，而对于二氢吡啶衍生物，睡前给药可显著降低外周水肿的风险。肾素-血管紧张素-醛固酮系统具有高度的昼夜节律性，并在夜间睡眠时激活。因此，晚上/睡前服用血管紧张素转换酶抑制剂（ACEI）贝那普利、卡托普利、依那普利、赖诺普利、培哚普利、喹那普利、雷米普利、螺普利、trandolapril 和佐芬普利对睡眠时收缩压（SBP）和舒张压（DBP）的影响比清醒时更明显。同样，与早晨相比，在睡前服用血管紧张素 II 受体阻滞剂（ARB）厄贝沙坦、奥美沙坦、替米沙坦和缬沙坦对睡眠时 BP 的治疗效果更大，同时显著增加睡眠时间内相对 BP 下降，此外，独立于药物终端半衰期，将 24 小时 BP 谱转化为更正常的下降模式。ARB-CCB、ACEI-CCB 和 ARB-利尿剂药物的睡前与醒来方案也是如此。传统高血压药物的时间治疗学构成了一种新的、具有成本效益的策略，可增强对白天和夜间 SBP 和 DBP 水平的控制，使 24 小时模式的下降状态正常化，并可能降低 CVD 事件和终末器官损伤的风险，例如血管和心脏、大脑、肾脏和视网膜组织。
