Hermida Ramón C, Calvo Carlos, Ayala Diana E, Domínguez María J, Covelo Manuel, Fernández José R, Mojón Artemio, López José E
Bioengineering and Chronobiology Labs, University of Vigo, Campus Universitario, Vigo, Spain.
Hypertension. 2003 Sep;42(3):283-90. doi: 10.1161/01.HYP.0000084855.32823.DA. Epub 2003 Jul 21.
This study investigated the administration time-dependent antihypertensive efficacy of valsartan, an angiotensin II receptor blocker. We studied 90 subjects (30 men and 60 women), 49.0+/-14.3 (mean+/-SD) years of age with stage 1 to 2 essential hypertension; they were randomly assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring every 20 minutes during the day and every 30 minutes at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per-subject basis. The highly significant blood pressure reduction after 3 months of treatment with valsartan (P<0.001) was similar for both treatment times (17.0 and 11.3 mm Hg reduction in the 24-hour mean of systolic and diastolic blood pressure with morning administration and 14.6 and 11.4 mm Hg reduction with bedtime administration; P>0.174 for treatment time effect). Valsartan administration at bedtime as opposed to on wakening resulted in a highly significant average increase by 6% (P<0.001) in the diurnal-nocturnal ratio of blood pressure; this corresponded to a 73% relative reduction in the number of nondipper patients. The findings confirm that valsartan efficiently reduces blood pressure throughout the entire 24 hours, independent of treatment time. They also suggest that time of treatment can be chosen according to the dipper status of a patient to optimize the effect of antihypertensive therapy, an issue that deserves further investigation.
本研究调查了血管紧张素II受体阻滞剂缬沙坦的给药时间依赖性降压疗效。我们研究了90名受试者（30名男性和60名女性），年龄为49.0±14.3（均值±标准差）岁，患有1至2期原发性高血压；他们被随机分配接受缬沙坦（160mg/d）单药治疗，分别于晨起或睡前服用。在治疗3个月前后，通过动态监测每20分钟测量一次白天血压，每30分钟测量一次夜间血压，连续测量48小时。同时通过手腕活动记录仪每分钟监测一次身体活动，以便准确计算每个受试者的日间和夜间平均血压。缬沙坦治疗3个月后血压显著降低（P<0.001），两种治疗时间的降压效果相似（晨起给药时24小时收缩压和舒张压平均降低17.0和11.3mmHg，睡前给药时降低14.6和11.4mmHg；治疗时间效应P>0.174）。与晨起给药相比，睡前服用缬沙坦导致血压昼夜比平均显著增加6%（P<0.001）；这相当于非勺型血压患者数量相对减少73%。研究结果证实，缬沙坦在整个24小时内均能有效降低血压，与治疗时间无关。研究结果还表明，可以根据患者的勺型血压状态选择治疗时间，以优化降压治疗效果，这一问题值得进一步研究。
