From the Department of Medicine, Silkeborg Regional Hospital, Silkeborg, Denmark (N.B.R., K.W.H.); and Department of Endocrinology and Internal Medicine (N.B.R., S.T.K., E.E., P.L.P.), Medical Research Laboratory (J.F.), and Department of Clinical Biochemistry (A.-M.H.), Aarhus University Hospital, Aarhus, Denmark.
Hypertension. 2014 Nov;64(5):1080-7. doi: 10.1161/HYPERTENSIONAHA.114.03958. Epub 2014 Aug 4.
Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduction in daytime (1.3 mm Hg; P=0.336) systolic BP. We did not find morning BP surge to be different between dosing regimens. Levels of C-reactive protein were significantly lower with bedtime administration, which may indicate an effect on low-grade inflammation. We found no difference in urinary albumin excretion, regardless of albuminuria status. Urinary sodium/creatinine was significantly increased and urinary osmolality significantly reduced with bedtime administration, which can be interpreted as increased nocturnal natriuresis. In patients with type 2 diabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention.
几项针对不同人群的研究表明，夜间血压（BP）比日间血压更能预测心血管事件。因此，针对夜间血压的治疗策略成为关注焦点。本研究旨在探讨改变降压药物给药时间的效果。我们纳入了 41 例 2 型糖尿病伴夜间高血压（夜间收缩压>120mmHg）患者，进行了一项开放标签、交叉研究。患者被随机分为两组，分别接受 8 周的晨起或睡前给药方案，然后再进行 8 周的转换治疗方案。睡前给药方案可显著降低夜间（7.5mmHg；P<0.001）和 24 小时（3.1mmHg；P=0.014）收缩压，而对日间收缩压（1.3mmHg；P=0.336）无显著影响。我们没有发现两种给药方案之间的晨峰血压有差异。睡前给药时 C 反应蛋白水平显著降低，这可能表明其对低度炎症有影响。我们发现无论白蛋白尿状态如何，尿白蛋白排泄量均无差异。无论白蛋白尿状态如何，无论白蛋白尿状态如何，尿钠/肌酐比值显著增加，尿渗透压显著降低，提示夜间排钠增加。在 2 型糖尿病伴夜间高血压患者中，睡前服用每日一次的降压药可能更有利。夜间排钠增加可能反映了睡前给予噻嗪类和肾素-血管紧张素系统抑制剂的效果增加，这表明了时间治疗干预对血压产生影响的潜在机制。
