Ambulatory blood pressure pattern in patients with resistant hypertension as a function of the circadian time of antihypertensive therapy

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Hypertensive patients with high blood pressure (BP) after treatment with 3 or more antihypertensive drugs present elevated cardiovascular risk, and high prevalence of a non-dipper BP pattern (<10% decline in the nocturnal relative to the diurnal BP mean). Recent results indicate that non-dipping in treated patients may be related to the absence of 24-hour therapeutic coverage [J Hypertens. 2002;20:1097-1104]. Accordingly, we studied the impact of the time of treatment on the circadian pattern of BP in patients with resistant hypertension. We studied 444 patients with resistant hypertension (228 men), 58.9±11.0 years of age. Among them, 210 patients received all their medication upon awakening. In the remaining 234 patients, one drug was prescribed to be taken before bedtime. BP was measured at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours. Physical activity was simultaneously monitored every minute by wrist actigraphy, and the information used to determine diurnal and nocturnal means of BP for each patient according to individual resting time. In comparison with patients who received all their antihypertensive medication upon awakening, subjects with one drug before bedtime were characterized by a significant reduction in the 24-hour mean of systolic BP (4.9 mm Hg, P<0.001). This reduction was much more prominent during nocturnal resting hours (7.5 mm Hg, P<0.001). The reduction in nocturnal mean was also significant in diastolic BP (2.3 mm Hg, P=0.011). Patients receiving one drug before bedtime also showed a significant reduction in the 24-hour mean of pulse pressure (4.3 mm Hg, P<0.001). A very high 82.9% of the patients with all drugs on awakening were non-dippers. This percentage was significantly reduced to just 51.7% in patients who received one antihypertensive drug before bedtime (P<0.001). In patients with resistant hypertension, pharmacological therapy should take into account when to treat with respect to the rest-activity cycle of each patient, as a function of the therapeutic coverage of the drugs and the baseline circadian BP profile of the patient. This chronopharmacology therapeutic approach allows to reduce the prevalence of an altered non-dipper BP profile, associated with an increased cardiovascular risk. Am J Hypertens (2004) 17, 41A–41A; doi: 10.1016/j.amjhyper.2004.03.098