Abstract
Previous results have indicated that valsartan administration at bedtime as opposed to on wakening improves the diurnal/nocturnal ratio of blood pressure without loss in efficacy and therapeutic coverage. We hypothesized that increasing this ratio could reduce microalbuminuria. We conducted a prospective, randomized, open-label, blinded endpoint trial on 200 previously untreated nonproteinuric patients with grade 1 to 2 essential hypertension, assigned to receive valsartan (160 mg/d) as a monotherapy either on awakening or at bedtime. Blood pressure was measured by ambulatory monitoring 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 significant blood pressure reduction after 3 months of therapy was similar for both treatment times. The diurnal/nocturnal blood pressure ratio was unchanged after valsartan on awakening, but significantly increased from 7.5 to 12.2 (P<0.001) when valsartan was administered at bedtime. Urinary albumin excretion was significantly reduced by 41% after bedtime treatment. This reduction was independent of the 24-hour blood pressure decrease but highly correlated with the decrease in nocturnal blood pressure and mainly with the increase in diurnal/nocturnal ratio (P<0.001). Bedtime valsartan administration improves the diurnal/nocturnal blood pressure ratio to a more dipper profile. This normalization of the circadian blood pressure pattern is associated with a significant decrease in urinary albumin excretion and plasma fibrinogen, and could thus reduce the increased cardiovascular risk in nondipper hypertensive patients.
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