Toward a personalized chronotherapy of high blood pressure and a circadian overswing

Yoshihiko Watanabe, Franz Halberg, Kuniaki Otsuka, Germaine G Cornelissen-Guillaume

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Timing can greatly affect the response to a stimulus, including antihypertensive medications. Herein, we assess the response of 30 patients to losartan/hydrochlorothiazide (L/H), administered for at least 1 month at a given circadian stage to each patient, this stage being changed during consecutive spans to cover six treatment times from awakening to bedtime at approximately 3-hour intervals. At the end of each stage, each patient underwent a 7-day around-the-clock ambulatory blood pressure (BP) profile, analyzed chronobiologically. A larger reduction of the midline estimating statistic of rhythm (MESOR; a rhythm-adjusted mean) of diastolic BP was achieved by L/H administration in the early morning for more patients (P < .05), while treatment upon awakening was the best choice for most patients to reduce the circadian amplitude of BP the most (P < .01). The optimal treatment time varied considerably among patients, however. Special attention should be given to the effect on the circadian amplitude since treatment can increase it above a threshold, beyond which there is a marked increase in cardiovascular disease risk. The results indicate the desirability to individualize the optimization of the antihypertensive effect of L/H by timing along the circadian scale.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalClinical and Experimental Hypertension
Issue number4
StatePublished - Jun 26 2013


  • Blood pressure
  • CHAT
  • Chronotherapy
  • Circadian
  • Hypertension


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