title: Toward a personalized chronotherapy of high blood pressure and a circadian overswing.
abstract: 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.
authors.affiliation: Department of Medicine, Tokyo Women's Medical University, Medical Center East, Tokyo, Japan. yoshi-w@jd5.so-net.ne.jp
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Watanabe
authors.forename: Franz
authors.initials: F
authors.lastname: Halberg
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Otsuka
authors.forename: Germaine
authors.initials: G
authors.lastname: Cornelissen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D018660:Blood Pressure Monitoring, Ambulatory; D002940:Circadian Rhythm / Q000502:physiology; D055870:Drug Chronotherapy; D004338:Drug Combinations; D005260:Female; D006801:Humans; D006852:Hydrochlorothiazide / Q000008:administration & dosage; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D019808:Losartan / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular; D057285:Precision Medicine
chemical_list: D000959:Antihypertensive Agents; D004338:Drug Combinations; C505809:hydrochlorothiazide, losartan drug combination; D006852:Hydrochlorothiazide; D019808:Losartan