Document Detail


Perspectives on the chronotherapy of hypertension based on the results of the MAPEC study.
MedLine Citation:
PMID:  20854140     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Appreciation of chronotherapy in hypertension continues to lag, despite clear demonstrations by many studies of (i) clinically relevant dosing-time differences of the beneficial and adverse effects of most blood pressure (BP) medications and (ii) significant association between reduced sleep-time BP decline of non-dippers and their heightened risk of cardiovascular disease (CVD). The Syst-Eur and HOPE outcome trials showed evening administration of nitrendipine and ramipril in these respective studies impacts sleep-time BP, converting the 24-h BP pattern to a more dipper one and in the HOPE study decreasing CVD risk. The CONVINCE study intended to compare BP control and CVD protection afforded by conventional β-blocker and diuretic medications versus a special drug-delivery verapamil formulation as a bedtime hypertension chronotherapy; however, the trial was terminated prematurely, not based on inadequate performance of the chronotherapy but on a corporate business decision. The just completed MAPEC study is the first trial specifically designed to prospectively test the hypothesis that bedtime administration of ≥1 conventional medications exerts better BP control and CVD risk reduction than the traditional approach of scheduling all medications in the morning. The results of this 5.6-yr median follow-up study establish that bedtime chronotherapy more effectively improves BP control, better decreases prevalence of non-dipping, and, most importantly, best reduces CVD morbidity and mortality. This chronotherapeutic approach to hypertension is justified by the fact that BP is usually lowest at night as is sodium excretion, but when sodium intake is excessive or its daytime excretion hampered, nocturnal BP is adjusted higher, to a level required for compensation overnight, via the pressure/natriuresis mechanism, resulting in non-dipping 24-h BP patterning. In diurnally active persons, the entire circadian BP pattern may be reset to a lower mean level and to a "more normal" day-night variation, simply by enhancing natriuresis during the night-the time-of-day when it can be most effective. A modification as simple and inexpensive as switching ≥1 hypertension medications from morning to evening may be all that is needed to normalize nighttime BP, exerting an effect exactly like sodium restriction. Current clinical concepts such as "normotensive non-dipper" (with higher CVD risk than a hypertensive dipper), broad recommendation of pharmacotherapy with exclusively high "smoothness index" medications (without attention to individual patient needs defined by the features of the 24-h BP pattern), and reliance upon static daytime diagnostic BP thresholds based solely on single office cuff assessment necessitate urgent reconsideration.
Authors:
Francesco Portaluppi; Michael H Smolensky
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Chronobiology international     Volume:  27     ISSN:  1525-6073     ISO Abbreviation:  Chronobiol. Int.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-21     Completed Date:  2011-01-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8501362     Medline TA:  Chronobiol Int     Country:  England    
Other Details:
Languages:  eng     Pagination:  1652-67     Citation Subset:  IM    
Affiliation:
Hypertension Center, Department of Medicine, University Hospital S. Anna of Ferrara, Ferrara, Italy. prf@unife.it
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MeSH Terms
Descriptor/Qualifier:
Antihypertensive Agents* / administration & dosage,  pharmacology,  therapeutic use
Blood Pressure / drug effects,  physiology
Cardiovascular Diseases
Chronotherapy / methods*
Circadian Rhythm / physiology*
Humans
Hypertension / drug therapy*,  physiopathology
Randomized Controlled Trials as Topic
Risk Factors
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antihypertensive Agents

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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