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Chronotherapy of Blood Pressure Medications to Improve Management of Hypertension and Reduce Vascular Risk

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Circadian Clocks: Role in Health and Disease

Part of the book series: Physiology in Health and Disease ((PIHD))

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Abstract

Correlation between blood pressure (BP) and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than daytime in-clinic measurements. Additionally, consistent evidence from numerous studies substantiates that ABPM-determined asleep BP mean is an independent and stronger predictor of CVD risk than the awake or 24 h means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of six different classes and their combinations significantly impacts the beneficial and/or adverse effects of these drugs. For example, because the high-amplitude circadian rhythm of the renin-angiotensin-aldosterone system activates during nighttime sleep, bedtime versus morning ingestion of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) better controls the asleep BP mean, with additional benefit, independent of medication terminal half-life, of converting the 24 h BP profile into more normal dipper patterning. The MAPEC Study, first prospective randomized treatment-time investigation testing the worthiness of bedtime chronotherapy with ≥1 conventional hypertension medications to specifically target attenuation of asleep BP, demonstrated, relative to conventional morning therapy, significantly better reduction of CVD risk: adjusted hazard ratio (HR) of total CVD events (HR = 0.39, 95 %CI [0.29–0.51]; P < 0.001) and major CVD events, i.e., CVD deaths, myocardial infarctions, and ischemic and hemorrhagic strokes (HR = 0.33 [0.19–0.55]; P < 0.001). CVD risk reduction was strongest when bedtime treatment included an ARB. The MAPEC Study documents that the asleep BP mean is the most significant prognostic marker of CVD and stroke morbidity and mortality. Moreover, the MAPEC study also substantiates attenuation of the asleep BP mean by a bedtime hypertension treatment strategy since the entire daily dose of ≥1 hypertension medications significantly reduces CVD risk, both in the general hypertension population and in patients of greater vulnerability and enhanced CVD risk, i.e., those diagnosed with chronic kidney disease, diabetes, and resistant hypertension.

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Sources of Support

Research supported by unrestricted grants from Ministerio de Ciencia e Innovación, Spanish Government (SAF2009-7028-FEDER); Instituto de Salud Carlos III, Ministerio de Economia y Competitividad, Spanish Government (PI14-00205); Consellería de Economía e Industria, Xunta de Galicia (09CSA018322PR); European Research Development Fund and Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia (CN2012/251 & CN2012/260); Atlantic Research Center for Information and Communication Technologies (AtlantTIC); and Vicerrectorado de Investigación, University of Vigo.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Bioengineering and Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC), E.I. Telecomunicación, University of Vigo, Campus Universitario, Vigo, Pontevedra, 36312, Spain

    Ramón C. Hermida Ph.D. & Diana E. Ayala M.D., M.P.H., Ph.D.

  2. Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA

    Michael H. Smolensky Ph.D.

  3. Hypertension Center, University Hospital S. Anna, Ferrara, Italy

    Francesco Portaluppi M.D., Ph.D.

  4. Department of Medical Sciences, University of Ferrara, Ferrara, Italy

    Francesco Portaluppi M.D., Ph.D.

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  1. Ramón C. Hermida Ph.D.
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  2. Diana E. Ayala M.D., M.P.H., Ph.D.
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  3. Michael H. Smolensky Ph.D.
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  4. Francesco Portaluppi M.D., Ph.D.
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Correspondence to Ramón C. Hermida Ph.D. .

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  1. University of Florida, Gainesville, Florida, USA

    Michelle L. Gumz

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Hermida, R.C., Ayala, D.E., Smolensky, M.H., Portaluppi, F. (2016). Chronotherapy of Blood Pressure Medications to Improve Management of Hypertension and Reduce Vascular Risk. In: Gumz, M. (eds) Circadian Clocks: Role in Health and Disease. Physiology in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3450-8_11

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