REVIEW Hypertension: New perspective on its definition and clinical management by bedtime therapy substantially reduces cardiovascular disease risk Ram on C. Hermida 1 | Diana E. Ayala 1 | Jos  e R. Fern andez 1 | Artemio Moj on 1 | Michael H. Smolensky 2 1 Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC), University of Vigo, Vigo, Spain 2 Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, Austin, TX, USA Correspondence Ram on C. Hermida, Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC), University of Vigo, Vigo, Spain. Email: rhermida@uvigo.es Funding information The MAPEC Study and subsequent ongoing Hygia Project are independent investigator-promoted trials supported by unrestricted grants from Instituto de Salud Carlos III, Ministerio de Econom  ıay Competitividad, Spanish Government (PI14-00205); Ministerio de Ciencia e Innovaci on, Spanish Government (SAF2006-6254-FEDER; SAF2009-7028- FEDER); Conseller  ıa de Econom  ıae Industria, Xunta de Galicia (09CSA018322PR); European Research Development Fund and Conseller  ıa de Cultura, Educaci on e Ordenaci on Universitaria, Xunta de Galicia (CN2012/ 251; CN2012/260; GPC2014/078; ED431B-2017/078); Atlantic Research Center for Information and Communication Technologies (AtlantTIC); and Vicerrectorado de Investigaci on, University of Vigo. Abstract Diagnosis of hypertension—elevated blood pressure (BP) associated with increased cardiovascular disease (CVD) risk—and its management for decades have been based primarily on single time-of-day office BP measurements (OBPM) assumed representative of systolic (SBP) and diastolic BP (DBP) during the entire 24-hours span. Around-the-clock ambulatory blood pressure monitoring (ABPM), however, reveals BP undergoes 24-hours patterning characterized in normotensives and uncomplicated hypertensives by striking morning-time rise, 2 daytime peaks—one ~2-3 hours after awakening and the other early evening, small midafternoon nadir and 10-20% decline (BP dipping) in the asleep BP mean relative to the wake-time BP mean. A growing number of outcome trials substan- tiate correlation between BP and target organ damage, vascular and other risks is greater for the ABPM-derived asleep BP mean, independent and stronger predic- tor of CVD risk, than daytime OBPM or ABPM-derived awake BP. Additionally, bedtime hypertension chronotherapy, that is, ingestion of ≥1 conventional hyper- tension medications at bedtime to achieve efficient attenuation of asleep BP, bet- ter reduces total CVD events by 61% and major events (CVD death, myocardial infarction, ischaemic and haemorrhagic stroke) by 67%—even in more vulnerable chronic kidney disease, diabetes and resistant hypertension patients—than custom- ary on-awaking therapy that targets wake-time BP. Such findings of around-the- clock ABPM and bedtime hypertension outcome trials, consistently indicating greater importance of asleep BP than daytime OBPM or ambulatory awake BP, call for a new definition of true arterial hypertension plus modern approaches for its diagnosis and management. KEYWORDS ambulatory blood pressure monitoring, asleep blood pressure, bedtime hypertension chronotherapy, cardiovascular risk, hypertension definition, MAPEC study Received: 15 November 2017 | Accepted: 4 February 2018 DOI: 10.1111/eci.12909 Eur J Clin Invest. 2018;48:e12909. https://doi.org/10.1111/eci.12909 wileyonlinelibrary.com/journal/eci © 2018 Stichting European Society for Clinical Investigation Journal Foundation | 1 of 12