Ambulatory blood pressure monitoring-based definition of true arterial hypertension

Guidelines for the design and conduct of human clinical trials on ingestion-time differences – chronopharmacology and chronotherapy – of hypertension medications

“…In so doing, they assume the time during the 24 h when BP measurement is performed is clinically irrelevant. Most of these guidelines, nonetheless, now promote ABP monitoring (ABPM) of adult patients (≥18 years of age), if "economically and logistically feasible" (Williams et al 2018) to confirm the traditional wake-time OBPM-based diagnosis of hypertension (Chiang et al 2015; National Institute for Health and Clinical Excellence 2019; Piper et al 2015;Rabi et al 2020;Umemura et al 2019;Unger et al 2020;Wang 2015;Whelton et al 2018;Williams et al 2018), a recommendation founded on the well-documented significantly better value of ABPM than wake-time OBPM in prognosticating CVD risk (Clement et al 2003;Dolan et al 2005;Eguchi et al 2008;Hermida et al 2011aHermida et al , 2020aHermida et al , 2018Hermida et al , 2020dHermida et al , 2015Minutolo et al 2011;Roush et al 2014a;Salles et al 2008;Verdecchia et al 1994).…”

“…(ii) Selection of treatment times according to either nonspecific "morning" and "evening" periods or arbitrary clock times rather than distinctive biological markers of the circadian stage, e.g. upon waking and at bedtime, that takes into account differences between individuals in the 24 h activity/sleep rhythm (Hermida et al 2017), including those emanating from an advanced and delayed phase sleep disorder and circadian chronotypes of extreme morningness and eveningness (Curtis et al 2019;Roenneberg et al 2007;Zhang et al 2019 (Hermida et al 2012(Hermida et al , 2020d). (iv) Dependence, as the outcome variable, upon wake-time OBPM or wake-time HBPM that does not enable evaluation of the effects of timed hypertension treatment on the most relevant characteristics of the BP 24 h pattern and level, i.e.…”

“…(iv) Dependence, as the outcome variable, upon wake-time OBPM or wake-time HBPM that does not enable evaluation of the effects of timed hypertension treatment on the most relevant characteristics of the BP 24 h pattern and level, i.e. the asleep SBP mean and sleep-time relative SBP decline, now identified as the strongest prognostic markers of CVD risk (Astrup et al 2007;Ben-Dov et al 2007;Boggia et al 2007;Brotman et al 2008;Dolan et al 2005;Fagard et al 2008;Fan et al 2010;Hermida et al 2011aHermida et al , 2013cHermida et al , 2020aHermida et al , 2018Hermida et al , 2020dIngelsson et al 2006;Minutolo et al 2011;Nakano et al 1998;Ohkubo et al 2002;Roush et al 2014a;Salles et al 2016;Sturrock et al 2000), and thus the highest priority therapeutic targets for CVD prevention (Hermida et al 2011a(Hermida et al , 2018(Hermida et al , 2020d). (v) When ABPM is utilized, reliance solely on the 24 h or "daytime" or awake BP mean as the unique or major response variable, which masks the much more valuable clinical information conveyed by the specific features of the circadian BP pattern that are known to be most strongly associated with BP-targeted organ pathology and elevated CVD risk.…”

“…Current guidelines (Chiang et al 2015; National Institute for Health and Clinical Excellence 2019; Piper et al 2015;Rabi et al 2020;Umemura et al 2019;Unger et al 2020;Wang 2015;Whelton et al 2018;Williams et al 2018) define "normotension" and "sustained hypertension," respectively, as in-clinic and out-of-clinic measured BP both being normal or elevated. Discrepancies between diagnostic conclusions of the two measures have been defined as either isolatedoffice hypertension (also termed white-coat hypertension) -although the more accurate and preferred term is masked normotension (Hermida et al 2013e) -when the wake-time OBPM is elevated but the out-of-office BP is normal by ABPM-based criteria, or masked hypertension when the wake-time OBPM is normal but the out-ofoffice BP is elevated by ABPM-based criteria (Hermida et al 2012(Hermida et al , 2020d). These two highly prevalent disparate diagnostic categories are associated with markedly different CVD risk (Coccina et al 2020;Fagard and Cornelissen 2007;Hermida et al 2012;Pierdomenico and Cuccurullo 2011).…”

“…misleading findings due to the high likelihood of including >20% low CVD risk participants with masked normotension and excluding >27% otherwise high CVD risk participants with masked hypertension, mainly those with normal OBPM but elevated asleep BP mean and/or nondipper BP pattern (Hermida et al 2018(Hermida et al , 2020d. Furthermore, focusing recruitment on treated hypertensive individuals whose BP is already properly controlled according to ABPM-based diagnostic and therapeutic thresholds is also inappropriate and leads to misleading findings when evaluating ingestion-timedependent effects of BP-lowering therapies.…”