New perspectives on the definition, diagnosis, and treatment of true arterial hypertension

ABSTRACT

Introduction

Office blood pressure measurements (OBPM), still used today for diagnosis and management of hypertension, fail to reveal clinically important features of the mostly predictable blood pressure (BP) 24 h pattern, and lead to >45% of individuals being misclassified. Current hypertension guidelines do not provide recommendation on when-to-treat, despite multiple prospective clinical trials documenting improved normalization of 24 h BP pattern and significant reduction in cardiovascular disease (CVD) events when hypertension medications are ingested at bedtime rather than upon waking.

Areas covered

In this review, the authors discuss current evidence on the: (i) most relevant attributes of the 24 h BP pattern deterministic of CVD risk; (ii) asleep systolic BP (SBP) mean as the most significant therapeutic target for CVD risk reduction; (iii) ingestion-time differences in pharmacodynamics of BP-lowering medications as reported with high consistency in multiple clinical trials; and (iv) enhanced prevention of CVD events achieved by bedtime hypertension chronotherapy.

Expert opinion

Several prospective trials consistently document asleep SBP mean and sleep-time relative SBP decline (dipping) constitute highly significant CVD risk factors, independent of OBPM. Bedtime, compared to customary upon-waking, hypertension chronotherapy reduces risk of major CVD events. Collectively, these findings call for new definition of true hypertension and, accordingly, its proper diagnosis and management.

KEYWORDS:

• Ambulatory blood pressure monitoring
• asleep blood pressure
• bedtime hypertension chronotherapy
• cardiovascular risk reduction
• chronic kidney disease
• diabetes
• diagnosis of hypertension
• Hygia Project
• MAPEC study

Highlights

• Increased CVD risk is jointly associated only with elevated asleep SBP mean – regardless of OBPM and awake or 24h SBP mean – plus non-dipping pattern (sleep-time relative SBP decline <10%), leading to the perspective provided by around-the-clock ABPM of a novel definition of true arterial hypertension.

• Treatment-induced decline of the asleep SBP mean, but not the daytime OBPM or awake or 24 h SBP mean, plus enhanced sleep-time relative SBP decline are the strongest independent prognostic BP markers of attenuated CVD risk. On this basis, they constitute novel therapeutic targets for both prolongation of CVD event-free survival and prevention for hypertension patients.

• Many prospective clinical trials and several meta-analyses verify better normalization of asleep BP and sleep-time relative BP decline towards the desired dipper profile when BP-lowering medications are ingested at bedtime rather than upon awakening, and without increased risk for adverse effects.

• Bedtime hypertension therapy that entails ingestion of the entire daily dose of ≥1 BP-lowering medications, especially ACEIs and ARBs, at bedtime, compared with the usual regimen of therapy that entails ingesting all such medications upon-waking, significantly diminishes CVD morbidity and mortality.

• Findings of the Hygia Chronotherapy Trial additionally demonstrate the bedtime hypertension treatment strategy is safe; the risk for adverse effects is comparable to the more common morning-time treatment strategy, in agreement with other publications that report bedtime versus morning-time BP therapy significantly improves ABP reduction, mainly during sleep, and without increase in adverse effects.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

The Hygia Project is an independent investigator-promoted research network supported by unrestricted grants from Ministerio de Ciencia e Innovación, Spanish Goverment (SAF2009-7028-FEDER); the Instituto de Salud Carlos III, the Ministerio de Economía y Competitividad, of the Spanish Government (PI14-00205); the Consellería de Economía e Industria, Dirección Xeral de Investigación e Desenvolvemento, Galician Regional Government (INCITE08-E1R-322063ES; INCITE09-E2R-322099ES; 09CSA018322PR; IN845B-2010/114); the Consellería de Cultura, Educación e Ordenación Universitaria, Galician Regional Government (CN2012/251; GPC2014/078; ED431B-2017/78); the European Regional Development Fund (ERDF) and the Galician Regional Government under agreement for funding the Atlantic Research Center for Information and Communication Technologies (AtlantTIC); and Vicerrectorado de Investigación, University of Vigo.