Send to

Choose Destination
Eur Heart J. 2019 Oct 22. pii: ehz754. doi: 10.1093/eurheartj/ehz754. [Epub ahead of print]

Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial.

Author information

Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC), University of Vigo, E.I. Telecomunicación, Campus Universitario, Vigo 36310, Spain.
Estructura de Xestión Integrada de Vigo, Servicio Galego de Saúde (SERGAS), Vigo, Spain.
Servicio de Nefrología, Complejo Hospitalario Universitario, Estructura de Xestión Integrada de Ourense, Verín e O Barco de Valdeorras, Servicio Galego de Saúde (SERGAS), Ourense 32005, Spain.
Estructura de Xerencia Integrada Pontevedra e O Salnés, Servicio Galego de Saúde (SERGAS), Pontevedra, Spain.
Estructura de Xestión Integrada de Lugo, Cervo e Monforte de Lemos, Servicio Galego de Saúde (SERGAS), Lugo, Spain.
Estructura de Xestión Integrada de Santiago de Compostela, Servicio Galego de Saúde (SERGAS), Santiago de Compostela, Spain.



The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction.


In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n = 9552) or all of them upon awakening (n = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio-adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event-of the primary CVD outcome [0.55 (95% CI 0.50-0.61), P < 0.001] and each of its single components (P < 0.001 in all cases), i.e. CVD death [0.44 (0.34-0.56)], myocardial infarction [0.66 (0.52-0.84)], coronary revascularization [0.60 (0.47-0.75)], heart failure [0.58 (0.49-0.70)], and stroke [0.51 (0.41-0.63)].


Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events.

TRIAL REGISTRATION:, number NCT00741585.


Ambulatory blood pressure monitoring; Angiotensin-II receptor blockers; Angiotensin-converting enzyme inhibitors; Asleep blood pressure; Bedtime hypertension chronotherapy; Cardiovascular risk; Coronary revascularization; Heart failure; Myocardial infarction; Stroke


Supplemental Content

Full text links

Icon for Silverchair Information Systems
Loading ...
Support Center