{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,8]],"date-time":"2026-11-08T13:10:37Z","timestamp":1794143437380,"version":"4.8.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"48","license":[{"start":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T00:00:00Z","timestamp":1571702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Instituto de Salud Carlos III, Ministerio de Econom\u00eda y Competitividad, Spanish Government","award":["PI14-00205"],"award-info":[{"award-number":["PI14-00205"]}],"id":[{"id":"https:\/\/ror.org\/01txxn211","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men\/8470 women, 60.5\u2009\u00b1\u200913.7\u2009years of age) were assigned (1:1) to ingest the entire daily dose of \u22651 hypertension medications at bedtime (n\u2009=\u20099552) or all of them upon awakening (n\u2009=\u20099532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48\u2009h. 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\u2014adjusted 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\u2014of the primary CVD outcome [0.55 (95% CI 0.50\u20130.61), P\u2009&amp;lt;\u20090.001] and each of its single components (P\u2009&amp;lt;\u20090.001 in all cases), i.e. CVD death [0.44 (0.34\u20130.56)], myocardial infarction [0.66 (0.52\u20130.84)], coronary revascularization [0.60 (0.47\u20130.75)], heart failure [0.58 (0.49\u20130.70)], and stroke [0.51 (0.41\u20130.63)].<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Routine ingestion by hypertensive patients of \u22651 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, number NCT00741585.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>\u2003<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurheartj\/ehz754","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T15:27:38Z","timestamp":1569943658000},"page":"4565-4576","source":"Crossref","is-referenced-by-count":384,"title":["Bedtime hypertension treatment improves cardiovascular risk reduction: the Hygia Chronotherapy Trial"],"prefix":"10.1093","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-5901","authenticated-orcid":false,"given":"Ram\u00f3n C","family":"Hermida","sequence":"first","affiliation":[{"name":"Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC) , University of Vigo, E.I. Telecomunicaci\u00f3n, Campus Universitario, Vigo 36310, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J","family":"Crespo","sequence":"additional","affiliation":[{"name":"Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC) , University of Vigo, E.I. Telecomunicaci\u00f3n, Campus Universitario, Vigo 36310, Spain"},{"name":"Estructura de Xesti\u00f3n Integrada de Vigo, Servicio Galego de Sa\u00fade (SERGAS) , Vigo 36214, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Dom\u00ednguez-Sardi\u00f1a","sequence":"additional","affiliation":[{"name":"Estructura de Xesti\u00f3n Integrada de Vigo, Servicio Galego de Sa\u00fade (SERGAS) , Vigo 36214, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfonso","family":"Otero","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda, Complejo Hospitalario Universitario, Estructura de Xesti\u00f3n Integrada de Ourense , Ver\u00edn e O Barco de Valdeorras, Servicio Galego de Sa\u00fade (SERGAS), Ourense 32005, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Moy\u00e1","sequence":"additional","affiliation":[{"name":"Estructura de Xerencia Integrada Pontevedra e O Saln\u00e9s, Servicio Galego de Sa\u00fade (SERGAS) , Pontevedra 36156, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda T","family":"R\u00edos","sequence":"additional","affiliation":[{"name":"Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC) , University of Vigo, E.I. Telecomunicaci\u00f3n, Campus Universitario, Vigo 36310, Spain"},{"name":"Estructura de Xesti\u00f3n Integrada de Vigo, Servicio Galego de Sa\u00fade (SERGAS) , Vigo 36214, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elvira","family":"Sineiro","sequence":"additional","affiliation":[{"name":"Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC) , University of Vigo, E.I. Telecomunicaci\u00f3n, Campus Universitario, Vigo 36310, Spain"},{"name":"Estructura de Xerencia Integrada Pontevedra e O Saln\u00e9s, Servicio Galego de Sa\u00fade (SERGAS) , Pontevedra 36156, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda C","family":"Casti\u00f1eira","sequence":"additional","affiliation":[{"name":"Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC) , University of Vigo, E.I. Telecomunicaci\u00f3n, Campus Universitario, Vigo 36310, Spain"},{"name":"Estructura de Xesti\u00f3n Integrada de Lugo, Cervo e Monforte de Lemos, Servicio Galego de Sa\u00fade (SERGAS) , Lugo 27002, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9970-1613","authenticated-orcid":false,"given":"Pedro A","family":"Callejas","sequence":"additional","affiliation":[{"name":"Bioengineering & Chronobiology Laboratories, Atlantic Research Center for Information and Communication Technologies (AtlantTIC) , University of Vigo, E.I. 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