title: Bedtime hypertension chronotherapy: concepts and patient outcomes.
abstract: Recent findings indicate cardiovascular disease (CVD) risk is best predicted by asleep systolic blood pressure (SBP), and lowering it by scheduling ≥1 conventional long-acting hypertension medications, alone or in combination, at bedtime significantly lessens vascular-associated risks. Some 20 years ago, four controlled-onset extended-release drug-delivery systems incorporating a calcium channel or β-blocker, with the treatment goal specifically being attenuation of morning rather than asleep BP, were conceived as one type of bedtime hypertension chronotherapy. However, the CONVINCE outcomes trial failed to substantiate the merit of targeting morning and daytime BP to decrease CVD risk. The HOPE trial, entailing bedtime ramipril treatment for high CVD risk patients, showed substantial reduction of vascular-related events, theorized as the beneficial treatment-time-dependent strong asleep BP lowering. The MAPEC trial was the first prospective randomized treatment-time outcomes investigation to test the worthiness of bedtime hypertension chronotherapy entailing ≥1 conventional long-acting medications (BTCT), in comparison to the conventional morning-time therapeutic scheme for all medications (CMTT), to normalize asleep BP and diminish CVD risk. BTCT compared to CMTT significantly better lowered asleep BP and most importantly major CVD-associated morbidity and mortality, including myocardial infarction and ischemic and hemorrhagic stroke, by ~60%. CVD risk reduction was strongest when the BTCT included an angiotensin receptor blocker. The HOPE and MAPEC trials provide positive evidence of very significant CVD risk reduction by a BTCT strategy that specifically targets normalization of asleep BP, evidence that awaits conformation by the ongoing Hygia and other outcomes trials.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Smolensky
authors.forename: Ramon C
authors.initials: RC
authors.lastname: Hermida
authors.forename: Diana E
authors.initials: DE
authors.lastname: Ayala
authors.affiliation: Department of Biomedical Engineering, Cockrell School of Engineering, The University of Texas at Austin, 1 University Station C0800, Austin, Texas 78712-0238. Michael.H.Smolensky@uth.tmc.edu.
authors.forename: Francesco
authors.initials: F
authors.lastname: Portaluppi
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D019454:Chronotherapy; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000959:Antihypertensive Agents