Chronotherapy with conventional blood pressure medications improves management of hypertension and reduces cardiovascular and stroke risks

• Published in: Hypertension research Vol. 39; no. 5; pp. 277 - 292
• Main Authors: Hermida, Ramón C, Ayala, Diana E, Smolensky, Michael H, Fernández, José R, Mojón, Artemio, Portaluppi, Francesco
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-05-2016
• Subjects: Antihypertensive Agents - administration & dosage; Antihypertensive Agents - therapeutic use; Blood Pressure - drug effects; Blood Pressure Monitoring, Ambulatory; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; Drug Administration Schedule; Drug Chronotherapy; Humans; Hypertension - complications; Hypertension - drug therapy; Risk Reduction Behavior; Stroke - etiology; Stroke - prevention & control; Treatment Outcome
• ISSN: 0916-9636; 1348-4214
• DOI: 10.1038/hr.2015.142

Correlation between blood pressure (BP) and target organ damage, vascular risk and long-term patient prognosis is greater for measurements derived from around-the-clock ambulatory BP monitoring than in-clinic daytime ones. Numerous studies consistently substantiate the asleep BP mean is both an independent and a much better predictor of cardiovascular disease (CVD) risk than either the awake or 24 h means. Sleep-time hypertension is much more prevalent than suspected, not only in patients with sleep disorders, but also among those who are elderly or have type 2 diabetes, chronic kidney disease or resistant hypertension. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of six different classes and their combinations significantly affects BP control, particularly sleep-time BP, and adverse effects. For example, because the high-amplitude circadian rhythm of the renin-angiotensin-aldosterone system activates during nighttime sleep, bedtime vs. morning ingestion of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers better reduces the asleep BP mean, with additional benefit, independent of medication terminal half-life, of converting the 24 h BP profile into more normal dipper patterning. The MAPEC (Monitorización Ambulatoria para Predicción de Eventos Cardiovasculares) study, first prospective randomized treatment-time investigation designed to test the worthiness of bedtime chronotherapy with ⩾1 conventional hypertension medications so as to specifically target attenuation of asleep BP, demonstrated, relative to conventional morning therapy, 61% reduction of total CVD events and 67% decrease of major CVD events, that is, CVD death, myocardial infarction, and ischemic and hemorrhagic stroke. The MAPEC study, along with other earlier conducted less refined trials, documents the asleep BP mean is the most significant prognostic marker of CVD morbidity and mortality; moreover, it substantiates attenuation of the asleep BP mean by a bedtime hypertension treatment strategy entailing the entire daily dose of ⩾1 hypertension medications significantly reduces CVD risk in both general and more vulnerable hypertensive patients, that is, those diagnosed with chronic kidney disease, diabetes and resistant hypertension.