• cardiovascular and cerebrovascular events per year of follow-up
• circadian pattern of blood pressure determined by ambulatory monitoring
• total cardiovascular mortality per year of follow-up

• Influence of circadian time of antihypertensive treatment in BP control and the remodeling of the circadian BP pattern of hypertensive patients. [ Time Frame: Five years ] [ Designated as safety issue: Yes ]
• Prevalence of an altered BP profile as a function of the circadian time of treatment. [ Time Frame: Five years ] [ Designated as safety issue: Yes ]

The MAPEC study was designed to investigate whether normalizing the circadian blood pressure profile towards a more dipper pattern (increasing the diurnal/nocturnal ratio of blood pressure) by the use of Chronotherapy (that is, taking into account the time of day of administration of antihypertensive medications) reduces cardiovascular risk.

Target organ damage is more closely associated with ambulatory (ABPM) than with clinic blood pressure (BP). In particular, the reduction of the normal 10 to 20% sleep-time BP decline (non-dipper pattern) is associated with elevated risk of end-organ injury, particularly to the heart, brain and kidney. These results suggest that cardiovascular risk could be influenced not by BP elevation alone, but also by the magnitude of the circadian BP variability. Moreover, at least two independent prospective studies have suggested that nighttime BP is a better predictor of risk than daytime BP. Common to all previous trials is that prognostic significance of ABPM has relied on a single baseline profile from each participant, without accounting for possible changes in the BP pattern, mainly associated to antihypertensive therapy and aging during follow-up. The MAPEC study investigates, first, the comparative prognostic value of several BP parameters (including, among many others, BP variability, the diurnal/nocturnal ratio, diurnal and nocturnal means, slope of morning rise, etc) in the prediction of cardiovascular morbidity and mortality; and, second, whether potential changes in the circadian BP pattern after Chronotherapy with antihypertensive drugs are associated to changes in cardiovascular risk.

• Device: Ambulatory blood pressure monitoring
• Procedure: Chronotherapy, timing of antihypertensive medication
• Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril)
• Drug: ARB (including valsartan, telmisartan, olmesartan)
• Drug: beta blockers (including nebivolol, atenolol, carvedilol)
• Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin
• Procedure: Combination therapy in essential hypertension

• Active Comparator: Treatment on awakening
• Active Comparator: Treatment at bedtime

Inclusion Criteria:

• Essential hypertension

Exclusion Criteria:

• AIDS
• shift workers
• secondary hypertension
• intolerant to ABPM

• Hospital Clinico Universitario de Santiago
• Xunta de Galicia
• Ministerio de Educacion y Ciencia, Spain