Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk (the MAPEC Study).

Conditions
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Hypertension

Intervention / Treatment
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* 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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Essential hypertension Exclusion Criteria: AIDS shift workers secondary hypertension intolerant to ABPM

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Treatment on awakening | Device: Ambulatory blood pressure monitoring<br>* Sampling at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours<br>Procedure: Chronotherapy, timing of antihypertensive medication<br>* Comparison of effects of awakening versus bedtime dosing<br>Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril)<br>* Treatment at awakening versus bedtime<br>Drug: ARB (including valsartan, telmisartan, olmesartan)<br>* Treatment at awakening versus bedtime<br>Drug: beta blockers (including nebivolol, atenolol, carvedilol)<br>* Treatment at awakening versus bedtime<br>Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin<br>* Treatment at awakening versus bedtime<br>Procedure: Combination therapy in essential hypertension<br>* Treatment at awakening versus bedtime<br>|
| Active Comparator: 2<br>Treatment at bedtime | Device: Ambulatory blood pressure monitoring<br>* Sampling at 20-min intervals from 07:00 to 23:00 hours and at 30-min intervals at night for 48 consecutive hours<br>Procedure: Chronotherapy, timing of antihypertensive medication<br>* Comparison of effects of awakening versus bedtime dosing<br>Drug: ACEI (including spirapril, enalapril, quinapril, lisinopril)<br>* Treatment at awakening versus bedtime<br>Drug: ARB (including valsartan, telmisartan, olmesartan)<br>* Treatment at awakening versus bedtime<br>Drug: beta blockers (including nebivolol, atenolol, carvedilol)<br>* Treatment at awakening versus bedtime<br>Drug: diuretics (torasemide, indapamide, HTCZ) and doxazosin<br>* Treatment at awakening versus bedtime<br>Procedure: Combination therapy in essential hypertension<br>* Treatment at awakening versus bedtime<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prognostic value of ABPM, impact of changes in ambulatory BP and impact of circadian time of antihypertensive treatment in cardiovascular, cerebrovascular and renal risk assessment. |  | Five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Influence of circadian time of antihypertensive treatment in BP control and the remodeling of the circadian BP pattern of hypertensive patients. |  | Five years | 
| Prevalence of an altered BP profile as a function of the circadian time of treatment. |  | Five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ambulatory blood pressure monitoring, cardiovascular risk, chronotherapy, circadian pattern