Decreasing Sleep-Time Blood Pressure Determined by

Ambulatory Monitoring Reduces Cardiovascular Risk

The MAPEC StudyDr Muhammad ArshadPGR FCPS (Cardiology)

Objectives: To investigate whether reduced cardiovascular risk is more related to the progressive decrease of asleep or awake blood pressure.

Abstract

Background: Independent studies have concluded that elevated sleep-time blood pressure is a better predictor of cardiovascular risk than awake or 24-h blood pressure means. However, the impact on cardiovascular risk of changes in these ambulatory blood pressure characteristics has not been properly investigated.

Methods: They prospectively studied 3,344 subjects (1,718 men and 1,626 women), 52.6 ± 14.5 years of age, during a median follow-up of 5.6 years. Those with hypertension at baseline were randomized to ingest all their prescribed hypertension medications upon awakening or  1 of them at bedtime. Blood pressure was measured for 48 h at baseline and again annually or more frequently (quarterly) if treatment adjustment was required

Results: When asleep blood pressure was adjusted by awake mean, only the former was a significant predictor of outcome in a Cox proportional hazards model also adjusted for sex, age, and diabetes. Analyses of changes in ambulatory blood pressure during follow-up revealed a 17% reduction in cardiovascular risk for each 5-mm Hg decrease in asleep systolic blood pressure mean (p < 0.001), independently of changes in any other ambulatory blood pressure parameter.

Conclusions: The sleep-time blood pressure mean is the most significant prognostic marker of cardiovascular morbidity and mortality. Most importantly, the progressive decrease in asleep blood pressure was the most significant predictor of event-free survival. (Prognostic Value of Ambulatory Blood Pressure Monitoring in the Prediction of Cardiovascular Events and Effects of Chronotherapy in Relation to Risk [the MAPEC Study];

During past two decades many studies have established

Early morning BP surge---Increased cardiovascular risk

Non-dippers---Increased cardiovascular risk Asleep BP mean---Better predictor of CVD

riskLimitation of previous studies : No one

studied the effect of change in asleep BP on CVD risk

Introduction

So the MAPEC study answers the question “ Whether the decrease in ambulatory asleep

time BP mean is associated with the reduction in CVD risk and with better survival? ”

The MAPEC study is a single centre study done between 2000 and 2007 at University of Vigo, Vigo, Spain.

Inclusion Criteria Age ≥ 18 years Normotensive, untreated hypertensive or

resistant hypertensiveExclusion Criteria Pregnancy Drug/alcohol abuse Night shift work AIDS Diabetes type 1

Methods

Secondary hypertension CVD disorders(Unstable angina, heart

failure, arrhythmias) Kidney failure Grade III or IV retinopathy Intolerance to ABPM

3344 subjects (1718 men, 1626 women. Age 52.6±14.5 years)

Median follow up was 5.6 yearsHypertension Diagnostic CriteriaAwake BP mean ≥ 135/85 mmHgAsleep BP mean ≥ 120/70 mmHg At recuitment 734 were normotensive, 2610

hypertensive and 776 resistant hypertensive.

Subjects and Diagnostic Criteria

Untreated hypertensive subjects

Study Design

2610

Morning dose

Sleep-time dose

Resistant hypertension subjects

776

Morning time dose

Night time dose

Before ABPM, six clinic blood pressure readings were obtained

Blood samples collected Subjects had to wear actigraphs to monitor

their physical activities

At inclusion i.e. baseline and then annually or quarterly if required.

Automatic BP measurements every 20 minutes during awake time (7 AM to 11 PM) and every 30 minutes during asleep time for the consecutive 48 hours.

Routine activity during awake time

ABPM

Subjects were also monitored for their physical activity through an actigraph

This same procedure( ABPM, Clinic BP+, Blood tests, Actigraphy ) was done annually for the follow up period or quarterly when required.

48-Hour ABPM (Baseline) was used to derive Sleep time relative BP decline Morning BP surge Ambulatory arterial stiffness index

CVD risk was evaluated using 48-hour ABPM Follow up changes in BP parameters

Statistical Methods

Primary End Point = Total CVD morbidity and mortality (All cause death, MI, angina pectoris, PCI, heart failure, acute arterial occlusion of lower extremities, thrombotic occlusion of retinal artery, hemorrhagic stroke, ischemic stroke and TIAs)

Additional primary end point = Major CVD events ( A composite of CVD death, MI and stroke)

Demographic and clinical characteristics were compared by t test (continuous variable) and chi-square test (proportions)

Cox proportional hazards model, with adjustments for significant confounding variables, was used to estimate hazard rations( HRs) with 95% confidence intervals.

Cox regression analysis was used to estimate association between changes in study parameters and CVD risk and survival benefit

Median follow up =5.6 years Total events= 331 first events ( 58 deaths,

45 MI, 51 angina pectoris, 35 coronary revascularizations, 44 CVAs, 46 heart failures, 21 aortic occlusive disease, 31 thrombotic occlusions of the retinal artery)

Event subjects were predominantly men, of older age and likely to have type-2 diabetes.

Results

At baseline, 48-hours mean SBP but not DBP was significantly higher among event subjects

The largest difference was seen among groups in asleep SBP mean

The sleep-time relative BP decline was significantly lower and the prevalence of nondipping higher among event subjects

Baseline clinic and ambulatory BP as predictors of CVD

Cox proportional hazards model with adjustments to calculate hazard ratios of CVD events

The MAPEC study is the first to assess prospectively the prognostic value of changes in ABPM parameters for a sufficient duration of time

It suggests that ABPM has a higher prognostic value than clinic BP measurements

Among ABPM parameters the asleep SBP mean is the most significant predictor of CVD events

Discussion and Conclusion

The progressive decrease in asleep BP mean is significantly associated with event free survival

The relationship between decreasing asleep BP mean and reduced CVD risk is significant for both normotensive and hypertensive patients

This study establishes for the first time that decreasing asleep BP mean significantly reduces CVD risk.

This study strongly suggests sleep-time BP mean a target for the therapeutic intervention and more frequent use of ABPM for the evaluation of treatment efficacy.

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