Dr Muhammad Arshad PGR FCPS (Cardiology)

1. Decreasing Sleep-Time Blood Pressure Determined by Ambulatory Monitoring Reduces Cardiovascular RiskThe MAPEC Study Dr Muhammad Arshad PGR FCPS (Cardiology)

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

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

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

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

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

7. Introduction 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 risk Limitation of previous studies : No one studied the effect of change in asleep BP on CVD risk

8. 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.

9. Methods Inclusion Criteria • Age ≥ 18 years • Normotensive, untreated hypertensive or resistant hypertensive Exclusion Criteria • Pregnancy • Drug/alcohol abuse • Night shift work • AIDS • Diabetes type 1

10. Secondary hypertension • CVD disorders(Unstable angina, heart failure, arrhythmias) • Kidney failure • Grade III or IV retinopathy • Intolerance to ABPM

11. Subjects and Diagnostic Criteria • 3344 subjects (1718 men, 1626 women. Age 52.6±14.5 years) • Median follow up was 5.6 years Hypertension Diagnostic Criteria Awake BP mean ≥ 135/85 mmHg Asleep BP mean ≥ 120/70 mmHg • At recuitment 734 were normotensive, 2610 hypertensive and 776 resistant hypertensive.

12. Study Design • Untreated hypertensive subjects

13. Resistant hypertension subjects

14. Before ABPM, six clinic blood pressure readings were obtained • Blood samples collected • Subjects had to wear actigraphs to monitor their physical activities

15. ABPM • 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

16. 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.

17. Statistical Methods 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

18. 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)

19. 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

20. Results • 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.

22. Baseline clinic and ambulatory BP as predictors of CVD • 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

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

28. Discussion and Conclusion • 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

29. 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.

30. 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.

31. THANK YOU