Decreasing Sleep-Time Blood Pressure Determined by Ambulatory Monitoring Reduces Cardiovascular Risk

Study Questions:

Does antihypertensive therapy directed at sleep-time blood pressure lower cardiovascular risk more than generalized efforts to reduce daytime blood pressure?

Methods:

The authors reported the results of the Monitorizacio´n Ambulatoria para Prediccio´n de Eventos Cardiovasculares (MAPEC) study, a randomized, prospective trial of time of day of hypertension therapy. Subjects with untreated hypertension were randomly assigned, separately for each individual hypertension medication, to either morning or bedtime administration. Subjects with resistant hypertension were randomized to either medication changes with maintenance morning dosing, or shifting administration of one medication to bedtime. Subjects remaining uncontrolled could be prescribed additional medications in either group (maintaining morning administration only in the morning administration group), or have additional morning medications shifted to bedtime administration in the bedtime administration group. More simply stated, subjects were randomized to either ingest all hypertension medications upon awakening, or at least one of them at bedtime. Continuous ambulatory 48-hour blood pressure measurement was performed at baseline and annually, or more frequently when dose adjustments were made. The outcome of interest was cardiovascular morbidity and mortality (including deaths from all causes, myocardial infarction, angina, coronary revascularization, heart failure, acute arterial occlusion of the lower extremities, retinal artery thrombosis, hemorrhagic stroke, ischemic stroke, and transient ischemic attack).

Results:

Among 3,344 eligible subjects, 1,718 were men, 1,626 women, mean age was 52.6 ± 14.5 years, and median follow-up was 5.6 years. After adjusting asleep blood pressure for awake mean blood pressure, only asleep blood pressure was a significant predictor of outcome, using a Cox proportional hazards model further adjusting for sex, age, and diabetes. The authors reported a 17% reduction in cardiovascular event risk for each five mm Hg decrease in asleep systolic blood pressure mean (p < 0.001), independent of other ambulatory blood pressure parameters. Furthermore, there was a dose-related reduction in cardiovascular event risk associated with reductions in sleep time blood pressure mean, such that those subjects whose asleep systolic blood pressure mean decreased at least 10 mm Hg saw a roughly threefold reduction in cardiovascular event risk compared with those subjects whose asleep systolic blood pressure mean did not change from baseline.

Conclusions:

The authors concluded that sleep-time blood pressure mean was the most significant prognostic marker of cardiovascular morbidity and mortality, and that progressive decrease in asleep blood pressure was the most significant predictor of event-free survival. The authors pointed out in their conclusions that this novel therapeutic target requires ambulatory monitoring for proper assessment.

Perspective:

This fascinating study serves to further underline the importance of assessing blood pressure and blood pressure control outside of clinic blood pressure measurements. It is now well understood that multiple measures of blood pressure—preferably outside of the stressful, hypertension-inducing office or clinic environment—will more properly assess hypertension risk, and should more properly be used to guide antihypertensive therapy. It has also been fairly well established that the loss of a normal, nocturnal drop in blood pressure seen on ambulatory monitoring is a marker of increased cardiovascular risk related to hypertension. The present study adds the exciting and novel observation that therapeutic reduction of nocturnal or asleep blood pressure appears to be far more directly related to cardiovascular risk reduction. If corroborated by future studies, these data suggest that the use of ambulatory blood pressure monitoring should be greatly expanded to guide therapy. Or possibly better still, future studies could be directed at determining if simply moving routine antihypertensive medication administration to evening hours is associated with greater cardiovascular risk reduction. The potential therapeutic benefit seems great for a small change in treatment.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Hypertension, Sleep Apnea

Keywords: Stroke, Myocardial Infarction, Ischemic Attack, Transient, Follow-Up Studies, Risk Reduction Behavior, Sleep, Blood Pressure, Proportional Hazards Models, Heart Failure, Blood Pressure Monitoring, Ambulatory, Cardiovascular Diseases, Blood Pressure Determination, Retinal Artery, Hypertension


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