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Asleep Blood Pressure: Significant CVD Risk Marker
Study Questions:
Is cardiovascular disease (CVD) risk reduction more often associated with a progressive decrease of either office or ambulatory awake or asleep blood pressure (BP) mean?
Methods:
The authors evaluated 18,078 individuals with baseline ambulatory BP ranging from normotension to hypertension, who were recruited between 2008 and 2015. At inclusion and at scheduled visits (mainly annually) during follow-up, ambulatory BP (ABP) was measured for 48 consecutive hours. Hypertension was defined according to current ABP monitoring (ABPM) criteria: awake systolic BP (SBP)/diastolic BP (DBP) mean ≥135/85 mm Hg, or asleep SBP/DBP mean ≥120/70 mm Hg, or BP-lowering treatment. A total of 15,674 participants were hypertensive at the time of recruitment (9,709 untreated). Hypertension treatment per recommended protocol was selected by participating physicians. Physicians had standardized office BPM (OBPM) at every visit and were provided the ABP results. If above the ABPM threshold on maximal recommended dose(s), additional therapy could be added. Minimal follow-up was 1 year. Primary outcome was the composite of CVD death, myocardial infarction, coronary revascularization, heart failure, and stroke.
Results:
Mean age was 59 ± 14.3 years; 54% were men. During the 5.1-year median follow-up, 2,311 individuals had events, including 1,209 for the composite primary outcome. The asleep SBP mean was the most significant BP-derived risk factor for the primary outcome (hazard ratio 1.29 per standard deviation [SD] elevation, p < 0.001), regardless of office and awake SBP. Most important, the progressive attenuation of asleep SBP was the most significant marker of event-free survival (0.75 per SD decrease, p < 0.001), regardless of changes in or awake SBP mean during follow-up. When the asleep BP mean was adjusted for the OBPM or awake BP mean, only the former remained a significant predictor of CVD outcome, regardless of whether the OBPM or awake BP mean was normal or elevated. Relying on OBPM for diagnosing hypertension is associated with a very high 47% misclassification.
Conclusions:
Asleep SBP is the most significant BP-derived risk factor for CVD events. Furthermore, treatment-induced decrease of asleep, but not awake SBP, a novel hypertension therapeutic target requiring periodic patient evaluation by ambulatory monitoring, is associated with significantly lower risk for CVD morbidity and mortality.
Perspective:
Among the unique aspects of this report is the preferred use of annual 48-hour ABPM as published by the Hygia Project, which was designed by very experienced and thoughtful hypertension investigators. Two of the main objectives of the Hygia Project are to compare the value of multiple ABPM compared to OBPM as markers of CVD morbidity and mortality, and as emphasized in this report, whether specific treatment targets such as decrease in asleep mean BP might be preferable to the average or other time periods. Results document that daytime OBPM is neither an independent significant marker nor a proper therapeutic target for reducing CVD risk when the asleep BP mean is taken into account. Patients assigned to take at least one BP-lowering medication at bedtime (intention-to-treat analysis) had a significantly lower hazard ratio of CVD outcome than those ingesting all such medications upon awakening. The cost, cost/benefit, and ability to implement the process outside of the clinical trial environment remain to be seen.
Keywords: Blood Pressure, Blood Pressure Determination, Diastole, Heart Failure, Hypertension, Monitoring, Ambulatory, Myocardial Infarction, Myocardial Revascularization, Primary Prevention, Risk Factors, Risk Reduction Behavior, Sleep, Stroke, Systole, Vascular Diseases
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