The selection of appropriate study participants with homogenous characteristics is of vital importance for clinical research. By using HBPM instead of office measurements, a hypertension phenotype is accurately defined and subjects with intermediate phenotypes, such as white coat or masked hypertension, can be identified and excluded [14–16]. Subjects with white coat hypertension (WCH) show minimal response to antihypertensive drug treatment compared to sustained hypertensives [17] and may create diluting effects in the assessment of reductions in blood pressure.

Studies of resistant hypertension, defined as uncontrolled blood pressure on triple antihypertensive drug therapy, demonstrated the importance of using ABPM or HBPM for the exclusion of the WCH, which is common even among treated subjects [18]. Recent studies assessing the effectiveness of renal denervation have clearly demonstrated the importance of out-of-office blood pressure monitoring for the reliable diagnosis of resistant hypertension [19].

Moreover, because of its superior reproducibility, HBPM as well as ABPM provides a more accurate classification of the true baseline blood pressure of an individual.

The reproducibility of a blood pressure measurement method, expressed as the standard deviation of differences, is an important factor in the calculation of the sample size required for a clinical trial. Because of its superior reproducibility (Fig. 19.1), HBPM as well as ABPM when used in a clinical trial comparing the antihypertensive efficacy of two drugs allow the same difference in blood pressure lowering effect to be identified with higher precision [3]. Alternatively, HBPM and ABPM allow a smaller sample size to be recruited in order to identify a difference in the blood pressure lowering effect of two drugs with the same study power (Fig. 19.1) [20–23].

The power curves of a randomized cross-over clinical trial comparing the antihypertensive efficacy of two drugs using clinic, ambulatory, or home blood pressure measurements are shown in Fig. 19.2 [24]. According to these data, for a trial aiming to detect a difference in the hypotensive effect of the drugs of 10 mmHg for systolic blood pressure, 5 mmHg for diastolic, or 3 mmHg for pulse pressure, the study power is much higher when using HBPM and ABPM instead of office measurements (Fig. 19.2) [24].

Because of its superior reproducibility, HBPM allows for the identification of antihypertensive drug treatment-induced blood pressure changes with greater precision and without the placebo effect , which largely affect clinical trials using clinic blood pressure measurements [25]. A randomized parallel design-controlled study, which evaluated the antihypertensive efficacy of the angiotensin converting enzyme inhibitor trandolapril versus placebo, showed no difference in blood pressure lowering effect compared to placebo when clinic measurements were used [26]. However, a significant placebo-corrected blood pressure lowering effect was observed when HBPM was employed (Fig. 19.3) [26]. Another randomized parallel design clinical trial comparing the beta-blocker bisoprolol with the calcium channel blocker nitrendipine found no difference in the antihypertensive effect of these two drugs when clinic or daytime ambulatory blood pressure was used, whereas self-home and daytime ambulatory blood pressure measurements demonstrated a significantly larger effect with bisoprolol (Fig. 19.4) [21]. For this particular study to have the sensitivity to identify a 10 mmHg difference between the effects of the two drugs on systolic blood pressure, at total of 118 subjects would be required if clinic blood pressure measurement were used, compared to 70 with ABPM and 56 with HBPM [21].

Another randomized cross-over clinical trial comparing the antihypertensive efficacy of the angiotensin converting enzyme inhibitor lisinopril with the angiotensin receptor blocker losartan showed that although all the blood pressure measurement methods (clinic, ambulatory, and home) suggested that lisinopril was more effective (Fig. 19.5), the difference between the two drugs was demonstrated with greater precision using HBPM (p < 0.001) than 24-h ABPM (p < 0.01), and the poorest precision for demonstrating this difference was provided by clinic measurements (p < 0.05) [24]. Lisinopril was also found to be more effective in reducing home pulse pressure (p < 0.01) and 24-h ambulatory pulse pressure (p < 0.03), whereas no such difference was detected using clinic measurements (Fig. 19.5) [24].

These data clearly demonstrate that the use of HBPM increases the sensitivity and precision of clinical trials assessing the efficacy of antihypertensive drug action . The benefits of HBPM are attributed to its superior reproducibility, the absence of the placebo effect , the regression dilution bias (regression to the mean), and the observer prejudice and bias (when electronic devices with automated memory are used), all of which limit the reliability of clinical trials based on clinic blood pressure measurements.

The duration of antihypertensive action and 24-h coverage are usually assessed using the trough-to-peak ratio (T/P), which is based on 24-h ambulatory or on clinic blood pressure measurements [27]. The morning-to-evening (M/E) home blood pressure ratio assessed by self-monitoring can provide information of the “trough” effect of the drug by obtaining morning measurements before drug intake and the “plateau” effect in the evening [28]. Studies have shown that the M/E home blood pressure ratio might be a useful alternative to the T/P ambulatory blood pressure ratio for assessing the duration of antihypertensive drug action [29–31]. A randomized clinical trial that compared the duration of the antihypertensive drug action of the angiotensin converting enzyme inhibitor lisinopril with the angiotensin receptor blocker losartan showed higher T/P and M/E blood pressure ratios (evaluated by ABPM and HBPM respectively) with lisinopril, which was consistent when the analysis was restricted to subjects with significant blood pressure response to treatment (Fig. 19.6) [29].

A similar mathematical expression is the difference between morning and evening home blood pressure values (morning-evening difference), which has been shown to be a significant determinant of echocardiographic left ventricular hypertrophy (LVH) , geometry, and diastolic function [32]. It should be mentioned, however, that the M/E home blood pressure ratio does not provide information on the peak effect of treatment and might therefore fail to identify an excessive hypotensive effect at peak.

ABPM is regarded as a unique tool, because it allows the evaluation of blood pressure during nighttime sleep and thereby the detection of non-dippers. This advantage appears to have major clinical relevance because of the accumulating evidence suggesting that, compared to other aspects of the blood pressure profile, nocturnal blood pressure is the strongest predictor of cardiovascular risk. Non-dippers have demonstrated a higher risk of preclinical organ damage and cardiovascular events than dippers [33].

Advancement in technology of automated home blood pressure monitors provided the ability to obtain automated readings throughout nighttime sleep [34]. There is evidence that nocturnal home monitoring gives reproducible blood pressure values [34]. A cross-sectional study showed similar daytime and nighttime blood pressure levels assessed with home and ambulatory blood pressure and good agreement between the two methods in diagnosing non-dippers [35]. More importantly, these devices can provide nocturnal blood pressure evaluation for more than a single 24-h period, which is the case with ambulatory monitoring. The Japan Morning Surge—Home Blood Pressure (J-HOP) Study showed that automated asleep home blood pressure evaluated three times per night for at least two (average 9) nights gave comparable blood pressure values with nighttime ambulatory blood pressure [36]. More importantly, nocturnal systolic home blood pressure was more closely associated with indices of cardiac and renal organ damage than nocturnal ambulatory blood pressure [36]. Ishikawa et al. also reported significant association of nighttime home blood pressure with hypertensive target organ damage [37].

Thus, HBPM appears to be a useful alternative to ABPM even for the evaluation of nocturnal hypertension and might be more appropriate for the evaluation of treatment-induced changes in nocturnal blood pressure in clinical trials, because it can provide multiple assessments on different days and at lower cost.