Ambulatory blood pressure monitoring: its time to move on!

The diagnosis of hypertension has traditionally relied upon repeated office or clinic blood pressure (BP) measurements taken by a health professional generally using a mercury sphygmomanometer. Increasingly, ambulatory BP monitoring is being used to expedite the diagnosis of hypertension and categorize it into different types [1]. Currently, it is only approved for reimbursement (United States) to diagnose white-coat hypertension (i.e. elevated BP in the physicians' office or clinic and normal BP outside these settings) [2]. Ambulatory BP monitoring also provides important information on BP level during the sleep period (nocturnal hypertension, nondipping BP pattern) [3]. Several studies have shown that these parameters are important harbingers of poor cardiovascular prognosis and that nighttime pressures more accurately predict the occurrence of death and cardiovascular events than daytime pressures, independent of other confounders [4,5]. The observational study by Fan et al.[6] in the current issue of the Journal adds to the growing body of evidence on the clinical importance of nighttime pressures, such that even isolated nocturnal hypertension (INH) is not a benign condition. Individuals with elevated mean BP readings at night were at increased risk for total mortality and all cardiovascular events compared with the normotensive reference group even after accounting for differences in age, sex and several covariates. The study further showed that with additional adjustment for the office BP (20.8% of the INH group had office hypertension), the INH group was still at increased risk. A major challenge in identifying patients with INH is accurately determining the onset and duration of the nighttime period. A variety of methods have been advocated including arbitrarily fixed clock times to self-reported sleep times using diary entries, or even polysomnographically verified sleep times [3]. In studies using intraarterial recordings, BP of healthy adults generally falls at least 10% from awake levels with the onset of sleep and rises sharply upon awaking from sleep [7]. Thus, errors in accurately defining the nighttime period will result in a blend of awake and sleep pressures and an overestimation of mean nocturnal pressure. In the study of Fan et al.[6], they used narrow time intervals, which excludes the transition hours between wakefulness and sleep in the evening and in the morning. This approach is an improvement over the wide fixed time method (i.e. inclusion of all 24 recording hours), and in a study of different definitions of awake–sleep to classify nocturnal BP dipping, yielded results that were comparable with wide and narrow diary time methods on repeat testing [8]. Nonetheless, in conditions such as INH or isolated clinical hypertension (ICH) ambulatory BP must reliably determine not only nocturnal pressures, but also daytime pressures where BP, by definition, should be normal. Several studies of repeated ambulatory BP monitoring have examined the reproducibility of diagnosing nocturnal hypertension and determining normal daytime pressures, using prespecified cut-off values. In a study of 611 never-treated hypertensive patients who underwent two 24 h periods of ambulatory BP monitoring at 1–4 week intervals, more than 90% of patients with sustained hypertension on the first recording remained in the same category on the second recording. In sharp contrast, only 53.4% of individuals with ICH on the first 24 h BP recording had normal daytime BP on the second recording 4 weeks later [9]. In another study, 91% of untreated hypertensive patients with nocturnal hypertension on the initial 24 h BP recording maintained that status on the second recording 4–8 weeks later. However, there was poor reproducibility of normal mean daytime BP on repeat measurement [10]. The results of these studies suggest that errors in defining the nighttime period would bias results in the direction of higher nocturnal pressures and possibly by this means account for the high reproducibility of nocturnal hypertension. On the contrary, the possible inclusion of the generally lower nighttime pressures and variations in daily life activities affect the reproducibility of normal mean daytime ambulatory BP [11]. Thus, it is not surprising that the reproducibility of INH, which was based on a single 24 h ambulatory measurement in the study of Fan et al.[6], is low. The poor reproducibility, potentially at least, has important clinical implications. In the study of Cuspidi et al.[9], individuals with reproducible and nonreproducible ICH had different cardiovascular risk profiles. Whether this is also true for individuals with INH remains to be determined. In an editorial commentary 3 years ago, O'Brien [12] mused about what it would take to make ambulatory BP monitoring an indispensable tool in the management of hypertension. Observational studies such as that of Fan et al.[6], which document the prognostic superiority of ambulatory BP monitoring to conventional clinic readings, may help but clearly they are insufficient. Diffusion of new medical information into clinical practice is a complex process, which is still poorly understood. A good starting point is the perceived burden on practicing physicians and acceptance by patients of new procedures. A new technique that offers to reduce physician workload and seemingly provides immediate benefits is more likely to be incorporated into clinical practice than a cumbersome procedure that does not provide direction at the point of care. For example, the increasingly popular in-office electronic automated sphygmomanometer, BPTRU (BPM100 or 200; BP TRU Medical Devices; Coquitlam, BC, Canada), reduces the problem of office hypertension from white coat reaction, and unlike ambulatory BP monitoring, allows physicians to provide immediate feedback to patients [13]. Furthermore, in a survey of patients' preferences, ambulatory BP monitoring ranked lower than other modalities of BP measurement such as self-readings at home [14]. Another barrier is the apparent absence of international standards on ambulatory BP measurement. A case in point, and relevant to the article by Fan et al.[6], is the diagnostic threshold levels for nocturnal hypertension. In Europe the accepted values are a nighttime BP of 120 mmHg systolic and 70 mmHg diastolic [1], whereas in the United States, the more commonly used BP threshold values are 125 mmHg for systolic and 75 mmHg diastolic [2]. The different thresholds have major implications on prevalence estimates. This is apparent in the article by Fan et al.[6], where the prevalence of hypertension based on widely accepted office values of at least 140 mmHg systolic or 90 mmHg diastolic was 40.6%, whereas by ambulatory BP it was 55.9%. The higher prevalence by ambulatory BP imposes a greater clinical burden on physicians and their patients and has major cost implications. It is well known that there is no threshold value for BP below which there is no increase in cardiovascular risk [15]. Observational data, while of help in identifying parameters and values associated with increased risk, cannot be used to guide therapeutic decisions. By relying on such data, we have been misled too often, sometimes with devastating consequences [16,17]. In the case of ambulatory BP monitoring, there is a wealth of observational studies, but a paucity of clinical trials to guide decision-making [18]. Thus, it is not surprising that physicians are confused about the relative importance of the different components of ambulatory BP monitoring (elevated 24 h BP average, daytime hypertension, nocturnal hypertension, nondipping of BP at night, morning surge, morning hypertension, BP variability) that herald increased risk to their patients and which components should be the target for treatment. This confusion breeds inaction and slows adoption. There are also major financial considerations. Presently, European guidelines list a limited number of situations where 24 h ambulatory BP monitoring should be considered [1]. O'Brien indicated that this test should also be performed in patients who have had a cardiovascular event, but stopped short of recommending it for everyone [12]. However, the implication from the study of Fan et al.[6] is quite clear. INH is a heterogeneous disorder with no readily identifiable clinical characteristics and in most instances is hidden from physicians, as approximately 80% of individuals with INH had normal office BP readings. Thus, the only means for physicians to identify this disorder is to perform ambulatory BP monitoring on all adult patients. However, without a better understanding of incremental gains in performing this test (i.e. its cost-effectiveness relative to other seemingly worthy medical services), it is unlikely that healthcare providers will be allotting more financial resources to perform ambulatory BP monitoring. The next steps are obvious if the hypertension community does consider ambulatory BP monitoring to be an indispensable component of good clinical practice. Foremost, there is a need to update the methodological standards for the performance of the procedure and recommendations for its use that are based on high-level evidence. In this regard, it is important to secure broad acceptance of guidelines among major hypertension societies and leagues and eliminate as much as possible small differences that can be a source of confusion. The community also needs to determine areas where more clinical studies are necessary to make a compelling case for its inclusion into every day clinical practice. To increase adoption by practicing physicians, the focus should be on intervention studies and particularly on studies demonstrating that correcting abnormalities in ambulatory BP measurements improves outcomes. Additionally, it will be important to engage physicians who are considered practice leaders in their community in discussions on ways to overcome barriers to the wider dissemination of ambulatory BP monitoring in the management of hypertensive patients. Finally, to engage patients it will be necessary to find ways of integrating ambulatory BP monitoring into self-care programs that are designed to involve patients in the management of their hypertension. Acknowledgment There are no conflicts of interest.

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