Ambulatory Blood Pressure Monitoring: New Directions and Uncertainties Arise From the U.S. Preventive Services Task Force Recommendation on the Diagnosis of Hypertension

The recently finalized Recommendation from the U.S. Preventive Services Task Force (USPSTF) entitled “Hypertension in Adults: Screening and Home Monitoring”1 is an important contribution to the field. It makes clear that out-of-office blood pressure (BP) measurement is an established and reliable method to confirm an initial diagnosis of hypertension based on an in-office BP measurement. This recommendation applies to adults 18 years and older and is expressed succinctly in the associated clinical summary: “Screen for high blood pressure; obtain measurements outside of the clinical setting for diagnostic confirmation.” The recommendation received the USPSTF's Grade A rating, indicating that there is high certainty of net benefit from following the recommendation. Ambulatory BP monitoring (ABPM)2 was considered to be the best confirmatory test for hypertension. The alternative of home BP monitoring3 may also be a reasonable strategy, although there is less evidence supporting its value.1 BP assessment is widely performed in physicians’ offices, being employed both as an indicator of general health status and as a diagnostic tool for hypertension. Given this approach to hypertension diagnosis, the following fact is paradoxical: while it is remarkably easy to obtain a BP reading, it can be disturbingly difficult to estimate the correct BP level.4 Pickering and colleagues5 observed that “Any clinical measurement of BP may be regarded as a surrogate for the ‘true’ BP of the patient, which may be defined as the mean level over prolonged periods.” ABPM may be well suited to the spirit of this observation. There is no shortage of hypertension guidelines in the literature,6 and ABPM is discussed in several of them (although not in the 2014 report from the Eighth Joint National Committee [JNC 8] panelists7). There are also position papers and guidelines addressing ABPM specifically,8, 9 and well-reasoned arguments for its employment in the diagnosis of hypertension.10 As a corollary, ABPM is specifically targeted at identifying and excluding white-coat hypertension (also termed isolated clinic hypertension). It may also be useful in the detection of masked hypertension, which also requires out-of-office BP assessment,11 although this topic was not addressed by the USPSTF and accordingly is not discussed in this editorial. The United Kingdom's National Institute for Health and Care Excellence (NICE) updated their recommendations addressing the diagnosis of hypertension in 2011 as follows:12 If the clinic BP is 140/90 mm Hg or higher, offer ABPM to confirm the diagnosis of hypertension. If a person is unable to tolerate ABPM, home BP monitoring is a suitable alternative to confirm the diagnosis of hypertension. The 2015 Canadian Hypertension Education Program recommendations for the diagnosis and assessment of hypertension are similar: for patients with elevated office readings, early use of out-of-office BP measurement, preferably via ABPM, is recommended to identify patients with white-coat hypertension.13 The USPSTF recommendation is therefore an endorsement of those in the United Kingdom and Canada. The USPSTF recommendation may well have ramifications for the diagnosis and treatment of hypertension in the United States. Despite accumulated evidence, ABPM is presently a rarity in clinical practice here, largely because there is inadequate reimbursement by the organizations that fund healthcare.14 In a paper published shortly after the 2011 NICE recommendations, Bloch and Basile15 observed regarding its employment in the United States: “Even if we believe that routine use of ABPM will better secure the diagnosis of hypertension and save money in the long-run, there is simply no group that is appropriately incentivized to make the needed short-term investment required to make it practical in our system” (see Bloch and Basile16 for their latest thoughts). It is not yet known whether the USPSTF's recommendation will increase financial support for ABPM. Despite these recent developments, we should now consider how the USPSTF recommendation could expose fundamental uncertainties and risks in relying on this application of ABPM to guide clinical practice. What are the consequences of ABPM and its ability to identify patients whose hypertension cannot be confirmed outside of the office? The most obvious implication is that for a meaningful proportion of people initially labeled as hypertensive, the burden of this diagnosis could be lifted, and there would be significant cost savings for the health plans responsible for their treatment. Even so, there are limitations to these assumptions. For instance, while it seems apparent that patients with nonconfirmed (white-coat) hypertension might not need immediate antihypertensive therapy, they can still exhibit clinical findings typical of hypertension. Several years ago, and also more recently, it has been reported that, compared with truly normotensive controls, patients with white-coat hypertension can have increased activity of their renin-angiotensin and sympathetic systems and are more likely to exhibit insulin resistance and lipid abnormalities as well as early hypertrophic changes in their left ventricular walls.17, 18 Moreover, patients with white-coat hypertension will require frequent follow-up visits—at least annually according to the USPSTF—because ultimately almost all adults, in the process of aging, will become hypertensive and require therapy.19 Therefore, it is critical to clearly understand that a “normal” ambulatory monitoring result does not justify the avoidance of treatment, it simply might allow a delay. Which leads to an obvious question: Given the importance of timely treatment in these vulnerable patients, should additional confirmatory ambulatory monitoring procedures be performed whenever the BP readings are high during routine office visits? If this logic is followed, even in a modified form, the process of diagnosing hypertension in this large group of people could become a time-consuming and costly undertaking. Those who advance the cause of ambulatory monitoring for diagnostic confirmation must be prepared to answer a further, more important question: What is the harm in exposing patients with white-coat hypertension to antihypertensive treatment? Based on the very recent publication of results from the Systolic Blood Pressure Intervention Trial (SPRINT),20 there was clearly greater cardiovascular protection in patients treated intensively to a systolic BP target <120 mm Hg compared with those treated only to a target <140 mm Hg. Likewise, the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial,21 conducted in diabetes patients with hypertension, reported that stroke rates were dramatically reduced when systolic BPs were reduced below 120 mm Hg. So, we can conclude from SPRINT and ACCORD that treating patients down to “normal” BP levels—using modern well-tolerated drugs—offers more benefit than harm, a compelling consideration that surely encompasses the majority of patients with white-coat hypertension. Indeed, we should take this argument one step further and consider the fundamental basis for identifying and treating hypertension. According to the data cited by the USPSTF, from 5% to 65% of patients with high office BPs have white-coat hypertension demonstrated by ambulatory monitoring. From this, it is perfectly plausible to assume that the landmark clinical trials22-24 that established the benefits of hypertension treatment and guided practice recommendations, all of which were conducted in patients with office-diagnosed hypertension, would have included a similar proportion (approximately one third) of patients with white-coat hypertension. While we cannot be certain that the patients with white-coat hypertension and the other study patients contributed equally to the positive results of these trials, in the absence of contrary data it is a very reasonable assumption—as asserted previously by others24—that treating patients with white-coat hypertension with modern drugs provides them with meaningful cardiovascular protection. In addition, as summarized in a recent review,25 we cannot overlook the fact that treatment of hypertension based on office diagnosis during the past several years has been a highly successful contributor to reducing community stroke rates, again demanding careful consideration before adopting new recommendations that would very likely exclude large numbers of such individuals from access to therapy. Indeed, it could be argued that the use of ambulatory monitoring to make treat vs no-treat decisions in patients with office hypertension should be undertaken only with great caution until there is robust evidence that the USPSTF's new-found plan to withhold antihypertensive therapy in white-coat patients provides outcome benefits or, at the very least, does not diminish the benefits these patients currently receive. ABPM is a valuable procedure that has taught us about the circadian pattern of BP and has drawn attention to such issues as the clinical and prognostic importance of nighttime BP. Its reproducibility and lack of bias has made it a critical part of studying the efficacy of antihypertensive therapies as well as a sensitive tool for measuring the potentially adverse BP effects of drugs being evaluated for noncardiovascular indications.26 This procedure is also now recognized as integral to evaluating patients with apparent treatment-resistant hypertension in whom identifying white-coat hypertension can obviate the need for unnecessary drug manipulations or futile searches for secondary forms of hypertension. The issue now at hand is the new USPSTF recommendation that ambulatory monitoring be used routinely to confirm the diagnosis of hypertension in patients presenting with high BP in the office or clinic. This improvement in diagnostic accuracy could be an important step, but we have argued in this discussion that the primary implication of this recommendation—in particular, that antihypertensive therapy should be withheld in patients found to have white-coat hypertension—might have the unintended consequence of depriving these individuals of the cardiovascular protection provided by modern drug therapy. Before this big change is incorporated into clinical practice, we are entitled to see persuasive evidence that diagnostic ambulatory monitoring is of genuine clinical value and is not being promoted primarily by a desire for short-term cost savings. The authors report no specific funding in relation to the preparation of this paper. No editorial support was used.

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