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Heart, Lung and Circulation

The Role of Ambulatory Blood Pressure Monitoring in Current Clinical Practice

Published:August 04, 2022DOI:https://doi.org/10.1016/j.hlc.2022.06.670
      Hypertension continues to be the leading modifiable risk factor for stroke, kidney disease and cardiovascular disease, and it also plays a key role in a significant proportion of preventable deaths globally. Ambulatory blood pressure monitoring (ABPM) is an underutilised tool that augments the accurate diagnosis of hypertension. Out-of-office blood pressure measurements such as ABPM, permits the diagnosis of white coat hypertension and masked hypertension as well as determining a patient’s nocturnal dipping status. These common clinical phenotypes have relevance with regard to clinical outcomes and may impact management. Overall, the diagnosis and management of hypertension presents numerous challenges, requiring the complementary use of multimodal blood pressure monitoring. Familiarity with the use of ABPM is important in the optimal management of patients, particularly as it becomes more accessible with the recent introduction of a Medicare Benefits Schedule item number.

      Keywords

      Introduction

      Hypertension affects one in three Australians over the age of 18 [
      • Australian Bureau of Statistics
      Hypertension and measured high blood pressure.
      ]. It is the leading risk factor for preventable deaths, with 10.8 million attributable deaths reported globally in 2019 [
      • Murray C.
      GBD 2019 Risk Factors Collaborators
      Global burden of 87 risk factors in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.
      ]. Despite its prevalence and significance, an accurate diagnosis of hypertension remains challenging. Office blood pressure measurements (OBPM) remain the most common method of diagnosing hypertension in clinical practice. While relatively quick and easy to perform, clinicians should be aware of the limitations of OBPM including false negatives in patients with masked hypertension (MH) and false positives in patients with white coat hypertension (WCH). False negatives may result in a lack of appropriate treatment while false positives can lead to unnecessary lifelong antihypertensive therapy. Ambulatory blood pressure monitoring (ABPM) has been demonstrated to have a higher sensitivity and specificity than OBPM for the diagnosis of hypertension [
      • Guirguis-Blake J.M.
      • Evans C.V.
      • Webber E.M.
      • Coppola E.L.
      • Perdue L.A.
      • Weyrich M.S.
      Screening for hypertension in adults: updated evidence report and systematic review for the US Preventive Services Task Force.
      ]. The purpose of this review is to highlight the role of ABPM in diagnosis and management of hypertension in clinical practice in Australia, particularly with recent recognition on the Medicare Benefits Schedule (MBS).

      Methods for Measuring Blood Pressure

      Broadly, the modalities available for measuring blood pressure (BP) in clinical practice can be divided into two distinct categories: in office and out-of-office. In office measurements include manual office blood pressure (MOBP) and automated office blood pressure (AOBP), while out-of-office measurements include home blood pressure monitoring (HBPM) and ABPM. Each of these modalities have unique benefits and applications.

      Office blood pressure measurements

      Blood pressure is routinely measured during clinical consultations in an ‘office’ based setting and can be performed either manually or in an automated fashion. While widely available and familiar, MOBP varies in accuracy depending on measurement procedures [
      • Gulati M.
      • Peterson L.A.
      • Mihailidou A.
      Assessment of blood pressure skills and belief in clinical readings.
      ]. Manual office blood pressure may also be limited by inherent inaccuracies such as an increased susceptibility to the white coat effect, particularly when measured by medical staff [
      • Head G.A.
      • Mihailidou A.S.
      • Duggan K.A.
      • Beilin L.J.
      • Berry N.
      • Brown M.A.
      • et al.
      Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study.
      ]. Automated office blood pressure uses an oscillometric device to execute BP measurements automatically. The National Heart Foundation of Australia’s hypertension guideline recommend three measurements taken 1 to 2 minutes apart following a 5-minute rest period. The average of the last two automated recordings should be used [
      • National Heart Foundation of Australia
      Guideline for the diagnosis and management of hypertension in adults - 2016.
      ]. The major advantages of AOBP are its ability to produce comparable results to out of office measurements and that the white coat effect is diminished compared to MOBP measurements [
      • Roerecke M.
      • Kaczorowski J.
      • Myers M.G.
      Comparing automated office blood pressure readings with other methods of blood pressure measurement for identifying patients with possible hypertension: a systematic review and meta-analysis.
      ,
      • Pappaccogli M.
      • Monaco S.D.
      • Perlo E.
      • Burrello J.
      • D’Ascenzo F.
      • Veglio F.
      • et al.
      Comparison of automated office blood pressure with office and out-off-office measurement techniques.
      ].
      Whilst AOBP ameliorates some of the shortcomings of MOBP, its performance is not sufficient to replace ABPM in the diagnosis of hypertension. Nevertheless, AOBP has an important role in routine BP measurements to screen for hypertension, and can help identify those who may benefit from ABPM. However, a major limitation of both MOBP and AOBP is the inability to diagnose masked and nocturnal hypertension.

      Home blood pressure monitoring

      Home blood pressure monitoring, is one form of out-of-office BP monitoring that is commonly utilised in practice. Using the patient’s own oscillometric BP device, or one lent to the patient, the patient is instructed to measure and record their BP over a period of days in order to model a representative day-to-day BP. Integral to the use of HBPM is patient education. In order to achieve accurate measurements, patients need to be clearly advised to be seated with their arm relaxed and supported at an appropriate height. Patients are instructed to take two readings twice daily around the same time for 7 days. The home blood pressure is calculated as the average of all values, excluding the first day, with the threshold for hypertension being 135/85 mmHg [
      • Sharman J.E.
      • Howes F.S.
      • Head G.A.
      • McGrath B.P.
      • Stowasser M.
      • Schlaich M.
      • et al.
      Home blood pressure monitoring: Australian expert consensus statement.
      ].
      Current evidence suggests that HBPM is an effective means of measuring BP, with a cohort study in 2011 finding that HBPM more closely approximated ABPM than OBPM [
      • Souza W.K.
      • Jardim P.C.
      • Porto L.B.
      • Araújo F.A.
      • Sousa A.L.
      • Salgado C.M.
      Comparison and correlation between self-measured blood pressure, casual blood pressure measurement and ambulatory blood pressure monitoring.
      ]. Home blood pressure monitoring and ABPM can function as complementary tools in the diagnosis and management of hypertension. A systematic review in 2015 showed that BP measurements on ABPM and HBPM were separately associated with an increased risk of cardiovascular events and death, but a determination of superiority was unattainable due to the small number of cohorts using both modalities [
      • Shimbo D.
      • Abdalla M.
      • Falzon L.
      • Townsend R.R.
      • Muntner P.
      Studies comparing ambulatory blood pressure and home blood pressure on cardiovascular disease and mortality outcomes: a systematic review.
      ]. One cohort study of 573 untreated patients had each participant undergo OBPM, ABPM and HBPM with the result being that HBPM had a high specificity, but low sensitivity in detecting WCH and MH [
      • Kang Y.-Y.
      • Li Y.
      • Huang Q.-F.
      • Song J.
      • Shan X.-L.
      • Dou Y.
      • et al.
      Accuracy of home versus ambulatory blood pressure monitoring in the diagnosis of white-coat and masked hypertension.
      ]. Nonetheless, HBPM is easily repeatable, more economical for longer term use and has higher levels of patient acceptance, which renders it as an alternative for ABPM in certain situations. For these same reasons, HBPM has further utility in intermittent use for monitoring the adequacy of BP control.
      An additional, promising function for HBPM is the use of automated measurements overnight. Currently there is no standardised protocol for the number of measurements or timing of measurements, with studies ranging from one isolated night time measurement to six measurements at hourly intervals [
      • Asayama K.
      • Fujiwara T.
      • Hoshide S.
      • Ohkubo T.
      • Kario K.
      • Stergiou G.S.
      • et al.
      Nocturnal blood pressure measured by home devices: evidence and perspective for clinical application.
      ]. These nocturnal measurements with a HBPM device produces BP readings comparable to ABPM [
      • Asayama K.
      • Fujiwara T.
      • Hoshide S.
      • Ohkubo T.
      • Kario K.
      • Stergiou G.S.
      • et al.
      Nocturnal blood pressure measured by home devices: evidence and perspective for clinical application.
      ] and similarly, nocturnal hypertension defined by HBPM was associated with an increased risk of cardiovascular events including coronary artery disease and stroke [
      • Mokwatsi G.G.
      • Hoshide S.
      • Kanegae H.
      • Fujiwara T.
      • Negishi K.
      • Schutte A.E.
      • et al.
      Direct comparison of home versus ambulatory defined nocturnal hypertension for predicting cardiovascular events.
      ].

      Wrist cuff BP monitors

      Wrist cuff BP devices have been available for self-measurement of BP with the potential to be less cumbersome, more acceptable by patients and have less impact on the quality of BP readings due to discomfort, although they are not recommended in international guidelines as the position of the wrist results in limited measurement accuracy [
      • Kikuya M.
      • Chonan K.
      • Imai Y.
      • Goto E.
      • Ishii M.
      Accuracy and reliability of wrist-cuff devices for self-measurement of blood pressure.
      ,
      • Emerick D.R.
      An evaluation of non-invasive blood pressure (NIBP) monitoring on the wrist: comparison with upper arm NIBP measurement.
      ,
      • Altunkan S.
      • Yildiz S.
      • Azer S.
      Wrist blood pressure-measuring devices: a comparative study of accuracy with a standard auscultatory method using a mercury manometer.
      ,
      • Casiglia E.
      • Tikhonoff V.
      • Albertini F.
      • Palatini P.
      Poor reliability of wrist blood pressure self-measurement at home.
      ]. While tronco-conical cuffs are generally preferred [
      • Palatini P.
      • Asmar R.
      • O'Brien E.
      • Padwal R.
      • Parati G.
      • Sarkis J.
      • et al.
      Recommendations for blood pressure measurement in large arms in research and clinical practice: position paper of the European society of hypertension working group on blood pressure monitoring and cardiovascular variability.
      ], wrist devices have demonstrated promising results in use among obese patients where a well fitted cuff is not available [
      • Irving G.
      • Holden J.
      • Stevens R.
      • McManus R.J.
      Which cuff should I use? Indirect blood pressure measurement for the diagnosis of hypertension in patients with obesity: a diagnostic accuracy review.
      ]. The use of wrist BP devices for night-time BP measurements has been proposed with limited evidence suggesting that three night-time measurements at ‘clock-based’ time points (ie. 2am, 3am, 4am) provided reliable results [
      • Tomitani N.
      • Kanegae H.
      • Kario K.
      Reproducibility of nighttime home blood pressure measured by a wrist-type nocturnal home blood pressure monitoring device.
      ,
      • Tomitani N.
      • Kanegae H.
      • Kario K.
      Comparison of nighttime measurement schedules using a wrist-type nocturnal home blood pressure monitoring device.
      ]. Despite wrist cuff devices being more comfortable and well tolerated, up to one third of night-time measurements were unsuccessful [
      • Zeng W.W.
      • Chan S.W.
      • Tomlinson B.
      Patient preferences for ambulatory blood pressure monitoring devices: wrist-type or arm-type?.
      ]. Due to paucity of data on validation of wrist cuff BP devices at the time of writing of the guidelines, their use is not endorsed and therefore should not be used to guide clinical decision making.

      Ambulatory blood pressure monitoring

      Ambulatory blood pressure monitoring is a method of out-of-office BP monitoring that is widely regarded as the gold standard for BP measurement. Ambulatory blood pressure monitoring involves a wearable device consisting of a cuff and a monitor which the patient keeps on for 24–48 hours. The inflatable cuff is generally placed on the non-dominant arm unless there are contraindications to measuring BP on that side, such as axillary clearance or arteriovenous fistula. Concurrent BP measurements with ABPM and a sphygmomanometer or validated monitor are taken at the time of initiation to ensure it is adequately configured. The device is programmed to measure and record the patient’s BP every 15–30 minutes while awake and every 30–60 minutes during a pre-specified sleeping period. The patient is instructed that the cuff will inflate automatically, and of the need to keep their arm still and relaxed until the cuff is fully deflated. To aid interpretation of the results, ABPM is often performed on a typical day and patients are encouraged to keep an accurate diary of their activities and sleep for the day. A test may be inadequate if there are an insufficient number of measurements or significant sleep disturbance which affects night-time measurements. Only validated devices should be used for ABPM, and clinicians can reference the list available from several websites such as STRIDE BP [
      • Stergiou G.S.
      • O'Brien E.
      • Myers M.
      • Palatini P.
      • Parati G.
      STRIDE BP: an international initiative for accurate blood pressure measurement.
      ], the British and Irish Hypertension Society (BIHS) website [

      British and Irish Hypertension Society. BP monitors. https://bihsoc.org/bp-monitors/. [accessed 21.7.22].

      ], and the American VALIDATE BP [
      • Cohen J.B.
      • Padwal R.S.
      • Gutkin M.
      • Green B.B.
      • Bloch M.J.
      • Germino F.W.
      • et al.
      History and justification of a national blood pressure measurement validated device listing.
      ].

      ABPM Interpretation

      Following the monitoring period, the data is downloaded onto a software platform which produces a report (Figure 1), with the most commonly utilised results being the average 24-hour BP, average daytime BP (average BP during waking hours), average night-time BP (average BP during sleeping hours) and nocturnal dipping (percentage decrease of night-time compared to daytime BP). The thresholds for average 24-hour, daytime and night-time BPs equivalent to an OBPM of ≥140/90 mmHg are ≥130/80, ≥135/85 and ≥120/70 mmHg respectively, which are also correlated with prognostic outcomes [
      • National Heart Foundation of Australia
      Guideline for the diagnosis and management of hypertension in adults - 2016.
      ,
      • Cheng Y.-B.
      • Thijs L.
      • Zhang Z.-Y.
      • Kikuya M.
      • Yang W.-Y.
      • Melgarejo J.D.
      • et al.
      Outcome-driven thresholds for ambulatory blood pressure based on the new American College of Cardiology/American Heart Association Classification of Hypertension.
      ]. Based on the measurements obtained on ABPM and OBPM, patients can be classified into the different hypertensive subclasses (Figure 2).
      Figure thumbnail gr1
      Figure 1Clinical Blood Pressure Profiles on ABPM. ABPM reports produced by different software. The patients’ systolic and diastolic blood pressures are depicted through the 24-hour period. The horizontal bars illustrate the thresholds for grade 1 hypertension and the grey region is the predetermined night-time period. Four ABPM reports are included showing: A) normotension, B) moderate hypertension with white coat effect. Office BP 179/123; average 24-hour BP 151/102, C) non-dipping and D) severe hypertension.
      Abbreviations: APBM, ambulatory blood pressure monitoring; BP, blood pressure.
      Figure thumbnail gr2
      Figure 2Hypertensive subclasses based on ABPM and OBPM.
      Abbreviations: APBM, ambulatory blood pressure monitoring; OBPM, office blood pressure monitoring.
      Whilst digital programs are able to evaluate ABPM recordings, an understanding of the interpretation is required to effectively establish management. One method which we use is a three-step approach to the interpretation of ABPM [
      • Omboni S.
      • Palatini P.
      • Parati G.
      Standards for ambulatory blood pressure monitoring clinical reporting in daily practice: recommendations from the Italian Society of Hypertension.
      ]. The first step involves appraising the quality of the recording. Typically, this includes excluding invalid data due to movement (as indicated in their activity diary), ensuring >70% and >21 hours of readings are valid, and having at least 20 daytime and 7 night-time readings. Inadequate tests should be repeated and any further interpretation should be held with caution. The second step is a comparison of the patient’s BP parameters to the reference standards. Finally comes an overall comment on the 24-hour pattern of BP fluctuations as well as the hypertensive status of the patient.
      Other indices that are derived include the BP variability (usually defined by the standard deviation of systolic BP at day and night), the BP load (the proportion of BP measurements above the threshold) and the morning BP surge (the difference between morning BP and the nocturnal nadir).

      Benefits and Use of ABPM

      There are a number of studies establishing the superiority of ABPM over OBPM in providing prognostic information on the development of cardiovascular events [
      • Minutolo R.
      • Agarwal R.
      • Borrelli S.
      • Chiodini P.
      • Bellizzi V.
      • Nappi F.
      • et al.
      Prognostic role of ambulatory blood pressure measurement in patients with nondialysis chronic kidney disease.
      ,
      • Roush G.C.
      • Fagard R.H.
      • Salles G.F.
      • Pierdomenico S.D.
      • Reboldi G.
      • Verdecchia P.
      • et al.
      Prognostic impact of sex–ambulatory blood pressure interactions in 10 cohorts of 17 312 patients diagnosed with hypertension: systematic review and meta-analysis.
      ,
      • Piper M.
      • Evans C.
      • Burda B.
      • Margolis K.
      • O’Connor E.
      • Whitlock E.
      Diagnostic and predictive accuracy of blood pressure screening methods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force.
      ,
      • Yang W.-Y.
      • Melgarejo J.D.
      • Thijs L.
      • Zhang Z.-Y.
      • Boggia J.
      • Wei F.-F.
      • et al.
      Association of office and ambulatory blood pressure with mortality and cardiovascular outcomes.
      ], chronic kidney disease (CKD) [
      • McMullan C.J.
      • Hickson D.A.
      • Taylor H.A.
      • Forman J.P.
      Prospective analysis of the association of ambulatory blood pressure characteristics with incident chronic kidney disease.
      ], ischaemic stroke [
      • Cai A.
      • Liu C.
      • Zhou D.
      • Liu X.
      • Zhong Q.
      • Li X.
      • et al.
      Ambulatory blood pressure is superior to clinic blood pressure in relation to ischemic stroke in both diabetic and nondiabetic patients.
      ,
      • Mesquita-Bastos J.
      • Bertoquini S.
      • Polónia J.
      Cardiovascular prognostic value of ambulatory blood pressure monitoring in a Portuguese hypertensive population followed up for 8.2 years.
      ] and mortality [
      • Böhm M.
      • Schwantke I.
      • Mahfoud F.
      • Lauder L.
      • Wagenpfeil S.
      • de la Sierra A.
      • et al.
      Association of clinic and ambulatory heart rate parameters with mortality in hypertension.
      ]. Moreover, ABPM has repeatedly been shown to have a superior reliability compared to OBPM [
      • Mansoor G.A.
      • McCabe E.J.
      • White W.B.
      Long-term reproducibility of ambulatory blood pressure.
      ,
      • Palatini P.
      • Mormino P.
      • Canali C.
      • Santonastaso M.
      • Venuto G.D.
      • Zanata G.
      • et al.
      Factors affecting ambulatory blood pressure reproducibility. Results of the HARVEST trial. Hypertension and Ambulatory Recording Venetia Study.
      ]. An Australia-wide cohort study reported that the mean, seated OBPM recorded by doctors were 15 and 9 mmHg higher than mean daytime systolic and diastolic BP measured by ABPM respectively [
      • Head G.A.
      • Mihailidou A.S.
      • Duggan K.A.
      • Beilin L.J.
      • Berry N.
      • Brown M.A.
      • et al.
      Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study.
      ]. These discrepancies can result in misinformed management decisions in clinical practice. Correspondingly, to achieve similar levels of BP control, antihypertensive therapy titrated off ABPM is less intensive than therapy titrated off OBPM [
      • Staessen J.A.
      • Byttebier G.
      • Buntinx F.
      • Celis H.
      • O'Brien E.T.
      • Fagard R.
      Antihypertensive treatment based on conventional or ambulatory blood pressure measurement: a randomized controlled trial.
      ]. Because of these benefits of ABPM over OBPM, ABPM has been shown to be a cost-effective strategy for diagnosis of hypertension in the primary care setting, regardless of the initial OBPM result [
      • Beyhaghi H.
      • Viera A.J.
      Comparative cost-effectiveness of clinic, home, or ambulatory blood pressure measurement for hypertension diagnosis in US adults.
      ].
      The widespread use of ABPM is impeded by a few practical considerations. Firstly, implementation at any given practice will require the costs associated with the equipment, software and training for staff. The cost of the test and the discomfort and inconvenience for patients also needs to be taken into consideration. The use of ABPM may also cause temporary sleep disturbance and bruising [
      • Guirguis-Blake J.M.
      • Evans C.V.
      • Webber E.M.
      • Coppola E.L.
      • Perdue L.A.
      • Weyrich M.S.
      Screening for hypertension in adults: updated evidence report and systematic review for the US Preventive Services Task Force.
      ], with one study reporting that up to 36% experienced arousal from sleep due to cuff inflation [
      • Mokwatsi G.G.
      • Hoshide S.
      • Kanegae H.
      • Fujiwara T.
      • Negishi K.
      • Schutte A.E.
      • et al.
      Direct comparison of home versus ambulatory defined nocturnal hypertension for predicting cardiovascular events.
      ]. Reassuringly, patient tolerance of ABPM does not appear to have a significant impact on the result obtained [
      • Iannucci G.
      • Petramala L.
      • La Torre G.
      • Barbaro B.
      • Balsano C.
      • Curatulo P.G.
      • et al.
      Evaluation of tolerance to ambulatory blood pressure monitoring: analysis of dipping profile in a large cohort of hypertensive patients.
      ], although this should be taken into account during interpretation. It should also be noted that risk assessment calculators for cardiovascular disease risk associated with hypertension, are only validated using OBPM measurements.
      Current clinical indications for ABPM include suspicion of WCH, MH, postural hypertension, nocturnal hypertension and treatment resistant hypertension [
      • National Heart Foundation of Australia
      Guideline for the diagnosis and management of hypertension in adults - 2016.
      ,
      • Whelton P.K.
      • Carey R.M.
      • Aronow W.S.
      • Casey D.E.
      • Collins K.J.
      • Himmelfarb C.D.
      • et al.
      2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.
      ,
      • Williams B.
      • Mancia G.
      • Spiering W.
      • Agabiti Rosei E.
      • Azizi M.
      • Burnier M.
      • et al.
      2018 ESC/ESH Guidelines for the management of arterial hypertension: the Task Force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH).
      ]. Additionally, ABPM can be used for assessing the response to antihypertensive therapy where clinic measurements are inconclusive.

      Medicare Benefits Schedule Item

      Prior to 1 November 2021 Australia did not have an MBS item for ABPM which significantly limited its uptake in clinical practice. The new MBS item (11607) has been introduced for ABPM to diagnose hypertension [
      • Australian Government - Department of Health
      New Medical Benefits Schedule (MBS) item for diagnosis of hypertension through Ambulatory blood pressure monitoring.
      ] and is only applicable for patients who are suspected of having hypertension, not on antihypertensive therapy and who have office systolic BP reading between 140–180 mmHg or diastolic BP between 90–110 mmHg. Eligibility for this Medicare item number requires the establishment of a detailed treatment plan and can be utilised only once every 12 months. It is anticipated that in due course, awareness of this MBS item among medical practitioners will increase and subsequently improve its uptake in clinical practice.
      The introduction of this MBS item addresses the financial barrier for patients and practitioners in implementing the current best practice recommendations for hypertension diagnosis. However, clinicians should be aware that the limited scope of the MBS item number prevents its use for the diagnosis of masked hypertension or assessing refractory hypertension which are common clinical indications for the use of ABPM.

      Clinical Blood Pressure Phenotypes

      White coat hypertension

      White coat hypertension is a well-known phenomenon whereby OBPM meet hypertension criteria, but out-of-office BP measurements are within the normotensive range, for an untreated individual. The prevalence of WCH globally varies greatly depending on geographical location, but can be up to 23% [
      • Schwartz J.E.
      • Burg M.M.
      • Shimbo D.
      • Broderick J.E.
      • Stone A.A.
      • Ishikawa J.
      • et al.
      Clinic blood pressure underestimates ambulatory blood pressure in an untreated employer-based US population.
      ,
      • Omboni S.
      • Aristizabal D.
      • De la Sierra A.
      • Dolan E.
      • Head G.
      • Kahan T.
      • et al.
      Hypertension types defined by clinic and ambulatory blood pressure in 14 143 patients referred to hypertension clinics worldwide. Data from the ARTEMIS study.
      ,
      • Tientcheu D.
      • Ayers C.
      • Das S.R.
      • McGuire D.K.
      • de Lemos J.A.
      • Khera A.
      • et al.
      Target organ complications and cardiovascular events associated with masked hypertension and white-coat hypertension: analysis from the Dallas Heart Study.
      ], and the only identified risk factor for WCH is female sex [
      • Sheppard J.P.
      • Fletcher B.
      • Gill P.
      • Martin U.
      • Roberts N.
      • McManus R.J.
      Predictors of the home-clinic blood pressure difference: a systematic review and meta-analysis.
      ,
      • Ben-Dov I.Z.
      • Mekler J.
      • Bursztyn M.
      Sex differences in ambulatory blood pressure monitoring.
      ]. One study suggested that the prevalence of WCH in Australia is 11% among untreated and 21% among treated individuals [
      • Omboni S.
      • Aristizabal D.
      • De la Sierra A.
      • Dolan E.
      • Head G.
      • Kahan T.
      • et al.
      Hypertension types defined by clinic and ambulatory blood pressure in 14 143 patients referred to hypertension clinics worldwide. Data from the ARTEMIS study.
      ]. White coat effect is a term used to describe the difference between an elevated office BP and a lower home or ambulatory BP in both untreated and treated patients.
      Traditionally, WCH was seen as a benign diagnosis which did not require any specific treatment, but more recent evidence challenges this assumption. In 2019, a systematic review and meta-analysis was published showing that untreated WCH was associated with an increased risk for cardiovascular events, cardiovascular mortality and all-cause mortality [
      • Cohen J.
      • Lotito M.
      • Trivedi U.
      • Denker M.
      • Cohen D.
      • Townsend R.
      Cardiovascular events and mortality in white coat hypertension.
      ]. White coat hypertension in patients who received antihypertensive therapy was not associated with any of these outcomes. Moreover, WCH has been consistently shown to be associated with an increased risk of developing sustained hypertension [
      • Mancia G.
      • Bombelli M.
      • Brambilla G.
      • Facchetti R.
      • Sega R.
      • Toso E.
      • et al.
      Long-term prognostic value of white coat hypertension.
      ,
      • Mancia G.
      • Bombelli M.
      • Facchetti R.
      • Madotto F.
      • Quarti-Trevano F.
      • Friz H.P.
      • et al.
      Long-term risk of sustained hypertension in white-coat or masked hypertension.
      ].
      In light of this, guidelines recommend aggressive lifestyle modifications in patients with WCH [
      • National Heart Foundation of Australia
      Guideline for the diagnosis and management of hypertension in adults - 2016.
      ], including smoking cessation, reduction in alcohol use, dietary modification, exercise and weight loss. Routine administration anti-hypertensive therapy is not recommended in these patients. However, due to the risk of developing sustained hypertension, patients should be monitored with some form of out-of-office BP monitoring 6–12 monthly depending on concurrent risk factors.

      Masked Hypertension

      Conversely, MH exists when a patient’s OBPM is within the normotensive range, but out-of-office BP measurements are elevated. Masked uncontrolled hypertension (MUCH) is present when individuals on antihypertensive therapy demonstrate this BP response. Not dissimilar to WCH, the prevalence of MH varies by country, but is in the range on 10–20%, with the prevalence in Australia of MH and MUCH being 9% among untreated and 12% among treated individuals respectively [
      • Schwartz J.E.
      • Burg M.M.
      • Shimbo D.
      • Broderick J.E.
      • Stone A.A.
      • Ishikawa J.
      • et al.
      Clinic blood pressure underestimates ambulatory blood pressure in an untreated employer-based US population.
      ,
      • Omboni S.
      • Aristizabal D.
      • De la Sierra A.
      • Dolan E.
      • Head G.
      • Kahan T.
      • et al.
      Hypertension types defined by clinic and ambulatory blood pressure in 14 143 patients referred to hypertension clinics worldwide. Data from the ARTEMIS study.
      ,
      • Tientcheu D.
      • Ayers C.
      • Das S.R.
      • McGuire D.K.
      • de Lemos J.A.
      • Khera A.
      • et al.
      Target organ complications and cardiovascular events associated with masked hypertension and white-coat hypertension: analysis from the Dallas Heart Study.
      ]. Risk factors for MH include male sex, increasing body mass index (BMI), tobacco smoking, CKD and diabetes [
      • Sheppard J.P.
      • Fletcher B.
      • Gill P.
      • Martin U.
      • Roberts N.
      • McManus R.J.
      Predictors of the home-clinic blood pressure difference: a systematic review and meta-analysis.
      ,
      • Velasquez M.T.
      • Beddhu S.
      • Nobakht E.
      • Rahman M.
      • Raj D.S.
      Ambulatory blood pressure in chronic kidney disease: ready for prime time?.
      ,
      • Franklin S.S.
      • Thijs L.
      • Li Y.
      • Hansen T.W.
      • Boggia J.
      • Liu Y.
      • et al.
      Masked hypertension in diabetes mellitus: treatment implications for clinical practice.
      ]. Patients with a normal OBPM (particularly on the upper limit of normal) and these risk factors, other cardiovascular risk factors or evidence of target-organ damage, should be considered for out-of-office BP monitoring to detect MH (Figure 3).
      Figure thumbnail gr3
      Figure 3Evaluation and management of hypertension. ∗Target organ damage may include left ventricular hypertrophy, ischaemic heart disease, heart failure, chronic kidney disease, cerebrovascular disease or hypertensive retinopathy. ∗∗This indication for ABPM does not qualify for the MBS item number.
      Abbreviations: BP, blood pressure; ABPM, ambulatory blood pressure monitoring; HBPM, home blood pressure monitoring; MH, masked hypertension; WCH, white coat hypertension.
      Masked hypertension has been repeatedly shown to be associated with an increased risk of cardiovascular events approaching that of sustained hypertension [
      • Tientcheu D.
      • Ayers C.
      • Das S.R.
      • McGuire D.K.
      • de Lemos J.A.
      • Khera A.
      • et al.
      Target organ complications and cardiovascular events associated with masked hypertension and white-coat hypertension: analysis from the Dallas Heart Study.
      ,
      • Pierdomenico S.D.
      • Lapenna D.
      • Bucci A.
      • Tommaso R.D.
      • Mascio R.D.
      • Manente B.M.
      • et al.
      Cardiovascular outcome in treated hypertensive patients with responder, masked, false resistant, and true resistant hypertension.
      ]. Hence, patients diagnosed with MH should commence treatment with lifestyle modifications and anti-hypertensive therapy as for classically diagnosed hypertension. Up to 31.1% of treated patients with controlled OBPM have MUCH and similarly, should be treated as for uncontrolled hypertension with intensification of pharmacologic therapy [
      • Banegas J.R.
      • Ruilope L.M.
      • de la Sierra A.
      • de la Cruz J.J.
      • Gorostidi M.
      • Segura J.
      • et al.
      High prevalence of masked uncontrolled hypertension in people with treated hypertension.
      ].

      Nocturnal Dipping

      Normal individuals experience a physiological drop in BP of 10–20% while asleep, a phenomenon termed nocturnal dipping. Non-dippers are those whose nocturnal dip in BP is <10% of their awake values, and this may be associated with obstructive sleep apnoea, CKD or diabetes [
      • Baguet J.-P.
      • Hammer L.
      • Lévy P.
      • Pierre H.
      • Rossini E.
      • Mouret S.
      • et al.
      Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients.
      ,
      • Agarwal R.
      • Andersen M.J.
      Prognostic importance of ambulatory blood pressure recordings in patients with chronic kidney disease.
      ]. Other nocturnal BP characters include extreme dipping (>20% drop in nocturnal BP) and reverse dipping (increase in nocturnal compared to waking BP).
      In a large meta-analysis of 10 cohorts consisting of 17,312 hypertensive patients, the proportion of each dipping status were 27–54% for normal dippers, 32–46% for non-dippers, 4–20% for extreme dippers and 5–19% for reverse dippers [
      • Salles G.F.
      • Reboldi G.
      • Fagard R.H.
      • Cardoso C.R.L.
      • Pierdomenico S.D.
      • Verdecchia P.
      • et al.
      Prognostic effect of the nocturnal blood pressure fall in hypertensive patients.
      ]. The same study established that non-dipping, reverse dipping and untreated patients with extreme dipping were associated with an increased risk of cardiovascular events. There have been numerous proposed mechanisms for this association, but they remain largely speculative at this stage. Furthermore, non-dipping has been demonstrated to be associated with an increase in cardiovascular risk regardless of overall BP load [
      • Ohkubo T.
      • Hozawa A.
      • Yamaguchi J.
      • Kikuya M.
      • Ohmori K.
      • Michimata M.
      • et al.
      Prognostic significance of the nocturnal decline in blood pressure in individuals with and without high 24-h blood pressure: the Ohasama study.
      ]. The increased risk associated with any abnormal nocturnal dipping status provides further support for the use of ABPM or the aforementioned nocturnal HBPM.

      Special Populations

      Chronic kidney disease

      The diagnosis of hypertension can be particularly challenging in patients with CKD as they are more likely to have abnormal circadian BP patterns. Patients with CKD have a higher incidence of nocturnal hypertension, non-dipping and MH and a lower incidence of WCH [
      • Velasquez M.T.
      • Beddhu S.
      • Nobakht E.
      • Rahman M.
      • Raj D.S.
      Ambulatory blood pressure in chronic kidney disease: ready for prime time?.
      ]. Subsequently, office BP measurements are less reliable in patients with CKD. In an observational study of 275 patients with CKD and a clinic systolic BP<140 mmHg, both systolic and diastolic AOBP were lower than the corresponding daytime ABPM readings [
      • Agarwal R.
      Implications of Blood Pressure Measurement Technique for Implementation of Systolic Blood Pressure Intervention Trial (SPRINT).
      ]. A further cohort study determined that while ABPM was independently associated with significant cardiovascular events in patients with stage 3–5 CKD, AOBP was not [
      • Seo J.W.
      • Park S.H.
      • Lee C.J.
      • Choi D.H.
      422Comparison of the prognostic significance of blood pressure measurement by unattended automatic office blood pressure and ambulatory blood pressure in subjects with chronic kidney disease.
      ]. Hence, ABPM has an important role in diagnosing hypertension in patients with CKD.

      Diabetes

      Similar to patients with CKD, patients with both type 1 and type 2 diabetes demonstrate altered circadian BP patterns and are more likely to be non-dippers [
      • Gorostidi M.
      • de la Sierra A.
      • González-Albarrán O.
      • Segura J.
      • de la Cruz J.J.
      • Vinyoles E.
      • et al.
      Abnormalities in ambulatory blood pressure monitoring in hypertensive patients with diabetes.
      ]. Furthermore, they are also more likely to have MH. In an analysis of the International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO), MH occurred more frequently in untreated normotensive patients with diabetes (29.3%) than nondiabetics (18.8%) [
      • Franklin S.S.
      • Thijs L.
      • Li Y.
      • Hansen T.W.
      • Boggia J.
      • Liu Y.
      • et al.
      Masked hypertension in diabetes mellitus: treatment implications for clinical practice.
      ]. Given the particular importance of adequate BP control in reducing end organ damage in patients with diabetes, strong consideration should be given to ABPM.

      Pregnancy

      Women have higher white coat effect than men [
      • Ben-Dov I.Z.
      • Mekler J.
      • Bursztyn M.
      Sex differences in ambulatory blood pressure monitoring.
      ], and therefore ABPM has an important role for pregnant women who have elevated clinic BP early in pregnancy to confirm diagnosis and management of essential hypertension or WCH to reduce the risk of cardiovascular disease in mother and fetus. Blunted nocturnal dipping is associated with developing hypertensive disorders of pregnancy (HDP) including pre-eclampsia [
      • Saremi A.T.
      • Shafiee M.A.
      • Montazeri M.
      • Rashidi N.
      • Montazeri M.
      Blunted overnight blood pressure dipping in second trimester; a strong predictor of gestational hypertension and preeclampsia.
      ,
      • Salazar M.R.
      • Espeche W.G.
      • Leiva Sisnieguez C.E.
      • Leiva Sisnieguez B.C.
      • Balbín E.
      • Stavile R.N.
      • et al.
      Nocturnal hypertension in high-risk mid-pregnancies predict the development of preeclampsia/eclampsia.
      ]. Importantly, the ABPM monitor that is selected must be validated for use in pregnancy to ensure valid measures. Further, if women have experienced pre-eclampsia or HDP then it is important to ensure that these women are monitored since BP may return to normal following delivery, however these women have greater lifetime risk of permanent hypertension, CKD, and cardiovascular disease [
      • Behrens I.
      • Basit S.
      • Melbye M.
      • Lykke J.A.
      • Wohlfahrt J.
      • Bundgaard H.
      • et al.
      Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study.
      ], including left ventricular remodelling and hypertrophy [
      • Countouris M.E.
      • Villanueva F.S.
      • Berlacher K.L.
      • Cavalcante J.L.
      • Parks W.T.
      • Catov J.M.
      Association of hypertensive disorders of pregnancy with left ventricular remodeling later in life.
      ].

      Conclusion

      Ambulatory blood pressure monitoring is an effective and powerful diagnostic tool to provide further information beyond what can be obtained from OBPM. The use of ABPM in selected populations permits detection of WCH, MH and nocturnal dipping status which is otherwise unachievable with OBPM. The diverse modalities of BP monitoring available, including OBPM, AOBP, HBPM and ABPM each have unique benefits and applications and should be used complementary to each other in the diagnosis and management of hypertension.

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