Hypertension has been shown to be a major cause of death worldwide.1 A clear relationship exists between hypertension (HTN) and cardiovascular (CV) events, with an increase in risk of total mortality, mortality due to heart disease, stroke, chronic kidney disease (CKD) and heart failure (HF) as well as morbidity associated with non-fatal CV disease.2 Despite there being clear demonstrable CV benefits from blood pressure (BP) reduction in large clinical trials,3-5 BP control remains poor worldwide6 and mortality due to hypertension rates are high.
BP exhibits a circadian pattern.7 BP tends to be lowest between 2 and 4am, with systolic and diastolic readings approximately 13 and 17% lower than daytime values. After 4am there is an 'early morning surge' in BP readings, reaching a peak at about 6am. There is then a gradual decline towards the evening, followed by lower readings at night. The 'early morning surge' is associated with an increase in CV events8,9 including acute myocardial infarction, ischaemic and haemorrhagic stroke and sudden cardiovascular death.10,11 An office/clinic BP reading only offers an instantaneous reading or snapshot of a patients BP in a day and cannot give a true reflection of BP readings throughout the day or abnormalities in the circadian rhythms.
However, in the past most clinical studies have used conventional cuff BP measurements at clinic/office visits to measure BP and still demonstrated CV outcome benefits. With better understanding of circadian BP changes, should we be looking at BP measurement away from the clinic/office in order to improve patient outcomes?
This article aims to outline the options available for clinicians in daily practice and the potential benefits of adopting out-of-office/clinic BP measurements in clinical practice with regards to accurate diagnosis of hypertension, risk stratification and how these techniques may be utilised to improve BP control and CV outcomes.
Options Available for Out-of-office/Clinic Blood Pressure Measurements
Ambulatory Blood Pressure Monitoring
Ambulatory BP monitoring (ABPM) is an automated technique utilising a cuff that is usually attached to a small monitor/recorder worn on a belt. Multiple BP measurements are taken at regular intervals (15-30 minutes) over a 24-48 hour period. The data are downloaded to a computer at the end of the recording period for interpretation and action by the physician. There are also newer devices worn at the wrist that have been well validated and found to give accurate BP readings12 and these are now commercially available.
ABPM is more accurate than office BP readings,5 which are associated with white-coat hypertension (WCH) and, hence, false-positive diagnoses of hypertension.13,14 It is far superior to office readings in risk stratification and predicting CV events15 and provides a more reliable and more accurate representation of overall BP than office-based measurements.16,17
There are limitations of ABPM that need to be considered. These include set-up costs that are not inconsiderable, including equipment purchase and staff training.18 During the recording period, patients may experience complications including uncomfortable cuff pressure, sleep disturbance, petechiae and bruising.19 Should 24 hour on-call personnel be made available for patients who experience these possible complications, this will add further to the cost of providing an ABPM service. Variations in BP readings may occur due to readings being taken during activity, for example, exercise and driving or when taken in the presence of arrhythmias, e.g. atrial fibrillation.1,9 For an ABPM recording to be considered acceptable, at least 85% of readings must be deemed suitable for inclusion in the analysis.1,9 Although ABPM has clear benefits in terms of diagnosis and prognostication, the practical limitations do not make it the ideal tool for regular BP monitoring.
Home Blood Pressure (Self) Monitoring
Home blood pressure (self) monitoring (HBPM) is performed using commercially available monitors by patients themselves. There are currently three types of monitors available.
The cuff-arm monitors that are available are mostly fully automated and patients only need to place the cuff correctly around the arm and press a button to activate the machine to inflate the cuff and take BP readings, although some machines require manual inflation. Most machines also have a memory function allowing serial BP readings to be stored for later review.
Wrist monitors are also available. It is important that the wrist is held at the same level as the heart when readings are taken to minimise errors. Although finger monitors are also available, they are not currently recommended for HBPM due to inaccuracies.20
It is very important that HBPM monitors have been independently validated for accuracy according to international protocols. Dedicated websites listing devices which have been validated are readily accessible (for example: www.dableducational.org/, www.bhsoc.org/blood_pressure_list.stm and www.hbprca.com.au/ validated-bp-monitors-in-australia). Currently, there are fewer validated wrist monitors than arm monitors.
BP values obtained using HBPM are similar to ABPM and substantially lower than office-based values.21 The technique has proven reproducibility - in a study using standard deviation of the differences as a measure, home BP had the most superior reproducibility, followed by ABPM and office/clinic measurements.22 This may be due to HBPM readings being taken under less variable circumstances.
Patients find HBPM more convenient and it is therefore preferred over ABPM.23,24 In the US, there has been a steady increase in HBPM use over the past few years.25 Forty seven per cent of patients in this poll reported that a physician had recommended the use of a home monitor. Of those who had received no recommendation from their physician, 46% had also bought monitors. An important pre-requisite for HBPM is patient education and training26 and HBPM should be instituted under medical supervision.
Potential Benefits of Out-of-office/Clinic Blood Pressure Measurements in Clinical Practice
White Coat Effect and White Coat Hypertension
The white coat effect (WCE) is defined as the difference between office BP and the BP measured at home or during the day by ABPM. This phenomenon has been attributed to anxiety, a hyperactive alerting response or a conditioned response.27
WCH is defined as high BP occurring only in a medical care setting. It is the major reason why office/clinic BP readings are higher than out-of-office/clinic BP readings28 and has been reported in as many as 20% of patients in whom hypertension has been diagnosed by office BP.18-20 Studies comparing office BP and ABPM have shown that WCH has a relatively benign prognosis.29,30 Obtaining a correct diagnosis is important to ensure that unwarranted treatment is avoided31 and patients are not put at a disadvantage regarding employment prospects or for insurance purposes.32
In the Treatment of Hypertension Based on Home or Office Blood Pressure (THOP) study, using ABPM as a benchmark, the sensitivity and specificity of HBPM in detecting WCH was found to be 68.4 and 88.6%, respectively.33 In the Ohasama study, HBPM had a superior predictive value over office BP in demonstrating that patients with WCH had a relatively low risk.34 HBPM is thus suitable for identifying patients suspected of WCH.
This condition is the opposite of WCH, where clinic BP levels are normal (<140/90) and home BP levels are high (>135/85).35 It is also known as reverse white-coat hypertension or isolated home or isolated ambulatory hypertension. The prevalence has been found to increase with age, being 5% in hypertensives below 70 years of age and rising to 16.6% in those above 80 years of age.36 Other studies have found prevalence of 42 and >50%, depending on study population.37,38 It is important that this condition is diagnosed as it confers the same CV risk as sustained hypertension.39,40
No significant difference in prevalence of masked hypertension was demonstrated whether ABPM or HBPM was used36 and HBPM can be used to identify such patients.
In this condition, blood pressure remains above the goal despite the use of three antihypertensive drugs of different classes at optimal doses. Up to 30% of patients with resistant hypertension have controlled BP when assessed by 24-hour ABPM41 or HBPM42 and it would be appropriate for either of these techniques to be used when assessing patients presenting with apparent resistant hypertension.
Day-to-night Blood Pressure Variability
As has been previously mentioned, BP follows a circadian pattern, with night-time BP values between 10 and 20% lower than daytime values.43,44 The prognostic significance of this difference between day- and night-time BP was demonstrated in the Ohasama study, where patients were divided into four categories based on the quantum of difference.
'Extreme dippers' were those whose decline in nocturnal blood pressure was 20% or more of daytime BP, 'dippers' were those whose decline was between 10 and 20%, 'non-dippers' had a BP decline of between 0 and 10% and 'inverted dippers' had no nocturnal BP decline. Over a mean follow-up period of about five years, the highest mortality risk was in inverted dippers followed by non-dippers, whereas there was no difference between dippers and extreme dippers.44
The importance of day-to-night variation in BP in relation to CV mortality has also been born out in other studies.45,46 ABPM would be the modality of choice to detect and classify nocturnal BP decline. HBPM would not be useful as BP readings would not be taken when asleep.
Early Morning Surge
In addition to the nocturnal lowering of BP, there is a 'morning surge' in BP that is associated with an increase in CV events,8,9 including acute myocardial infarction, ischaemic and haemorrhagic stroke and sudden cardiovascular death.10,11 Clinical trials have shown differences in early morning surge BP control between different agents within the same antihypertensive class47 as well as differing antihypertensive classes.48 Use of ABPM will allow identification of patients who experience a morning surge and allow selection of suitable antihypertensive regimes to overcome this.48
Although HBPM (as opposed to ABPM) would not be considered a suitable modality for providing information regarding nocturnal BP decline (dipper status) or early morning BP surge (both of which have prognostic significance), it has been shown that HBPM is superior to office/clinic BP readings in assessing overall risk of CV morbidity and mortality33,49,50 as well as predicting target end organ damage.17,51,52
Improvements in Blood Pressure Control
As was previously alluded to, despite there being ample evidence that BP reduction has significant CV benefits,3-5 BP control remains poor worldwide6 and hypertension has remained a major cause of death worldwide.1 Can HBPM be utilised to improve BP control?
A previous meta-analysis of 18 randomised clinical trials showed small improvements in BP readings (2.2/1.9mmHg) in patients with HBPM compared with usual care.53 These findings have been supported by a recently published meta-analysis by Agarwal of 37 randomised controlled trials showing similar reductions in BP (2.7/1.7) in patients in whom HBPM was utilised compared with those in whom HBPM was not utilised.54
One possible way in which HBPM may improve BP control is through improvement in medication adherence. A meta-analysis of 11 randomised controlled trials revealed that the majority of the trials reported a significant improvement in medicine adherence attributable to HBPM, the greatest effects being seen in trials employing other concurrent adherence-enhancing measures.54 Recent studies have shown that HBPM in conjunction with telemonitoring of readings by the physician improves treatment compliance.55,56 These findings are supported by Agarwal's meta-analysis, which also showed a significant reduction in BP readings with HBPM utilisation, the effect being more pronounced when concomitant telemonitoring was utilised compared with HBPM alone.53
Another possible reason why hypertensive patients do not achieve targets is therapeutic inertia, i.e. the failure to intensify therapy either by increasing the dosage of current medications or adding different agents in order to achieve BP goals.57,58 This phenomenon is not confined to management of hypertension alone but other chronic diseases such as diabetes and hyperlipidaemia.59 An innovative approach incorporating detailed patient education, patient self-titration of treatment according to BP readings obtained via self-monitoring with HBPM combined with data transmitted via tele-transmission to a core centre for monitoring demonstrated that this approach was feasible, well accepted by patients and physicians and safe.60 Moreover, both office and HBPM BP readings were significantly lower at the end of the study period. Agarwal's meta-analysis further supports these findings, showing that HBPM overcomes therapeutic inertia with resultant greater changes in antihypertensive medications.53
Experience from clinical studies show that HBPM is preferred to ABPM and well accepted by patients.5,24,60 However, initial enthusiasm might not always be matched by long term sustainability, with evidence that only 50% of patients preferring to continue with HBPM with telemonitoring after one year.61
There is evidence that HBPM is well-accepted by physicians in clinical studies.60 The percentage of patients reporting their physicians recommending HBPM increased by 12% over a five-year period.25 HBPM with or without telemonitoring will still require the resources and time of a physician in reviewing data and advising necessary changes to treatment.
Differences in payments for healthcare delivery systems need to be taken into consideration. Physicians practicing in a fee-for-service system (mainly private practice) may be reluctant to replace office/clinic visits self monitoring with or without telemonitoring unless these can be charged as a service. On the other hand, physicians under a high volume, capitation fee system and those working in busy, high-volume public hospitals may embrace these changes as they have the potential to reduce clinic loads.
The obvious cost involved is in the purchase of the monitors. In the US, HBPM is more commonly used by older and more affluent patients.38 In patients who do not own monitors, 14% gave expense as the reason. A very similar 14.3% of patients reported they could not afford to purchase monitors in a developed Asian country.6 Other costs involved include validation of machines, education and training of patients in correct usage of HBPM, data transmission if telemonitoring is practiced and cost of physicians reporting the data.
A joint scientific statement calling for the use and reimbursement of HBPM systems is recommending that purchase of HBPM equipment should be reimbursable in the US, as should the providers for services related to HBPM.63
ABPM and HBPM are both superior to office BP measurements in the overall management of hypertension. HBPM is the preferred choice of patients and, despite shortcomings, has the potential to significantly improve BP control. Used appropriately, out of office/clinic BP measurement will enhance the management of hypertensive patients.