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Update on Noninvasive Ambulatory
Blood Pressure Monitoring

Gary L. Schwartz, MD

Division of Hypertension, Mayo Clinic, Rochester, MN, USA

INTRODUCTION
     Epidemiological studies have determined that elevated blood pressure (BP) is associated with increased risk for cardiovascular morbidity and mortality. Prospective, placebo-controlled treatment trials have determined that treatment of hypertension lowers this risk. The results of both epidemiological studies and treatment trials have been based on measures of BP made in the clinic or office setting. Although these studies are excellent at predicting risk related to BP level or benefit from treatment in a population, they are much less able to predict risk or benefit for an individual patient. (Fig. 1)

   For example, the figure above illustrates the relationship between risk of cardiovascular morbidity and increasing BP in a population study. A point along the regression line represents the mean level of risk for the population as a whole at the given level of BP. The 95% confidence interval about that point is the range of risk (uncertainty) for any given individual in the population with that level of BP. There are many factors responsible for the uncertainty of risk for the individual patient. One important factor is that for many individuals, BP measured at a single point in time in the clinic or office setting may not be representative of their average level over the course of the day and night. In some, clinic BP may underestimate their average BP over time. These individuals would be at the higher end of the risk range for their BP. In others, clinic BP may overestimate their average BP over time. These individuals would be at the lower end of the risk range for their clinic BP. It is recognized that BP changes from minute-to-minute in response to changes in numerous factors associated with activities of daily life. These changes and their effect on average BP over time may not be accurately reflected in a single office or clinic BP measurement. Over the past 30 years, portable, programmable, noninvasive devices have been developed that are capable of obtaining 100-200 measures of BP over the course of 24-hours while patients engage in their usual activities of daily life (ambulatory BP monitoring). Initially, the use of these devices was largely restricted to research uses, however, accumulating evidence suggests that they may have an important role to play in the diagnosis and management of hypertension in clinical practice. Specifically, use of these devices may allow a more accurate estimate of risk from BP in the individual patient and narrow the confidence interval noted in the figure above. For example, multiple cross-sectional studies have shown that BP level determined by ambulatory monitoring is a better predictor of target organ injury than office or clinic BP. The optimal use of ambulatory BP monitoring (ABPM) in clinical practice remains controversial, however, increasing clinical experience suggests a role for ABPM in specific clinical situations. This report will review the current status of ABPM in clinical practice.

EQUIPMENT
   Several ABPM devices are available for use. The British Hypertension Society and the Association for the Advancement of Medical Instrumentation have protocols for validation of ABPM devices. One should consider using devices that have been subjected to validation by one or both of these protocols.

   ABPM devices are battery driven and can be programmed to obtain BP and heart rate readings at regular intervals over a 24-48 hour period. BP and pulse measurements are stored for later retrieval. Newer devices are lightweight (less than 2 Kg) and can be easily applied by a nurse or technician. BP is measured by detection of Karotkoff's sounds (auscultatory method) or by detection of oscillations transmitted from the brachial artery to the cuff (oscillometric method). The latter devices detect systolic and mean BP and use an algorithm to calculate diastolic BP.

   Accuracy of the auscultatory devices is affected by ambient noise. This problem can be lessened in some devices by use of EKG leads to gate the microphones to the R wave of the EKG. Microphones are often able to identify Koratkoff sounds that are inaudible to most humans. Thus, they may record higher systolic and lower diastolic BPs than would be obtained by clinic measurement. On the other hand, these devices are good at measuring BP in settings of unusually low BP. Vibrations and muscle tremors can affect accuracy of the oscillometric devices.

TECHNIQUE
   Attention to several details when attaching the device to the patient is critical to the accuracy of the BP readings obtained. The device can be programmed to obtain readings less frequently at night than during the day. This practice is associated with fewer disturbances of sleep and improved compliance. Patients need to be instructed to keep the arm motionless and free of noise or vibration during the measurements. Patients are advised to turn the device off when engaged in activities that could result in inaccurate readings (such as riding in an automobile). At the time of attachment and removal of the device simultaneous readings are made in the lying, sitting, and standing positions by the device and the technician using a mercury sphygmomanometer. An appropriate sized cuff for the arm should be selected. Agreement of the readings to within ± (plus or minus) 5 mm Hg suggests that the interval BP readings are accurate. ABPM devices are not accurate in patients who have irregular heart rates such as frequent ectopic beats or atrial fibrillation or large arms. While wearing the device, patients are instructed to keep a detailed diary that includes information about physical activities, mealtimes, sleep, and medication use. Validation of the BP readings from the ABPM is analyzed by a computer using one of several available algorithms. In practice, a nurse or technician can be easily trained in the proper use of the device.

   Ambulatory devices are generally well tolerated. Some patients experience arm discomfort from repeated cuff inflation. Occasionally patients develop swelling and petechiae distal to the cuff. Rarely, patients may be allergic to the cuff materials.

MEASURES AND NORMAL VALUES
   ABPM provides multiple measures of BP level and variability. Some of these are shown in the Table 1:

   For clinical purposes, average levels are used most often. A variety of methods have been used to define normal BP averages for ABPM. These have included using the 95th percentile values for a normal population, identification of the average awake BP that corresponds to a clinic BP of 140/90 mm Hg using regression analyses or using evidence of target organ damage related to ambulatory averages. Another method of defining normal ABPM has been by using the concept of "BP load". This is the percentage of ambulatory readings above a threshold value during the awake or asleep period. Based on these studies, general recommendations regarding the upper limit of normal for ABPM have been made and are shown below (Table 2):

NORMAL PROFILES
   In normal individuals BP profiles over a 24-hour period are characterized by a circadian pattern. BP is higher during daytime hours and falls to a nadir during the nighttime. BP begins to rise in the early morning hours with a peak to daytime levels soon after rising. The activity level of persons is an important determinant of BP level. BP tends to be highest when individuals are in their work environment, lower at home, and lowest during supine rest or sleep. Change in position from supine to upright is associated with an increase in BP level.

CLINICAL USES OF ABPM

Clinical Situations Where ABPM May be Useful

Suspected "White-Coat" Hypertension
Resistant Hypertension
Disproportionate Target Organ Damage
Borderline Hypertension
Nocturnal Hypertension
Hypotensive Symptoms with Therapy
Suspected Autonomic Dysfunction
Episodic Hypertension
Pregnancy
Guide to Drug Treatment

WHITE-COAT HYPERTENSION
   Identification of white-coat hypertension is the most common clinical indication for ABPM. White-coat hypertension is generally defined as elevated BP only in the clinic setting. Other terms used to describe this syndrome are office hypertension or isolated-clinic hypertension. The exact definition depends on what level of BP is considered to be normal by ABPM and this has varied in publications referring to this syndrome. Cutoff points for awake average ambulatory BP have ranged from 131 to 140 mm Hg systolic and from 80 to 90 mm Hg diastolic with the clinic BP cutoff 139/89 mm Hg. The prevalence estimates range from 12% to 53% of the hypertensive population depending on the cutoff used for ABPM. It is especially common in the elderly (overestimation of isolated systolic hypertension) and pregnant women.

   Studies show that patients with white-coat hypertension are at considerably less risk than patients with sustained hypertension, although risk may be higher in patients with white-coat HTN compared to individuals with normal BP. The best study that addressed the issue of risk for adverse outcomes in white-coat versus sustained hypertension is the study of Verdecchia. This prospective cohort study enrolled 1,187 patients with essential hypertension defined by office BP > (greater than) 140/90 mm Hg. All patients underwent ABPM and they were classified as having white-coat hypertension if their awake average ambulatory BP was < (less than) 131/86 mm Hg (women) or l< (less than) 136/87 mm Hg (men). A control group of 205 normotensives was also included. Follow-up was over a 5-year period. The incidence of adverse cardiovascular outcomes adjusted for traditional risk factors was similar in white-coat hypertensive group to that seen in the normotensive control group and significantly less than that seen in the group with sustained hypertension.

   There are no specific characteristics that assist in diagnosis. It is suspected in patients who show little response of office BP to treatment or who develop symptoms suggesting hypotension with treatment but who have persistent hypertension by office measures.

   Patients with white-coat hypertension require follow-up. White-coat hypertension may be a precursor to sustained hypertension in some patients. Julius observed that the metabolic profile of patients with white-coat hypertension is more similar to that seen in hypertensives than normotensives, so white-coat hypertensives may be a group that is at higher risk for cardiovascular morbidity.
Comparison of Metabolic Profiles (Table 3):

RESISTANT HYPERTENSION
   Patients can be classified as having resistant HTN if BP remains > (greater than) 150/90 mm Hg despite treatment with 3 or more drugs. Some of these patients have a "white-coat" effect and out-of-office BP is actually normal. In others, the duration of effect of therapy may be inadequate. ABPM is a good method to determine the duration of effect of antihypertensive drug therapy.

DISPROPORTIONATE TARGET ORGAN DAMAGE
   Occasionally, target organ involvement seems out-of-proportion to office BP levels. It is recognized that, as exists "white-coat" hypertension, also exists "white-coat" normo-tension. The prevalence of this phenomenon is less well known but ABPM has clearly identified patients in whom out-of-office BP is clearly much higher than office BP. Such patients are under-treated and remain at higher risk for adverse cardiovascular outcomes. This phenomenon may be more common in people who smoke cigarettes. In some patients, elevated BP at night may be observed. In others, normal ABPM suggests that BP may not be responsible for the target organ damage and other factors need to be considered.

BORDERLINE HYPERTENSION
   Some patients with borderline office measures may benefit from ABPM. Young patients in particular may benefit because it may lessen the risk of inappropriate drug treatment for a lifetime and the consequences of being labeled as having hypertension.

NOCTURNAL HYPERTENSION
   ABPM is the only non-invasive technique that allows measurement of BP during sleep. Elevated BP during the nighttime is independently associated with increased risk of target organ damage above the risk associated with daytime BP levels. In addition, studies have shown that in normal persons, average BP is approximately 10% lower during the nighttime compared to the daytime. Individuals whose BP drops normally at night are referred to as "dippers". It has been observed that BP fails to decline normally compared to daytime values in some individuals who are referred to as "non-dippers". Conditions associated with nocturnal hypertension or loss of the normal nocturnal fall in BP are listed below (Table 4):

Studies demonstrating benefit of treating nocturnal hypertension are not currently available.

HYPOTENSIVE SYMPTOMS WITH THERAPY
   Transient hypotension related to drug therapy may be difficult to identify simply by office measures as detecting it is based on measuring BP at the appropriate time following drug ingestion. In addition, patients with autonomic dysfunction have unique BP profiles identified by ABPM (below). Carotid sinus syncope and pacemaker syndromes can often be assessed with the combination of ABPM and Holter monitoring.

SUSPECTED AUTONOMIC DYSFUNCTION
   ABPM can be used to both diagnose autonomic dysfunction and determine the severity of BP disturbances associated with its' presence. The results of ABPM can be used to guide treatment and to aid counseling of these difficult patients. BP profiles characteristic of autonomic dysfunction are: (1) labile hypotensive episodes associated with postural change, prolonged standing or activity in the upright position or following the ingestion of food, (2) supine hypertension and loss of the usual nocturnal fall in BP, (3) little or no variation in heart rate associated with declines in BP. Post-prandial hypotension is common in elderly hypertensive patients and may occur as an isolated manifestation of autonomic dysfunction. It can be easily diagnosed with ABPM.

EPISODIC HYPERTENSION
   Patients may present with symptoms that suggest paroxysmal disturbances of BP and heart rate that can be difficult to assess by office BP measures. Some patients may have pheochromocytoma and others may have anxiety or panic syndrome. Correlation of symptoms recorded in the diary with the BP and heart rate may allow clarification of the patients symptoms.

PREGNANCY
   The major role for ABPM during pregnancy is to identify white-coat hypertension. Recent studies suggest that it may occur in up to 30% of pregnant women. Recognition is important because it would avoid unnecessary drug treatment or hospitalization in these patients.

GUIDE TO DRUG TREATMENT
   This is the subject of ongoing research. At present, it is not recommended that ABPM be part of the routine management of the hypertensive patient. However, studies have shown that when ABPM guides treatment as compared to conventional office measures, significantly less antihypertensive drug therapy is prescribed. It is possible that with the use of ABPM, fewer office visits may be required to monitor therapy. These consequences of ABPM may lead to more appropriate treatment and cost savings. At present, information from prospective studies relating risk of cardiovascular morbidity and mortality related to BP levels from ABPM or benefit from BP treatment based on ABPM is lacking. Ongoing trials will provide much needed information in this regard which will provide the basis for a probable expanded role of ABPM in clinical practice.

REFERENCES

1. The National High BP Education Program Coordinating Committee. National High BP Education Program Working Group Report on Ambulatory BP Monitoring. Arch Intern Med. 1990;150:2270-2280.

2. The Scientific Committee. Consensus document on non-invasive ambulatory BP monitoring. Journal of Hypertens. 1990;8(suppl 6):135-140.

3. Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP. The 6th Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High BP (JNC VI). Arch Intern Med. 1997;157:2413-2446.

4. O'Brien E, Coats A, Owens P et al. Use and, interpretation of ambulatory blood pressure monitoring: recommendations of the British Hypertension Society. BMJ 2000;320:1128.

5. Verdecchia P, Porcellati C, Schillaci G et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. 1994 Hypertension;24(6):793-801.

6. Pickering T. Recommendations for the use of home (self) and ambulatory blood pressure monitoring (American Society of Hypertension Ad Hoc Panel). 1995 AJH;9:1-11.

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