Ambulatory blood pressure monitoring. (Review Article).

Abstract

Noninvasive, 24-hour ambulatory blood pressure monitoring (ABPM) has evolved over the past 25 years from a novel research tool of limited clinical use into an important and useful modality for stratifying cardiovascular risk and guiding therapeutic decisions. Early clinical uses of ABPM were mostly focused on identifying patients with white-coat hypertension; however, accumulated evidence now points to greater prognostic significance in determining risk for hypertensive end-organ damage compared with office blood pressure measurements. Ambulatory measurement of blood pressure using automated devices has also demonstrated benefit in other indications, such as treatment resistance and borderline hypertension, and is recommended by the Joint National Committee for the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure in a number of clinical scenarios. Medicare recently announced plans to begin reimbursement for ABPM, which will likely increase demand for ABPM services. Clinicians should become familiar with the role of this technology in the care of the hypertensive patient.

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Ambulatory blood pressure monitoring (ABPM) has emerged in the past 25 years as an important yet underused tool for the management of hypertension. Recent clinical outcome studies have prompted recommendations that ABPM should assume a more prominent role in establishing the diagnosis and monitoring for managing patients with elevated office blood pressure. (1-6) This review is intended to familiarize the clinician with applications of ABPM in the management of hypertension.

Ambulatory Blood Pressure Devices

Ambulatory blood pressure monitors measure blood pressure by means of auscultatory or oscillometric methods. Auscultatory monitors use a microphone on the bladder cuff to detect the Korotkoff sounds. The advantage of this technique is that arm movement does not interfere with the recording; however, these monitors are sensitive to background noise. Oscillometric monitors sense arterial pressure vibrations and calculate systolic and diastolic values using an algorithmic approach. They are unaffected by background noise, but arm movement can cause errant readings. Both types of monitors are validated by the British Hypertension Society and the Association for the Advancement of Medical Instrumentation. (7) Advantages of ABPM are shown in Table 1.

Patients wear the monitor for a 24-hour period, usually during a working day. The monitor is preprogrammed to record blood pressure, usually every 15 to 20 minutes during daytime hours and every 20 to 30 minutes during nighttime hours. Patients are instructed to keep an activity log throughout the testing period for evaluation of stress- and activity-related blood pressure changes.

The cuff is attached to a small central unit containing the pump and memory chip (Fig. 1). Deflation rates, frequency of measurement, and maximal-minimal inflation pressure are programmable. The blood pressure recordings are retrieved by interfacing the monitor with a desktop software program. A report is generated containing all blood pressure readings for the testing period, heart rate, mean arterial pressure, blood pressure load, and summary statistics for overall 24-hour, daytime, and nighttime periods. Figure 2 shows examples of ABPM graphs generated.

Ambulatory blood pressure monitoring is well tolerated. In a study of 672 patients, sleep disturbance was commonly reported followed by pressure from the cuff, awkwardness of the machine, difficulty in driving, local discomfort, and noise. (8) However, more than 90% of patients would agree to a second recording if it were necessary.

Clinical Applications of Ambulatory Blood Pressure Monitors

Published recommendations exist for the clinical use of ABPM. (1-6) The most recent Joint National Committee report outlines clinical situations where ABPM may be helpful, including suspected white-coat hypertension, drug resistance, hypotensive symptoms, episodic hypertension, and autonomic dysfunction. (3) These and other indications are shown in Table 2.

The utility of ABPM in clinical practices has been assessed. In a case series of 318 patients, the principal reasons for referral to ABPM were blood pressure lability, disparity between home and office readings, poor blood pressure control, suspected secondary cause of hypertension, and suspected white-coat hypertension. (9) Almost half of the patients receiving medication had changes in antihypertensive therapy in response to the data obtained from ABPM, and 9% were able to discontinue at least one medication. In the second report, 60 patients were referred by their physician to a clinical pharmacist 24-hour ABPM service. (10) Primary reasons for referal included evaluation of suspected isolated office hypertension, drug resistance, blood pressure control in diabetic patients, and suspected drug-induced orthostatic hypotension. Unnecessary antihypertensive therapy was avoided in 12 of 40 patients confirmed from ABPM to have white-coat hypertension.

White-Coat Hypertension, or "Alerting" Reaction

Suspected white-coat hypertension is a widely recognized indication for ABPM. Because decisions regarding antihypertensive therapy are often made on the basis of isolated office blood pressure readings, patients with white-coat hypertension may be incorrectly diagnosed with sustained hypertension. This phenomenon has been reported in 15 to 35% of patients currently labeled and treated as hypertensive. (11) Although controversy exists regarding whether white-coat hypertension should be treated, several studies have suggested it signals a "prehypertensive" state that eventually evolves into sustained hypertension. Thus, white-coat hypertension may precede sustained hypertension, much as impaired glucose tolerance can precede diabetes. Noninvasive ABPM is helpful for identifying patients with elevated office pressure and normal pressure outside the health care setting.

Treatment Resistance

Resistant hypertension is defined as the inability to reach target blood pressure lower than 140/90 mm Hg despite triple-drug regimens in appropriate dosages. (3) Ambulatory monitoring of blood pressure helps evaluate whether additional therapy is needed. It also helps determine whether a "white-coat" element is superimposed on existing hypertension. Brown et al. used ABPM to evaluate 611 patients with elevated office pressure, divided into three groups: those not taking antihypertensives (n = 277), those taking one to two antihypertensives (n = 216), and those taking three or more antihypertensives (n 1 18). (12) Twenty-eight percent of the resistant hypertensives had normal awake ambulatory blood pressure (ABP). They concluded that approximately one in four patients with apparent resistant hypertension actually have controlled blood pressure, and ABPM is an appropriate initial step before ordering further workup in these patients.

Borderline Hypertension

Patients with borderline elevations in blood pressure can benefit from ABPM. No consensus definition of borderline hypertension exists, but it generally refers to patients with some (but not all) elevated office and/or home blood pressure. Patients with "high-normal" blood pressure according to the Sixth Report of the Joint National Committee may also be included. Because of the disparate readings often obtained during infrequent office visits, clinicians are challenged with the decision of whether medications are necessary. A high proportion of patients with borderline hypertension may actually exhibit white-coat hypertension. (13) Measurements obtained be means of ABPM can provide additional information for risk stratification in patients with borderline elevations in blood pressure.

Therapeutic Intervention

Ambulatory monitoring of blood pressure is useful for assessing adequacy of antihypertensive therapy. Investigators in the Ambulatory Blood Pressure Monitoring and Treatment of Hypertension trial (14) investigated whether the use of ABPM compared with conventional measurement leads to less intensive treatment with drugs and fewer side effects while maintaining blood pressure control. In this trial, 419 patients were assessed by either office blood pressure or ABPM measurements performed at baseline and at 1, 2, 4, and 6 months. Antihypertensive therapy was adjusted in a stepwise fashion on the basis of these measurements. By the end of the 6-month study, significantly more patients in the ABPM group had discontinued all antihypertensive therapy (26.3 versus 7.3%; P < 0.001) and fewer progressed to multiple-drug treatment compared with the conventional measurement group (27.2 versus 42.7%; P < 0.001).

Prognostic Significance of Ambulatory Blood Pressure Monitors

Cross-sectional studies have examined the relationship between surrogate measures of end-organ damage, including left ventricular hypertrophy (LVH), diastolic function, funduscopic changes, microalbuminuria, progression of renal damage, atherosclerosis, stroke, and silent cerebrovascular disease, and their relationship to ABP. (15-19) The collective results of these studies show that ABPM measurements such as blood pressure load and dipping status correlate more closely to these surrogates of cerebrovascular and cardiovascular disease than office blood pressure.

Blood Pressure Load

Blood pressure load is an integrated measure of the 24-hour blood pressure. It is defined as the proportion of 24-hour blood pressure recordings that are increased relative to the thresholds for waking and sleep blood pressure (usually higher than 140/90 mm Hg during the awake period and higher than 120/80 mm Hg during the sleep hours). Blood pressure load is useful in diagnosing hypertension and is closely correlated with LVH. (20) In a study of 30 previously untreated hypertensive patients, the incidence of LVH approached 90% in patients with systolic blood pressure loads of more than 50%, and 70% of patients with diastolic blood pressure loads of more than 40% also had LVH. (21)

Dipping

The ability of ABPM to capture the circadian variation in blood pressure allows stratification into "dipper" or "nondipper" status. (18) A person whose blood pressure decreases by at least 10% during sleep is considered normal, or a dipper. (22,23) Nondippers have been found to have higher prevalence of LVH, albuminuria, peripheral arterial changes, and cerebral lacunae compared with dippers. (15,16,19) Nondippers have also been reported to suffer increased cardiovascular mortality rates compared with dippers (relative risk, 2.56; P = 0.02). (24) Evaluation of circadian blood pressure changes is also important because a blunted noctumal decline in blood pressure suggests a possible secondary cause of hypertension, such as sleep apnea. (25,26)

In a prospective registry of morbidity and mortality in subjects with essential hypertension whose off-therapy initial diagnostic workup included ABPM, cardiovascular morbidity significantly increased in ambulatory hypertension in dippers (relative risk, 3.70), with a further increase of morbidity in nondippers (relative risk, 6.26). In a subanalysis of the Systolic Hypertension in Europe study, the night-to-day ratio of systolic ABP was an independent predictor of cardiovascular events. After controlling for confounders, the hazard rate for total cardiovascular events was 1.41 (95% confidence interval [CI], 1.03-1.94; P = 0.03) for every 10% higher nightto-day ratio of systolic blood pressure. (27)

Clinical Outcome Studies

The prognostic value of ABPM has been validated in prospective, event-based studies of nearly 7,000 subjects. In 1983, Perloff et al (28) followed 1,076 patients who underwent a single 24-hour ABPM, for an average duration of 5 years. Patients were classified according to whether their daytime ABP was high or low relative to their clinic blood pressure at the time of ABPM. The results showed that patients with higher daytime ABP had significantly higher cardiovascular morbidity and mortality than those with lower daytime ABP.

In an analysis of 1,300 patients ages 20 and older, mortality risk during 5 years of follow-up was increased in the highest quintile of the distribution of average 24-hour systolic blood pressure, even after controlling for confounders. (29) No similar association was found for office blood pressure and mortality.

In elderly patients with systolic hypertension, 24-hour ABP has been shown to be a better predictor of cardiovascular risk compared with conventional blood pressure. (27) In the Syst-Eur study, 808 patients with isolated systolic hypertension underwent ABPM at the time of randomization. After adjusting for other prognostic factors such as age, gender, smoking, active treatment, previous events, and office blood pressure, the average nighttime systolic blood pressure independently predicted total, cardiac, and cerebrovascular events. The authors also found that for every 10-mm Hg increase in nighttime systolic blood pressure, the hazard rate was 1.20 (95% CI, 1.08-1.35) for cardiovascular events and 1.31 (95% CI, 1.06-1.62) for cerebrovascular events.

Barriers to Use

Although evidence supports the role of ABPM in the diagnosis and management of hypertension, the technology remains underused. These barriers primarily include lack of experience interpreting the results of ABPM, lack of familiarity with the technology, and economic issues.

Definition of "Normal" Ambulatory Blood Pressure

The incorporation of ABPM into routine clinical practice requires that criteria be adopted for defining normal and abnormal ABP. Several large population studies have attempted to define "normal" ABPM results. (30-35) All of the studies have found that both normotensive and hypertensive patients have blood pressure readings measured by ABPM that are lower than office blood pressure. The main reason for this finding is that ABPM measures blood pressure during sleep. Therefore, clinicians should not equate blood pressure obtained from ABPM with office blood pressure. Several methods have been used to define normal ABP, including averaging the 95th percentiles of ABP for normotensive subjects in large-scale studies, and performing regression equations linking clinic blood pressure with ABP. In truth, the different methods result in similar values. Table 3 shows the operational thresholds for ABPM currently agreed on by the British Hypertension Society and the American Society of Hypertension.

Reimbursement and Cost-effectiveness

The charge for ABPM in the United States usually ranges from $100 to $350. (36) Until recently, many third-party insurers, including Medicare, would not pay for the test because it was labeled as "investigative" technology. This lack of reimbursement probably explains the lower use of ABPM in the United States compared with other countries, where cost is not prohibitive. Reimbursement policies for ABPM are now changing. Medicare has announced plans to begin reimbursing for ABPM performed in patients with suspected white-coat hypertension. This policy change will likely lead to increased demand and use of ABPM services.

The issue of cost effectiveness is controversial. Moser argued that ABPM performed on 3 to 5 million hypertensive patients each year would add an additional $600 million to the cost of treatment. (37) However, several studies have demonstrated that ABPM used appropriately does not increase the cost of care. (38-40) In the Ambulatory Blood Pressure Monitoring and Treatment of Hypertension trial, (14,38) the cast of medication was less for people assessed with ABPM compared with office blood pressure measurement ($4,188 versus $3,390/100 patients/mo), and physician fees were less because patients returned less frequently for evaluation of blood pressure. Pierdomenico et a1 (40) performed ABPM on 255 consecutive untreated patients and evaluated the impact on cost of care of ABPM of two strategies: treating all patients according to casual blood pressure, or ABPM followed by drug treatment in sustained hypertensives only. Of the patients studied, 21% were determined to have white-coat hypertension. The authors e stimated that the strategy of monitoring all patients and treating only sustained hypertensives would result in cost savings of $110,000 over 6 years. It is important to note that many patients do not need ABPM. Given the potential impact of widespread clinical use of ABPM, it is imperative that clinicians use the technology judiciously. Figure 3 shows a strategy for the appropriate clinical use of ABPM.

Conclusion

The detection and treatment of hypertension is important for preventing long-term cerebrovascular and cardiovascular complications. Aggressive attempts to identify and treat hypertension must be carefully balanced with the risks of over-diagnosing and overtreating these patients. Noninvasive, ambulatory measurement of blood pressure has emerged in the past 25 years and evolved from an investigative research tool to a valuable mechanism for assisting the clinician in balancing these risks when making treatment decisions. Clinicians involved in the care of patients with hypertension should become familiar with the technology and use it appropriately.

[FIGURE 2 OMITTED]

Table 1

Advantages of ambulatory blood pressure monitoring


Provides multiple blood pressure measurements
Avoids potential for observer error and bias
Measurement occurs during usual activities of daily
 living and during sleep
Can evaluate circadian variation of blood pressure
Closer correlation to surrogate end points such as
 left ventricular hypertrophy than office blood pressure
Can assess white-coat hypertension and  white-coat, or
 "alerting" responses
More reproducible than clinic blood pressure

Table 2

Clinical situations in which ambulatory blood pressure monitoring may be
helpful


Borderline hypertension
Treatment resistance
Hypotensive symptoms associated with
 antihypertensive medications
Office or white-coat hypertension
Guide to antihypertensive drug treatment
Secondary hypertension
Episodic hypertension
Autonomic dysfunction

Table 3

Diagnostic thresholds for ambulatory  blood pressure monitoring (a)

Blood Pressure
Measure                              Normal            Borderline

Systolic average (mm Hg)
  Day                      [less than or equal to]135   135-140
  Night                    [less than or equal to]120   120-125
  24-hour                  [less than or equal to]130   130-135
Diastolic average (mm Hg)
  Day                      [less than or equal to]85     85-90
  Night                    [less than or equal to]70     70-75
  24-hour                  [less than or equal to]80     80-85
Systolic load (%)
  Day                                 <15                15-30
  Night                               <15                15-30
Diastolic load (%)
  Day                                 <15                15-30
  Night                               <15                15-30

Blood Pressure
Measure                    Abnormal

Systolic average (mm Hg)
  Day                        >140
  Night                      >125
  24-hour                    >135
Diastolic average (mm Hg)
  Day                         >90
  Night                       >75
  24-hour                     >85
Systolic load (%)
  Day                         >30
  Night                       >30
Diastolic load (%)
  Day                         >30
  Night                       >30

(a)Day is the awake period. Night is the sleep period. Because daytime
and nighttime pressures are estimated on a fixed time basis, they do not
necessarily correspond to awake and sleep. Threshold levels for estimate
of load are 140/90 mm Hg during waking hours and 120/80 mm Hg during
sleep.

Accepted April 22, 2002.

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RELATED ARTICLE: Key Points

* Ambulatory blood pressure monitoring (ABPM) has evolved from primarily a research tool into a clinically useful modality for stratifying cardiovascular risk and guiding therapeutic decisions.

* There is evidence that ABPM provides greater prognostic information than office blood pressure measurements for determining risk for hypertensive end-organ damage.

* Common scenarios in which ABPM can provide useful information include suspected white-coat hypertension, treatment resistance, borderline hypertension, and evaluation of antihypertensive efficacy.

* Several barriers exist to greater use of ABPM, including lack of familiarity with interpretation of ABPM results, and concern for overuse of the technology.

* Clinicians should use ABPM judiciously, in support of and not as a replacement for office and/or home blood pressure measurements.

From the Division of Clinical and Administrative Pharmacy, College of Pharmacy, and the Department of Family Medicine, College of Medicine, University of Iowa, Iowa City, IA.

Reprint requests to Michael E. Emst, PharmD, BCPS, Department of Family Medicine/0 1287 PFP, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242. Email: [e-mail]

Copyright [c] 2003 by The Southem Medical Association