use of ambulatory blood pressure monitoring to guide hypertensive therapy

Current Treatment Options in Cardiovascular MedicineDOI 10.1007/s11936-013-0255-4

Prevention (L Sperling, Section Editor)

Use of Ambulatory BloodPressure Monitoring to GuideHypertensive TherapyAmita Singh, MD1

Eugenia Gianos, MD1

Arthur Schwartzbard, MD1,2

Henry Black, MD1

Howard Weintraub, MD1,*

Address*,1Division of Cardiology, Center for the Prevention and Treatment of CardiovascularDiseases, NYU Langone Medical Center, New York, NY, USAEmail: [email protected] of Cardiology, Veteran’s Affairs Harbor Health Care System, New York,NY, USA

* Springer Science+Business Media New York 2013

Keywords Ambulatory blood pressure monitoring I (ABPM) I Hypertensive therapy I Cardiovascular events ICV events I White coat I Masked hypertension I Pathophysiology

Opinion statement

With the advent of noninvasive 24-hour ambulatory blood pressure monitoring (ABPM), cli-nicians have access to a wealth of individualized data for the hypertensive patient. This hasled to a greater understanding of the pathophysiology of hypertension and its complica-tions. This tool has provided more precise diagnostic criteria for hypertension and helpeddiscover those with white coat and masked hypertension. Patterns noted on ABPM and cor-related with outcomes have allowed for more accurate identification of patients at high riskof cardiovascular (CV) events, and have offered an additional prognostic tool. In addition,ABPM allows for the assessment of the efficacy and adequacy of blood pressure treatment. Inthe current paper, we will describe the essential components of ABPM, review the evidencedetailing the prognostic information that can be derived from its use, highlight clinical sce-narios wherein ABPM can offer invaluable diagnostic information, and describe applicationsof ABPM that evaluate the efficacy of treatment of the hypertensive patient.

IntroductionKnowing that blood pressure (BP) undergoes significantand spontaneous variations over a 24-hour period inboth normotensive and hypertensive individuals, clinic

BPmeasurements are amere glimpseof trueBP. The clin-ic BPmeasurement is static and subject to variability dueto the clinic environment, technique of the measurer,

and other factors, and only provides a tiny assessmentof the individual’s BP since there is a BP with everyheart beat [1]. Originally, 24-hour BP monitoring wasobtained intra-arterially, and used only for research pur-poses. With the introduction of portable, non-invasivemonitors that minimally interfere with the daily activi-ties of a patient, the application of ambulatory blood

pressuremonitoring (ABPM), has grown [2]. This greateruse ofABPMhas given rise to an improveddelineationofcircadian patterns and variability, which allowed for thecreation of new classifications of hypertensive states, theprovision of novelmarkers for prognostic use, and amo-re thorough evaluation of antihypertensive therapy bothin large trials as well as clinical practice.

Ambulatory blood pressure monitoring: techniquesand validation

ABPM devices that are currently in use are noninvasive and portable, typicallycomprised of an arm cuff and automatic monitor that measures BP readingsusing oscillometric technique every 15 to 30 min while worn during a 24-hour period, although some groups advocate longer durations of monitoringof up to 48 hours [3]. Patients are advised to keep an activity log to correlatewith device readings, and so a continuous 24-hour BP profile can beobtained during daytime activity as well as sleep. Although the obvious ad-vantage of ABPM over home BP monitoring or clinic BP is attainment ofmultiple readings as well as nocturnal BP, there are numerous devices andvaried protocols in use to ensure accuracy of monitors. While the EuropeanSociety of Hypertension and the American Society of Hypertension haveboth highlighted the importance of validation of ABPM instruments, theproposed protocols in use are not consistent [4, 5]. However, implementinga unified validation protocol to ensure ABPM accuracy is challenging, asevidenced by a recent meta analysis that found that 50 % of the eight vali-dation studies in the general population demonstrated differences of up to5 mmHg between devices and referent measurement, meaning device accu-racy was often inconsistent [6]. Furthermore, in specific populations of in-terest such as the elderly, pregnant women and patients with chronic kidneydisease (CKD), only 40 % of devices passed validation protocols [6]. Furtherstandardization of ABPM devices is needed, particularly as its use widens inclinical practice.

Components of ambulatory blood pressure: mean values,circadian rhythms and variability

Proponents of ABPM point to the its superior ability to define a “true” BP,based upon the mean of several 24-hour measurements, as well as the BPduring awake and sleep periods, as compared to clinic BP [7]. Additionally,cross-sectional and randomized studies comparing clinic BP with those fromABPM have demonstrated that correlations between the two can vary widely,with r values ranging from 0.4 to 0.7 [8, 9]. This discrepancy in correlationmay be more prevalent at the extremes of BP, as demonstrated by findingsfrom the Syst-Eur (Systolic Hypertension in Europe) trial, in which clinic BP


measurements in the placebo arm exceeded ABPM values by as much as20 mmHg, resulting in overestimation of risk for certain patients [10, 11].Therefore, if the majority of epidemiologic studies that first described acontinuously graded association between BP and risk for cardiovascular (CV)morbidity and mortality with the use of clinic BP, then a more refined esti-mate of 24-hour BP patterns with ABPM may result in a superior ability todefine at-risk patients who are at increased risk of CV events [12–16]. Themajor components of an individual ABPM report typically include: 24-hourmean BP (systolic and diastolic), daytime BP, nighttime or nocturnal BP,“dipping” pattern, morning or surge, and BP variability. The definitions andprognostic significance of most of these components is described in Table 1,and is discussed further below.

The circadian pattern of BP has been well described, and is comprisedof a physiologic decrease during sleep, due to a relative decrease insympathetic activity during sleep and concomitant increase in vagal tone.This nocturnal drop is then followed by an early morning rise (“surge”)during the transition from sleep to wakefulness, and finally gives way toa sustained increase in BP during normal daily activities, which may varyfurther based upon physical and psychological stressors [17] (See Fig. 1).The reproducibility of these diurnal patterns has been studied in shift-workers, who demonstrate rapid reversals in cycles during night-shiftwork within a matter of days [18].

Perhaps the two most clinically relevant features of the diurnal pattern ofBP that are captured by ABPM are the nighttime fall in BP, termed “dipping,”and the morning surge, with derangements in these two shown to be asso-ciated with target organ damage (TOD) as well as CV outcomes in cross-sectional and prospective cohort studies [19–21]. Blood pressure variabilityhas been defined as the standard deviation of daytime and nighttime BPfrom the 24-hour mean values, and has been inconsistently associated withTOD and CV risk [22–24].

The prognostic utility of ambulatory blood pressure

Numerous studies have shown that ABP is a superior prognostic indi-cator of CV risk compared to clinic BP, particularly in predicting TOD,most often represented by left ventricular mass index (LVMI), left ven-tricular hypertrophy (LVH), or microalbuminuria. One study using intra-arterial 24-hour BP monitoring examined the correlation between clinicBP, 24-hour BP and a composite score representing TOD (presence ofLVH, microalbuminuria, ophthalmologic disease, cerebrovascular and CVdisease) [22]. Results demonstrated that for patients with similar clinicBP values, those with higher 24-hour ABPM values consistently demon-strated a greater burden of TOD. Data from SAMPLE (Study onAmbulatory Monitoring of Pressure and Lisinopril Evaluation) foundthat in hypertensive patients with pre-existing LVH, 24-hour mean ABPMmeasurements correlated with baseline LVMI more closely than did clinicBP, and also correlated with regression in LVMI after treatment [25].When 24-hour mean systolic BP was compared with all traditional CVrisk factors in ELSA (European Lacidipine Study on Atherosclerosis),

Use of Ambulatory Blood Pressure Monitoring Singh et al.

findings demonstrated that 24-hour mean systolic BP correlated moreclosely with carotid intima-medial thickness and plaque burden than didlipids, with age as the only risk factor that was more predictive [26].

Importantly, ABPM has been shown to more accurately predict clinicaloutcomes. In the Office versus Ambulatory Blood Pressure study, 1,963treated hypertensive patients were followed for incident CV events over aperiod of 5 years, with results demonstrating an independent association ofelevated 24-hour mean systolic BP and diastolic BP with incident CV events

Table 1. Components of 24-hour ambulatory blood pressure monitoring, prognosis and use in clinical diagnosis

Measurement Consensus Definition Prognostic Value Associated Clinical Factors24-hour MeanBlood Pressure

NormalG130/80 mmHg [76]Elevated≥135/85 mmHg

Strong predictor ofCV events and stroke[29, 77]

Daytime BloodPressure


Modest predictor ofCV events and stroke[29, 77]

Nighttime BloodPressure


Likely strongest predictorof CV events and stroke[29, 77]

“Dipping” ProfileNormal ~10–15 % nocturnal BP dropNon-Dipper G 10 % nocturnal BP drop Associated with greater

TOD, predictive of CHF[34, 78, 79]

Age, DM, metabolicsyndrome, CKD, AfricanAmerican race

Reverse Dipper Rise in nocturnal BP Worse renal/CVDprognosis in CKDpopulation [80]

Obstructive sleep apnea,autonomic insufficiency

Extreme Dipper 9 20 % nocturnal BP drop Worst CV and strokeprognosis [81]

Seen with excess morningsurge, orthostatichypotension, glaucoma

Morning Surge Definitions vary: 9 25 mmHg,or by highest quartile [82]

Greater risk of CVA,cardiac events, andcardiac mortality [82]

Increased frequency ofsilent cerebral infarctson MRI [37]

Clinical Diagnosis Definition Prognostic Value Associated Clinical FactorsWhite CoatHypertension

Elevated Clinic BP Elevated long-term riskof stroke [53]

Increased prevalence withadvanced ageNormal 24-hour

mean ABPMasked Hypertension Normal Clinic BP Predicts CV mortality [83] Young patients, increased

physical activity, alcohol/tobacco use

Elevated 24-hourmean ABP

CV risk approaches thatof patients with SH [59]

Resistant HypertensionTrue Resistant“Pseudoresistant”

Elevated Clinic and24-hour mean ABP

Highest CV risk [59]

Elevated Clinic BPand normal 24-hourmean ABP

Lower CV risk comparedto SH [59]

Poor med adherence,white coat effect

BP = blood pressure; CHF = congestive heart failure; CKD = chronic kidney disease; CV = cardiovascular; DM = diabetes mellitus;MRI = magneticresonance spectroscopy; SH = sustained hypertension; TOD = target organ damage


even after adjustment for age, sex, smoking, cholesterol, and office BP values[27]. An ABPM substudy from the Syst-Eur trial performed in placebo-armpatients showed that ambulatory BP was a more accurate predictor of riskthan conventionally measured office BP, with each 10 mmHg rise in 24-hourmean ABP associated with a hazard ratio of 1.34 (95 % CI 1.03–1.75) for CVmortality [10].

With a large amount of data available from just one ABPM sampling,the question remains which of the many measurements offers thegreatest prognostic significance; 24-hour mean ABPM data, daytime andnighttime BP, dipping status, magnitude of the morning surge and BPvariability have all been described as prognostic markers of CV risk. Onelarge, multi-ethnic prospective cohort study of 7,458 participants un-dergoing 24-hour ABPM with a median follow-up of nearly 10 yearsfound that both daytime and nighttime BP were predictive of all CVevents, including stroke, but only nighttime BP consistently predictedboth total and CV mortality [28]. Similar results were illustrated by a2008 meta-analysis, which found that both daytime and nighttime sys-tolic BP independently predicted all-cause and CV mortality and stroke,but nighttime systolic BP was a better general predictor of cardiovascularevents, stroke and all-cause mortality [29].

Although there is some evidence that dipping status has limited reproduc-ibility on serial ABPM testing, it is widely acknowledged that non-dippers(nighttime BP reduction of G10 %), who may comprise up to 30 % of thehypertensive population, have a worse prognosis with greater frequency ofLVH and silent cerebral infarcts on magnetic resonance imaging. This worseprognosis noted for non-dippers is likely independent of the overall 24-hourmean BP [30–33]. In addition, there is a subgroup of patients deemed“reverse dippers,” who demonstrate actual increases in nocturnal BP that areassociated with greater risk of stroke, but may perhaps be of less prognosticsignificance in the elderly and in diabetic patients when compared to other

Fig. 1. Sample 24-hour ambulatory blood pressure monitoring recording.


factors, such as nocturnal mean BP and presence of orthostatic hypotension[34–36].

Interest in the morning BP surge is tied to the observation that incidenceof CV events is highest in the pre-awakening hours, likely the result of themyriad of physiologic changes associated with increased sympathetic activity,platelet reactivity and circulating catecholamines. However, definitions ofwhat constitutes an “excessive” morning surge have varied, and prospectivestudies have inconsistently demonstrated an association between an abnor-mal morning surge and the risk of stroke, CV events and all-cause mortality[19, 37, 38]. A recent prospective study examining the relationship betweennocturnal dipping and morning surge suggests that a blunted morning surge(the lowest quartile of early morning BP surge) was also independently as-sociated with future CV events in over 3,000 patients followed for over8 years [39••].

Two more recent components of ABPM that have gained interest as prog-nostic markers are BP variability and ambulatory arterial stiffness index(AASI). Blood pressure variability attempts to quantify the frequency withwhich BP measurements deviate above or below the median. It has beenhypothesized that the degree of these fluctuations might be a key mediator inthe process that leads to TOD [40]. BP can be thought of in the short-term, asmight be recorded on a 24-hour ABPM, or in the long-term, as with visit-to-visit BP variability. Though BP variability has been shown to increase with arising mean BP, and has an independent association with TOD, by its natureit is difficult to reproduce BP variability on serial ABPM exams. Furthermore,definitions of variability can refer to an entire 24-hours, or only daytimeversus nighttime values [41]. At present, there is no prospective data tosuggest that treatment that reduces BP variability improves outcomes in alarge clinical trial setting. A recent retrospective analysis from ELSA, whichfollowed patients for progression of carotid intimal medial thickening andoccurrence of clinical events, demonstrated that only on-treatment mean BP,whether based off of clinic or 24-hour ABPM, was associated with clinicalevents, and that 24-hour and visit-to-visit variability in BPs did not appearpredictive of CV outcomes in a moderately hypertensive population [42].Therefore, although evidence is limited, the role of BP variability may bemore similar to a marker of risk, rather than an overt risk factor, for adverseCV outcomes.

Arterial stiffness invariably occurs with aging, but loss of arterial compli-ance can also be seen in insulin resistant states, obesity, CKD and smoking[43]. Typically, carotid-femoral pulse wave velocity, which simultaneouslymeasures pulse pressures at the carotid and femoral artery, is accepted as aproxy of arterial stiffness and has been shown to predict CV mortality, cor-onary events and stroke in a longitudinal study of approximately 1,000 hy-pertensive patients followed for 5.7 years [44]. An index of arterial stiffnessderived from ABPM data, deemed the ambulatory arterial stiffness index(AASI), reflects the relationship between systolic and diastolic BP, and isdefined as 1 minus the regression slope of diastolic BP over systolic BP basedon a 24-hour ABPM recording [45]. In an Irish study of over 11,000 patientswith baseline ABPM recordings, AASI was calculated and found to bestrongly associated with incident stroke (HR 1.21, p value=0.02) after ad-justment for age, sex, diabetes mellitus (DM), smoking status and prior CV


disease [46]. A recent meta-analysis of 51 cross-sectional and longitudinalstudies of AASI in 14,320 patients reported a significant association withincreases in AASI and risk of stroke (HR 1.26, 95 % CI 1.08–1.45) as well[47]. Despite a growing number of studies validating AASI as a potential riskfactor, there are no studies to date that validate the use AASI as a therapeutictarget to alter CV or mortality outcomes.

The evolving discourse around these individual components of ABPM un-derscore that future, large scale prospective studies may help further charac-terize the individual prognostic accuracy of dipping status, the morningsurge, BP variability and AASI. Based upon the available evidence, nocturnalBP appears to have the greatest importance in assessing risk and prognosiswhen compared to other BP values.

Employing ABP for diagnosis

In addition to its prognostic capability, ABPM has an important role as adiagnostic tool. At this time, the most recent recommendations from the2005 American Heart Association Guidelines on Blood PressureMeasurement note that pursuing ABPM is appropriate in suspected cases ofepisodic hypotension, white coat hypertension (WCH), nocturnal hyper-tension and in evaluating management of resistant hypertension [48].Identifying these hypertensive states is essential, as it can alter managementsignificantly and either reduce, or intensify, antihypertensive treatment in theappropriate patient.

White coat hypertension is a condition in which 24-hour mean BP isnormal, but clinic BP is elevated, and is thought to be present in 18–30 % of patients thought to be hypertensive by screening BP measure-ments [49]. Multiple studies have established that prevalence increaseswith age, and possibly affects women more than men [50••, 51, 52]. Theprognosis of WCH, though once thought to be benign, is likely a morecomplex entity. An observational study that pooled 5,955 hypertensiveand normotensive subjects from four cohort studies, found an overallprevalence of 9 % (WCH) after initial ABPM recording [53]. Over amedian of 5.4 years of follow-up, there were a total of 213 new cases ofstroke noted. Results demonstrated that early in follow-up, patients withambulatory hypertension (elevated clinic BP, elevated ABPM) were atgreater risk for stroke (HR 2.01, 95 % CI 1.31–3.08), with WCH-onlypatients (elevated clinic BP, normal ABPM) showing a nonsignificant andmodestly elevated risk (HR 1.16, 95 % CI 0.61–2.16) of stroke.Interestingly, at 6 years, the incidence of stroke increased in the WCHgroup, and by 9 years, the rates of stroke matched that of hypertensivepatients. This finding proposed a need for long-term monitoring in pa-tients with WCH, with recent substudies even arguing that there may bebenefit in treatment of elderly patients with WCH to reduce risk ofstroke [50••].

Masked Hypertension (MH) is a diagnosis made with the aid of eitherhome monitoring or ABPM, and is defined by a normal clinic BP but ele-vated mean 24-hour ABPM. With an estimated prevalence of 10 %, MH isassociated with obesity, the metabolic syndrome and DM, CKD, younger


patients and patients who participate in rigorous physical activity [54–57]. Inaddition to an association with greater burden of TOD, MH also carries aCV risk comparable to that seen in resistant hypertension (hazard ratioof 2.28, p valueG0.05 for masked hypertensives versus hazard ratio of2.94, p valueG0.05 for resistant hypertensives) [58, 59]. Identification ofthese patients is paramount, particularly if they remained untreated orundertreated due to the provider andpatient being falsely reassured due to clinicBPs that are seemingly normal or at goal, Individuals with MH remain at asignificant risk of hypertension-related CV sequelae.

Ambulatory blood pressure in clinical research trials

Large clinical trials have employed ABPM, usually in prespecified substudies,to provide auxiliary data on the nature of BP differences and its respectiveeffects on clinical outcomes. Two such examples from recent large-scaleclinical trials are the ABPM substudies of ACCOMPLISH (AvoidingCardiovascular Events through Combination Therapy in Patients Living withSystolic Hypertension) and HOPE (Heart Outcomes Prevention Evaluation).In ACCOMPLISH, patients receiving combination benazepril andamlodipine experienced a 20 % reduction in CV events compared to patientsreceiving benazepril with the comparator drug hydrochlorothiazide, despitesimilar between-group reductions in BP [60]. A substudy of 573 patientsundergoing ABPM at baseline and year 2 showed no major differences be-tween mean 24-hour, daytime or nighttime BP. These findings demonstratethat the benefit of the benazepril-amlodipine combination compared tobenazepril-hydrochlorothiazide was not due to undetected differences in BP[61]. A very small ABPM substudy from HOPE, which showed significantreductions in the composite endpoint of myocardial infarction, stroke anddeath with use of ramipril in high risk patients, demonstrated that whileclinic BP was not significantly different between the treatment and controlarm, ABPM detected significant reductions in 24 h mean BP (10/4 mmHg,p=0.03) and nighttime BP (17/8 mmHg) which were not reported in theoriginal study [62, 63].

Occasionally, ABPM substudies may elucidate results that have the abilityto question, and perhaps even alter clinical practice. One such example ofthat is a recently published ABPM substudy from Hy-Vet (Hypertension inthe Very Elderly Trial), a seminal study of BP treatment in patients above theage of 80 years with baseline blood systolic BPs 160-199 mmHg. The ABPMsubstudy found that at baseline, up to 50 % of substudy participants hadevidence of WCH, with a mean clinic BP 32/10 mmHg higher than 24-hourmean ABP [50••]. Given that patients in the treatment arm of the originalHY-VET study experienced a significant 30 % reduction in the primary end-point of stroke, the authors suggest that there may indeed be benefit intreating elderly patients with WCH, a concept that is markedly different fromcurrent clinical practice [64].

Though ABPM provides additional information to original outcomes datain clinical trials, issues related to cost have led to its use largely within thecontext of small substudies. Although informative, there are associated lim-itations due to small sample sizes and less frequent follow-up. However, it


provides greater discernment of the efficacy and duration of hypertensivetherapy, and also is essentially unaffected by placebo treatment, making it anattractive tool for future research investigations.

Ambulatory blood pressure in clinical practice

In addition to diagnostic information, ABPM can offer useful insights intothe efficacy of different antihypertensive agents (smoothness index), and theappropriate timing of administration of medications (chronotherapy). Theideal antihypertensive medication should provide continuous coverage overa 24-hour period, to provide a consistent BP lowering effect. Early on, ABPMwas utilized to compare the BP lowering effects between drugs, and oftenhighlighted periods during the dosing interval where one drug remainedmore consistently effective than the other [65, 66]. A quantification of thisduration of coverage was termed the “trough to peak ratio,” but its utility waslimited, as it was often calculated over a duration less than 24 hours, couldbe altered by the placebo response as well as white coat effect, and did notcorrelate closely with measures of changes in LVMI in patients on treatment[67, 68]. An alternative index more commonly accepted for clinical use is the“smoothness index” (SI), which assesses the overall 24-hour BP reductionand the distribution of control of BP, with a value closer to or exceeding 1representing a consistent effect [68].

The SI has been studied both within antihypertensive classes and betweenthem. A meta-analysis of 11 clinical trials that randomized mild to moderatehypertensive (defined as grade 1 or 2 hypertension by ESC guidelines) pa-tients with baseline ABPM to treatment with telmisartan (40/80 mg),losartan (50 mg), valsartan (80/160 mg) ramipril (10 mg), amlodipine(10 mg) or hydrochlorothiazide (12.5/25 mg) compared to the SI of thesecommonly used agents and found that of the renin-angiotensin systemblockers, telmisartan had the highest SI, which was comparable to that ofamlodipine [69]. Furthermore, combination therapies appeared to havegreater SI when compared to monotherapy, regardless of the drug used.Though it is not widely used for clinical practice, SI allows for comparisonsof antihypertensive effect across drug classes and may help guide choice ofinitial treatment for hypertension.

Chronotherapy has gained appropriate interest for determining rationaltreatment of hypertension, particularly as many patients may have evidenceof nocturnal BP variations that warrant tailored treatment. MAPEC(Ambulatory Blood Pressure Monitoring for Prediction of CardiovascularEvents) tested the administration of at least one BP medication at nighttimecompared with conventional morning dosing in 2,156 randomized hyper-tensive patients [70]. Patients were followed for a mean of 5.6 years andunderwent periodic 48 hour ABPM, with a total of 255 CV events recorded atthe conclusion of the study. Though overall BP was similar at baseline be-tween the groups, the patients taking at least one anti-hypertensive at bed-time demonstrated a reduction in nighttime mean BP, a reduced prevalenceof non-dipping (34 % vs. 62 %, pG0.01), and an overall improvement in the% of subjects at goal with ABPM (62 % vs. 53 %, pG0.01) compared topatients in the who took all their medicines in the morning. This resulted in a


reduced risk of major adverse CV events (CV death, myocardial infarction,ischemic and hemorrhagic stroke) of RR 0.33 (95 % CI 0.19–0.55, pG0.001).A second cross-sectional study of 2,899 resistant hypertensive patients com-paring morning dosing, BID dosing and evening dosing of BP medicationsalso found that patients taking medications at night had less prevalence ofTOD, lower mean nighttime systolic BP and diastolic BP, and overall im-proved % of subjects at ABPM goal compared to the other two groups [71].These studies indicate that with appropriate patient selection (namely toavoid nocturnal medication-induced hypotension), some patients maybenefit from administration of BP medications at bedtime rather than in themorning.

The timing and choice of antihypertensives is critical to getting hyperten-sive patients to goal BP, as evidenced by the recent SURGE (Survey withhome BP monitoring and ABPM Under Real clinical conditions in Generalpractice to Evaluate BP control in the early morning), which found that of15,618 treated hypertensive patients, only 32 % of patients achieved BP goalduring the morning hours (6 AM to noon), with percentages even lower forhigh risk patients, such as those with DM or TOD (manifest as LVH) [72].Understanding an individual patient’s diurnal variation, as well as thecharacteristics of different antihypertensive drugs, may help to provide moreeffective management of hypertension.

ABPM in clinical use may be cost-effective

There are a limited number of studies that have exclusively evaluated the roleof ABPM in algorithms for management of hypertension. Perhaps the mostwell known study, The APTH (Antihypertensive treatment based on con-vention or ambulatory Blood Pressure Measurement) trial randomized 419patients with untreated, newly diagnosed hypertension (defined as a dia-stolic BP≥95 mmHg) to treatment using either clinic BP or ABPM to guidemedication titration [73]. The trial utilized a specific, stepwise algorithm foreither the addition of removal of agents, based upon the mean daytime di-astolic BP derived from ABPM, or the average of three clinic BP’s at 1,2, 4,and 6 months. At the conclusion of 6 months of follow-up, a greater pro-portion of patients in the ABPM arm had stopped antihypertensive treat-ment, and fewer required multiple drug treatment to control their BP.Furthermore, the costs of obtaining regular ABPM recordings was offset by areduced cost of medications and less frequent physician visits for the ABPMarm. With regards to symptoms and measures of TOD (LVMI), there was nodifference between the two groups.

The ramifications of ABPM in reducing the costs of treatment was demon-strated in a 2011 study which modeled three forms of diagnostic BP moni-toring (home, office and ambulatory) in a hypothetical middle-aged,primary care population with an elevated screening BP of 140/90 mmHg.The analysis demonstrated that ABPM was associated with an estimated cost-savings between $87 and $495 per patient, and increased quality-associatedyears of life compared to the alternative options of home-based or clinicmonitoring [74]. A recent review of cost-effectiveness analyses of both homeBP monitoring and ABPM monitoring support that ABPM use results in


overall lower costs, mainly due to improved diagnostic accuracy [75••].These findings were a likely contributor to the recently instituted NationalInstitute of Clinical Excellence guidelines, which recommend ABPM to con-clusively diagnose all patients with an elevated screening clinic BP. Similarguidelines in the United States have not yet been made the same recom-mendation.

Conclusion

Epidemiologic studies with ABPM have vastly enhanced our understandingof the dynamic nature of BP, and how it modifies CV risk. Though thereappears to be some inconsistency in standardization of protocols for ABPMdevices, the many components reported by an ABPM recording offer a host ofpreviously unappreciated prognostic information. At present, the data moststrongly supports the use of 24-hour mean BP, nocturnal BP, and dippingstatus to define risk and determine prognosis. Newer methods to assess riskand prognosis such as BP variability and the morning surge, which are de-rived from ABPM, and AASI (which is not derived from ABPM), are of in-terest, but their exact association in conferring greater CV risk requires furtherclarification. Beyond the application for prognosis, ABPM allows for the di-agnosis of WCH and MH, both of which have implications for antihyper-tensive management as well as patient outcomes. ABPM is also a reliablemodality to assess both the efficacy of antihypertensive medications as wellas timing of treatment. While the advantages of ABPM should be consideredalongside important issues such as the costs of monitoring and equipment,as well as patient inconvenience, analyses appear to support ABPM as anoverall effective and cost-lowering strategy for screening of select hyperten-sive patients. Although future prospective studies are warranted, in ourgroup’s opinion, ABPM offers the highest yield of clinical information in thefollowing settings: to assess WCH in patients with self-reported normal homeor ambulatory BPs but elevated clinic BPs, and to assess for MH in patientswith evidence of TOD (proteinuria, diastolic dysfunction or LVH) with ap-parently normal clinic BPs. It may be particularly helpful as well, to definewhat appear to be hypotensive episodes in patients who complain ofsymptoms consistent with a low BP.

In summary, to date, ABPM has proven to be an invaluable clinical tool inmanagement of hypertension, and further study will help to confirm itsability to redefine CV risk, as well as elucidate how it improves diagnosis andmanagement of hypertension in real-life clinical practice.

Compliance with Ethics Guidelines

Conflict of InterestDr. Amita Singh reported no potential conflicts of interest relevant to this article.Dr. Eugenia Gianos reported no potential conflicts of interest relevant to this article.Dr. Arthur Schwartzbard reported receiving consultancies from Gilead and Takeda.


Dr. Henry Black reported receiving a grant from New York University and travel/accommodations expensesreimbursed or covered to attend an investigators meeting in 2011.Dr. Howard Weintraub reported receiving a consultancy from Gilead, a grant from Amarin, and honorariafrom Takeda, Boehringer, AstraZeneca, Kowa, Gilead, and Abbott. Dr. Weintraub reported receiving pay-ment for development of educational presentations including service on speakers' bureaus from Gilead,Novartis, Abbott, and Takeda. Dr. Weintraub also reported travel/accommodations expenses covered or re-imbursed by Takeda, Abbott, AstraZeneca, Kowa, and Boehringer.

Human and Animal Rights and Informed ConsentThis article does not contain any studies with human or animal subjects performed by any of the authors.

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