Automated Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Patients with Elevated Office Blood Pressure

Automated Ambulatory Blood Pressure Monitoring for the Diagnosis of Hypertension in Patients with Elevated Office Blood Pressure Policy Number: 1.01.02 Last Review: 9/2015 Origination: 1/1989 Next Review: 9/2016 Policy Blue Cross and Blue Shield of Kansas City (Blue KC) will provide coverage for automated ambulatory blood pressure monitoring when it is determined to be medically necessary because the criteria shown below are met. These devices are contract exclusions on most policies. When Policy Topic is covered Automated ambulatory blood pressure monitoring over a 24-hour period is medically necessary for patients with elevated office BP, when performed one time to differentiate between white coat hypertension and true hypertension, and when the following conditions are met: Office blood pressure elevation is in the mild to moderate range (<180/110), not requiring immediate treatment with medications; There is an absence of hypertensive end-organ damage on physical examination and laboratory testing; Automated ambulatory blood pressure monitoring over a 24-hour period may be considered medically necessary for the detection of white coat hypertension in adult patients who appear to have resistant hypertension while adhering to full doses of an appropriate 3-drug regimen that includes a diuretic, prior to an increase in medication or invasive investigation of the underlying cause. When Policy Topic is not covered All other uses of ambulatory blood pressure monitoring for patients with elevated office BP, including but not limited to repeated testing in patients with persistently elevated office BP, is considered investigational. Description of Procedure or Service Ambulatory blood pressure monitors (24-hour sphygmomanometers) are portable devices that record blood pressure repeatedly while the patient is involved in daily activities. There are various types of ambulatory monitors; this policy addresses fully automated monitors, which inflate and record blood pressure at pre-programmed intervals. Ambulatory blood pressure monitoring (ABPM) performed over a 24-hour period is a more accurate method for evaluating BP compared with office measurements and home BP measurements. Reference values for normal and abnormal ABPM results have been derived from epidemiologic research for both adults and children. These reference values vary slightly among different sources but are available for clinical use. Data from large prospective cohort studies establish that ABPM correlates more strongly with cardiovascular outcomes compared with other methods of BP measurement. Prospective cohort studies also indicate that white coat hypertension (WCH), as defined by ABPM, is

associated with an intermediate risk of cardiovascular outcomes compared with normotensive and hypertensive patients. Studies comparing home BP monitoring and office monitoring to ABPM as the criterion standard report that the sensitivity and specificity of alternative methods of diagnosing hypertension are suboptimal. This is true for both adult and pediatric patients. Substantial percentages of patients with elevated office BP are found to have normal BP on ABPM, and these patients are at risk for overdiagnosis and overtreatment based on office BP measurements alone. Use of ABPM in these patients will improve outcomes by eliminating the inconvenience and morbidity of pharmacologic treatment in patients who are not expected to benefit. Therefore, ABPM may be considered medically necessary for the evaluation of patients with elevated office BP. Ambulatory blood pressure monitoring (ABPM), typically done over a 24-hour period with a fully automated monitor, provides more detailed blood pressure information than typically obtained during office visits. The greater number of readings with ABPM ameliorates the variability of single blood pressure measurements, and is more representative of the circadian rhythm of blood pressure compared to the limited number obtained during office measurement. There are a number of potential applications of ABPM. One of the most common is evaluating suspected white-coat hypertension (WCH), which is defined as an elevated office blood pressure with normal blood pressure readings outside the physician s office. The etiology of WCH is poorly understood but may be related to an alerting" or anxiety reaction associated with visiting the physician's office. In evaluating patients having elevated office blood pressure, ABPM is often intended to identify patients with normal ambulatory readings who do not have sustained hypertension. Since this group of patients would otherwise be treated based on office blood pressure readings alone, ABPM could improve outcomes by allowing these patients to avoid unnecessary treatment. However, this assumes patients with WCH are not at increased risk for cardiovascular events and would not benefit from antihypertensive treatment. This policy does not directly address other uses of ABPM, including the use of ABPM for the evaluation of masked hypertension. Masked hypertension refers to normal BP readings in the office and elevated BP readings outside of the office. This phenomenon has recently received greater attention, with estimates that up to 10-20% of individuals may exhibit this pattern. Other potential uses of ABPM include monitoring patients with established hypertension under treatment; evaluating refractory or resistant blood pressure; evaluating whether symptoms such as lightheadedness correspond with blood pressure changes; evaluating nighttime blood pressure; examining diurnal patterns of blood pressure; and/or other potential uses. Many ambulatory blood pressure monitors have received clearance to market through the U.S. Food and Drug Administration (FDA) 510(k) marketing clearance process. As an example of an FDA indication for use, the Welch Allyn ABPM 6100 is indicated as an aid or adjunct to diagnosis and treatment when it is necessary to measure adult or pediatric patients systolic and diastolic blood pressures over an extended period of time. The system is only for measurement, recording, and display. It makes no diagnosis. (2) Rationale This policy was originally created in 1995 and updated periodically with literature review. The most recent update with literature review covered the period through December 2, 2014. The evidence base for this policy originates from a 1999 TEC Assessment(3) and subsequent reanalysis of this report conducted for the Centers for Medicare and Medicaid Services in 2001.(4) The focus is on the use of ambulatory blood pressure monitoring (ABPM) in previously untreated patients with elevated office blood pressure (BP). In this situation, ABPM is primarily intended to evaluate white

coat hypertension (WCH), or isolated clinic hypertension. This entity is defined as an elevated office BP with normal BP readings outside the physician s office. It is diagnosed by obtaining multiple out-ofoffice BP measurements and comparing them with office readings. Evidence on whether ABPM improves health outcomes for patients with elevated office BP will be summarized in 3 general areas of research: 1. Reference values for ABPM 2. Impact of ABPM on outcomes a. Clinical trials b. Prospective cohort studies 3. Accuracy of ABPM as a diagnostic test for hypertension c. Prospective cohort studies d. Cross-sectional studies Reference Values for ABPM Monitoring One important area addresses the question of reference values for ABPM to provide guidelines for normal and abnormal ABPM readings.(5,6) Studies that have compared ABPM measurements with office measurement consistently reveal lower values for ABPM. Therefore, it is not possible to use reference values for office BP to evaluate the results of ABPM. Reference values for ABPM have been derived by several methods: (1) estimates of population-based ABPM results to define the range and distribution of ABPM values; (2) direct comparisons of average ABPM values and office BP to determine the level of ABPM that corresponds to an office BP of 140/90; and (3) correlations of ABPM results with cardiovascular outcomes to determine ABPM levels at which the risk for cardiovascular events increases, or is similar to the risk associated with an office BP of 140/90.(7,8) Although specific recommendations vary slightly, current thresholds for defining a normal ABPM are 24- hour average BP of 130/80 and daytime average BP of 135/85. An ABPM Consensus Conference task force on ABPM considered data on the statistical distribution of ABPM, correlation with office BP, and correlation with cardiovascular outcomes in deriving recommendations for reference values for ABPM.(9) Their recommendations are summarized in Table 2. Subsequent studies have identified racial and ethnic variation in ABPM results,(10) but impacts of these differences on clinical management may be minimal.(11) Table 2. ABPM Consensus Conference Task Force IV: Adult ABPM Thresholds(9) ABPM Measure 95th Percentile Normotension Hypertension 24-hour average 132/82 <130/80 >135/85 Daytime average 138/87 <135/85 >140/90 Nighttime average 123/74 <120/70 >125/75 ABPM: ambulatory blood pressure monitoring. Section Summary Reference values for normal and abnormal ABPM results have been derived from epidemiologic research. These reference values vary slightly among different sources but are available for clinical use. Impact of ABPM on Outcomes Clinical Trials Direct evidence of the efficacy of ABPM for improving outcomes in this setting would be obtained from randomized controlled trials (RCTs) comparing outcomes of (1) patients diagnosed and treated based on conventional BP measurements alone with (2) patients additionally undergoing ABPM used to guide therapy (eg, withholding or randomizing treatment among those with WCH). This notion parallels the

statement from the U.S. National High Blood Pressure Education Program Working Group on Ambulatory Blood Pressure Monitoring in 1992, Ideally, de novo longitudinal studies should be undertaken to determine which ambulatory profiles are associated with increased cardiovascular risk and what transformations of ambulatory profiles induced by antihypertensive therapy are associated with reductions in risk. (12) RCTs using ABPM for monitoring treatment response but not to diagnose hypertension have been conducted. However, a substudy of the Systolic Hypertension in Europe (Syst- Eur) trial did address this question indirectly.(13) The Syst-Eur trial, a large, multicenter RCT, enrolled patients 60 years of age or older with isolated systolic hypertension and randomized them to antihypertensive treatment or placebo.(13) A substudy evaluated 695 patients (from the total Syst-Eur sample of 4695 patients) who underwent 24-hour ABPM in addition to the usual study protocol. Conventional BP was defined from the mean of 6 baseline clinic BPs (2 readings obtained with the patient seated at each of 3 baseline visits at least 1 month apart). Participants were classified into 3 groups based on ABPM readings: nonsustained hypertension (ie, WCH), mild-sustained hypertension, and moderate-sustained hypertension. Reduction in cardiovascular events was compared between active and placebo groups among patients in each of the 3 categories. For patients with nonsustained hypertension, there was a numerically lower rate of adverse outcomes in the treated group for stroke (0 vs 2, p=0.16) and cardiovascular events (2 vs 6, p=0.17), ie, differences not reaching statistical significance. There was a significant reduction in events with treatment only among patients with moderate-sustained hypertension. Staessen et al (1999) analyzed follow-up data (median follow-up, 4.4 years) from an apparently overlapping subset of 808 older individuals from the Syst-Eur trial who had isolated systolic hypertension measured conventionally (ie, systolic BP [SBP], 160-219 mm Hg; diastolic BP [DBP], <95 mm Hg).(14) BPs also were measured by ABPM; average SBP and DBP were higher with conventional measurements (by 21.9 and 1.9 mm Hg, respectively). ABPM was significantly associated with cardiovascular end points, even when conventional BP was taken into account. Prospective Cohort Studies Well-designed, prospective cohort studies could provide indirect evidence on the potential benefit of treatment for patients with WCH. Ideally, prospective studies would compare outcomes of untreated patients with WCH with normotensive and sustained hypertensive patients (the latter being treated). Studies should control for important potential confounders such as adequacy of BP control, age, sex, smoking status, lipid levels, and diabetes. Well-designed and conducted prospective cohort studies finding that untreated WCH patients have a cardiovascular event risk similar to that of normotensive patients would imply these patients accrue little treatment benefit. In contrast, if the cardiovascular risk for patients with WCH is increased, then there is a potential benefit to treatment. Numerous large cohort studies have used ABPM to identify patients with WCH and compared subsequent cardiovascular outcomes in WCH patients, normotensive patients, and sustained hypertensive patients.(15-22) These studies have generally been consistent in reporting that cardiovascular risk for patients with WCH is intermediate, between that of hypertensive patients and normotensive patients. For example, a 2014 meta-analysis found that mean left ventricular mass index and mean left atrial diameter in patients with WCH was intermediate, between that of hypertensive patients and normotensive individuals.(23) A 2013 review found that in patients with WCH, prevalence of cardiovascular risk factors, such as glucose dysregulation, diabetes, increased left ventricular mass index, and sustained hypertension, was increased compared with normotensive individuals, but the risk of cardiovascular events was not.(24) The authors attributed the latter finding to the frequent use of antihypertensive treatment in WCH. At least 3 meta-analyses have been published that summarize results of the available cohort studies. Fagard and Cornelissen (2007) summarized data from 7 cohort studies that compared outcomes in 4 groups of patients: normotensive patients, WCH patients, masked hypertensive patients, and sustained hypertensive patients (total N=11,502).(25) Average follow-up in these studies was 8.0 years. Using normotensive patients as the reference standard, the risk for patients with WCH was not

significantly higher (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.84 to 1.50). There was an increased risk for patients with masked hypertension (HR=2.00; 95% CI, 1.58 to 2.52) and patients with sustained hypertension (HR=2.28; 95% CI, 1.87 to 2.78). Hansen et al (2007) used patient-level data from 4 previous cohorts of patients to construct an international database of ambulatory BP monitoring.(26) This database included 7069 patients from 4 cohorts in Europe and Japan that represented population-level patient samples. In this analysis, there was a trend toward increased cardiovascular events in patients with WCH that did not reach statistical significance (HR=1.22; 95% CI, 0.96 to 1.53; p=0.09). Statistically increased risks were found in patients with masked hypertension (HR=1.62; 95% CI, 1.35 to 1.96; p<0.001) or sustained hypertension (HR=1.80; 95% CI, 1.59 to 2.03; p<0.001). A third pooled analysis by Verdecchia et al (2005) included studies conducted in the United States, Italy, and Japan.(27) This analysis compared short- and long-term stroke risk among 4406 individuals with essential hypertension and 1549 normotensive controls; none were treated at baseline. WCH was present in 9% of the hypertensive group. During the first 6 years, follow-up stroke incidence appeared similar among WCH and normotensive groups. However, by 9 years, stroke incidence among WCH patients reached that of the hypertensive group (measured by ABPM). At the last telephone contact or clinic visit, similar proportions of those initially classified as WCH and normotensive were receiving antihypertensive medications from 5 different drug classes. This result suggests WCH may not be entirely benign. Section Summary Data from large prospective cohort studies establish that ABPM correlates more strongly with cardiovascular outcomes compared with other methods of BP measurement, and that WCH, as defined by ABPM, is associated with an intermediate risk of cardiovascular outcomes compared with normotensive and hypertensive patients. Accuracy of ABPM as a Diagnostic Test for Hypertension Studies of the accuracy of ABPM as a diagnostic test for hypertension are of 2 types. First, prospective cohort studies that correlate results of ABPM with future cardiovascular events, and compare this correlation with that of office BP measurements, provide indirect evidence on ABPM accuracy by assuming that the more accurate test will have a higher correlation with hypertension-related outcomes. Second, cross-sectional studies can directly compare the accuracy of ABPM compared with office BP, using a criterion standard for diagnosis. For these types of studies, ABPM is often considered the criterion standard, and accuracy of other methods of BP measurement is compared with ABPM. Prospective Cohort Studies Many prospective cohort studies have compared ABPM with office BP in predicting cardiovascular events. Although results of these studies are not entirely consistent, the majority report that ABPM has greater predictive ability for cardiovascular events compared with office BP measurement.(28,29) A summary of relevant systematic reviews and meta-analyses of these studies follows. Hansen et al (2007) conducted a patient-level meta-analysis using data from four populations in Belgium, Denmark, Japan, and Sweden (total N=7030).(26) Predictive value of ABPM and clinic BP for fatal and nonfatal cardiovascular events was reported. Both ABPM and office BP were predictors of outcomes in univariate and partially-adjusted multivariate models. In the fully adjusted model, ABPM remained a significant predictor of outcomes while office BP did not. Conen et al (2008) conducted a meta-analysis of 20 cohort studies that evaluated the correlation between ABPM and outcomes, controlling for office BP in the analysis.(30) These authors reported that ABPM was a strong predictor of cardiovascular outcomes and that controlling for office BP had little effect on risk estimates. These results support the hypothesis that risk information obtained from ABPM is independent of that obtained from office BP.

Cross-Sectional Studies Numerous studies have directly compared ABPM with office BP and/or home self-measured BP. Hodgkinson et al (2011) performed a systematic review of studies that compared ABPM with home or office BP and used clearly defined thresholds to determine the accuracy of diagnosis of hypertension.(31) Of 10 studies identified, 7 compared ABPM with office BP measurements, and 3 compared ABPM with home self-measurement. Using a 24-hour ABPM threshold of 135/85, clinic BP measurements had a sensitivity of 75% (95% CI, 61% to 85%) and a specificity of 75% (95% CI, 48% to 90%). Home BP self measurement had a sensitivity of 86% (78% to 91%) and a specificity of 62% (48% to 75%). The accuracy of office and home BP was not considered adequate for use as a single diagnostic test for hypertension, and it was hypothesized that the use of office and/or home measurements may lead to substantial overdiagnosis and overtreatment. In a similar systematic review, Stergiou and Bliziotis (2011) compared the accuracy of ABPM with home BP measurement for the diagnosis of hypertension.(32) A total of 16 studies were included in this analysis. Sensitivity of home BP measurement, compared with ABPM, ranged from 36% to 100% with a median value of 74%. Specificity ranged from 44% to 96%, with a median value of 84%. This study also reported the diagnostic agreement between the 2 methods of BP measurement, as measured by the statistic. Kappa could be calculated in 11 studies; the range of scores was 0.37 to 0.73, with a median value of 0.46. This level indicates moderate agreement between ABPM and home monitoring in the diagnosis of hypertension. Lovibond et al (2011) performed a cost-effectiveness study comparing ABPM with office BP measurement and home measurements.(33) For most patient indications, ABPM resulted in the greatest amount of quality-adjusted life years (QALYs) gained, and in individuals older than age 50 years, ABPM was consistently associated with the largest incremental gain in QALYs. ABPM was costsaving in all patient groups compared with alternatives and remained the most cost-effective alternative under the majority of sensitivity analyses. As a result of these findings, the authors recommended that ABPM be performed for most patients before the decision to start anti-hypertensive medications is made. Other Studies A number of trials have evaluated ABPM for the management of established hypertension, comparing the effect of ABPM use on BP control and medication use with usual care based on office measurements.34-36 Some studies have compared home self-monitoring with ABPM and office measurement for management of medication treatment.(37-39) Others have attempted to determine predictors of WCH based on clinical factors and office BP readings.(40) However, these areas of research do not provide specific evidence on the use of ABPM for diagnosing and treating patients with elevated office BP and thus are not included in the final evidence base for this policy. Section Summary Studies comparing home BP monitoring and office monitoring with ABPM as the criterion standard report that the sensitivity and specificity of alternative methods of diagnosing hypertension are suboptimal. ABPM in Children and Adolescents ABPM has been used in children and adolescents for similar purposes as in adults, including use in children and adolescents with elevated office BP to distinguish true hypertension from WCH. Evidence on use of ABPM in children and adolescents is of similar type as for adults but of smaller quantity. A representative sample of studies identified follows. Normative values for pediatric patients have been established by large population-based studies of children and adolescents.(41) Elevated readings are defined as values greater than the 95th percentile for sex, age, and height. These studies also have established that patterns of ambulatory BP in children differ from those in adults. In children, ambulatory BP is generally higher than the corresponding office BP, in contrast to adult ambulatory BP readings that are on average lower than office BP. This pattern

is more pronounced in younger children, and the difference progressively declines with age. Guidelines for classification of hypertension in children and adolescents were published by the American Heart Association in 2008 (see Policy Guidelines section for specific recommendations).(42) In a study from Europe, 139 children and adolescents between the ages of 4 to 19 years with elevated office BP were evaluated by ABPM monitoring.(43) Thirty-two (23.0%) of 139 participants had WCH, as evidenced by a normal 24-hour ABPM result. Of patients with true hypertension, 21 (19.6%) of 107 had evidence of target organ damage, compared with none of the patients with WCH. In a similar study from the United States, 67 otherwise healthy children underwent ABPM, 51 of whom had an elevated office BP.(44) Using 3 definitions of WCH of varying BP cutoffs, WCH was identified in 22% to 53% of children with elevated office BP. In a study from Japan, 206 children and adolescents between the ages of 6 to 25 years underwent ABPM, 70 of whom had elevated office BP.(45) Among the 70 patients with elevated office BP, 33 (47%) had WCH, as defined by a normal ABPM result. A white coat effect of 10 mm Hg or more was reported in 50% of patients with office hypertension and 25% of patients with normal office BP. Section Summary Reference values for normal and abnormal ABPM results in children and adolescents have been derived from epidemiologic research and have been used to differentiate WCH from true hypertension in pediatric patients. Ongoing and Unpublished Clinical Trials An online search of ClinicalTrials.gov identified 1 small RCT, a comparative effectiveness pilot study of ABPM versus office BP monitoring for diagnosing and managing hypertension (NCT02121041). Twentyfour untreated patients with office-diagnosed hypertension (clinic SBP, 126-150 mm Hg) will be randomized to usual care (office BP monitoring) or ABPM-guided care. For patients in the ABPMguided group, treatment decisions will be based on results of 3 ABPM sessions taken over 4 months. The trial is sponsored by the North Carolina Translational and Clinical Sciences Institute at the University of North Carolina. Estimated completion is June 2016. Summary of Evidence Ambulatory blood pressure monitoring (ABPM) performed over a 24-hour period is a more accurate method for evaluating blood pressure (BP) compared with office measurements and home BP measurements. Reference values for normal and abnormal ABPM results have been derived from epidemiologic research for both adults and children. These reference values vary slightly among different sources but are available for clinical use. Data from large prospective cohort studies establish that ABPM correlates more strongly with cardiovascular outcomes compared with other methods of BP measurement. Prospective cohort studies also indicate that white coat hypertension (WCH), as defined by ABPM, is associated with an intermediate risk of cardiovascular outcomes compared with normotensive and hypertensive patients. Studies comparing home BP monitoring and office monitoring to ABPM as the criterion standard report that the sensitivity and specificity of alternative methods of diagnosing hypertension are suboptimal. This is true for both adult and pediatric patients. Substantial percentages of patients with elevated office BP are found to have normal BP on ABPM, and these patients are at risk for overdiagnosis and overtreatment based on office BP measurements alone. Use of ABPM in these patients will improve outcomes by eliminating the inconvenience and morbidity of pharmacologic treatment in patients who are not expected to benefit. Therefore, ABPM may be considered medically necessary for the evaluation of patients with elevated office BP. Practice Guidelines and Position Statements National Institute for Health and Care Excellence

The U.K. s National Institute for Health and Care Excellence (NICE) issued updated hypertension guidelines in 2011.(46) For diagnosing hypertension, NICE made the following recommendations concerning ABPM: If the clinic BP is 140/90 mm Hg or higher, offer ABPM to confirm the diagnosis of hypertension. When using ABPM to confirm a diagnosis of hypertension, ensure that at least 2 measurements per hour are taken during the person s usual waking hours. Use the average of at least 14 measurements taken during usual waking hours to confirm a diagnosis of hypertension. Canadian Hypertension Education Program Guidelines for BP measurement, diagnosis, and risk assessment have been published annually by the Canadian Hypertension Education Program. Strength of evidence underlying recommendations is graded ranging from A (studies with high internal validity, statistical precision, and generalizability) to D (expert opinion). The 2014 recommendations(47) include: Ambulatory BP readings can be used in the diagnosis of hypertension (grade C). ABPM should be considered when an office-induced increase in BP is suspected in treated patients with: o BP that is not below target despite receiving appropriate chronic antihypertensive therapy (grade C); o symptoms suggestive of hypotension (grade C); or o fluctuating office BP readings (grade D). Physicians should use only ABPM devices that have been validated independently using established protocols (grade D). Therapy adjustment should be considered in patients with a 24-hour ambulatory SBP (systolic blood pressure) of 130 mm Hg or DBP (diastolic blood pressure) of 80 mm Hg or an awake SBP of 135 mm Hg or DBP of 85 mm Hg (grade D). The magnitude of changes in nocturnal BP should be taken into account in any decision to prescribe or withhold drug therapy based upon ambulatory BP (grade C) because a decrease in nocturnal BP of less than 10% is associated with increased risk of CV events. American Heart Association Recommendations for ABPM in Children and Adolescents The American Heart Association published consensus recommendations in 2008 developed by their Atherosclerosis, Hypertension, and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young and the Council for High Blood Pressure Research.(42) These recommendations were updated in 2014.(1) Consensus recommendations for routine ABPM include the following: To confirm the diagnosis of hypertension in a patient with hypertension according to casual BP measurements o Determine whether sustained hypertension or WCH exists. To evaluate for the presence of masked hypertension when there is a clinical suspicion of hypertension but normal or prehypertensive casual measurements To assess BP patterns in high-risk patients o Assess for abnormal circadian variation in BP, such as blunted dipping or isolated sleep hypertension in patients with diabetes mellitus, chronic kidney disease, solid organ transplants, and severe obesity with or without sleep-disordered breathing. o Assess the severity and persistence of BP elevation in patients at high risk for hypertensive target-organ damage. To evaluate effectiveness of drug therapy for hypertension o Confirm BP control in treated patients, especially those with secondary forms of hypertension.

o o Evaluate for apparent drug-resistant hypertension. Determine whether symptoms can be attributed to drug-related hypotension. European Society of Cardiology/European Society of Hypertension In 2013, the European Society of Cardiology and the European Society of Hypertension (ESH) published joint evidence-based guidelines for the management of arterial hypertension.(48) These guidelines recommend ABPM or home BP monitoring for out-of-office BP measurements depending on indication, availability, ease, cost of use, and patient preference (class 2b recommendation [usefulness/efficacy is less well established; use may be considered] based on level C evidence [consensus expert opinion and/or small studies, retrospective studies, or registries]). Guideline authors stated, Whether subjects with WCH can be equaled to true normotensive individuals is an issue still under debate because, in some studies, the long-term cardiovascular risk of this condition was found to be intermediate between sustained hypertension and true normotension, whereas in meta-analyses it was not significantly different from true normotension when adjusted for age, gender, and other covariates. (48) European Society of Hypertension Since 2003, ESH has published consensus-based guidelines on ABPM.(49,50) The most recent update in 2013 identified white coat phenomena, masked hypertension, and nocturnal hypertension as indications for ABPM.(51,52) British Hypertension Society The British Hypertension Society issued a 2011 guideline on hypertension which was produced in collaboration with NICE. Refer to the NICE Clinical Guideline (CG) 127 previously referenced.(46) This guideline is scheduled for update in September 2015. National High Blood Pressure Education Program The fourth report on the diagnosis, evaluation, and treatment of high BP in children and adolescents was published in 2004.(55) This report made the following statements concerning the use of ABPM in children and adolescents: ABPM is especially helpful in the evaluation of WCH, as well as the risk for hypertensive organ injury, apparent drug resistance, and hypotensive symptoms with antihypertensive drugs. ABPM is also useful for evaluating patients for whom more information on BP patterns in needed, such as those with episodic hypertension, chronic kidney disease, diabetes, and autonomic dysfunction. Conducting ABPM requires specific equipment and trained staff. Therefore, ABPM in children and adolescents should be used by experts in the field of pediatric hypertension who are experienced in its use and interpretation. Joint National Committee VII The seventh report of the Joint National Committee on the prevention, detection, evaluation, and treatment of high BP,(56) released in 2003, includes a brief section on the use of ABPM. The report states that [a]mbulatory blood pressure monitoring is warranted for the evaluation of (white-coat) hypertension in the absence of target organ damage. It is also helpful to assess patients with apparent drug resistance, hypotensive symptoms with antihypertensive medications, episodic hypertension, and autonomic dysfunction. U.S. Preventive Services Task Force The U.S. Preventive Services Task Force (USPSTF) published a recommendation that individuals 18 years and older be screened for hypertension in 2007. This recommendation does not define methods of screening or mention ABPM. A draft revision of this recommendation is in progress and is expected to be finalized in 2015. USPSTF also published a recommendation on screening for hypertension in children and adolescents which concluded that current evidence is insufficient to assess the balance of

benefits and harms of screening for primary hypertension in asymptomatic children and adolescents to prevent subsequent cardiovascular disease in childhood or adulthood. Medicare National Coverage Medicare considers ABPM eligible for coverage(57) as follows: At this point in time, ABPM will be covered for those patients with suspected WCH. Suspected WCH will be defined as office blood pressure >140/90 mm Hg on at least 3 separate clinic/office visits with 2 separate measurements made at each visit. In addition, there should be at least 2 blood pressure measurements taken outside the office that are <140/90 mm Hg. There should be no evidence of end-organ damage. The information obtained by ABPM is necessary in order to determine the appropriate management of the patient. References: 1. Flynn JT, Daniels SR, Hayman LL, et al. Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension. May 2014;63(5):1116-1135. PMID 24591341 2. U.S. Food and Drug Administration (FDA). Welch Allyn ABPM 1600 pre-market notification: 510(k) summary, 06/27/2002. http://www.accessdata.fda.gov/scripts/cdrh/devicesatfda/index.cfm?db=pmn&id=k021756. Accessed November 26, 2014. 3. Blue Cross and Blue Shield Association Technology Evaluation Center (TEC). 24-hour ambulatory blood pressure monitoring for the evaluation of patients with elevated office blood pressure. TEC Assessments 1999; Volume 14, Tab 8. 4. LeFevre F, Aronson N. Technology Assessment for ambulatory blood pressure monitoring for adults with elevated office blood pressure. February 2001. http://www.cms.gov/medicare-coveragedatabase/details/ncadetails.aspx?ncaid=5&ncaname=ambulatory+blood+pressure+monitoring& NCDId=254&ncdver=1&IsPopup=y&bc=AAAAAAAAAgAAAA%3d%3d& 5. Imai Y, Hozawa A, Ohkubo T, et al. Predictive values of automated blood pressure measurement: what can we learn from the Japanese population - the Ohasama study. Blood Press Monit. Dec 2001;6(6):335-339. PMID 12055412 6. Verdecchia P. Reference values for ambulatory blood pressure and self-measured blood pressure based on prospective outcome data. Blood Press Monit. Dec 2001;6(6):323-327. PMID 12055410 7. Head GA, Mihailidou AS, Duggan KA, et al. Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study. BMJ. 2010;340:c1104. PMID 20392760 8. Kikuya M, Hansen TW, Thijs L, et al. Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk. Circulation. Apr 24 2007;115(16):2145-2152. PMID 17420350 9. Staessen JA, Beilin L, Parati G, et al. Task force IV: Clinical use of ambulatory blood pressure monitoring. Participants of the 1999 Consensus Conference on Ambulatory Blood Pressure Monitoring. Blood Press Monit. Dec 1999;4(6):319-331. PMID 10602536 10. Muntner P, Lewis CE, Diaz KM, et al. Racial Differences in Abnormal Ambulatory Blood Pressure Monitoring Measures: Results From the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Am J Hypertens. Nov 4 2014. PMID 25376639 11. Martin U, Haque MS, Wood S, et al. Ethnicity and Differences Between Clinic and Ambulatory Blood Pressure Measurements. Am J Hypertens. Nov 13 2014. PMID 25398890 12. National High Blood Pressure Education Program (NHBPEP) Working Group Report On Ambulatory Blood Pressure Monitoring U.S.DHHS In: Program. NHBPE, ed1992. 13. Fagard RH, Staessen JA, Thijs L, et al. Response to antihypertensive therapy in older patients with sustained and nonsustained systolic hypertension. Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Circulation. Sep 5 2000;102(10):1139-1144. PMID 10973843 14. Staessen JA, Thijs L, Fagard R, et al. Predicting cardiovascular risk using conventional vs ambulatory blood pressure in older patients with systolic hypertension. Systolic Hypertension in Europe Trial Investigators. JAMA. Aug 11 1999;282(6):539-546. PMID 10450715

15. Gustavsen PH, Hoegholm A, Bang LE, et al. White coat hypertension is a cardiovascular risk factor: a 10-year follow-up study. J Hum Hypertens. Dec 2003;17(12):811-817. PMID 14704724 16. Khattar RS, Senior R, Lahiri A. Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study. Circulation. Nov 3 1998;98(18):1892-1897. PMID 9799210 17. Ohkubo T, Kikuya M, Metoki H, et al. Prognosis of "masked" hypertension and "white-coat" hypertension detected by 24-h ambulatory blood pressure monitoring 10-year follow-up from the Ohasama study. J Am Coll Cardiol. Aug 2 2005;46(3):508-515. PMID 16053966 18. Strandberg TE, Salomaa V. White coat effect, blood pressure and mortality in men: prospective cohort study. Eur Heart J. Oct 2000;21(20):1714-1718. PMID 11032699 19. Ugajin T, Hozawa A, Ohkubo T, et al. White-coat hypertension as a risk factor for the development of home hypertension: the Ohasama study. Arch Intern Med. Jul 11 2005;165(13):1541-1546. PMID 16009871 20. Verdecchia P, Porcellati C, Schillaci G, et al. Ambulatory blood pressure. An independent predictor of prognosis in essential hypertension. Hypertension. Dec 1994;24(6):793-801. PMID 7995639 21. Gaborieau V, Delarche N, Gosse P. Ambulatory blood pressure monitoring versus selfmeasurement of blood pressure at home: correlation with target organ damage. J Hypertens. Oct 2008;26(10):1919-1927. PMID 18806615 22. Salles GF, Cardoso CR, Muxfeldt ES. Prognostic influence of office and ambulatory blood pressures in resistant hypertension. Arch Intern Med. Nov 24 2008;168(21):2340-2346. PMID 19029499 23. Cuspidi C, Rescaldani M, Tadic M, et al. White-coat hypertension, as defined by ambulatory blood pressure monitoring, and subclinical cardiac organ damage: a meta-analysis. J Hypertens. Nov 6 2014. PMID 25380162 24. Martin CA, McGrath BP. White-coat hypertension. Clin Exp Pharmacol Physiol. Jan 2014;41(1):22-29. PMID 23682974 25. Fagard RH, Cornelissen VA. Incidence of cardiovascular events in white-coat, masked and sustained hypertension versus true normotension: a meta-analysis. J Hypertens. Nov 2007;25(11):2193-2198. PMID 17921809 26. Hansen TW, Kikuya M, Thijs L, et al. Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7,030 individuals. J Hypertens. Aug 2007;25(8):1554-1564. PMID 17620947 27. Verdecchia P, Reboldi GP, Angeli F, et al. Short- and long-term incidence of stroke in white-coat hypertension. Hypertension. Feb 2005;45(2):203-208. PMID 15596572 28. Pickering TG, Shimbo D, Haas D. Ambulatory blood-pressure monitoring. N Engl J Med. Jun 1 2006;354(22):2368-2374. PMID 16738273 29. Staessen JA, Asmar R, De Buyzere M, et al. Task Force II: blood pressure measurement and cardiovascular outcome. Blood Press Monit. Dec 2001;6(6):355-370. PMID 12055415 30. Conen D, Bamberg F. Noninvasive 24-h ambulatory blood pressure and cardiovascular disease: a systematic review and meta-analysis. J Hypertens. Jul 2008;26(7):1290-1299. PMID 18550999 31. Hodgkinson J, Mant J, Martin U, et al. Relative effectiveness of clinic and home blood pressure monitoring compared with ambulatory blood pressure monitoring in diagnosis of hypertension: systematic review. BMJ. 2011;342:d3621. PMID 21705406 32. Stergiou GS, Bliziotis IA. Home blood pressure monitoring in the diagnosis and treatment of hypertension: a systematic review. Am J Hypertens. Feb 2011;24(2):123-134. PMID 20940712 33. Lovibond K, Jowett S, Barton P, et al. Cost-effectiveness of options for the diagnosis of high blood pressure in primary care: a modelling study. Lancet. Oct 1 2011;378(9798):1219-1230. PMID 21868086 34. Addison C, Varney S, Coats A. The use of ambulatory blood pressure monitoring in managing hypertension according to different treatment guidelines. J Hum Hypertens. Aug 2001;15(8):535-538. PMID 11494091 35. Staessen JA, Byttebier G, Buntinx F, et al. Antihypertensive treatment based on conventional or ambulatory blood pressure measurement. A randomized controlled trial. Ambulatory Blood Pressure Monitoring and Treatment of Hypertension Investigators. JAMA. Oct 1 1997;278(13):1065-1072. PMID 9315764

36. Staessen JA, Den Hond E, Celis H, et al. Antihypertensive treatment based on blood pressure measurement at home or in the physician's office: a randomized controlled trial. JAMA. Feb 25 2004;291(8):955-964. PMID 14982911 37. Aylett M, Marples G, Jones K. Home blood pressure monitoring: its effect on the management of hypertension in general practice. Br J Gen Pract. Sep 1999;49(446):725-728. PMID 10756615 38. Rickerby J. The role of home blood pressure measurement in managing hypertension: an evidencebased review. J Hum Hypertens. Jul 2002;16(7):469-472. PMID 12080430 39. Weisser B, Mengden T, Dusing R, et al. Normal values of blood pressure self-measurement in view of the 1999 World Health Organization-International Society of Hypertension guidelines. Am J Hypertens. Aug 2000;13(8):940-943. PMID 10950404 40. Verdecchia P, Palatini P, Schillaci G, et al. Independent predictors of isolated clinic ('white-coat') hypertension. J Hypertens. Jun 2001;19(6):1015-1020. PMID 11403348 41. Stergiou GS, Karpettas N, Panagiotakos DB, et al. Comparison of office, ambulatory and home blood pressure in children and adolescents on the basis of normalcy tables. J Hum Hypertens. Apr 2011;25(4):218-223. PMID 20520632 42. Urbina E, Alpert B, Flynn J, et al. Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the council on cardiovascular disease in the young and the council for high blood pressure research. Hypertension. Sep 2008;52(3):433-451. PMID 18678786 43. Valent-Moric B, Zigman T, Zaja-Franulovic O, et al. The importance of ambulatory blood pressure monitoring in children and adolescents. Acta Clin Croat. Mar 2012;51(1):59-64. PMID 22920003 44. Sorof JM, Portman RJ. White coat hypertension in children with elevated casual blood pressure. J Pediatr. Oct 2000;137(4):493-497. PMID 11035827 45. Matsuoka S, Kawamura K, Honda M, et al. White coat effect and white coat hypertension in pediatric patients. Pediatr Nephrol. Nov 2002;17(11):950-953. PMID 12432440 46. Hypertension: Clinical management of primary hypertension in adults. NICE clinical guideline 127 www.nice.org.uk/guidance/cg127. Accessed November 2014. 47. Dasgupta K, Quinn RR, Zarnke KB, et al. The 2014 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension. Can J Cardiol. May 2014;30(5):485-501. PMID 24786438 48. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. Jul 2013;34(28):2159-2219. PMID 23771844 49. O'Brien E, Asmar R, Beilin L, et al. European Society of Hypertension recommendations for conventional, ambulatory and home blood pressure measurement. J Hypertens. May 2003;21(5):821-848. PMID 12714851 50. O'Brien E, Asmar R, Beilin L, et al. Practice guidelines of the European Society of Hypertension for clinic, ambulatory and self blood pressure measurement. J Hypertens. Apr 2005;23(4):697-701. PMID 15775768 51. O'Brien E, Parati G, Stergiou G, et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. Sep 2013;31(9):1731-1768. PMID 24029863 52. Parati G, Stergiou G, O'Brien E, et al. European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. J Hypertens. Jul 2014;32(7):1359-1366. PMID 24886823 53. Williams B, Poulter NR, Brown MJ, et al. Guidelines for management of hypertension: report of the fourth working party of the British Hypertension Society, 2004-BHS IV. J Hum Hypertens. Mar 2004;18(3):139-185. PMID 14973512 54. Appel LJ, Robinson KA, Guallar E, et al. Utility of blood pressure monitoring outside of the clinic setting. Evid Rep Technol Assess (Summ). Nov 2002(63):1-5. PMID 15523745 55. The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics. Aug 2004;114(2 Suppl 4th Report):555-576. PMID 15286277 56. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. May 21 2003;289(19):2560-2572. PMID 12748199

57. Coverage Determinations Manual, Part 1, Section 20.19, Ambulatory Blood Pressure Monitoring (Rev. 1, 10-03-03). Centers for Medicare and Medicaid Services 2008; http://www.cms.hhs.gov/manuals/downloads/ncd103c1_part1.pdf Billing Coding/Physician Documentation Information 93784 Ambulatory blood pressure monitoring, utilizing a system such as magnetic tape and/or computer disk, for 24 hours or longer; including recording, scanning analysis, interpretation and report 93786 Ambulatory blood pressure monitoring, utilizing a system such as magnetic tape and/or computer disk, for 24 hours or longer; recording only 93788 Ambulatory blood pressure monitoring, utilizing a system such as magnetic tape and/or computer disk, for 24 hours or longer; scanning analysis with report 93790 Ambulatory blood pressure monitoring, utilizing a system such as magnetic tape and/or computer disk, for 24 hours or longer; physician review with interpretation and report A4670 Automatic blood pressure monitor A series of CPT codes describe the various steps in ambulatory blood pressure monitoring, e.g., recording (93786), scanning analysis (93788), and physician review and report (93790). These separate CPT codes may be used if different individuals perform the individual tasks. However, if one physician performs all of the above services, CPT code 93784 may be used. Code 93784 is a comprehensive code describing recording, scanning analysis, and interpretation and report. Policy Implementation/Update Information 1/1/89 New policy. Added to medical section. Considered investigational in the diagnosis and management of hypertension. 5/1/00 No policy statement changes. 5/1/01 No policy statement changes. 5/1/02 No policy statement changes. 5/1/03 No policy statement changes. 5/1/04 Revised policy statement to include, These devices are contract exclusions on most policies. 5/1/05 Revised policy statement to read that the diagnosis of hypertension in patients with elevated office blood pressure is investigational. Added to DME section 4/1/06 Revised policy statement to include patients with an established diagnosis of hypertension as medically necessary. 4/1/07 No policy statement changes. 4/1/08 No policy statement changes. 4/1/09 No policy statement changes. 9/1/09 No policy statement changes. 9/1/10 No policy statement changes. 9/1/11 No policy statement changes. 1/1/12 Policy statement revised to include additional medically necessary indications for patients with elevated office blood pressure. 9/1/12 No policy statement changes. 9/1/13 No policy statement changes. 9/1/14 No policy statement changes. 9/1/15 No policy statement changes. State and Federal mandates and health plan contract language, including specific provisions/exclusions, take precedence over Medical Policy and must be considered first in determining eligibility for coverage. The medical policies contained herein are for informational purposes. The medical policies do not constitute medical advice or medical care. Treating health care providers are independent contractors and are neither employees nor agents Blue KC and are solely responsible for diagnosis, treatment and medical advice. No part of this publication may be reproduced, stored in a

retrieval system or transmitted, in any form or by any means, electronic, photocopying, or otherwise, without permission from Blue KC.