Ambulatory Blood Pressure Monitoring (ABPM)

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The Centers for Medicare & Medicaid Services (CMS) has determined that the evidence is sufficient to cover ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension in Medicare beneficiaries under the following circumstances: For beneficiaries with suspected white coat hypertension, which is defined as an average office blood pressure of systolic blood pressure greater than 130 mm Hg but less than 160 mm Hg or diastolic blood pressure greater than 80 mm Hg but less than 100 mm Hg on two separate clinic/office visits with at least two separate measurements made at each visit and with at least two blood pressure measurements taken outside the office which are <130/80 mm Hg. For beneficiaries with suspected masked hypertension, which is defined as average office blood pressure between 120 mm Hg and 129 mm Hg for systolic blood pressure or between 75 mm Hg and 79 mm Hg for diastolic blood pressure on two separate clinic/office visits with at least two separate measurements made at each visit and with at least two blood pressure measurements taken outside the office which are ≥130/80 mm Hg. ABPM devices must be: capable of producing standardized plots of blood pressure measurements for 24 hours with daytime and night-time windows and normal blood pressure bands demarcated; provided to patients with oral and written instructions and a test run in the physician’s office must be performed; and interpreted by the treating physician or treating non-physician practitioner. For eligible patients, ABPM is covered once per year. Coverage of other indications for ABPM are at the discretion of the Medicare Administrative Contractors. See Appendix B for the manual language.

Decision Memo: TO: Administrative File: CAG-00067R2 FROM: Tamara Syrek Jensen, JD Director, Coverage and Analysis Group Joseph Chin, MD, MS Deputy Director, Coverage and Analysis Group Lori Ashby, MA Director, Division of Policy and Evidence Review Rosemarie Hakim, PhD Acting Director, Evidence Development Division Joseph Hutter, MD, MA Medical Officer Carl Li, MD, MPH Medical Officer Stuart Caplan, RN, MAS Lead Analyst Ruth McKesson Analyst SUBJECT: National Coverage Determination for Ambulatory Blood Pressure Monitoring DATE: July 2, 2019 I. Decision The Centers for Medicare & Medicaid Services (CMS) has determined that the evidence is sufficient to cover ambulatory blood pressure monitoring (ABPM) for the diagnosis of hypertension in Medicare beneficiaries under the following circumstances: For beneficiaries with suspected white coat hypertension, which is defined as an average office blood pressure of systolic blood pressure greater than 130 mm Hg but less than 160 mm Hg or diastolic blood pressure greater than 80 mm Hg but less than 100 mm Hg on two separate clinic/office visits with at least two separate measurements made at each visit and with at least two blood pressure measurements taken outside the office which are <130/80 mm Hg. For beneficiaries with suspected masked hypertension, which is defined as average office blood pressure between 120 mm Hg and 129 mm Hg for systolic blood pressure or between 75 mm Hg and 79 mm Hg for diastolic blood pressure on two separate clinic/office visits with at least two separate measurements made at each visit and with at least two blood pressure measurements taken outside the office which are ≥ 130/80 mm Hg. ABPM devices must be: capable of producing standardized plots of blood pressure measurements for 24 hours with daytime and night-time windows and normal blood pressure bands demarcated; provided to patients with oral and written instructions and a test run in the physician’s office must be performed; and interpreted by the treating physician or treating non-physician practitioner. For eligible patients, ABPM is covered once per year. Coverage of other indications for ABPM are at the discretion of the Medicare Administrative Contractors. See Appendix B for the manual language. II. Background Throughout this document we use numerous acronyms, some of which are not defined as they are presented in direct quotations. Please find below a list of these acronyms and corresponding full terminology: ABPM – Ambulatory Blood Pressure Monitoring ACC – American College of Cardiology AHA – American Heart Association APWV - Aortic Pulse Wave Velocity BMI – Body Mass Index BP – Blood Pressure CDC: Centers for Disease Control and Prevention CHAP - Cardiovascular Health Awareness Program CI – Confidence Interval CIM – Coverage Issues Manual CINAHL – Cumulative Index to Nursing and Allied Health Literature CMS – Centers for Medicare & Medicaid Services CKD – Chronic Kidney Disease COR – Class of Recommendation CV – Cardiovascular CVD – Cardiovascular Disease DBP – Diastolic Blood Pressure DHS – Dallas Heart Study ENRICA – Spanish Nutrition and Cardiovascular Risk Survey FDA – Food and Drug Administration GFR – Glomerular Filtration Rate HF – Heart Failure HR – Hazard Ratio IDACO – International Database on Ambulatory Blood Pressure Monitoring in Relation to Cardiovascular Outcomes IHD – Ischemic Heart Disease JNC 7 – The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure JNC 8 – The Eighth Joint National Committee Guidelines and the Outpatient Management of Hypertension in the African-American Population LOE – Level of Evidence MES – Multi-Ethnic Study of Atherosclerosis MetS - metabolic syndrome MI – Myocardial Infarction mm Hg – Millimeters of Mercury NCA – National Coverage Analysis NCD –National Coverage Determination NHANES – National Health and Nutrition Examination Study NOS - Newcastle–Ottawa Quality Assessment Scale NT - Normotensive OBPM – Office Blood Pressure Monitoring OR – Odds Ratio PAMELA – Pressioni Arteriose Monitorate E Loro RR – Relative Risk SBP – Systolic Blood Pressure SD – Standard Deviation SPRINT – Systolic Blood Pressure Intervention Trial TA – Technology Assessment The Act – Social Security Act US –United States USPSTF – United States Preventive Services Task Force WCE – White Coat Effect WCH –White Coat Hypertension What is hypertension (high blood pressure)? The American Heart Association (AHA) defines blood pressure as a force that pushes blood through a network of arteries, veins and capillaries. The blood pressure reading is the result of two forces: the systolic pressure occurs as blood pumps out of the heart and into the arteries; diastolic pressure is created as the heart rests between heart beats (American Heart Association, 2018). Elevated blood pressure, or hypertension, leads to harm by causing tiny tears in the interior lining (intima) of the arteries and coronary vessels, stimulating a local immune response in the endothelial cells within the atrial walls. In these regions, the arterial intima retains apolipoprotein B, which attracts lipid-rich macrophages (foam cells). These preatherotic lesions develop into atherosclerotic plaques which become increasingly fibrotic and can form fissures, hematomas, thrombi, and calcifications (Swirski and Nahrendorf, 2013). The end result is stiff, thickened arteries that narrow the flow of blood to organs and limbs, which both increases pressure on target organs and limits oxygenation of them. There is also the risk of atherosclerotic plaque rupture, resulting in distal vascular obstruction and ischemia and infarction of end organs, such as stroke in the brain (U.S. Department of Health & Human Services, 2018). Population based risks of hypertension Global: According to a systematic analysis for the Global Burden of Disease Study 2010, hypertension was the number one risk factor for death, responsible for approximately 9.4 million deaths globally from cardiac disease, including ischemic disease and heart failure, cerebrovascular disease, peripheral vascular disease, aortic disease, and kidney disease in that year (Lim et al., 2012). Another global systematic analysis based on 844 studies from 154 countries estimated that the rate of elevated SBP increased substantially between 1990 and 2015, and deaths associated with elevated SBP also increased (Forouzanfar, et al., 2017). Projections based on this sample suggested that in 2015, an estimated 3.5 billion adults had SBP of at least 110 to 115 mmHg and 874 million adults had SBP of 140 mm Hg or higher. United States: In the 2013-2016 National Health and Nutrition Examination Survey (NHANES), the prevalence of hypertension (defined at that time as SBP ≥ 140 or DBP ≥ 90) in the US was 30.5% (CDC, 2017). The rate of uncontrolled hypertension among known hypertensives was 55.4%. Hypertension was somewhat more prevalent in men than women (31.5% vs. 29.3%, respectively), but men were much more likely to have uncontrolled hypertension (60.9% vs. 46.7%). Blacks had a higher prevalence of hypertension than whites, Latinos, or Asians (42.4%, 29.2%, 29%, and 27%, respectively). By age, 67.4% of women 65–74 years and 78.7% of women 75 years and older had hypertension. Among men, the prevalence was 61.1% and 67.4%, respectively (CDC, 2016). Impact of hypertension on patient outcomes Mortality, stroke and cardiovascular disease An analysis of US data from nationally representative health surveys and disease-specific mortality statistics reported that about 1 in 5 deaths in the US were attributable to hypertension (Danaei et al., 2009). The US mortality rate decreased among hypertensive adults between the 1970s and 1990s, but the mortality gap between adults with and without hypertension remained relatively constant (Ford et al., 2011). In a pooled meta-analysis of individual data on nearly one million adults in 61 prospective cohorts from Europe, Japan, North America, Australia and China, researchers found that the risk of death from stroke, ischemic heart disease (IHD), and other vascular causes increased from SBP levels < 115 mm Hg to > 180 mm Hg and from DBP levels <75 mm Hg to > 105 mm Hg (Lewington et al., 2002). In that analysis, at ages 40–69 years, each difference of 20 mm Hg usual SBP (or, approximately equivalently, 10 mm Hg usual DBP) was associated with more than a twofold difference in the stroke death rate, and with twofold differences in the death rates from IHD and from other vascular causes. A second study of more than one million UK individuals followed for a mean of 5 years found more specific relationships between elevated BP and cardiovascular disease (Rapsomaniki, et al., 2014). At every age increment the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral and subarachnoid hemorrhage (stroke), and stable angina; and weakest for abdominal aortic aneurysm. Elevated systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, while elevated diastolic blood pressure had a greater effect on abdominal aortic aneurysm. People with hypertension (defined as BP ≥ 140/90 mm Hg or those on BP lowering drugs) had a lifetime risk of cardiovascular disease at age 30 years of 63% compared with 46% for those with normal blood pressure, and developed cardiovascular disease 5 years earlier. Kidney disease Hypertension is the second leading cause of kidney failure. The nephrons in the kidneys are supplied with a dense network of blood vessels and high volumes of blood flow through them. Over time uncontrolled high blood pressure can cause arteries around the kidneys to narrow, weaken or harden. These damaged arteries are not able to deliver enough blood to the kidney tissue. Kidney damage and uncontrolled high blood pressure affect aldosterone production contributing to a negative spiral of increasing blood pressure and eventual kidney failure. Current definition and prevalence of hypertension The 2001 ABPM NCD (See Appendix C) was based on the existing definitions of BP > 140/90 mm Hg. The 2017 American College of Cardiology/American Heart Association Task Force guidelines revised that definition as follows (Table 1) (Whelton et al., 2017). This will be discussed further in the evidence section. Table 1. Categories of BP in Adults* BP Category SBP DBP Normal <120 mm Hg and <80 mm Hg Elevated 120–129 mm Hg and <80 mm Hg Hypertension Stage 1 130–139 mm Hg or 80–89 mm Hg Stage 2 ≥ 140 mm Hg or ≥ 90 mm Hg *Individuals with SBP and DBP in 2 categories should be designated to the higher BP category. This definition differs from that previously recommended in the JNC 7 report, with stage 1 hypertension now defined as an SBP of 130–139 or a DBP of 80–89 mm Hg, and with stage 2 hypertension in the present document corresponding to stages 1 and 2 in the JNC 7 report (Chobanian et al., 2003). This new definition (Table 2) effectively increases the population prevalence of hypertension (based on reported antihypertensive medication use) from 64% and 63% of men and women ages 64-74 years, respectively, to 77% and 75%; and from 71% and 78% in men and women ages 75 years and older, respectively, to 79% and 85% (Whelton et al., 2017). Table 2 Prevalence of Hypertension Based on 2 SBP/DBP Thresholds*† SBP/DBP ≥ 130/80 mm Hg or Self- Reported Antihypertensive Medication† SBP/DBP ≥ 140/90 mm Hg or Self- Reported Antihypertensive Medication‡ Overall, crude 46% 32% Men Women Men Women Overall, age-sex adjusted 48% 43% 31% 32% Age group, y 20–44 30% 19% 11% 10% 45–54 50% 44% 33% 27% 55–64 70% 63% 53% 52% 65–74 77% 75% 64% 63% 75+ 79% 85% 71% 78% Race-ethnicity § Non-Hispanic white 47% 41% 31% 30% Non-Hispanic black 59% 56% 42% 46% Non-Hispanic Asian 45% 36% 29% 27% Hispanic 44% 42% 27% 32% *130/80 and 140/90 mm Hg in 9623 participants ( ≥ 20 years of age) in NHANES 2011–2014. †BP cutpoints for definition of hypertension in the present guideline. ‡BP cutpoints for definition of hypertension in JNC 7. § Adjusted to the 2010 age-sex distribution of the U.S. adult population. BP indicates blood pressure; DBP, diastolic blood pressure; NHANES, National Health and Nutrition Examination Survey; and SBP, systolic blood pressure *130/80 and 140/90 mm Hg in 9623 participants ( ≥ 20 years of age) in NHANES 2011–2014. †BP cutpoints for definition of hypertension in the present guideline. ‡BP cutpoints for definition of hypertension in JNC 7. §Adjusted to the 2010 age-sex distribution of the U.S. adult population. BP indicates blood pressure; DBP, diastolic blood pressure; NHANES, National Health and Nutrition Examination Survey; and SBP, systolic blood pressure Effectiveness of treatment for high blood pressure There is solid evidence that pharmacologic interventions lower BP (Law et al, 2009) and that this in turn lowers the risk of cardiovascular disease. A recent meta-analysis combined 123 RCTs of BP- lowering treatment with more than 600,000 participants. The meta-regression showed reductions in the relative risk of cardiovascular disease proportional to the magnitude of the SBP reduction (Ettehad et al., 2016). Every 10 mm Hg reduction in systolic blood pressure significantly reduced the risk of major cardiovascular disease events (relative risk 0.80, 95% CI 0.77–0.83), coronary heart disease (0.83, 0.78–0·88), stroke (0.73, 0.68–0.77), and heart failure (0.72, 0.67–0.78), which, in the populations studied, led to a significant 13% reduction in all-cause mortality (0.87, 0.84–0.91). The Sprint MIND study, which measured the effect of intensive vs standard BP control on probable dementia, found that intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases/1000 person-years; HR 0.81; 95% CI 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases/1000 person-years; HR 0.85; 95% CI 0.74-0.97) (Williamson et al., 2019). White coat hypertension and the white coat effect White coat hypertension is defined as having a higher office BP (OBPM) than out-of-office BP (Whelton et al., 2017) among patients not being treated for high BP. Gorostidi, et al. (2015) defines WCH as an elevated office BP and a 24-h ambulatory BP of <130/80 mm Hg. The white coat effect (WCE) is defined as the transient blood pressure rise associated with the presence of a doctor (Verdecchia et al., 2002) among patients regardless of treatment. The true prevalence of white coat hypertension (WCH) is unknown in the US and reported prevalence figures vary by definition and composition of the population (Whelton et al., 2017). The likelihood of WCH increases with age, is more prevalent among males, and may be accompanied by diabetes and a history of prior cardiovascular events. WCH is not benign and a number of population based cohort studies have shown it to be related to incident metabolic syndrome and higher long term mortality and cardiovascular endpoints than normotensive controls (Tientcheu et al., 2015; Franklin et al., 2016; Huang et al., 2017; Banegas et al., 2018; Cuspidi et al., 2018). Masked hypertension Masked hypertension occurs when individuals with office based BP <130/80 mm Hg and have elevated ambulatory BP ≥ 130/80 (Whelton et al., 2017). It is estimated that 12.3% of adults and 28% of persons older than 65 years have masked hypertension (Wang et al., 2017). It is more prevalent in men and African Americans, increases with age and may be accompanied by diabetes. Like WCH, masked hypertension is associated with incident metabolic syndrome, long term mortality, and cardiovascular endpoints than normotensive controls (Tientcheu et al., 2015; Whelton et al., 2017; Banegas et al., 2018; Cuspidi et al., 2018). Blood pressure measurement Manual BP monitoring in the clinical office gives point-in-time BP readings. The most traditional method of measurement is the auscultatory method, in which a trained observer uses a stethoscope to detect Korotkoff sounds which are made by the turbulent flow of blood through the brachial artery past the restricted area created by the inflated cuff. The readings are made using a mercury or aneroid sphygmomanometer. Sources of observer error and bias in the auscultatory method include differences in auditory acuity and terminal digit rounding (Piper et al., 2014). Oscillometric sphygmomanometers use a pressure transducer to assess the oscillations of pressure in a cuff during gradual deflation. The point of maximum oscillation corresponds to the mean intra-arterial pressure. Systolic and diastolic measurements are then calculated based on an empirically derived algorithm (Piper et al., 2014). Although the auscultatory methods are inherently accurate, they are dependent on attention to detail, which may be lacking, and they provide only a momentary measurement of BP under circumstances that can influence the level of BP being measured (O’Brien et al., 2013). Blood pressure can be measured by patients at home or in other environments. A small body of evidence suggests, but does not confirm, that home blood pressure monitoring may predict patient outcomes (Piper et al, 2014). Whelton et al (2017) stated that home BP measurement maybe a more practical approach in clinical practice. It should be noted that patient used home BP readings are generally not accurate when compared to standardized mercury sphygmomanometry (Ringrose et al, 2017). ABPM devices provide a larger number of readings than OBPM and a profile of blood pressure in the patient’s usual environment. ABPM is intended to allow identification of white coat and masked hypertension, uncover nocturnal hypertension, and assess blood pressure variability over a 24-hour period as well as the 24-hour efficacy of antihypertensive medication (O’Brien et al, 2013). ABPM devices are small portable machines connected to a BP cuff worn by patients that record BP at regular intervals over 24 to 48 hours while patients go about their normal activities, including sleep. Measurements are typically taken at 20- to 30-minute intervals. Results may be reported for 24 hours, daytime (awake), and nighttime (asleep). Modern ambulatory devices use oscillometric techniques (Piper et al., 2014). The U.S. Preventive Services Task Force (USPSTF) recommends annual screening for high BP in adults aged 18 years or older and recommends obtaining measurements outside of the clinical setting (either ABPM or home BP monitoring) for diagnostic confirmation of high BP before starting treatment (Sui, 2015). The USPSTF specifically states that "In addition to office blood pressure measurement, ABPM and HBPM may be used to confirm a diagnosis of hypertension after initial screening" (US Preventive Services Task Force, 2019). III. History of Medicare Coverage CMS has covered ABPM since 2001 only for those patients with documented suspected white coat hypertension. On January 16, 2003, a technical correction for this NCD was issued to clarify that a physician is required to perform the interpretation of the data obtained through ABPM, but that there are no requirements regarding the setting in which the interpretation is performed. A. Current Request CMS received a complete, formal request for a reconsideration of the national coverage determination from the American Heart Association and American Medical Association. The formal request letter can be viewed on the tracking sheet for this NCA on the CMS website by clicking here . B. Benefit Category Medicare is a defined benefit program. For an item or service to be covered by the Medicare program, it must fall within one of the statutorily defined benefit categories outlined in the Social Security Act. ABPM may be considered to be within the benefits described under sections: other diagnostic tests §1861(s)(3). Medicare regulations at 42 CFR 410.32(a) state in part, that "…diagnostic tests must be ordered by the physician who is treating the beneficiary, that is, the physician who furnishes a consultation or treats a beneficiary for a specific medical problem and who uses the results in the management of the beneficiary’s specific medical problem." IV. Timeline of Recent Activities Date Action October 9, 2018 CMS posts a tracking sheet announcing the opening of an NCA. The initial 30- day public comment period begins. November 8, 2018 First public comment period ends. CMS receives 103 comments. April 9, 2019 Proposed Decision Memorandum posted. 30-day public comment period begins. V. Food and Drug Administration (FDA) Status Companies manufacturing devices intended for 24 Hour, Ambulatory Blood Pressure monitoring have obtained clearance for marketing of these devices under the Food and Drug Administration’s (FDA) 510(k) process. The FDA considers all BP Monitoring devices to be Class II devices. All Ambulatory Blood Pressure monitors with FDA clearance have demonstrated accuracy compared to reference blood pressure measurements. VI. General Methodological Principles In general, when making national coverage determinations under section 1862(a)(1) of the Social Security Act, CMS evaluates relevant clinical evidence to determine whether or not the evidence is of sufficient quality to support a finding that an item or service falling within one or more benefit categories is reasonable and necessary for the diagnosis or treatment of illness or injury or to improve the functioning of a malformed body member (§ 1862 (a)(1)(A)). The critical appraisal of the evidence during a national coverage analysis enables us to determine to what degree we are confident that: 1) the specific assessment of a clinical question relevant to the coverage request can be answered conclusively; and 2) the intervention will improve health outcomes for beneficiaries. An improved health outcome is one of several considerations in determining whether an item or service is reasonable and necessary. A detailed account of the methodological principles of study design that the Agency utilizes to assess the relevant literature on a therapeutic or diagnostic item or service for specific conditions can be found in Appendix A. In general, features of clinical studies that improve quality and decrease bias include the selection of a clinically relevant cohort, the consistent use of a single good reference standard, blinding of readers of the index test, and reference test results. Public commenters sometimes cite the published clinical evidence and provide CMS with useful information. Public comments that provide information based on unpublished evidence, such as the results of individual practitioners or patients, are less rigorous and therefore less useful for making a coverage determination. Public comments that contain personal health information will be redacted or, in some cases, will not be made available to the public. CMS responds in detail to the public comments on a proposed national coverage determination when issuing the final decision memorandum. VII. Evidence A. Introduction This section provides a summary of the evidence we considered during our review. The evidence reviewed to date includes the published medical literature on pertinent studies that link WCH and masked hypertension to end organ damage and death. B. Discussion of Evidence 1. Evidence Question(s) Our review and analysis of the evidence on the clinical utility of ABPM in patients with office-based elevated (white coat) blood pressure, and in patients being treated for hypertension who are suspected as having masked hypertension, is guided by the following questions: In patients with suspected white coat hypertension who are not on treatment for elevated blood pressure, does ABPM improve health outcomes? In patients with white coat hypertension, does ABPM improve health outcomes? In patients with suspected masked hypertension, does ABPM improve health outcomes? 2. External Technology Assessments While CMS did not request an external technology assessment (TA) as part of this reconsideration, a structured literature review and meta-analysis that focused on the effects of blood pressure monitoring was conducted by the US Preventive Services Task Force (USPSTF) and published by the Agency for Healthcare Research and Quality (AHRQ) in 2014. It was published in condensed form in the Annals of Internal Medicine in 2015. Piper MA, Evans CV, Burda BU, Margolis KL, O’Connor E, Smith N, Webber E, Perdue LA, Bigler KD, Whitlock EP. Screening for High Blood Pressure in Adults: A Systematic Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2014 Dec. Available from http://www.ncbi.nlm.nih.gov/books/NBK269495/ PMID: 25632496. And Piper MA, Evans CV, Burda BU, Margolis KL, O'Connor E, Whitlock EP. Diagnostic and predictive accuracy of blood pressure screening methods with consideration of rescreening intervals: a systematic review for the U.S. Preventive Services Task Force. Ann Intern Med. 2015 Feb 3;162 (3):192-204. doi: 10.7326/M14-1539. PubMed PMID: 25531400. The authors performed a technology assessment that included a systematic literature review and meta- analysis to support the USPSTF in updating its recommendation on screening for high blood pressure (BP) in nonpregnant individuals. The USPSTF report focused on screening for high BP. The USPSTF report evaluated the benefit of office based BP measurement and out-of-office measurement with an emphasis on ABPM. The USPSTF assessment was based on key questions that examined evidence for the benefits and harms of screening for high BP, diagnostic accuracy of OBPM, prediction of cardiovascular events by BP method and diagnostic accuracy of non-office measurement, and rescreening interval. The authors searched MEDLINE, PubMed, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from 2003 through August 2014 to review the benefits and harms of screening for high BP. The review used studies that followed cohorts over time and reported the hazard or risk ratios of BP as a continuous variable, measured by at least 2 methods at baseline. The authors required all studies to be from highly developed countries and enrolled previously untreated adults. The authors reviewed 19,309 abstracts and 1171 articles. To answer the question about the benefit of BP screening, the authors found one good quality cluster randomized controlled trial pharmacy-based BP screening of adults aged 65 years or older in Ontario Canada (Kaczorowski et al., 2011). This trial demonstrated fewer annual composite cardiovascular- related hospitalizations in the intervention group than in the control group (rate ratio 0.91 [95% CI, 0.86 to 0.97]; P = 0.002). When the data were analyzed by the number of unique patients hospitalized, only the reduction in admissions for acute myocardial infarction was statistically significant (rate ratio 0.89 [CI, 0.79 to 0.99]; P = 0.03). This study and its long term follow up are discussed in more detail later in this review. In the authors’ evaluation of the diagnostic accuracy of office based BP measurement using manual sphygmomanometry as the reference standard, they found sensitivities ranging from 51% to 68% for elevated BP defined as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg in three studies. A fourth study reported a sensitivity of 91%, but differed from the others in that it used an elevated BP (systolic BP ≥ 160 mm Hg or diastolic BP ≥ 95 mm Hg) and a more stringent design to minimize human error. The specificities ranged from 92% to 97% (in the more stringent study) and positive predictive value (PPV; the probability that a particular patient has the disease, given a positive test result) ranged from 76% to 84%. They also evaluated the effect of repeated OBPM measurements, finding that in one large US study, 27.5% were reclassified using the mean of all three BP measurements for diagnosis, and 35.5% were reclassified as normal using the mean of the second and third BP measurements for diagnosis. The authors conducted a meta-analysis to evaluate the best predictors of cardiovascular events by BP measurement method (ABPM, OBPM, and other out-of-office measurements). Where reported, all ABPM devices were oscillometric, and typically took measurements every 15 to 30 minutes during the day and every 30 to 60 minutes at night. Outcomes for 24-hour, daytime, and nighttime monitoring cycles were reported in 8, 10, and 9 studies, respectively. Results did not vary by geographic region or population baseline characteristics. Unadjusted hazard ratios (HRs) for systolic OPBM were not consistently statistically significant, ranging from 1.07 to 1.29 for stroke and 1.06 to 1.32 for CV events or mortality (Figure 1). This pattern of results for OBPM was similar across all ABPM versus OBPM comparisons and outcomes. Figure 1 Risk for Cardiovascular and Mortality Outcomes: OBPM, Not Adjusted for 24-hour ABPM Abbreviations: CI = confidence interval; CV = cardiovascular; HF = heart failure; HR = hazard ratio; MI = myocardial infarction Each 10-mm Hg increase in 24-hour systolic ABPM, adjusting for OPBM, was consistently associated with increased risk for fatal and nonfatal stroke events in four studies (Figure 2). Risk estimates ranged from an HR of 1.28 to 1.40 and were all statistically significant, indicating that systolic ABPM predicted stroke events statistically significantly and independently of OBPM. The largest risk estimate (HR 1.40 [95% CI, 1.21 to 1.62]) was reported for a community-based study in rural Japan, which enrolled 1,332 participants who were followed for a mean of 10.2 years. This study was the only study that did not limit participation to those with hypertension and had by far the lowest mean baseline OBPM (131/74 mm Hg). In 6 studies, each 10–mm Hg increment in 24-hour systolic ABPM, adjusted for OBPM, was associated with an increased risk for fatal and nonfatal cardiovascular events, which was statistically significant in 5 studies. Hazard ratios ranged from 1.11 to 1.42. The authors concluded that all studies reported lower event rates or risk estimates for participants with isolated clinic hypertension than for those with sustained hypertension. Figure 2. Risk for Cardiovascular and Mortality Outcomes: Systolic 24-hour ABPM, Adjusted for OBPM Abbreviations: CI = confidence interval; CV = cardiovascular; HF = heart failure; HR = Hazard ratio; MI = myocardial infarction. The authors evaluated the diagnostic accuracy of confirmatory BP measurement methods by using ABPM as the reference standard, subsequent to an elevated BP at screening. Daytime ABPM was measured in 18 nonoverlapping studies that evaluated diagnostic accuracy in 69 to 1,466 participants per study. The proportion of participants with elevated OBPM and true hypertension (as measured by daytime ABPM) ranged from 0.47 (95% CI, 0.40 to 0.55) to 0.93 (95% CI, 0.87 to 0.99) (Figure 3). Figure 3. Proportion of Elevated Office-Based Screening Results that are Confirmed Hypertension by ABPM The authors also evaluated whether there were any harms associated with BP screening and found no differences in psychological distress or quality of life when subjects were labeled as hypertensive or prehypertensive (excluding misdiagnosis and unnecessary treatment). There were, however, increases in overall absenteeism from work, absenteeism due to illness, and number and duration of illness episodes after labeling persons who were previously unaware of their hypertension status as hypertensive. The authors concluded that ABPM (24-hour, daytime, or nighttime) is a better predictor of long-term CV outcomes than OBPM (manual sphygmomanometry) and should be considered the reference standard for evaluating BP noninvasively. Initial screening with office-based methods variably predicts hypertension, as defined by ABPM, resulting in a significant population with isolated clinic hypertension. Limited evidence suggested that people with isolated clinic hypertension have outcomes more like normotensive than hypertensive persons. Failure to confirm initial elevated OBPM results may result in misdiagnosis and overtreatment. Limited evidence suggested that repeated measurements and improved procedural control (e.g., automation) may improve the diagnostic accuracy of OBPM when used to screen for high BP or confirm hypertension in the office. Studies of rescreening intervals at up to 6 years found a higher incidence of hypertension overall and at shorter intervals for persons with BP in the high-normal range, older adults, persons with an above normal BMI, and African Americans. These studies showed much lower incidence at longer rescreening intervals (up to 6 years) in persons without these risk factors. Based on the results of their metaanalysis, the authors stated that failure to confirm initial elevated OBPM results may result in misdiagnosis and overtreatment. 3. Internal Technology Assessment Literature Search Methods We searched PubMed and the Cochrane Library from 2014, the year that the USPSTF assessment was published (Piper et al, 2014) to the present. Search terms included ambulatory blood pressure monitoring (ABPM), white coat hypertension (WCH), and masked hypertension. We looked for: 1) studies that evaluated the prevalence of WCH and masked hypertension in representative populations; 2) studies that evaluated the effect of WCH and masked hypertension or stroke, cardiovascular morbidity, and cardiovascular and all-cause mortality; and 3) studies on clinical utility of ABPM in predicting and improving health outcomes including cardiovascular outcomes and mortality compared to office based BP monitoring (OBPM). Our search terms included "blood pressure monitoring", "ambulatory blood pressure monitoring (both systolic and diastolic)", "cardiovascular diseases/morbidity/mortality", "all-cause mortality", "stroke" , "white coat hypertension", "uncontrolled hypertension", "office blood pressure", "isolated clinic hypertension", and "masked hypertension". We excluded studies of home blood pressure monitoring. We identified two meta- analyses, one randomized control trial, six analyses of population based prospective longitudinal cohorts, and one nested case-control study. We also reviewed references submitted to us by the requester and commenters and performed a hand search of bibliographies to identify other pertinent articles. Kaczorowski J, Chambers LW, Dolovich L, et al. Improving cardiovascular health at population level: 39 community cluster randomised trial of Cardiovascular Health Awareness Program (CHAP). BMJ. 2011 Feb 7;342:d442. The aim of this study was to evaluate the effectiveness of the community based Cardiovascular Health Awareness Program (CHAP) on morbidity from cardiovascular disease. This was a randomized trial of municipalities (n=41) in Ontario Canada with populations of 10 to 60 thousand. The study was based in 39 of these municipalities (2 of the 41 were the location of the pilot test) with a total population of 973,246, including 140,542 people older than age 65 years. The 39 communities were stratified by population size and geographical location. The intervention (CHAP [n=20] vs. no intervention [n=19]) was randomly allocated to each stratum. Availability of usual health promotions and services was unchanged. The CHAP intervention was delivered by peer volunteers and consisted of 10 weeks of 3-hour weekday blood pressure and cardiovascular risk factor assessment and educational sessions held concurrently in all 20 intervention communities during the autumn of 2006. Blood pressure readings and other information on cardiovascular risk factors were recorded, provided to each participant, and with participants’ consent sent to their family physician and usual pharmacist. Of interest to this review is the out-of-office blood pressure program. Evaluation of the program relied on routinely collected population based administrative health data, including hospital discharge abstracts from the Canadian Institute for Health Information, physician service claims from the Ontario Health Insurance Program, and prescription drug claims from the Ontario Drug Benefit Program. The primary outcome measure was the change in the mean annual rate of hospital admissions with a "most responsible" (primary) discharge diagnosis of acute myocardial infarction, congestive heart failure, or stroke (composite end point) among community dwelling residents aged 65 years and over in the year before compared with the year after implementation of CHAP. Secondary outcome measures were mortality during the above hospital admissions, all-cause mortality, and newly prescribed antihypertensive drug treatment. Hospital admissions of interest occurred between September 1, 2005 and August 31, 2006 ("pre-intervention period") and between September 1, 2007 and August 31, 2008 ("post-intervention period"). The denominator was the number of community dwelling people aged 65 years and over who were alive and residing in each study community on the first day of the pre-intervention period. The mean number of residents aged 65 years and over in the 39 study communities was 3606, their mean age was 74.8 years, and 42.8% were male. There were statistically significant differences between the control and intervention communities with respect to rurality (28.96% vs. 31.63% rural), income status (16.95% vs. 18.57% lowest income quantile), average number of prescription drugs in the previous year (7.25 vs. 6.98), Charlson comorbidity index (0.57 vs. 0.58), history of heart failure (12.19% vs. 12.45%), and death rate per 1000 (3.45 vs. 3.55). The authors found statistically significant reductions favoring the intervention communities in hospital admissions for acute myocardial infarction (RR 0.87, 95% CI 0.79 to 0.97) and congestive heart failure (RR 0.90, 95% CI 0.81 to 0.99) but not for stroke (RR 0.99, 95% CI 0.88 to 1.12) for community residents aged 65 years and older (Table 3). These numbers may have included multiple admissions per person. A second analysis of individuals aged 65 and older, found statistically significant difference favoring the CHAP intervention in newly prescribed antihypertensive drug treatment (RR 1.10, 95% CI 1.02 to 1.20), a trend towards lower in hospital cardiovascular mortality (RR 0.86, 95% CI 0.73 to 1.01), and no difference in all-cause mortality (RR 0.98, 95% CI 0.92 to 1.03). Table 3 Comparison of mean hospital admission rates per 1000 by study arm Pre-intervention rate Post-inervention rate Hospital admissions CHAP (n=67 874) Control (n=72 768) CHAP (n=69 942) Control (n=75 499) Rate ratio (95% CI) Composite 30.15 29.36 27.90 30.13 0.91 (0.86 to 0.97) Acute myocardial infarction 10.24 10.26 9.54 10.81 0.87 (0.79 o 0.97) Congestive heart failure 11.19 11.11 10.51 12.22 0.90 (0.81 to 0.99) Stroke 8.71 7.99 7.86 7.10 0.99 (0.88 to 1.12) The authors discussed the following limitations: 1) the specific components of CHAP that were responsible for the observed reductions in hospital admissions are unknown; 2) other environment factors may have been at play such as an increase in the rate of newly prescribed antihypertensive treatment or improved adherence to guidelines for starting of drug treatment or lifestyle changes in the CHAP communities. The authors concluded that the CHAP community based health promotion and prevention program targeted at older adults can reduce cardiovascular morbidity at the population level. Dahrouge S, Kaczorowski J, Dolovich L, et al. Long term outcomes of cluster randomized trial to improve cardiovascular health at population level: The Cardiovascular Health Awareness Program (CHAP). PLoS One. 2018 Sep 6;13(9):e0201802. This study evaluated the impact of the CHAP intervention on morbidity and mortality related to cardiovascular events over the five years after the intervention. The authors followed all community- dwelling individuals 65 years of age and older who were eligible for the CHAP cluster randomized as described above from September 1, 2006 through August 31, 2011 using administrative health data. All residents of the 39 communities meeting the study eligibility criteria as of the intervention start date were identified to form the study cohort. The list was limited to individuals 65 years of age or older using a registered persons database, and to those residing in the community, and excluding residents of long term care facilities identified from a continuing care reporting system. The dataset comprised 143,976 individuals, 69,318 and 74,658 in the intervention and control communities, respectively, which was followed for 5 years. The main outcome was CVD-related hospitalizations; a composite endpoint indicating hospitalizations for which the most responsible diagnosis was stroke, CHF, or acute myocardial infarction. Secondary outcomes included hospitalizations for each condition separately, CVD-related in-hospital deaths and all-cause mortality. All analyses were intention-to-treat. The primary analytic endpoint was the count of CVD-related hospitalizations (Event level) per cumulative 100 person- years follow-up. Secondary outcomes included the rate of hospitalizations for each reason separately, mortality rates, and rates of individuals having at least one hospitalization (individual level). They used Kaplan-Meier plots to visually depict the time to first event for each outcome and assessed the hazard of an individual having the outcome of interest over time using a Cox regression model with frailty (random effects) to account for clustering at the community level and adjusting for the pre-intervention baseline rate of the outcome. The five-year cumulative rate ratio [95% confidence interval (CI)] for CVD-related hospitalizations was 0.958 [0.898±1.022], translates into an estimated 408 averted hospitalizations, or 5.9 per 1,000 individuals over the five-year period. Most estimates pointed to an advantage for individuals residing in the intervention communities, but only the hazard ratio for all-cause mortality was significantly different across the groups (HR [CI] = 0.955 [0.914±0.999], p = 0.0429). Accounting for the ruralit status of the individuals in the community in the post hoc analyses, the rate ratio [CI] 0.855 [0.750±0.976]) and HR 0.862 [0.770±0.965] of death occurring during CVD-related hospitalizations were statistically significantly in favor of the intervention arm. The authors acknowledged the following limitations: 1) Because the study relied exclusively on health administration data, there was not access to information that could help elucidate the findings such as determining participants' access to the recommended resources, and assessing changes in patient health behaviors, blood pressure levels, or other factors that could have helped explain the pathway through which the intervention imparted cardiovascular protection; 2) There was no data on the intensity with which the intervention communities maintained CHAP activities and how these might have been adapted to help understand the impact of these factors on the intervention 5-year effectiveness measures; 3) There were too few communities to allow an assessment of community resources available to participants; 4) The closed cohort approach did not account for migration of individuals across communities; 5) The increased awareness of cardiovascular disease could have led to an increased likelihood of assigning cardiovascular disease as a reason for hospitalization; and 6) The small number of clusters in the study may have reduced the study power. The last three limitations would reduce the ability of the study to find differences. The authors concluded that there was a consistent pattern favoring better health outcomes in the intervention compared to the control communities, with all-cause mortality reaching statistical significance. They concluded that the results suggest an apparent reduction in morbidity and mortality in the intervention arm over the five-year period with no evident attenuation of the observed effect over time, demonstrating a 9% reduction in the risk of CVD hospitalization in the first year following the intervention year and an average 4% [-2%-10%] risk reduction in the five years following the intervention: a lower yearly estimate, but potentially prolonged clinically meaningful consequences. Banegas JR, de la Cruz JJ, Graciani A, et al. Impact of Ambulatory Blood Pressure Monitoring on Reclassification of Hypertension Prevalence and Control in Older People in Spain. J Clin Hypertens (Greenwich). 2015 Jun;17(6):453-61. The aim of this study was to estimate the impact of ABPM on the prevalence and control of BP in older adults in Spain, to allow quantification of overtreatment or undertreatment and obtain a balanced view of the burden of hypertension in the population. This was an observational, cross- sectional analysis using data collected in the second wave (2012) of the Spanish Nutrition and Cardiovascular Risk Survey (ENRICA). Participants were randomly selected from the Spanish population aged 60 years and older. The second wave consisted of 2519 individuals and included a phone interview on health status, lifestyle, and morbidity; and a home visit to record BP, body mass measurements, diet, and medication. ABPM was offered to 1698 individuals and performed in 1328 patients (response rate, 78.2%). Casual BP was measured with validated automatic devices three times at 2-minute intervals after the patients rested for 5 minutes in a seated position and calculated as the mean of the last two readings. ABPM was performed with a validated oscillometric device programmed to read BP at 20-minute intervals during the day and at 30-minute intervals during the night for 24-hours. There were 1047 patients with 70% or more valid ABPM readings. The authors grouped patients by casual BP into 2 hypertension categories: 720 hypertensive (casual BP threshold ≥ 140/90 mm Hg) and 327 normotensive patients. They also grouped the patients by treatment status, antihypertensive drug treated (n=514) and untreated (n=533) patients. The latter included 206 untreated hypertensives and 327 normotensives. They used these categories to calculate the percentage of hypertensive patients according to casual BP and according to ABPM; and the percentage of patients at BP goal according to casual BP and according to ABPM. The authors then calculated the percentage of patients reclassified from above casual BP goal to the ABPM goal, and those reclassified the casual BP goal to above ABPM goal for the total sample and by BP medication status. The mean age of patients was 71.7 years, 50.8% were men, mean BMI was 28.1 kg/m2, 14.9% had diabetes, and 5.7% had previous CVD. Mean casual BP was 137.8/74.0 mm Hg, mean 24-hour BP was 123.6/69.8 mm Hg. Hypertensive patients were older, more likely to be obese and have diabetes than normotensive patients. Treated hypertensive patients were older, with higher BMI and higher frequency of obesity, diabetes, and history of CVD than untreated patients. Mean casual and ambulatory SBPs were higher in treated hypertensive patients than untreated participants. There was only moderate correlation between casual BP and ABPM. Compared with participants without ABPM, those with a 24-hour ABPM had similar age (71.8 years vs. 71.7 years), proportion of men (47% vs. 49%), education level (63% vs. 61% with ≤ primary studies), mean body mass index (BMI; 27.8 vs. 27.5 kg/m2), proportion of diabetes (15.1% vs. 16.1 %), current smoking (11.0% vs. 11.7%), and history of cardiovascular disease (CVD; 5.7% vs. 4.5%). The scatterplot (Figure 3) shows a marked overestimation of casual SBP compared to ambulatory SBP. The mean difference between casual and 24-hour SBP was 14.3 mm Hg. Figure 4. Bland-Altman plot for the association between casual and ambulatory s (SBP) There were 596 patients within casual BP normotensive range (56.9% CI, 53.9%–59.9%) and 749 were at 24-hour BP normal range or goal (71.5%; 95% CI 68.8%–74.2%; absolute difference, 14.6%; P < .001) (Table 4). There were 269 treated hypertensive patients at casual BP goal (52.4%) and 352 at 24-hour BP goal (68.5% difference, 16.1%; P < .001). There were 720 casual BP–based hypertensive patients and 650 ABPM–based hypertensive patients eligible for treatment. BP control among these patients with treatment-eligible hypertension increased from 37.4% with a casual BP target to 54.1% with a 24-hour ABPM target (absolute difference, 16.7%; P < .01). Total reclassifications were 21.7% from above normal casual BP to a normal 24-hour BP, and 7.1% from a normal casual BP to above normal 24-hour BP. TABLE 4. Reclassification of BP Control Status According to Ambulatory Monitoring by Treatment Status. Casual BP At casual and 24-hour BP Goal Reclassified to Above 24-hour BP Goal Not Hypertensive or at Casual BP <140/90 mmHg Total 522 (49.9%) 74 (7.1%) 596 (56.9%) Untreated 294 (55.2%) 33 (6.2%) 327 (61.4%) Treated 228 (44.4) 41 (8.0%) 269 (52.3%) Reclassified to 24-hour BP Goal Above Casual and 24-hr BP Goal Above Casual BP Goal ≥ 140/90 mmHg Total 227 (21.7%) 224 (21.4%) 451 (43.1%) Untreated 103 (19.3%) 103 (19.3%) 206 (38.6%) Treated 124 (24.1%) 121 (23.5%) 245 (47.7%) Abbreviations: BP, blood pressure; treated, hypertensive patients taking current BP medication; untreated, normotensive and untreated hypertensive patient