The term “home blood pressure‐monitoring (HBPM)” commonly refers to the self‐measurement of blood pressure (BP) at home, although in some studies, HBPM describes a provider or research assistant measuring an individual’s BP in his/her home. Both ambulatory blood pressure monitoring (ABPM) and HBPM can identify white‐coat hypertension (diagnostic disagreement between office and out‐of‐office BP in untreated subjects) and white‐coat uncontrolled hypertension (diagnostic disagreement in treated subjects) [41, 111, 156,178–182]. Although ABPM has been the preferred out‐of‐office measurement tool, the 2017 American Heart Association/American College of Cardiology (AHA/ACC) hypertension guidelines suggest that HBPM may be a more practical approach in clinical practice, particularly during antihypertensive therapy. A commonly recommended HBPM monitoring schedule consists of performing morning and evening BP measurements twice on each occasion over a minimum of three days with a preferred period of seven days (Figure 2.1) [183–185]. Several clinic‐based prospective studies have investigated the prognostic importance of home BP measurements in treated patients with hypertension (Table 2.1) [56,186–190]. All studies demonstrated that home BP is superior to office BP for the prediction of cardiovascular events. In the J‐HOP study, patients with masked hypertension had a worse prognosis with respect to stroke than those with well‐controlled or white‐coat hypertension, and the risk of stroke associated with masked hypertension was comparable to that of patients with sustained hypertension (Figure 2.2) [191] . Morning hypertension is the most important and effective clinical target in the management of hypertension. In particular, for medicated patients with hypertension, once daily dosing of antihypertensives means that BP‐lowering effects are weakest first thing in the morning, immediately prior to the next dose. Thus, morning BP control is the “blind spot” for current hypertensive medication. Morning BP can easily be self‐measured using a HBPM device. Two types of morning hypertension are detected by HBPM [156, 178]. One is the “morning surge” type, characterized by an exaggerated morning blood pressure surge (MBPS), and the other is the “sustained nocturnal hypertension” type with continuous hypertension from nocturnal hypertension (non‐dipper/riser type) (Figure 2.3). These two forms of morning hypertension both increase the risk of cardiovascular and renal diseases, but this occurs via different pathogenic mechanisms and each are associated with different conditions. The only way to reliably differentiate between “morning surge” and “sustained nocturnal hypertension” is to measure home BP during sleep, either using ABPM or newer automated HBPM devices. Table 2.1 Prospective, general practitioner‐based, home BP studies. Source: Modified from Kario et al. Hypertension. 2019; 74: 229–236 [192] . BP, blood pressure; CI, confidence interval; CSBP, clinic systolic BP; CVD, cardiovascular disease; HBPM, home BP monitoring; HR, hazard ratio; SBP, systolic BP; SD, standard deviation. †Self‐Measurement of Blood Pressure at Home in the Elderly: Assessment and Follow‐up (SHEAF) study ‡Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED‐BP) §Home Blood Pressure Measurement With Olmesartan Naive Patients to Establish Standard Target Blood Pressure (HONEST) study ||Japan Morning Surge‐Home Blood Pressure (J‐HOP) study. Figure 2.4 [171] shows the morning systolic blood pressure (SBP) control status and changes associated with application of new cut‐off values based on the AHA/ACC 2017 guidelines [178] compared with those classified by the previous Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) guidelines [193] using data from the Japan Morning Surge‐Home Blood Pressure (J‐HOP) study, a general practice‐based national registry of home BP (4310 patients with treated hypertension, mean age 64.9 years, 47% male). Prevalence rates for normotension, white‐coat hypertension, masked morning hypertension, and sustained morning hypertension changed from 31%, 15%, 19%, and 36%, respectively, using JNC7 definitions (140/90 mmHg for office BP and 135/85 mmHg for home BP) [193] to 14%, 17%, 10%, and 58%, respectively, based on the AHA/ACC 2017 definitions (130/80 mmHg for both office and home BP) (Figure 2.4) [171, 178]. The lower single BP threshold of 130/80 mmHg for both office and home BP values could be acceptable for two reasons. First, in general, the difference between office and out‐of‐office BP values decreases to reach a similar level to that shown in Figure 2.4 [171] . Second, clinically, the decrease in masked morning hypertension and the increase in sustained morning hypertension provides physicians with the opportunity to strictly treat hypertension without underestimation of cardiovascular risk due to undetected masked morning hypertension. A lower morning BP (SBP <125 mmHg) target may be ideal for minimization of cardiovascular risk, regardless of office BP level [56] . The Ohasama study of a general population‐based cohort first demonstrated that morning home BP is a better predictor of cardiovascular prognosis than office BP [194] . The J‐HOP study, one of the nationwide, general practitioner‐based cohorts of cardiovascular risk patients (Table 2.1) showed that morning home BP was a better predictor of stroke than evening home BP (Figure 2.5) [189] . An analysis of 349 patients aged ≥80 years from this trial found that higher morning SBP was a significant risk factor for composite cardiovascular events (hazard ratio [HR] per 10 mmHg increase in morning SBP, 1.23; 95% confidence interval [CI] 1.01–1.50) and stroke events (HR per 10 mmHg increase in SBP, 1.47; 95% CI 1.08–2.00) after adjustment for four‐year cardiovascular risk scores and office SBP (Figure 2.6) [195] . This association was not observed for office BP or evening home BP. In J‐HOP study, participants with nonelevated high‐sensitive cardiac troponin T level (hs‐cTnT; <0.014 ng/mL, n = 3307), an adjusted Cox hazard model showed that home SBP was associated with stroke risk (HR per 1 standard deviation [SD] increase, 1.62). In the group with elevated hs‐cTnT, lower home diastolic blood pressure (DBP) was associated with the risk of coronary artery disease (CAD; HR per 1 SD increase, 0.54). These findings suggest that excessive lowering of home DBP in patients with subclinical myocardial ischemia may be associated with a risk of incident CAD (Figure 2.7) [196] . On‐treatment morning home BP was also a stronger predictor of cardiovascular events than office BP in the Hypertension Objective treatment based on Measurement by Electrical Devices of Blood Pressure (HOMED‐BP) study [188] and the Home blood pressure measurement with Olmesartan Naïve patients to Establish Standard Target blood pressure (HONEST) study [56] . The HONEST trial is the largest real‐world prospective study in the field and included >21 000 patients with hypertension. The results showed that morning SBP of 145 mmHg was the threshold for a statistically significant increase in cardiovascular risk in medicated patients with hypertension. In addition, the morning SBP associated with minimum risk was 124 mmHg (Figure 2.8) [56] . Furthermore, the ability of morning home BP to detect the risk of CAD and stroke was similar, whereas office BP underestimated the risk of CAD (Figure 2.9) [197] . There was no significant J‐shaped curve for the association between morning home SBP and both stroke and coronary events until home SBP reached 110 mmHg (Figure 2.10) [197] . When on‐treatment morning home SBP was well controlled (<125 mmHg) during two‐year follow‐up, there was no increase in cardiovascular events even when office SBP remained ≥150 mmHg (Figure 2.11) [56] . Diabetes. In a subanalysis of patients with diabetes, those with morning home SBP 125–134 or 135–144 mmHg showed a tendency for, or a significant increase in, the risk of cardiovascular events compared to patients with well‐controlled hypertension (morning home SBP <125 mmHg) (Figure 2.12) [198] . Morning hypertension in patients with diabetes is associated with the non‐dipper/riser pattern of nighttime BP and nocturnal hypertension. In addition, morning hypertension was closely associated with advanced organ damage in patients with diabetes [199] . Elderly. Another subanalysis found that morning home SBP targets during antihypertensive therapy for patients aged <75 years can also be beneficial for reducing cardiovascular risk in those aged ≥75 years if this intensity of therapy is tolerated (Figure 2.13) [200] . High‐risk hypertension. In a post hoc analysis, where patients were grouped according to cardiovascular risk level showed that intensive antihypertensive therapy targeting a home SBP of <125 mmHg would be beneficial for high‐risk hypertensive patients (Figure 2.14) [201] . Difference between the first and second measurements. In the HONEST study, patients were asked to measure morning home BP twice. There was an interesting V‐shape association between the difference between the first and second readings and the rate of cardiovascular events (Figure 2.15) [202] . Risk was higher in those with the greatest variability between the first and second home BP measurements compared with patients whose BP readings were more stable. Target home BP levels. Real‐world findings from the HONEST study emphasize the importance of HBPM in clinical practice. This evidence suggests that it is essential to control morning home SBP to <145 mmHg as a first step, even in patients with controlled office BP. The second step is to target morning home SBP to <130 mmHg as per the guidelines, then a target of around 125 mmHg is the ultimate goal of home BP‐guided management of hypertension (Figure 2.8) [37, 50]. The All Nippon AF in the Elderly (ANAFIE) Registry home BP subcohort is the first prospective large observational study to investigate the impact of home BP control status on cardiovascular prognosis in elderly patients (age ≥75 years) with nonvalvular atrial fibrillation (NVAF; n = 5204) [203] . It is recommended that patients with NVAF receive anticoagulant therapy and that target BP office and home BP levels are <130/80 and <125/75 mmHg, respectively, to reduce the risk of both embolic and hemorrhagic cardiovascular events. However, early morning hypertension (morning home SBP ≥125 mmHg) was found in 66% of studied patients (Figure 2.16). Although 51.1% of patients had well‐controlled office SBP, 52.5% of these still had uncontrolled morning home SBP. In elderly patients with NVAF, morning home BP was poorly controlled, and masked uncontrolled morning hypertension remains significant. HBPM is the best practical method to detect the wide range of BP variability with different time phases, from relatively short‐term (diurnal), intermediate‐term (day‐by‐day), to long‐term (seasonal, and yearly) (Figure 2.17) [156] . HBPM could exclude the white‐coat effect to detect reproducible pathological BP variability. There are several measures of home BP variability that have clinical relevance in terms of cardiovascular prognosis (Figure 2.18) [3] . These are morning–evening difference (ME‐dif), standard deviation (SD), coefficient of variation (CV) average real variability (ARV), and variation independent of mean (VIM), all for home SBP, plus maximum home SBP (max home SBP) and seasonal variation. In both medicated and nonmedicated patients with hypertension, the ME difference of self‐measured home BP was associated with the left ventricular mass index (LVMI) and the risk of concentric hypertrophy, as well as with increased pulse wave velocity (PWV) [204–206]. ME‐dif has also been significantly associated with left ventricular hypertrophy (LVH) and increased brachial‐ankle pulse wave velocity (baPWV) (Figure 2.19) [204] . In addition, morning hypertension defined by the ME‐dif and the average of morning and evening BP readings (ME‐ave) was shown to be a determinant of concentric LVH (Figure 2.20) [199–205]. Even for patients with normal home BP (white‐coat hypertension), those with ME‐dif ≥15 mmHg had a higher percentage of concentric remodeling than those with ME‐dif <15 mmHg (32.5% vs. 14.7%, p = 0.017) [205] . Recently, ME‐dif assessed using ABPM or HBPM was reported to be associated with cardiovascular risk independently of the ME‐ave. [51, 207] The ME‐dif from ABPM was an independent predictor of future stroke events in elderly patients with hypertension [51] . Measurement of evening BP is recommended, in addition to morning BP, especially for patients with both hypertension and diabetes, because reduction of both evening and morning BP is closely correlated with a decrease in the urinary albumin‐creatinine ratio (UACR) [208] . Increased SD of home BP readings is associated with organ damage. In a study of unmedicated patients with hypertension, the SD of home BP readings measured three times at a single time‐point in the morning and evening for 14 days was associated with the UACR, LVMI, and carotid intima‐media thickness (IMT) (Figure 2.21) [209] . The Ohasama study of a community‐dwelling population also demonstrated that an increase in the SD of home BP self‐measured in the morning was an independent risk for cardiovascular mortality [125] . In addition, in the recent population‐based prospective Finn Home study, the variability of home BP, defined as the SD values of ME‐dif, day‐by‐day, and first minus second measurements, was associated with future cardiovascular events, independent of BP [207] . The association with cardiovascular risk was stronger for BP variability of morning SBP than that for evening SBP. Thus, BP variability assessed by self‐measured home BP has clinical relevance independently of average home BP levels. The impact of three different measures of home BP variability (CV, ARV, and VIM) were evaluated in the J‐HOP study (Figure 2.22), and the incidence of cardiovascular events was found to increase significantly as the quartile for all measures of home BP variability increased (Figure 2.23) [210] . In addition, the impact of increased home BP variability (SD, CV, ARV) on cardiac stress (serum amino terminal pro B‐type natriuretic peptide [NT‐proBNP]) was greater in those with advanced arterial stiffness (baPWV >1800 cm/sec) than in those with less‐advanced arterial stiffness (Figure 2.24) [211] . This is indicative of the systemic hemodynamic atherothrombotic syndrome (SHATS), in which BP variability and vascular disease have synergistic effects on cardiovascular overload. Invasive strategies may reduce exaggerated BP variability and pulse wave reflection, resulting in the suppression of the vicious cycle of SHATS. Carotid artery stenting (CAS) significantly reduces the day‐by‐day variability of home BP levels in patients with carotid artery disease [212] . Maximum home SBP was significantly associated with increases in LVMI and carotid IMT (evaluated by echocardiography) and microalbuminuria, independent of BP level in unmedicated patients with hypertension (Table 2.2) [209] . In this study, even when home BP was well controlled (<135/85 mmHg), maximum home SBP was significantly correlated with LVMI and carotid IMT. The maximum home SBP was found in the morning BP readings in 67% of all samples. An increase in maximum morning SBP and/or increased SD of morning SBP readings reflects the instability of MBPS. An analysis of the J‐HOP study using a Cox regression showed that the hazard ratios of a 1‐SD increase in maximum mean home SBP for incident stroke were 1.89 (95%CI, 1.23–2.89) including MEave SBP and 1.68 (1.33–2.14) including the VIM of MEave SBP. The patients in the highest maximum mean home SBP group had a significantly higher incidence rate of stroke compared with the patients in the other groups (Figure 2.25).
CHAPTER 2
Scientific rationale for HBPM
Five prospective, general practitioner‐based, home BP studies
Morning hypertension
Name of study
Study subjects and follow‐up
BP measurement schedule
Outcomes
1. SHEAF study† Bobrie G, et al. (JAMA. 2004)
France (4939 treated hypertensive patients; mean age, 70 years; mean follow‐up, 3.2 years)
4‐day HBPM (baseline HBP) (24 readings)
Adjusted HR of fatal or non‐fatal cardiovascular events with a BP increase of 1 mmHg was 1.02 (95% CI, 1.01 to 1.02; P < 0.001)
2. Fagard RH, et al. (J Hum Hypertens. 2005)
Belgium (391 older outpatients; mean age, 71 years; follow‐up, 10.9 years)
1‐day HBPM (baseline HBP) (3 readings) (not by self‐measurement, by a physician or assist physician with mercury device)
Adjusted relative HR of cardiovascular events with a HBP increase of 1 SD. (22.9 mmHg) was 1.32 (95%CI, 1.06–1.64; P = 0.01)
3. HOMED BP‡
Asayama K, et al. (Hypertens Res. 2012)
Japan (3,518 hypertensive patients; mean age, 59.6 years; median follow‐up, 5.3 years)
5‐day HBPM (follow‐up HBP) (5 readings)
Adjusted HR of fatal or non‐fatal cardiovascular events with a HBP increase of 1 s.d. (13.2 mmHg) was 1.47 (95% CI 1.23–1.75, P < 0.0001)
4. HONEST§
Kario K, et al. (Hypertension. 2014)
Japan (21,591 hypertensive patients, mean age, 64.9 years, mean follow‐up, 2.02 years)
2‐day HBPM (follow‐up HBP) (8 readings)
HR of incidence of cardiovascular events for morning HSBP>=145 mHg and CSBP >=150 mmHg compared to morning HSBP 125 mmHg and CSBP <130 mmHg was 3.92, 95% CI 2.22–6.92)
5. JHOP||
Hoshide S, et al. (Hypertension. 2016)
Japan (4310 patients with a history of and/or risk factors for cardiovascular disease; mean age, 65 years, mean follow‐up, 4 years)
14‐day HBPM (baseline HBP) (84 readings)
Adjusted HR of stroke events with a home SBP increase of 10 mmHg was 1.36 (95%CI, 1.19 to 1.56; P < 0.001)
6. JHOP Nocturnal BP study Kario K, et al. (Hypertension 2019)
Japan (2547 patients with a history of and/or risk factors for cardiovascular disease; mean age, 63 years, mean follow‐up, 7.1 years)
14‐day HBPM (baseline HBP) (morning and evening 84 readings + nighttime 42 readings)
A 10‐mm Hg increase of nighttime home SBP was associated with an increased risk of CVD events (hazard ratios [95% CIs]: 1.201 [1.046–1.378]), after adjustments for covariates including office and morning home SBPs.
Control status of morning home BP in the J‐HOP study
Evidence for morning hypertension control
J‐HOP study
HONEST study
ANAFIE Study
Home BP variability
Morning–evening difference (ME‐dif)
SD, CV, ARV, and VIM of home BP
Maximum home SBP
Orthostatic Home BP Change