The Importance of the Early Detection of Masked Hypertension

Cardiovascular disease (CVD), i.e., coronary artery disease, stroke, and heart failure is the leading cause of mortality worldwide.1 Hypertension is one of the most important factors for CVD,1 and the recently published international guidelines for the management of hypertension emphasize the measurement of both office blood pressure (BP) and out-of-office BP.1,2 Masked hypertension is defined as having BP that is in the nonhypertensive range of office BP and the hypertensive range of out-of-office BP.3 The reported estimated prevalence of masked hypertension in the United States is >10% of patients,4 and the risk that masked hypertension presents for cardiovascular and all-cause mortality is more than double that of BP in the nonhypertensive range of both office and out-of-office BP.5 The phenotype of masked hypertension is divided into morning, nocturnal, and daytime hypertension according to the period.2 The measurement of nighttime BP has revealed its association with target organ damage beyond daytime BP and has shown better prognostic power than daytime BP.6,7 In addition, reduced nocturnal BP leads to a reduction of left ventricular hypertrophy, whereas this association was not found in daytime BP.8 Thus, the identification of individuals with nocturnal hypertension (who are at high risk of developing CVD) and the control of their nocturnal BP could lead to a reduction in the rate of CVD events. Generally, nocturnal hypertension can be detected by ambulatory BP monitoring (ABPM). ABPM can provide BP values during a patient’s daily life on specific days and at specific times throughout the day, and a significant amount of evidence from evaluations of out-of-office BP by ABPM has been obtained.1 However, restrictions such as sleep disturbances and discomfort from wearing the ABPM device during daily activities have been a concern,9 as has the cost of performing ABPM; physicians and patients sometimes find the use of ABPM cumbersome. Thus, ABPM is not routinely performed in clinical practice. The question of how to determine which patients should undergo ABPM in clinical practice has therefore arisen. Sakhuja et al. addressed this question by using the combined data of the Jackson Heart Study (JHS) and the Coronary Artery Risk Development in Young Adults (CARDIA) study.10 The JHS was an observational cohort study of 738 Black subjects, and it revealed that (i) the prevalence of masked hypertension in this cohort (defined as hypertension during the daytime, nighttime, or 24-hour day by ABPM) was 52.2% and (ii) the prevalences of masked hypertension defined by hypertension during the daytime, nighttime, and 24-hour day were 28.2%, 48.2%, and 31.7%, respectively. After a median 8.2 years of follow-up, all types of masked hypertension were associated with a risk of cardiovascular events.11 In their study, Sakhuja et al. analyzed data from 1,486 patients aged 40–79 years who underwent ABPM at the Year 30 exam in the CARDIA study and the baseline data in the JHS exam. They evaluated the association between an increase in the 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk (which has been widely established using the Pooled Cohort risk equations) and the presence of awake or nocturnal hypertension, and they reported that the increase in the 10-year predicted ASCVD risk was associated with the presence of awake or nocturnal hypertension in patients with office systolic BP (SBP)/diastolic BP (DBP) <130/85 mm Hg but not those with office BP ≥130/85 mm Hg. Based on these data, Sakhuja et al. stated that ABPM should be performed in patients with both a higher 10-year predicted ASCVD risk and office SBP/DBP <130/85 mm Hg.10 The 2017 U.S. blood pressure guidelines recommended the use of the 10-year predicted ASCVD risk for the management of hypertension, and the guidelines stated that physicians should provide antihypertensive medication for patients with a 10-year predicted ASCVD risk ≥10% and office SBP/DBP at 130–139/80–89 mm Hg, and that nonpharmacological therapy should be provided to patients with a 10-year predicted ASCVD risk <10% and office SBP/DBP at 130–139/80–89 mm Hg.1 Sakhuja et al. showed that the prevalence of awake or nocturnal hypertension was high in patients with both office SBP/DBP <130/85 mm Hg and a higher 10-year predicted ASCVD risk, and they emphasized the potential usefulness of ABPM to detect masked hypertension. Their study provides an opportunity to reconsider how we take care of patients with an ASCVD risk ≥10% but normal office BP levels. Although further research is needed to determine whether these patients are at risk of future CVD events, we believe that the early detection of high-risk patients such as those with a higher 10-year ASCVD risk is important, as are early interventions. We have proposed the hypothesis of a synergistic “vicious cycle” between hemodynamic stress and vascular disease as systemic hemodynamic atherothrombotic syndrome (SHATS).12,13 In this hypothesis, the synergistic risk of exaggerated hemodynamic stress and vascular disease could result in both target organ damage and 1 or more cardiovascular events. Hemodynamic stress includes BP variability (surge) and central pressure. Vascular components in SHATS are both large arterial atherosclerosis with arterial stiffness and microvascular disease in strain vessels,14 which are small vessels being branched off from a large vessel.15 In large arterial atherosclerosis, exaggerated power such as a BP surge is not fully absorbed by conduit arteries and is transmitted to peripheral atherothrombotic plaques. In strain vessels, the excessive power is not properly absorbed by conduit arteries and is transmitted to peripheral organs, inducing damage. This eventually leads to plaque rupture and atherothrombotic events. We have also proposed the use of a SHATS score, consisting of a BP score and a vascular score.16 The BP score consists of the levels of SBP (morning/evening/nighttime/24-hour) and SBP variability, diurnal variation, and the presence of atrial fibrillation. This score is evaluated by office BP, home blood pressure (HBP) measurements, and ABPM. The vascular score depends on the presence of overt CVD, asymptomatic CVD, or microvascular disease. The SHATS score is based on the synergistic effect of hemodynamic stress (such as from BP) and vascular diseases, not an additive effect; we therefore propose the SHATS score which is calculated by multiplying the BP score and vascular score.16 Masked hypertension is associated with atherosclerosis, and hemodynamic stress to the arterial wall (such as that due to masked hypertension) from an early age could cause endothelial cell damage, resulting in atherosclerosis.15 On the other hand, changes in hemodynamic stress in response to cardiac function and vascular tone and atherosclerosis could increase hemodynamic stress.15 Vascular disease is one of the components of the 10-year ASCVD risk, and masked hypertension would provide hemodynamic stress. Therefore, the findings reported by Sakhuja et al. about the linkage between masked hypertension and the 10-year ASCVD risk may replace the concept of SHATS. From this point of view, we suggest that masked hypertension or the 10-year ASCVD risk or both should be detected and addressed as soon as possible, thus disrupting the vicious cycle and leading to the prevention of CVD events (Figure 1). The “vicious cycle” between masked hypertension and atherosclerotic cardiovascular disease (ASCVD) in systemic hemodynamic atherothrombotic syndrome (SHATS). Abbreviations: ABPM, ambulatory blood pressure monitoring; BP, blood pressure; CV, cardiovascular; HBP, home blood pressure; SBP, systolic blood pressure. The “vicious cycle” between masked hypertension and atherosclerotic cardiovascular disease (ASCVD) in systemic hemodynamic atherothrombotic syndrome (SHATS). Abbreviations: ABPM, ambulatory blood pressure monitoring; BP, blood pressure; CV, cardiovascular; HBP, home blood pressure; SBP, systolic blood pressure. A recent study demonstrated the usefulness of measuring HBP in clinical settings. In the Japan Morning Surge-Home Blood Pressure (J-HOP) study, which is a nationwide practice-based study of Japanese subjects with a history of and/or risk factors for CVD, it was observed that masked hypertension defined as office BP <140/90 mm Hg and home BP ≥135/85 mm Hg was associated with an increased risk of stroke events. This association was independent of conventional cardiovascular risk factors and hypertensive organ damage compared with a control group (office BP <140/90 mm Hg, home BP <135/85 mm Hg; hazard ratio 2.77).17 In the J-HOP Nocturne study, which examined the J-HOP study participants who measured their nighttime HBP, it was revealed that nighttime BP measured by HBP could be an independent predictor of CVD events.18 In another study, masked nocturnal hypertension defined as average morning and evening HBP <135/85 mm Hg and nocturnal HBP ≥120/70 mm Hg was associated with an increase of target organ damage and an increased risk of cardiovascular events compared with a controlled BP group (average morning and evening HBP <135/85 mm Hg, nocturnal HBP <120/70 mm Hg; hazard ratio 1.57).19 Thus, currently, HBP can provide prognostic information that is similar to that obtained with ABPM. Sakhuja et al. noted that it is probably not feasible for all patients to undergo ABPM, and they suggested that 1 approach for identifying individuals with awake/nocturnal hypertension could be performing ABPM for those with either office BP ≥140/90 mm Hg or a 10-year predicted ASCVD risk ≥10%.10 It is clear that ABPM is useful for a limited population of patients at high cardiovascular risk. The use of HBP measurement instead of ABPM for patients at high cardiovascular risk should be considered. Further studies designed to identify patients who need not only the measurement of HBP but also ABPM for the management of their hypertension are expected. K. Kario received research funding from Omron Healthcare, Fukuda Denshi, and A&D.