Masked Hypertension: Does It Lead to CVD or CKD?

LVH

LVMI

LV wall

cIMT

CV events

CVA

ESRD

Sega et al. [3]

Liu et al. [2]

Sega et al. [3]

Kotsis et al. [5]

Bobrie et al. [10]

Hara et al. [11]

Agarwal and Andersen [12]

Tomiyama et al. [24]

Sega et al. [3]

Hanninen et al. [4]

Bjorklund et al. [6]

Pierdomenico et al. [19]

Kotsis et al. [5]

Hansen et al. [8]

Mancia et al. [9]

Hanninen et al. [4]

Kuriyama et al. [23]

Matsui et al. [7]

Pierdomenico et al. [19]

Pogue et al. [25]

Hansen et al. [8]

Franklin et al. [15]

Angeli [20]

Bold-treatment naïve population

LVH left ventricular hypertrophy, LVMI left ventricular mass index, LV wall Left ventricular wall thickness, cIMT carotid intimal medial thickness, CV events cardiovascular events, CVA cerebrovascular accidents, ESRD end-stage renal disease

^aNot all results are statistically significant, but may trend towards higher risk than referent normotension

The data for the masked hypertension and CKD are much more sparse. One study, albeit small, did demonstrate that patients with masked hypertension and CKD did exhibit an increased risk to the development of end-stage renal disease (ESRD) compared to normotensive patients [12]. Much of the available data, however, relate to the prevalence of masked hypertension in a CKD population [13, 14].

A large database of over 7000 individuals from four countries that included treated hypertensives examined outcomes based on both ABP and clinic BP. The adjusted hazard ratios for all CV events with normotensive as the referent were 1.22 (95 % CI = 0.96–1.53; P = 0.09) for white-coat hypertension (OBP ≥ 140/90 and ABP < 135/85 mmHg); 1.62 (95 % CI = 1.35–1.96; P < 0.0001) for masked hypertension (< 140/90 and ≥ 135/85 mmHg); and 1.80 (95 % CI = 1.59–2.03; P < 0.0001) for sustained hypertension (≥ 140/90 and ≥ 135/85 mmHg) [8].

More recently, an analysis of an 11-country International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes (IDACO) revealed that untreated diabetics with masked hypertension exhibited higher risk. During the median of 11 years of follow-up, using a composite CV end point (fatal and nonfatal stroke, transient ischemic attack (TIA), death from ischemic heart disease, sudden death, nonfatal MI, angina pectoris, coronary revascularization, fatal and nonfatal heart failure, and fatal and nonfatal peripheral artery disease), the adjusted risk for untreated masked diabetic patients was almost twice as high as normotensives (HR, 1.96; 95 % CI 0.97–3.97; P = 0.059) and similar to untreated stage 1 hypertensives (HR, 1.07;CI, 0.58–1.98; P = 0.82) and less than untreated stage 2 hypertensives (HR, 0.53; CI, 0.29–0.99; P = 0.048). A major limitation of these data is the relatively small numbers of patients and events in each group [15].

Limitations

Among the limitations affecting the calculations of the true prevalence of masked hypertension in CKD are several factors. From study to study, there are key differences in their methodology. These differences range from the timing of BP readings, the number of readings performed, and even the definition of what constitutes the threshold reading to confirm the diagnosis of hypertension in the CKD population. Further complexity is added by including within the analysis two, perhaps very different, populations—the treatment naïve and the currently treated. Only one utilized a treatment-naïve population [7] while others incorporated treated patients [16–20].

Traditionally, masked hypertension refers to treatment-naïve patients, but the definition has been expanded by many to include those patients who are treated with antihypertensive medications and whose patterns resemble those of masked hypertension–normal OBP with elevated HBP or ABP. These partially treated patients have been included, to at least some extent, in many of the studies assessing risk (see Table 10.2). The inclusion of these partially treated patients with the treatment-naïve masked hypertensives makes the assessment of true risk more difficult. The extent to which this influences the assessment of risk for TOD is unknown. Some authors believe that the definition of masked hypertension should be restricted to only those treatment-naïve patients—all others on treatment should be considered as patients with incomplete control of hypertension with partially treated sustained hypertension [21]. Others contend that the pattern of BP may be either sustained, masked, or white coat, all reflective of an underlying pattern of hypertensive phenotype.

Table 10.2

Treatment status of masked hypertensives in outcome studies

Includes treated	Treatment naive
Bobrie et al. [10]	Bjorklund et al. [6]
Pierdomenico et al. [19, 20]	Franklin et al. [15]
Pogue et al. [25]	Selenta et al. [36]
Hara et al. [11]	Sega et al. [3]
Tomiyama et al. [24]	Matsui et al. [7]
Ohkubo et al. [37]
Ben-Dov et al. [31]
Uchida et al. [18]
Kuriyama et al. [23]
Hanninen et al. [4]
Mancia et al. [9]
Kotsis et al. [5]
Hansen et al. [8]

The pretreatment patterns are not known for these patients. Were clinic BP readings less proportionally elevated than the HBP and ABP readings prior to treatment? Could these partially treated patients represent part of the spectrum of masked hypertension? Some data may suggest that. In a small prospective trial on nondiabetic treated hypertensives, those patients who were able to achieve BP control in both OBP and ABP settings demonstrated reduction in LVMI and microalbuminuria, along with other indices. In contrast, those patients whose OBP was controlled, but not the out-of-office readings, demonstrated no such benefit [22]. These data have been confirmed by other authors in different CKD populations. Even in treated hypertensives whose OBP has achieved normalization, if HBP or ABP remain elevated, there exists an increased risk for adverse outcomes including increased LVMI in diabetics with CKD [23], carotid artery disease and LVH [24], LVH and cardiac events [19], and prevalence of LVH [24], and stroke [25]. The extent to which this simply represents the impact of hypertension load upon TOD is not known. Interestingly, in the African-American Study in Kidney Disease (AASK) of 61 % of patients with controlled clinic BP, 70 % demonstrated elevated BP outside the office setting—a masked pattern [26].

Home Versus Ambulatory Blood Pressure Measurement

Defining a patient as exhibiting masked hypertension requires measurement of blood pressure out of the usual office setting. It may be done with either self-measurement at home or with ABPM. There is no general agreement regarding the use of HPM or ABPM to diagnose masked hypertension. Sega and colleagues found only a 57 and 45 % association between ambulatory and home diastolic BP (DBP) and systolic BP (SBP), respectively, suggesting that these measurements are not equivalent [3]. Others have suggested little difference [27]. A recent paper suggested that the method by which BP is measured in the office may also influence the diagnosis of masked hypertension. It appears that an automated measurement of office BP results in a lower prevalence rate of masked hypertension compared to the conventional manual readings. The manual method also results in a greater inconsistency from visit to visit [28]. This concern is addressed to some extent by the work of Ben-Dov and colleagues who found that 72 % of patients initially classified as masked hypertension remained so upon repeat ABPM [29]. Work of Pickering et al. gave evidence that a single ABPM may not prove sufficient to phenotype hypertensive patterns [30].

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