Blood pressure (BP) diagnosis and management of hypertension have been based on conventional office measurements for decades. However, accumulated evidence reports that out-of-clinic BP, measured by ambulatory BP monitoring and home BP monitoring, has a strong association with the risk of cardiovascular disease and mortality.1–4 Both ABPM and HBPM are more reproducible, diagnosis-valued, and accurate predictors of preclinical target organ damage (TOD) than office BP recording.5,6 Therefore, many guidelines propose that out-of-clinic BP, either home or ambulatory, could be used to confirm the diagnosis of hypertension.7–9
Ambulatory monitoring, which is limited by its high cost and restricted availability, also causes some discomfort and sleep disturbance, especially in patients with severe hypertension.10 However, obtaining BP during sleep is a useful tool in the diagnosis of nocturnal hypertension and morning surge and in the assessment of BP variability.11 Conversely, home monitoring is of low cost and feasible and has the benefits of ABPM without the aforementioned discomfort. Unfortunately, BP readings cannot be obtained during sleep with most HBPM devices.
Although both ambulatory and home BP monitoring share many similarities, cross-sectional studies that compare home and ambulatory BPs in TOD have conflicting results.12–15 In addition, possible ethnicity-related differences in both measurements exist.16,17 The role of race factors in predicting cardiovascular risk should be investigated. The objective of this study was to evaluate whether ambulatory or home BP monitoring was associated with preclinical hypertensive cardiovascular TOD.
The subjects of this study were selected among the participants of the Taiwan Biospecimen Bank and Consortium of Hypertension-associated Cardiac Disease. All participating institutions had the approval of their own institutional review board to conduct this study, and written informed consent was obtained from all study participants. Patients with the early stages of hypertension (prehypertension and stage 1 hypertension) were included. The definitions of prehypertension (systolic BP [SBP], 120–139 mm Hg; diastolic BP [DBP], 80–89 mm Hg) and stage 1 hypertension (SBP, 140–159 mm Hg; DBP, 90–99 mm Hg) were based on the 2014 guideline of hypertension management established by the Eighth Joint National Committee.18 The exclusion criteria were a recent history of cardiovascular or cerebrovascular events (within 6 months), current hemodialysis treatment, chronic inflammatory disease, or secondary hypertension. The institutional review board of each medical center approved this study, and written informed consent was obtained from all the participants. The study subjects were enrolled by physicians between January 2014 and December 2015.
During the baseline survey, trained healthcare workers collected detailed information on sociodemographic characteristics, lifestyle, and medical history using a laptop computer-based questionnaire. Each participant also had measurements taken, including height, weight, and BP.
Blood Pressure Measurements
Clinical Blood Pressure
Blood pressure was measured twice by trained staff using a digital sphygmomanometer (Microlife BP A200 AFIB; Microlife AG Swiss Corporation, Widnau, Switzerland) after participants remained at rest in the seated position for at least 5 minutes. If the difference between the 2 measurements was greater than 10 mm Hg for the SBP, a third measurement was obtained, and the last 2 measurements were recorded. The mean of the 2 recorded values of SBP and DBP was used in all the analyses. All devices were regularly maintained and calibrated to ensure consistency of the measurements. Participants were considered hypertensive if they had a measured SBP of at least 140 mm Hg or a measured DBP of at least 90 mm Hg or were receiving treatment of hypertension. The latter was defined as those who reported a diagnosis of hypertension by a physician and were using antihypertensives at the time of the baseline survey.
Morning and Evening Home Blood Pressure
Home BP was self-measured with a validated autonomic oscillometric device (Macrolife BP A200 AFIB; Microlife AG Swiss Corporation). Patients were instructed to measure their BP two times in the sitting position at 2-minute intervals every morning and evening on 7 consecutive days. Morning BP was measured between 6:00 and 9:00 AM, and evening BP was measured before going to bed. The patients were reminded not to measure BP after taking a bath, smoking, or consuming alcohol. Morning home BP was defined as the mean of the morning values recorded at home. Evening home BP was also defined as the mean of the evening measurement values.
Ambulatory Blood Pressure
Ambulatory BPs were recorded with a validated automatic device (Microlife, BP3MZ1-1, WatchBP O3) using an oscillometric method at 15-minute intervals during daytime (6:00 AM to 10:00 PM) and at 30-minute intervals during nighttime (10:00 PM to 6:00 AM). The patients recorded the times of going to bed and waking up, which was considered the nighttime period. The mean BP during this period was defined as ambulatory nighttime BP, and the ambulatory awake BP was defined as the mean BP during the rest of the day.
Clinical and ambulatory BPs were measured on the same day. Home BP was recorded for 7 consecutive days. These 3 different BP measurements are summarized in Table 1, Supplemental Digital Content, http://links.lww.com/JCN/A60.
Measurement of Cardiovascular End-Organ Damage
Left Ventricular Mass Index and Left Atrial Volume Index
The patients were imaged in the supine position using an ultrasonography system (iE33 xMATRIX echocardiography system; Philips Healthcare, Best, the Netherlands). Two-dimensional images were acquired with the standard parasternal and apical (apical 4-chamber, apical 2-chamber, and apical long-axis) views at a frame rate of 30 frames/s, and 3 cardiac cycles were recorded. Researchers blinded to the patients’ clinical characteristics performed left atrial and ventricular measurements to calculate the left ventricular mass index (LVMI) and left atrial volume index (LAVI) according to the recommendations of the American Society of Echocardiography.19
Arterial Stiffness Assessment
The carotid-femoral pulse wave velocity was recorded by using a validated noninvasive automatic device (OMRON, VP1000 Plus, BP203RPE III; JA Davey Pty Ltd, Port Melbourne, Victoria, Australia) when patients were in the supine position and after 10 minutes of resting. Three consecutive readings were measured from each patient, and the mean of these recordings was defined as the carotid-femoral pulse wave velocity.20 These 2 measurements of cardiovascular organ damage were performed on the same day of the clinical and ambulatory BP recordings.
Continuous data were described as mean (SD), and categorical data were reported as percentages. Between 2013 and 2015, 740 consecutive patients were enrolled. We excluded patients with incomplete data on clinical BP (n = 18), nighttime home BP (n = 71), nighttime ambulatory BP (n = 69), awake ambulatory BP (n = 14), or echocardiography (n = 7). Among 561 patients, we evaluated the relationships between CV TOD and awake home, nighttime home, awake ambulatory, and nighttime ambulatory BP by using Pearson correlation coefficients (in the linear models) for continuous variables. Stepwise multiple regression analyses were performed to identify which BP measurement methods best determine TOD. Tolerance and variance inflation factors were calculated to assess the possible existence of substantial multicollinearity among the BP measurements; the values of more than 1.5 were considered collinearity. In addition, we used forced-entry multiple regression analysis to add BP measurements incrementally to achieve the improvement of the goodness of fit in both the linear and quadratic equation models. The covariates included age, sex, body mass index, antihypertensive medications, and presence of diabetes mellitus, hyperlipidemia, heart failure, and previous stroke. The computer software package SPSS 19.0 (SPSS Inc, Chicago, Illinois) was used for all analyses. A P < .05 was considered statistically significant.
The mean (SD) age of the subjects was 65.0 (10.8) years, and 344 (61.3%) were men. They were all overweight, and 236 subjects (42.1%) were smokers. The diagnoses of prehypertension and stage 1 hypertension were based on office BP, and 336 subjects (59.9%) were diagnosed with stage 1 hypertension. Regarding antihypertensive medications, calcium channel blockers were the most commonly used. Table 1 lists the demographic characteristics of the patients.
Measurement of Office, Home, and Ambulatory Blood Pressures and Cardiovascular Organ Damage
The measurements of clinical, ambulatory, and home BPs are listed in Table 2. Home BP was slightly higher than ambulatory BP. Morning and evening home BPs were higher than the respective ambulatory BPs (the mean [SD] difference for morning-daytime/evening-nighttime SBP, 5.3 [4.2]/3.3 [8.5] mm Hg, P < .001; for morning-daytime/evening-nighttime DBP, 5.4 [9.4]/7.3 [6.1] mm Hg, P < .001). The correlation coefficients for the relationships between the morning home and daytime ambulatory SBPs and DBPs were 0.52 was 0.42, respectively. The coefficients for the evening home and nighttime ambulatory SBP and DBP were 0.69 and 0.71, respectively. The measurements of cardiovascular organ damage are also listed in Table 2. Although the mean values of left ventricular mass index and pulse wave velocity were within their reference ranges, they were at the upper limit. The left atrial chamber size was mildly dilated.
Clinical Blood Pressure and Cardiovascular Organ Damage
The results of the Pearson correlation analysis for the association between clinical BP and organ damage are presented in Table 3. Left ventricular mass index was well correlated with SBP and DBP (systolic, r = 0.309; diastolic, r = 0.206). Left atrial volume index and pulse wave velocity were only correlated with systolic clinical BP (LAVI, r = 0.258; pulse wave velocity, r = 0.241).
Morning Home Blood Pressure and Left Ventricular Mass Index
The relationship between home and ambulatory BP and LVMI is shown in Table 3. In the Pearson correlation analysis of the linear models, LVMI was found to be correlated with all the SBP values (morning home, r = 0.310; evening home, r = 0.220; daytime ambulatory, r = 0.114; nighttime ambulatory, r = 0.130). In terms of SBP, the positivity of the correlation between LVMI and SBP was different for each SBP measurement. No significant differences were observed in the correlation coefficients for the relationships between morning/daytime SBP and LVMI and evening/nighttime SBP and LVMI in either home (P = .64) or ambulatory BP monitoring (P = .79). However, the correlation coefficients for the relationships between morning SBP and LVMI obtained using home BP monitoring were significantly greater than those for the relationships between evening home SBP and LVMI and were greater than those for the relationships between nighttime ambulatory SBP and LVMI (P = .02).
With regard to DBP, only morning (r = 0.136) and evening (r = 0.132) home BPs were found to be associated with LVMI. No significant differences were found in the correlation coefficients for the relationships between morning home DBP and LVMI and between evening home DBP and LVMI.
In the multiple linear regression analysis, in which clinical, morning home, evening home, daytime ambulatory, and nighttime ambulatory SBPs were entered in a stepwise manner, daytime home SBP (B = 0.560, SE = 0.101, β = 0.310, P < .001) and clinical BP (B = 0.190, SE = 0.086, β = 0.137, P = .028) were found to be significantly associated with LVMI. In the parallel analysis of DBP, morning home DBP (B = 0.390, SE = 0.154, β = 0.012, P = .012) was significantly associated with LVMI.
In a multiple linear regression model of SBP, the goodness of fit of the relationship between SBP and LVMI was most improved by adding morning home SBP to clinical BP and confounding factors, followed by evening home SBP, daytime ambulatory SBP, and nighttime ambulatory SBP (Table 4). It suggested that morning home SBP is mostly associated with LVMI. In terms of DBP, only adding morning home DBP to clinical DBP improved the goodness of fit.
Morning Home Blood Pressure and Left Atrial Volume Index
Several studies have shown that regression of LVMI and LAVI during treatment reflects the reduction of risk of impending morbid and cardiovascular events, thereby offering valuable information on whether or not patients are protected by the treatment strategies adopted.21,22 In the Pearson correlation analysis of the linear models, LAVI was found to be correlated with all of the SBP values (morning home, r = 0.235; evening home, r = 0.219; daytime ambulatory, r = 0.138; nighttime ambulatory, r = 0.150; Table 3). Regarding DBP, however, no significant association was observed between the DBP value and LAVI. No significant differences were found in the correlation coefficients for the relationships between morning/daytime SBP and LAVI, and between evening/nighttime SBP and LAVI, in either home (P = .62) or ambulatory BP monitoring (P = .35). Conversely, the correlation coefficients for the relationships between morning SBP and LAVI (P = .002) and evening SBP and LAVI (P = .01), obtained using home BP monitoring, were significantly greater than those obtained for the same relationships using ambulatory BP monitoring.
In the multiple linear regression analysis of the association between LAVI and SBP using a stepwise method, morning home SBP (B = 0.212, SE = 0.067, β = 0.230, P = .002) was more significantly associated with LAVI than other measurements. Likewise, the relationship between BP and LAVI became even more significant after adding morning home SBP to the models (Table 4). With regard to DBP, none of the daytime ambulatory, nighttime ambulatory, morning home, or evening home DBPs improved their association with LAVI.
Daytime Home Blood Pressure and Pulse Wave Velocity
In the Pearson correlation analysis of the linear models, pulse wave velocity was found to be correlated with all the SBP values (morning home, r = 0.197; evening home, r = 0.224 daytime ambulatory, r = 0.187; nighttime ambulatory, r = 0.227; Table 3). No significant association was observed between the DBP value and pulse wave velocity. In addition, no significant difference in the correlation coefficients was found for the relationships between SBP and pulse wave velocity, regardless of morning/daytime, evening/nighttime, home, or ambulatory BP monitoring. In addition, pulse wave velocity was only associated with clinical BP (B = 0.096, SE = 0.076, β = 0.248, P = .045) in the multiple linear regression analysis. In addition, the goodness of fit of the relationship between SBP and pulse wave velocity only improved by using clinical BP and the confounding factor model (Table 4). As for DBP, none of these measures improved their association with pulse wave velocity.
In our present study, we enrolled a multicenter nationwide cohort with early-stage hypertension. We not only recorded entire hypertension profiles, including home BP, office BP, and ambulatory BP, for all the patients from the Taiwan Biospecimen Bank and Consortium of Hypertension-associated Cardiac Disease but also evaluated detailed TOD conditions through pulse wave velocity measurement and echocardiography. The consortium received support from the government and included 11 Taiwan medical centers throughout the country to lessen the regional patient bias. Our findings support that morning home SBP, in addition to other SBP measurements, has the highest correlation to early cardiovascular TOD in an Asian population. Echocardiography and pulse wave velocity measurement could differentiate the early physiological response to hypertension and could therefore accurately predict the severity of TOD in the early stage of hypertension.
Data from the Framingham study showed that SBP ranging from 130 to 139 mm Hg or DBP ranging from 85 to 89 mm Hg (prehypertension stage) was associated with an increased risk of cardiovascular disease.23 Compared with the group with normotension, the group with prehypertension had a greater left ventricular mass, an impaired diastolic function, and an increased carotid intima-media thickness, suggesting that cardiovascular organ damage had already started in this stage.24,25 Given that 40% of the subjects in our cohort were prehypertensive, the cardiovascular organ damage was relatively trivial. However, all the SBP measures were found to be associated with LVMI, LAVI, and pulse wave velocity. There were established evidences demonstrating a better prognostic value of ambulatory BP monitoring compared with office BP.5 Likewise, ambulatory SBP was significantly correlated with TOD in our analysis, whereas the values of correlation coefficients were less than office SBP. However, in the goodness-of-fit analysis, there was still an additional prognostic value when adding ambulatory SBP to office SBP. Compared with daytime ambulatory SBP, the correlation for TOD was more obvious for nighttime ambulatory SBP. The causes underlying this finding were 40% of subjects with prehypertension and trivial preclinical TOD, reflecting nighttime ambulatory SBP more correlated with subclinical cardiovascular risks.4 On the other hand, daytime home SBP demonstrated the strongest relationship with LVMI. Furthermore, adding home daytime SBP in the goodness-of-fit analysis could improve the association between SBP and LVMI. Similar findings were observed for SBP when LAVI was used as the dependent variable. In addition, morning home morning was more strongly related to LVMI and improved the goodness of fit of the association between DBP and LVMI compared with other measures. This is the first study to demonstrate that morning home SBP measurement is significantly associated with preclinical hypertensive cardiovascular damage in the early stage of hypertension among the Asian population.
Several studies and meta-analyses have observed that home BP monitoring is as good as ambulatory BP monitoring and superior to office measurements in their association with TOD.26,27 These studies enrolled either patients with treated or untreated hypertension who were at a greater risk of cardiovascular events and TOD than patients with prehypertension.28 Although 30% of our cohort comprised patients with prehypertension, our study supports the results of the previous studies. In addition, home BP measured during sleep could improve the association of BP with hypertensive TOD when added to other BP measures.15
Our results on home SBP are consistent with previous reports, showing slightly higher values for home SBP than ambulatory SBP. In contrast to ambulatory BP readings, which were taken numerous times in a single day, home BP readings were taken on multiple days and were more significantly associated with TOD, especially nighttime BP.15,29 Likewise, morning home SBP was more significantly associated with hypertensive TOD than daytime ambulatory SBP. Furthermore, nighttime HBPM might be a reliable substitute for ambulatory monitoring for the detection of nondippers or those patients with elevated nocturnal BP, which is a well-known risk factor of CV events.30 However, patients with either a nondipper pattern or a high nocturnal BP represent long-standing hypertension, an advanced stage of organ damage, or multiple comorbidities.31 In our study, the values of LVMI, LAVI, and pulse wave velocity were close to the upper limit of the reference range, implying preclinical target organ change and early-stage hypertension in our population. Therefore, morning/daytime BP, rather than evening/nighttime BP, might reflect the imbalance of the mechanisms regulating BP and might be more significantly associated with TOD.
Prehypertension affects 25% to 50% of adults worldwide and 30% of the patients in our cohort. It increases the risk of the development of not only hypertension, with an annual rate of 8% to 20%, but also cardiovascular events, with an annual incidence of approximately 1% in middle-aged adults.32 Our results suggest that morning home BP monitoring could be an informative predictor of cardiovascular damage. In contrast to ambulatory devices, home BP measurement could be of relatively low cost, with high acceptance by patients, and repeated more frequently than ambulatory BP monitoring.33
From a clinical standpoint, our findings suggest that morning home BP assessment could be useful in risk stratification. Moreover, to evaluate cardiovascular damage among individuals with prehypertension and mild hypertension, home BP measurement might be the most effective modality for both physicians and patients. In addition, the control of prehypertension or mild hypertension is important in preventing further cardiovascular events in patients with metabolic syndrome and macrovascular disease.34
Because of our rather selective hypertensive cohort and high proportion of prehypertension, the generalizability of our results is limited. Furthermore, the cross-sectional nature of our study limits our ability to link morning home BP to outcomes, as neither LVMI nor LAVI is a validated surrogate for CV events. In addition, approximately 30% of our subjects with prehypertension received only lifestyle interventions, without medications, during the study period. As a result, the diurnal BP pattern may have strengthened the impact of daytime BP on the evaluation of TOD because the administration of antihypertensive drugs would diminish the diurnal change.
Measuring morning home SBP, in addition to other SBP measures, improves the association between SBP and cardiovascular TOD. The relationship between morning home SBP and TOD was stronger than other measures, including clinical, daytime ambulatory, nighttime ambulatory, and evening home BP, in patients with prehypertension and mild hypertension. These findings imply that physicians should encourage wide use of home BP monitoring for morning BP evaluation in clinical practice at the initial diagnostic phase of prehypertension and early stage of hypertension.
What’s New and Important
- Morning home SBP was correlated with LVMI and LAVI.
- Morning home SBP is a good predictor of CV organ damage in early-stage hypertension.
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