Most past ABPM patient studies were performed with measurements gathered every 15 to 60 min over a single 24-h span, mainly using mean BP values as criteria to diagnose hypertension (Chobanian et al., 2003; Head et al., 2012; Mancia et al., 2007; Pickering et al., 2005) and assess hypertension therapy (Waeber & Brunner, 1999). In actuality, the sampling requirements for ABPM have only been occasionally addressed (Enström & Pennert, 2001; Hermida & Ayala, 2003; Hermida et al., 2007c, 2013d). Previous reports have documented the expected increased reproducibility of mean BP values associated with the increased number of BP measurements per 24 h, i.e., greater sampling rate (Mancia et al., 1994). In addition, ABPM has been also
validated against direct intra-arterial BP measurement, documenting that sampling at 30- to 60-min intervals
precisely reproduces the “true” beat-to-beat mean BP
values (di Rienzo et al., 1983).
The majority of these previous studies have focused on 24-h ABPM to primarily investigate only the influence of BP sampling rate on reproducibility of 24-h mean BP values. Thus, most past studies have not evaluated the
impact of the duration of ABPM on the reproducibility
of results. Along these lines, the findings of previous studies have already documented advantages of extend-
ing the duration of ABPM from 24 to ≥48 h in terms of
the reproducibility of derived clinical parameters (Hermida & Ayala, 2003; Hermida et al., 2002b, 2007c, 2013d; Mochizuki et al., 1998; Tamura et al., 1990). In summary, these studies have consistently documented the reproducibility of BP characteristics, including mean BP values and sleep-time relative BP decline (measure of BP dipping), depends markedly on the dur- ation, and to a much lesser extent on the frequency, of BP sampling.
A recent study evaluated the influence of the duration (48 vs. 24 h) and sampling rate of BP measurement (from every 20 to 30 min up to every 2 h) on the prognostic value of ABPM utilizing the data from the prospective
MAPEC Study in which 3344 participants whose baseline BP ranged from normotension to sustained hypertension were systematically evaluated by periodic, at least
annually, 48-h ABPM (Hermida et al., 2013d). The ABPM profiles of these participants were modified to generate reconstructed time series of identical 48-h dur-
ation but with data sampled at different intervals–every 1
or 2 h – or shorter time series for just the first 24-h span
with data sampled at the original rate, i.e., at 20- to 30- min intervals. The authors compared the reproducibility of the 48-h, awake, and asleep BP means, and of the sleep-time relative BP decline derived from the complete BP profiles (original 48-h time series with BP measure- ments obtained at 20- to 30-min intervals from each participant) against each set of modified BP series. Additionally, the Cox proportional-hazard model, adjusted for significant confounding variables, was used to estimate the HR with 95% CI for events associated with each tested potential prognostic BP parameter, cal- culated from the original complete 48-h BP profiles and from each set of modified BP series.
As an illustrative example, Figure 15 shows the limits of agreement for the asleep means of SBP (top) and DBP (bottom) of the original complete 48-h ABPM pro- files versus the modified ABPM series, i.e., less-dense sampling of either one BP measurement per hour for 48 h or the original sampling rate of one BP measure- ment per 20 to 30 min for the first 24-h span. Each Bland-Altman plot represents the difference between the asleep BP mean calculated from the original series and the value calculated from the modified series (in the vertical axis), plotted against the average of those two values (in the horizontal axis) (Bland &
Guidelines for ambulatory blood pressure monitoring
C h r o n o b i o l I n t D o w n l o a d e d f r o m i n f o r m a h e a l t h c a r e . c o m b y 1 7 8 . 6 0 . 1 5 6 . 1 5 6 o n 0 3 / 2 2 / 1 3 F o r p e r s o n a l u s e o n l y .
Altman, 1986, 1995). The average of the individual differ- ences in the asleep BP mean was slightly, but, nonethe- less, significantly greater for data sampled every 20 to 30 min during the first 24 h than for the reconstructed time series that simulated data sampled every 1 h for 48 h (.3 ± 4.4 vs. -.1 ± 1.6 mmHg in asleep SBP mean; .2
± 3.0 vs. -.1 ± 1.4 mmHg in asleep DBP mean; p< .001).
Of more direct clinical relevance, Figure 15 further illus- trates the asleep SBP and DBP means obtained from the original complete 48-h ABPM profiles were much better reproduced with data sampled every 1 h for 48 h (time series composed of up to 48 of the maximum original 128 BP measurements/participant; right panels of Figure 15) than with the data obtained at the original sampling rate of 20- to 30-min intervals for the first 24 h, only (time series composed of up to 64 BP measure- ments/participant; left panels of Figure 15). In particular, reduction of ABPM duration to just 24 h resulted in very significant error, in the range of -21.4 to +23.9 mmHg, totally unacceptable in clinical practice, in estimating the asleep SBP mean, the most significant prognostic marker of CVD events. Similar findings related to the advantages of extending the duration of ABPM versus in- creasing the sampling rate were documented for the esti- mation of the 48-h and awake BP means and sleep-time relative BP decline (Hermida et al., 2013d). Additionally, Cox proportional-hazard analyses revealed a comparable HR for mean BP values and sleep-time relative BP decline
derived from the original complete 48-h ABPM profiles and those modified to simulate a sampling rate of one BP measurement every 1 or 2 h for 48 h. However, when the duration of ABPM was reduced from 48 to only 24 h, the HRs were markedly overestimated for SBPand underestimated for DBP (Hermida et al., 2013d). This study on the impact of the duration and the fre- quency of sampling by ABPM on the reproducibility and accurate estimation of BP parameters currently used to establish the diagnosis of hypertension, evaluate patient response to treatment, and assess CVD risk fully corroborates previous findings (Hermida & Ayala, 2003; Hermida et al., 2002b, 2007c; Tamura et al., 1990), thereby establishing the estimation of BP indices is
much more dependent on the duration than sampling
rate of ABPM. The HR of CVD events associated with in- creased ambulatory BP is less accurately estimated by relying on 24-h than 48-h ABPM, indicating ABPM con- ducted for only 24 h may be insufficient to reliably make the diagnosis of hypertension, identify dipping status, evaluate treatment efficacy, and, most important, stratify CVD risk. These collective findings indicate ABPM should ideally be performed at least hourly for two consecutive 24-h periods to achieve best reproduci- bility of mean BP values and to accurately classify dipping status. Moreover, expanding the length of moni- toring to 48 h, even at the reduced sampling rate of, e.g., one measurement per hour that does not compromise FIGURE 15. Bland-Altman plots assessing agreement in estimates of the asleep means of SBP (top) and DBP (bottom) for data originally sampled by ABPM every 20 to 30 min for 48 consecutive hours versus those for modified time series reconstructed with data sampling every 1 h for 48 consecutive hours (right), or atthe original rate of every 20 to 30 minfor thefirst24 h only (left). Dotted horizontal line of each plot represents the average of the differences across the entire studied population. Dashed lines represent the values of the average difference ±2 SD (assumingly containing 95% of the individual values). Updated from Hermida et al. (2013d).
R. C. Hermida et al. C h r o n o b i o l I n t D o w n l o a d e d f r o m i n f o r m a h e a l t h c a r e . c o m b y 1 7 8 . 6 0 . 1 5 6 . 1 5 6 o n 0 3 / 2 2 / 1 3 F o r p e r s o n a l u s e o n l y .
accurate determination of the indices of the 24-h BP profile, does not impact patient compliance (Hermida & Ayala, 2003; Hermida et al., 2002a, 200b), rendering ABPM an individually reproducible approach for proper
BP measurement.
10.2. Time Interval between Repeated ABPM Evaluations
ABPM is the recommended means for the diagnosis of true hypertension, proper CVD risk assessment, and evaluation of treatment efficacy in the general population. Moreover, among the different individual parameters derived from ABPM, the asleep SBP mean is the most significant predictor of CVD events, both individually as well as jointly when combined with other ABPM-derived
potential prognostic markers (Hermida et al., 2011c). Most important, the progressive decrease in the asleep BP mean is the most significant predictor of event-free interval (Ayala et al., 2013a; Hermida et al., 2010b, 2011b, 2011c, 2011d, 2012b, 2013b). Accordingly, ABPM should be considered as a requirement for systematic follow-up of individual subjects, and this, in turn, requires a standard protocol for repeated ABPM evaluations. So far, periodic (at least yearly) 48-h ABPM evaluations on the same subjects have been performed in the MAPEC Study (Hermida et al., 2010b, 2011b, 2011c, 2011d) and the on-going Hygia Project (Ayala et al., 2013b; Crespo JJ et al., 2013; Hermida et al., 2013j; Mojón et al., 2013; Moyá et al., 2013; Ríos et al., 2013).
As a general guide, the following protocol is rec- ommended for periodic evaluation and follow-up of patients by ABPM: (i) for uncomplicated persons with either normotension or masked normotension, accord- ing to the ambulatory BP reference thresholds listed in Table 3, and unaffected by compelling clinical conditions
associated with increased CVD risk – including diabetes,
CKD, and past CVD events – ABPM should be repeated
within 2 yrs; the time interval should be reduced to 1 yr for complicated normotensive subjects; (ii) for hyperten- sive patients, diagnosed according to the ambulatory BP reference thresholds given in Table 3 and whose thera- peutic regimen is modified in any way (prescription of treatment to naïve patients, prescription of additional medications to previously treated patients, exchange of medications, change of dose or time-of-day of medi- cations, etc.), ABPM should be repeated preferably within the ensuing 3 mo; (iii) for hypertensive patients whose BP is established to be properly controlled accord- ing to the ambulatory BP reference thresholds shown in Table 3 and whose therapeutic regimen, therefore, necessitates no modification, ABPM should be repeated every 6 mo (complicated patients) to every 12 mo (uncomplicated patients).
10.3. Editing and Validation of ABPM
As previously discussed in more extensive detail (Section 3), ABPM should not be analyzed in terms of the clock time of BP sampling, neither on a population nor on an individual basis. Proper synchronization of BP data so
that they are expressed in terms of the actual rest-activity cycle of the individual evaluated, e.g., hours from bedtime or hours after awakening, is strongly rec- ommended. In so doing, information on the rest-activity cycle must be properly collected from each person undergoing ABPM evaluation, either by requesting the individual to keep a diary or, preferably, by wrist actigraphy.
Although not free from controversy (O’Brien et al., 2003), it is recommended that ABPM profiles be edited to correct for measurement errors and outliers. Several methods for the editing of ABPM-derived data have been proposed and evaluated in terms of reproducibility (Winnicki et al., 1997). As a general rule, SBP readings >250 or <70 mmHg, DBP >150 or <40 mmHg, and PP (difference between SBP and DBP) >150 or <20 mmHg should be eliminated. Moreover, ABPM measurements may be invalid when taken during physical exercise, ex- cessive movement, driving, or under unusual mood/ emotional states.
As a general recommendation, ABPM data series
should be considered invalid for analysis if ≥30% of the
scheduled measurements are absent, if data are lacking for >2 consecutive hourly intervals, if data are obtained while patients maintain an irregular rest-activity sched- ule during consecutive 24-h periods of monitoring, or if the nighttime sleep span is <6 h or >12 h.
10.4. Requirements for Healthcare Personnel in Charge of ABPM
ABPM is a specialized diagnostic technique that requires initial and periodic updated training to specific protocols for both BP measurement and ABPM analysis and interpretation. Accordingly, only properly trained per- sonnel should perform ABPM. Analyses and interpret- ation of ABPM results, in particular, require proper training. The recommended approach is to use a standard- ized data entry booklet (DEB) to record patient medical history and, in addition, a separate standardized report to detail ABPM findings. This helps ensure that all evalu- ated patients undergo equivalent diagnostic procedures and that healthcare personnel utilize identical criteria and therapeutic approaches for optimal BP control and CVD risk reduction. Such a standardized approach might be easily implemented on-line; thus, all patient information might be obtained with an electronic DEB, allowing automatic validation programs to check for data discrepancies in the DEB and by appropriate error messages to prompt the clinical site staff for verification or modification of data in question. Most important, ABPM profiles can be analyzed on-line in real time, thus avoiding costly maintenance and actualization of software programs required to generate an adequate ABPM report in keeping with the recommendations pro- vided above in Sections 3, 4, and 8. This approach has already proven valuable for conducting not only individ- ualized patient assessments but also long-term popu- lation-based morbidity and mortality outcome studies
Guidelines for ambulatory blood pressure monitoring
C h r o n o b i o l I n t D o w n l o a d e d f r o m i n f o r m a h e a l t h c a r e . c o m b y 1 7 8 . 6 0 . 1 5 6 . 1 5 6 o n 0 3 / 2 2 / 1 3 F o r p e r s o n a l u s e o n l y .
(Ayala et al., 2013b; Crespo JJ et al., 2013; Hermida et al., 2013j; Mojón et al., 2013; Moyá et al., 2013; Ríos et al., 2013).
10.5. Maintenance and Utilization of ABPM Devices
ABPM should be performed using only properly vali- dated devices that have been verified to meet published international standards (American National Standard, 2009; O’Brien et al., 1993, 2010). ABPM devices should be calibrated regularly, at least yearly. The internal battery of each ABPM device should be checked regularly and replaced as needed.
At the time of initializing the device for use in a new patient, trained personnel must program the correct sampling interval for daytime and nighttime measure- ments, confirm the internal clock of the computer is set to the correct date and clock time, and set the ABPM device to the so-called “blind function”, i.e., to block display of BP measurements to avoid potential additional stress to the patient. Some devices sound a warning tone just preceding each BP measurement; this feature must
be switched off during the nighttime span to minimize sleep disturbances. To ensure BP measurement through- out the entire monitoring time span, use of rechargeable, e.g., nickel metal hydride, batteries is highly rec- ommended. Since these batteries have little memory effect, they can be recharged many times to their maximum capacity thereby enabling the ABPM device to operate during many consecutive days (Ayala et al., 2013b; Hermida et al., 2004d). The use of rechargeable batteries saves great expense (>750$/yr per ABPM device) as compared to the use of alkaline batteries that requires replacement prior to every ABPM application. The batteries should be removed when the ABPM device is not in use.
It is essential to choose the correct cuff size to avoid measurement errors due to use of inadequately sized cuffs. Proper cuff size must be determined by measure- ment of the upper arm circumference at each study visit. The BP cuff should be worn on the non-dominant arm and an actigraph, if used, on the dominant wrist. The cuff and the handling bag for the ABPM device must be washed regularly to ensure hygienic conditions.
10.6. Patient Instructions
Individuals should be given detailed information about the advantages of ABPM, procedure of BP measurement, and handling and operation of the ABPM device. The provision of a written set of instructions is recommended to complement verbal instructions provided by trained healthcare personnel. Patients must be aware of the potential discomfort of ABPM mainly during sleep, the programmed sampling rate, the setting of the blind-func- tion (so that the non-display of BP readings is not mistak- enly interpreted as malfunctioning of the device), and the programmed feature on most devices to automatically repeat a BP measurement 2 min after the occurrence of a measurement error. Finally, patients should be
informed of the precise date and time the ABPM device is to be returned to the clinical setting.
Patients must be specifically instructed to: keep the cuff at heart level, cease moving or talking, keep the arm still and relaxed, and breathe normally when the cuff starts to inflate; fit and properly adjust the cuff to the non-dominant arm; preferably wear a thin layer of cotton clothing under the cuff to minimize risk of bruising and thus increase compliance; switch the device off every time it is removed, e.g., to shower/ bathe, change clothes, etc., and switch it on again there- after; keep the device on during nighttime sleep and not switch it off; adhere to usual activities with minimal restrictions, but to keep a similar activity-rest schedule and avoid daytime napping during the days of ABPM; avoid activities that might interfere with operation of the device or ascertainment of representative BP values; and fill in all required entries in the diary.
All individuals undergoing ABPM must maintain a diary listing the time of retiring to bed at night, awakening in the morning, consumption of meals, ingestion of all medications, participation in exercise, and episodes of unusual physical activity, mood/emotional states, and other atypical events that might affect BP. This individual- ized information can be utilized to edit the ABPM data, if required, and to determine the commencement and ter- mination of the daytime activity and nighttime sleep spans to accurately derive the awake and asleep BP means of each subject, after referring each individual’s clock-hour BP values to, e.g., hours after awakening from nighttime sleep.
10.7. Scheduling of Patient Appointments for ABPM
To optimize the utilization of the available ABPM devices, it is recommended that healthcare personnel in charge of ABPM keep a calendar of the date and clock time of all
programmed appointments in keeping with the follow- up recommendations presented in Section 10.2. A suffi- cient amount of time, typically more than an hour, is rec- ommended between the scheduled return time of the device and the next appointment time for its application to another patient. This allows for possible delays by patients in returning the device and permits sufficient time for personnel to transfer measurement data from the device to the computer, perform data analyses, gen- erate the medical report, and re-initialize the device. Special seasonal periods, such as holidays, local festiv- ities, and vacation time, should be avoided when sched- uling a patient for ABPM. Special attention should be given when performing ABPM on shiftworkers; ideally, ABPM should be avoided during the first days following
a non-daytime work shift.
11. CONCLUSIONS
Worldwide, elevated BP is responsible for at least 7.6 million, i.e., nearly 13%, of all deaths annually, more than any other medical condition, and for 57 million,
R. C. Hermida et al. C h r o n o b i o l I n t D o w n l o a d e d f r o m i n f o r m a h e a l t h c a r e . c o m b y 1 7 8 . 6 0 . 1 5 6 . 1 5 6 o n 0 3 / 2 2 / 1 3 F o r p e r s o n a l u s e o n l y .
i.e., approximately 3.7%, of total disability-adjusted life yrs. Moreover, around 54% of strokes and 47% of coron- ary heart disease cases are attributed to suboptimal BP control (Arima et al., 2011). The worldwide reported prevalence of hypertension, based only on clinic BP measurements, is >40%, while in most Western countries the prevalence of poor hypertension control is extremely high, >65%. Thus, according to the WHO, uncontrolled BP is epidemic worldwide, affecting in total an estimated
1 billion adults≥25 yrs. Unfortunately, the prevalence of
BP control has not improved in recent years, despite the increased intensity of therapy and progressive increase in
the proportion of patients treated with ≥2 hypertension
medications (Catalá-López et al., 2012; Tocci et al., 2012). Hence, the pharmacotherapy of hypertension is markedly suboptimal and must be improved by: (i) proper early identification of at-risk individuals, more feasible with ABPM as clearly summarized above and documented in numerous publications (e.g., Ayala & Hermida, 2013; Clement et al., 2003; Dolan et al., 2005; Eguchi et al., 2008; Hansen et al., 2007; Hermida & Ayala, 2002, 2004, 2010; Hermida et al., 2011c, 2012a, 2012b, 2013b; Minutolo et al., 2011; Perloff et al., 1983; Salles et al., 2008; Staessen et al., 1999; Verdecchia et al., 1994); (ii) establishment of more cost-effective in- dividualized therapeutic schemes, more feasible by the combined use of ABPM and bedtime chronotherapy regi- mens (Hermida & Ayala, 2009; Hermida & Smolensky, 2004; Hermida et al., 2003d, 2004c, 2005a, 2007a,