Comparison of arbitrary definitions of circadian time periods with those determined by wrist actigraphy in analysis of ABPM data

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1 Journal of Human Hypertension (1999) 13, Stockton Press. All rights reserved /99 $ ORIGINAL ARTICLE Comparison of arbitrary definitions of circadian time periods with those determined by wrist actigraphy in analysis of ABPM data MAH Eissa, RJ Yetman, T Poffenbarger and RJ Portman Hermann Center for Chronobiology & Chronotherapeutics, 6410 Fannin, Suite 833, Houston, TX , USA Determining blood pressure (BP) values at different daily time periods is a well recognised measure to assess the risk of end-organ damage. However, the use of various definitions of these periods, eg, day vs night, sleep vs wake or arbitrary definitions, makes clinical decisions based on available data difficult. In the present study, we compared BP loads in actual sleep wake periods to default day night definition provided by the ambulatory BP monitoring (ABPM) software (day ; night ) as well as to an arbitrary definition of sleep wake periods in children published in Journal of Pediatrics (Soergel et al, 1997) (awake :00 and sleep ). We used an actigraph, an accelerometer, to define the actual sleep wake periods in 46 patients with essential hypertension who are on various treatment regimens. BP data were obtained by using Spacelabs monitors for a full 24 hours. There were significant differences between actual sleep wake and default definition for BP load. No similar findings were noted when arbitrary definition was used. The proportion of hypertensives was not significantly different when default and arbitrary definitions were used. Classification of dippers and non-dippers is greatly affected by the definition of sleep interval using the default method. Although some of the misclassifications were not statistically significant, their clinical importance must be considered. Determination of sleep and wake periods for analysis of ABPM data should be based on careful determination of actual periods. Using other definitions may not provide complete information or accommodate for individual variation. Keywords: ABPM; actigraphy; circadian rhythms Introduction Previous research has indicated that circadian blood pressure (BP) variability may be a significant determinant of hypertensive end-organ damage. 1 4 A nocturnal decrease (dip) in BP occurs in normal people and uncomplicated essential hypertension; lack of such a dip has been associated with secondary hypertension and hypertensive end-organ damage. 4 6 Unfortunately these studies varied in the method of sleep determination (actigraphy, patient diary or arbitrary fixed time periods). Since sleep has been identified as an important component of circadian BP decline during nocturnal hours, 7 utilising a fixed day night time definition of sleep, which may not reflect the actual patient s wake sleep, may lead to patients receiving an inappropriate classification of hypertension. Also, an inconsistent definition of the sleep period makes comparison of data between studies difficult. The purpose of the study was to determine the Correspondence: Dr Mona AH Eissa, University of Texas- Houston, Medical School, Division of Pediatric Nephrology and Hypertension, 6431 Fannin Street, Houston, TX 77030, USA Received 4 March 1999; accepted 5 March 1999 effect of various definitions of the sleep period in the determination of hypertension among patients undergoing ambulatory BP monitoring (ABPM). Specifically, the number of patients classified as having hypertension during an ambulatory monitoring period were compared when the definition of sleep was variably defined by actigraphy, by an arbitrary definition, or the default setting of the ambulatory equipment. Materials and methods Study population Study subjects were 46 consecutive patients with a diagnosis of essential hypertension referred to the Hermann Hospital Center for Chronobiology and Chronotherapeutics, Texas, USA. These patients were being managed with varying regimens of antihypertensive medications. The mean age of the group was 42.9 ± 21.8 years (range 7 90). Thirtyeight percent of the patients were males; 58% were Caucasians, 28% African-Americans, and 14% represented a variety of ethnicities.

2 450 Ambulatory BP monitoring ABPM was performed for a 24-h period with a Space Labs monitor (SpaceLabs, Redmond, WA, USA). Blood pressures were measured every 20 min from and every 30 min otherwise. Patients also wore a Mini Logger Actigraph (Ambulatory Monitoring, Inc, Ardsley, NY, USA) as the criterion standard to identify all sleep and wake periods during the 24-h monitoring period. This device is worn on the wrist of the non-dominant arm and senses motion in three planes as accelerations above the threshold of normal motion of human beings. 8 The data were stored in the device s memory by clock time and calendar date; the device has been validated to distinguish sleep from wakefulness with over 88% accuracy. 9 For adults, BP load was defined as the percent of BP measurements exceeding 135 mm Hg and 85 mm Hg for systolic and diastolic measurements, respectively, during the awake period and 120 mm Hg and 80 mm Hg for systolic and diastolic measurements, respectively, during the sleep period. For children, BP load was defined as the percent of systolic and diastolic BPs exceeding the 95th percentile for height age during the awake period. Sleep time BP loads for children were calculated by reducing the awake period BP limit by 10%. The phenomenon of decreasing BPs at night during sleep is known as dipping. Patients in this study who did not demonstrate at least a 10% drop in mean BP at night were considered to be non-dippers. Three definitions of sleep wake were considered. The criterion or actual definition included a summation of BPs during all sleep periods throughout the day as identified by the wrist actigraphy as described above. An arbitrary period of sleep was based on a study of children which arbitrarily defined awake BPs to include those during the period from to and asleep BPs to be those from to The default definition of the sleep period is based on the common default settings of the ABPM hardware which defines BPs gathered during to to be awake and those BPs gathered from through to be asleep. Statistical analysis For each patient the absolute difference in BP loads (systolic and diastolic) when using actual wake sleep periods vs arbitrary and default methods were calculated for the sleep and for the wake periods. The statistical significance of the means of these differences was determined by paired t-test. The number and percentage of the patients whose hypertension status (hypertension or normotension) during wake and sleep periods was changed when arbitrary or default definitions were used were calculated. The statistical significance was examined by Fisher s exact test. Also, this test was used to determine the statistical significance in the number of patients whose dipper status changed when arbitrary or default methods were used. Two-tailed probabilities (P) are given and were considered significant if P Results Using the above definitions of the sleep period(s), the mean actual sleep period for our patients as Figure 1 Individual absolute difference (Delta) in BP load between actual vs arbitrary and default in wake period.

3 determined by the actigraph was 7.3 hours (range 3.5 to 12.5 h). The arbitrary definition includes 6 h of sleep for each patient and the default definition assumes 8 h of sleep for each patient. By using arbitrary or default definition up to h difference than actual sleep time is noted for some individuals. The change in BP load for each subject based on their actual sleep period compared to the default and the arbitrary definition (Figures 1 and 2) shows wide inter-subject variability. The individual absolute difference in BP loads between actual vs default or arbitrary sleep time in wake period was as high as 23% in some subjects. Also, for other individuals, the difference in BP loads in sleep period was as high as 40%. When compared to default and arbitrary definitions of sleep period, the actual sleep period resulted in higher BP loads during the wake hours for many patients. In contrast, these same comparisons resulted in lower BP loads for many patients during the sleep periods. This observation was more consistent when actual sleep period was compared to the default, not for arbitrary, classification. Overall, the default definition of the sleep period resulted in larger differences in BP loads than did the arbitrary definition. A significant difference in BP loads was found when actual method was compared to default methods (Table 1). Although some difference is noted for the actual vs the arbitrary method comparison (Table 1), the difference did not reach statistical significance. Use of the arbitrary definition of sleep resulted in underdiagnosis of nocturnal hypertension for about 11% of patients. In contrast, use of the default Table 1 Mean and standard error ( ) of absolute difference in systolic and diastolic BP loads based on various definitions of the sleep period Arbitrary vs actual Default vs actual sleep period (%) sleep period (%) Awake Sleep Awake Sleep Systolic BP 4.8 (0.7) 3.7 (1.3) 7.7* (0.8) 9* (1.4) Diastolic BP 5.0 (0.6) 3.5 (0.9) 2.6* (0.6) 7* (1.1) *Statistically significant at P definition of sleep resulted in overdiagnosis of nocturnal hypertension for approximately 11% of patients (Table 2). In general, 11 to 13% of the subjects had change of their hypertension status when arbitrary classification was used compared to 9 to 15% when default classification was utilised. These differences are not statistically significant. Dipper status similarly was affected by the choice of sleep period definition (Table 3). Use of the default definition of sleep resulted in approximately 28% of the subjects erroneously being classified as non-dippers when in reality they were (P 0.01). The classification of dipper status based on the arbitrary definition of sleep agreed somewhat more closely with the actual definition of sleep where 87% of subjects dipper status was not changed; approximately 9% of patients were erroneously classified as dippers when in reality they were not (P 0.05). 451 Figure 2 Individual absolute difference (Delta) in BP load between actual vs arbitrary and default in sleep period.

4 452 Table 2 Classification of hypertension status of patients when arbitrary and default definitions of sleep period were used Actual Arbitrary Default Awake Sleep Awake Sleep HTN n (%) NTN n (%) HTN n (%) NTN n (%) HTN n (%) NTN n (%) HTN n (%) NTN n (%) HTN 33 (72) 4 (9) 23 (50) 5 (11) 34 (74) 3 (7) 25 (55) 2 (4) NTN 2 (4) 7 (15) 0 (0) 18 (39) 1 (2) 8 (17) 5 (11) 14 (30) (n) number of patients, (HTN) hypertensives, (NTN) normotensives P 0.05 for all. Table 3 Classification of dipper status of patients when arbitrary and default definition of sleep period were used Actual Arbitrary Default* Dipper Non- Dipper Nonn (%) dipper n (%) dipper n (%) n (%) Dipper 32 (70) 2 (4) 21 (46) 13 (28) Non- 4 (9) 8 (17) 1 (2) 11 (24) dipper *Classification of dipper status was significantly changed when default sleep definition was used (P 0.01), (n) number of patients. Discussion Ambulatory monitoring of BP is increasingly used for diagnosis and management of hypertension as well as in clinical research. Accurate identification of the sleep period is critical to appropriate interpretation of ambulatory monitoring Bursztyn et al 11 demonstrated that naptime blood pressures fall considerably from wake levels, comparable to the night-time sleep blood pressures. The authors of that study recommend that blood pressures obtained during naps should be included as sleep blood pressures and not awake blood pressures. In a study using mean blood pressures, 12 true daytime BP was significantly higher than the value calculated over the arbitrary period and a significant proportion of hypertensive patients were misclassified as normotensive when daytime BP was calculated over arbitrary periods. Rozansky et al 13 found no correlation of mean blood pressures obtained during various definitions of the sleep period with endorgan damage in chronic renal patients; however, a significant change in dipper classification was noted when actual sleep times were used. Using a variety of sleep definitions for an ambulatory monitoring period, little difference in mean BP levels was noted; however sleep BP loads varied by more than 10% in 30 of the 50 patients studied. 14 These studies have lead some to suggest that actual sleep and wake times should be used for defining day and night for analysis of ABPM data. 15 In the present study, data gathered with the ambulatory monitor were converted into BP loads. In most of the previous research, absolute blood pressures rather than BP load data are presented. Use of absolute BP changes among various paediatric age groups is inappropriate as no basis of comparison exists. Presentation of the data with BP loads for children of widely different ages and sizes may be imperative. Soergel s study of children arbitrary defined awake BPs to be those during the period from to and asleep BPs to be those from to Using these definitions of awake and sleep periods results in 25% of the daily blood pressures being eliminated as part of the analysis. The appropriateness of this approach can be questioned based on the findings in our study in which 24% of patients had their hypertension classification status changed when an entire day s values were considered. The default settings of awake and sleep periods also results in a large of misclassifications of hypertension status in both sleep and wake periods as well as in the dipper status. Although some of the misclassifications were not statistically significant, their clinical importance must be considered. It is worth noting that this study showed remarkable inter-individual variation in BP loads when different definitions of sleep time were used. Conclusions Data from the ABPM should be analysed by the awake and sleep periods rather than by day and night, ideally accomplished with actigraphy or accurate diary entries. Complete 24-h data should be used since omitting part of the database may lead to misclassification of BP status. Reliance on arbitrary definitions fails to accommodate for individual variations and can inaccurately define hypertension resulting in significant clinical and research implications. References 1 Soergel M et al. Oscillometric twenty-four-hour ambulatory blood pressure values in healthy children and adolescents: a multicenter trial including 1141 subjects. J Pediatr 1997; 130: White WB, Dey HM, Schulman P. Assessment of the daily blood pressure load as a determinant of cardiac function in patients with mild-to-moderate hypertension. Am Heart J 1989; 118: Perloff D, Sokolow M, Cowan RM, Juster RP. Prognostic value of ambulatory blood pressure measurements: further analyses. J Hypertens 1989; 7 (Suppl 3): S3 S10. 4 Verdecchia Petal. Circadian blood pressure changes and left ventricular hypertrophy in essential hypertension. Circulation 1990; 81:

5 5 Consensus document on non-invasive ambulatory blood pressure monitoring. J Hypertens 1990; 8 (Suppl): S135 S Devereux RB, Pickering TG. Relationship between the level, pattern and variability of ambulatory blood pressure and target organ damage in hypertension. J Hypertens 1991; 9 (Suppl): S34 S98. 7 Halberg F, Halberg E, Halberg J, Halberg F. Chronobiologic assessment of human blood pressure variation in health and disease. In: Weber, MA, Drayer, JM (eds). Ambulatory Blood Pressure Monitoring. Steinkopff: Darmstadt, 1984, pp Sadeh A, Alster J, Urbach D, Lavie P. Actigraphically based automatic bedtime sleep-wake scoring: validity and clinical applications. J Ambulat Monitoring 1989; 2: Cole RJ et al. Automatic sleep/wake identification from wrist activity. Sleep 1992; 15: Gatzka CD, Schmieder RE. Improved classification of dippers by individualized analysis of ambulatory blood pressure profiles. Am J Hypertens 1995; 8: Bursztyn M, Mekler J, Wachtel N, Drori B. Siesta and ambulatory blood pressure monitoring: comparability of the afternoon nap and night sleep. Am J Hypertens 1994; 7: Gosse P, Ansoborlo P, Lemetayer P, Clementy J. Daytime & nighttime ABPM should be calculated over true sleep/wake cycle; not over arbitrary periods. Am J Hypertens 1996; 9: Rozansky SJ, Menachery SJ, Wagner CM, Jackson K. The effect of sleep intervals on analysis of 24-hour ABPM data. Am J Hypertens 1995; 8: Peixoto AJ, Mansoor GA, White WB. Effects of actual versus arbitrary awake and sleep times on analyses of 24-h blood pressure. Am J Hypertens 1995; 8: Pickering TG. How should the diurnal changes of BP be expressed? Am J Hypertens 1995; 8: