, Germaine Cornelissen2 and Franz Halberg2
(1)
Department of Chronomics & Gerontology, Tokyo Women’s Medical University Medical Center East, Arakawa-ku, Tokyo, Japan
(2)
Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA
Abstract
Currently, 24-hour monitoring of blood pressure (BP) by ambulatory functioning devices is a gold standard, reserved for special cases of high BP, left uninterpreted in terms of its time structure. General reliance upon a single measurement (or a single 24-hour profile) of BP, however, has been dubbed “flying blind” and is at variance with the documented need to meet requirements, stated repeatedly for over a century by opinion leaders, i.e., that we must evaluate periodic BP variations before a patient is examined. We review the relative merits of long-term BP monitoring, analyzed time-structurally (chronomically, from chronome = time structure). Among-day BP variability, including “masked non-dipping” (dipping on day 1, but non-dipping on at least 1 of the following 6 days), may underlie cardiovascular disease accompanying a key component of psychological depression.
Keywords
7-day/24-hour ambulatory BP monitoringAmong-day variability of circadian BP characteristicsMonday morning surge in BPDisruption of circadian rhythm in systolic BPCommunity-based comprehensive medical assessment17.1 Within-Day and Among-Day Variability Assessed by 7-Day/24-Hour Ambulatory Blood Pressure Monitoring
Blood pressure (BP) being highly variable, ambulatory BP monitoring (ABPM) more thoroughly depicts the underlying BP behavior and predicts cardiovascular risk better than conventional measurements [1–4]. ABPM also assesses the extent of BP decrease (“dip”) during sleep. “Non-dipping,” defined as a day-night ratio (DNR) <10 %, is reportedly associated with target organ damage and cardiovascular events, independently of the overall BP mean [1, 2]. Day-to-day variability in circadian BP characteristics is often observed in 7-day ABPM records. Changes with age in the extent of day-to-day variability in 24-hour SBP mean and DNR are examined herein.
A greater morning BP surge on Mondays was found in Uraus, a rural northern Japanese town, as shown in Fig. 17.1 [5], but not in Tosa, a southern Japanese city. Geographic differences in changes with age in circadian features of BP are explored herein between these two cities and Tokyo.
Fig. 17.1
Repeated ambulatory monitoring reveals a Monday morning surge in BP in a community-dwelling population (Am J Hypertens 2004;17:1179–83)
From the 644 community-dwelling subjects, living in Tokyo, Uraus (Hokkaido Prefecture), or Tosa (Kochi Prefecture) initially recruited, 609 subjects (368 women and 241men, 23–79 years of age) who provided ABPM records spanning at least 6 days were included in this study. As reported earlier [5–9], BP was measured oscillometrically at 30-min (07:00–22:00) or 60-min (22:00–07:00) intervals, using TM-2431 monitors (A&D Co., Japan), validated for accuracy [10]. Daily (24-hour) averages and DNR values were computed.
Hypertension (HT) was defined as a 24-hour BP mean above 130/80 mmHg. Non-dipping (ND) was defined as a DNR of systolic (S) BP <10 %. The 24-hour BP mean and DNR served to subdivide the 609 subjects into four groups. In one classification, groups I–IV consisted of consistent normotension (NT), NT on day 1 but HT on at least 1 of the following 6 days (masked “HT”), HT on day 1 but NT on at least 1 of the following 6 days (“masked NT”), and consistent HT, respectively. In the other classification, groups I–IV consisted of consistent dipping (DP), DP on day 1 but ND on at least 1 of the following 6 days (“masked ND”), ND on day 1 but DP on at least 1 of the following 6 days (“masked DP”), and consistent ND, respectively.
The incidence of consistent and inconsistent classification was compared by the Kruskal-Wallis test (significance at the 0.05 probability level) for subjects in three age groups (23–49 years, N = 113; 50–64 years, N = 257; 65–79 years, N = 239), for all subjects, men and women separately, and subjects in each of the three cities.
Inconsistent classifications from day-to-day increased with age (p < 0.0001), “masked NT” being more frequent than “masked HT.” Results were significant for women (p < 0.0001) but not for men (p = 0.2154) (Table 17.1), for citizens of Uraus (p = 0.0007) and Tosa (p = 0.0048) but not Tokyo (p = 0.7201) (Table 17.2). Inconsistent DNR classifications also increased with age, overall, and for men and women separately (all p = 0.0008) (Table 17.3), being significant in Uraus (p = 0.0130) but not in Tosa (p = 0.0907) or Tokyo (p = 0.5364) (Table 17.4).
Table 17.1
Gender difference of day-to-day variability in mean 24-hour blood pressure
Table 17.2
Difference of day-to-day variability in mean 24-hour blood pressure among three Japanese cities
Table 17.3
Day-to-day variability in day-night ratio (nocturnal dipping) of blood pressure in women and men
Table 17.4
Difference of day-to-day variability in day-night ratio (nocturnal dipping) of blood pressure among three Japanese cities
Depressive mood affects BP and BP variability [6, 7, 11], depressed citizens showing a more prominent circaseptan component in SBP, associated with subjective sleep disturbances. Aging is herein found to affect the extent of day-to-day BP variability, more so in women than in men, perhaps because day-to-day variability is already high in younger men. An age effect was not found in Tokyo, where the incidence of consistent HT was already high in the younger age group.
An age effect in DNR classification was significant for men and women but only in Uraus in northern Japan, where winters are cold. Results in Tosa are similar but not significant, perhaps because the clement weather of southern Japan favors a higher incidence of consistent dippers in all age groups. A busy and noisy lifestyle in Tokyo may account for the largest percentage of inconsistent day-to-day classification (80.2 %).
DNR classification is almost invariably more inconsistent than BP-mean classification. Habituation to the monitor may account for the numerically higher incidence of “masked-normotension” than “masked-hypertension,” observed primarily in the elderly (p = 0.0216).
In conclusion, aging affects day-to-day BP variability in the 24-hour BP mean and in the DNR. Several consensus meetings advocated 7-day/24-hour ABPM for a refined diagnosis to decide on a treatment plan, especially in the elderly. They proposed a chronobiological interpretation of the data in the light of time-specified reference values derived from healthy peers matched by gender and age to identify vascular variability anomalies (VVAs) for an assessment of cardio-, cerebro-, and renovascular disease risk [12]. Even within the conventionally accepted normal range, VVAs have been associated with a statistically significant increase in risk. Results herein corroborate the need for prolonged, preferably continuous ABPM.
17.2 Circadian Disruption of Blood Pressure Observed by 7-Day/24-Hour Ambulatory Blood Pressure Monitoring
Many biological variables are circadian periodic. Most of them are partly endogenous with a period of about 24 hours, coordinated by a biological circadian clock [13], also involved in the circadian coordination of blood pressure (BP) [14]. Disruption of circadian rhythms can seriously impact overall health and increase the risk of adverse cardiovascular outcomes [13]. In mammals, including humans, aging is associated with alterations in circadian rhythm characteristics, usually involving a phase advance and/or a reduced amplitude [15]. Age-related alterations of the circadian rhythm of BP measured oscillometrically for 7 days (TM-2431, A&D Co., Tokyo, Japan) are examined herein.
A comprehensive community-based medical assessment examined any association between adverse cardiovascular outcomes and disruption of the circadian BP rhythm. Subjects were fitted with an ambulatory monitor programmed to record BP and heart rate (HR) every 30 (07:00–22:00) or 60 (22:00–07:00) minutes for 7 days. From the 292 subjects living in a rural Japanese town (Tosa) initially recruited, 283 (170 women and 113 men), aged 39–74 years, who completed monitoring for 5 (N = 3), 6 (N = 4), or 7 (N = 276) days, were included in the study.
The circadian period of BP was estimated by the Maximum Entropy Method, using the MemCalc software (GMS Co., Tokyo) [16]. A circadian rhythm with an estimated period in the range of 22.5–25.5 hours was found in 266 citizens. The average period (± standard deviation; SD) was 24.04 ± 0.46 hours (range from 22.52 to 25.17 hours). A model consisting of cosine curves with periods of 24 and 12 hours fitted by least squares to the data was used to estimate the MESOR (midline estimating statistic of rhythm) and the 24-hour amplitude and acrophase (time of predicted maximum) [12]. The acrophase (± SD) of systolic (S) and diastolic (D) BP and of heart rate (HR) averaged 13:57 ± 1:39, 13:55 ± 1:37, and 14:41 ± 1:51, respectively.
Subjects were subdivided into four age groups: I (35–44 years, N = 34), II (45–54 years, N = 44), III (55–64 years, N = 79), and IV (65–74 years, N = 126). The incidence of circadian SBP disruption increased with age (p = 0.0343). The relationship may be J-shaped (Fig. 17.2), however, with 2 (5.9 %), 0, 2 (2.5 %), and 13 (10.3 %) cases of disrupted SBP rhythm in groups I–IV, respectively (increased incidence statistically significant only for group IV vs. groups I–III, p = 0.035).
Fig. 17.2
The incidence of circadian SBP disruption increased with age
SBP was also higher in group IV than in younger groups (7-day MESOR, daytime and nighttime means, office and morning home measurements), despite the fact that elderly subjects were more likely to be treated with antihypertensive medication (Table 17.5). Whereas there was no difference in the circadian amplitude of SBP or DBP among the four groups, all acrophases were statistically significantly advanced with increasing age (p < 0.0001) (Fig. 17.3).
Table 17.5
The J-shaped prevalence of age-related disruption of circadian rhythm in systolic BP
Fig. 17.3
Advance in time of circadian acrophase of systolic blood pressure (left) and heart rate (right)
Although there were no intergroup differences in depressive mood, subjective quality of life (health and happiness), or times of falling asleep and getting up, sleep duration was longer in the elderly (Fig. 17.4).
Fig. 17.4
Duration in bed for sleep increases with age
As compared to subjects with an about 24-hour SBP variation, subjects with a disrupted circadian rhythm had an earlier acrophase (12:12 ± 3:36 vs. 13:57 ± 1:39; p < 0.0001), smaller double amplitude (12.5 ± 7.7 vs. 30.5 ± 10.6; p < 0.00001), as shown in Table 17.6 and Fig. 17.5, and a smaller nightly BP dip (7.0 ± 11.6 % vs. 19.5 ± 10.0 %; p < 0.0001). They were older (65.0 vs. 59.9 years, p = 0.0440) and included a larger proportion of subjects on antihypertensive medication (p = 0.0179).
Table 17.6
Characteristic factors associated with a disrupted circadian rhythm group of systolic BP
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