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Background: Blood pressure (BP) variability is involved in the appraisal of threat and safety, and can serve as a potential marker of psychological resilience against stress. The relationship between biological rhythms of BP and resilience was cross-sectionally assessed by 7-day/24-hour chronobiologic screening in a rural Japanese community (Tosa), with focus on the 12-hour component and the "circadian-circasemidian coupling" of systolic (S) BP., Subjects and Methods: Tosa residents (N = 239, 147 women, 23-74 years), free of anti-hypertensive medication, completed 7-day/24-hour ambulatory BP monitoring. The circadian-circasemidian coupling was determined individually by computing the difference between the circadian phase and the circasemidian morning-phase of SBP. Participants were classified into three groups: those with a short coupling interval of about 4.5 hours (Group A), those with an intermediate coupling interval of about 6.0 hours (Group B), and those with a long coupling interval of about 8.0 hours (Group C)., Results: Residents of Group B who showed optimal circadian-circasemidian coordination had less pronounced morning and evening SBP surges, as compared to residents of Group A (10.82 vs 14.29 mmHg, P < 0.0001) and Group C (11.86 vs 15.21 mmHg, P < 0.0001), respectively. The incidence of morning or evening SBP surge was less in Group B than in Group A (P < 0.0001) or Group C (P < 0.0001). Group B residents showed highest measures of wellbeing and psychological resilience, assessed by good relation with friends (P < 0.05), life satisfaction (P < 0.05), and subjective happiness (P < 0.05). A disturbed circadian-circasemidian coupling was associated with elevated BP, dyslipidemia, arteriosclerosis and a depressive mood., Conclusion: The circadian-circasemidian coupling of SBP could serve as a new biomarker in clinical practice to guide precision medicine interventions aimed at achieving properly timed rhythms, and thereby resilience and wellbeing., Competing Interests: The authors declare no competing financial and non-financial interests in relation to the work described. There is no sponsor’s role., (© 2023 Otsuka et al.)

The effect of mild depression on blood pressure (BP) was assessed in 116 Japanese (32-79 years). As compared to non-depressive (Geriatric Depression Scale, GDS-15 score <5) subjects, mild depressives (GDS-15 score: 1-15) had shorter sleep duration (p = 0.021), lower subjective quality of life (health: p = 0.016; life satisfaction: p < 0.001; and happiness: p < 0.001), and higher 7-d systolic BP (p < 0.05). "Masked non-dipping" (dipping on day 1, but non-dipping on at least 1 of the following 6 d) was more frequent among depressive than non-depressive normotensives (p = 0.008). Among-day BP variability may underlie cardiovascular disease accompanying a key component of psychological depression.

Analytical global and local methods applied to human blood pressure (BP) records of around-the-clock measurements. The chronobiological interpretation of ambulatory BP monitoring records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability disorders (VVDs) for an assessment of cardio-, cerebro-, and renovascular disease risk. VVD includes circadian BP over-swinging (CHAT, short for circadian hyper-amplitude tension), deficient heart rate variability, MESOR (midline-estimating statistic of rhythm) hypertension, excessively elevated pulse pressure over 60 mmHg, BP ecphasia (an odd timing of the circadian rhythms in BP but not in that of heart rate) and frequency alteration. The term MESOR-hypertension indicates only one of several VVDs that can combine to for sets of 2, 3 and n-component vascular variability syndromes.

Chronobiology is the study of biological rhythms. Chronomics investigates interactions with environmental cycles in a genetically coded autoresonance of the biosphere with wrangling space and terrestrial weather. Analytical global and local methods applied to human blood pressure records of around-the-clock measurements covering decades detect physiological-physical interactions, a small yet measurable response to solar and terrestrial magnetism. The chronobiological and chronomic interpretation of ambulatory blood pressure monitoring (C-ABPM) records in the light of time-specified reference values derived from healthy peers matched by sex and age identify vascular variability anomalies (VVAs) for an assessment of cardio-, cerebro-, and renovascular disease risk. Even within the conventionally accepted normal range, VVAs have been associated with a statistically significant increase in risk. Long-term C-ABPM records help to "know ourselves," serving for relief of psychological and other strain once transient VVAs are linked to the source of a load, prompting adjustment of one's lifestyle for strain reduction. Persistent circadian VVAs can be treated, sometimes by no more than a change in timing of the daily administration of antihypertensive medication. Circadian VVA assessment is an emergency worldwide, prompted in the United States by 1,000 deaths per day every day from problems related to blood pressure. While some heads of state met under United Nation and World Health Organization sponsorship to declare that noncommunicable diseases are a slow-motion disaster, a resolution has been drafted to propose C-ABPM as an added tool complementing purely physical environmental monitoring to contribute also to the understanding of social and natural as well as personal cataclysms.

Seasonal variations in blood pressure (BP) have often been attributed to meteorological factors, especially changes in outdoor temperature. We evaluated the direct association between meteorological factors and circadian BP variability. Twenty-four-hour ambulatory BP was monitored continuously for 7 days in 158 subjects. Mean awake, asleep, morning (first 2 h after waking) BP, prewaking morning BP surge (morning systolic BP (SBP)-mean SBP during the 2-h period before waking) and nocturnal BP decline were measured each day. We compared BP values for the lowest and highest days with regard to the daily mean outdoor temperature and mean atmospheric pressure. Morning BP and prewaking morning BP surge on the coldest day were significantly higher than those on the warmest day (morning SBP, 136.6 ± 1.6 vs. 133.1 ± 1.5 mm Hg, P = 0.002; morning diastolic BP, 84.4 ± 0.9 vs. 82.6 ± 0.9 mm Hg, P = 0.02; and prewaking morning BP surge, 20.8 ± 1.3 vs. 15.3 ± 1.3 mm Hg, P = 0.0004). The magnitude of nocturnal BP decline on the coldest day was significantly greater than that on the warmest day (15.8 ± 0.7 vs. 13.9 ± 0.7%, P = 0.01). Outdoor temperature is an important determinant of morning BP, prewaking morning BP surge and the magnitude of nocturnal BP decline. These findings may have important implications in management of hypertension and prevention of cardiovascular events.

Effects of Micardis (Telmisartan), alone or with low-dose aspirin, on blood pressure and other cardiovascular endpoints are examined in 20 patients with MESOR-hypertension in a crossover, double-blind, randomized study consisting of three stages, each lasting 7 days: I-placebo, II-Micardis, and III-Micardis with low-dose aspirin. Treatment was administered each day at a different circadian stage, upon awakening, and 3, 6, 9, 12, 15 and 18 hr after awakening. During each stage, the following variables were measured at 3-hr intervals during waking: systolic and diastolic blood pressure, heart rate, ejection fraction, intrarenal resistive index, acceleration time, and serum creatinine. Each data series was analyzed by single cosinor. Results were summarized by population-mean least squares spectra. At matched treatment times, the MESOR and circadian amplitude of each variable were compared among the three treatments by paired t-tests. A prominent circadian rhythm characterizes all variables. Micardis was associated not only with a lowering of blood pressure, but also with a reduction of the circadian blood pressure amplitude. The ejection fraction was increased, and the resistive index and acceleration time were decreased, the effect being more pronounced when low-dose aspirin was added to Micardis. Any circadian-stage dependent effect of Micardis, with or without low-dose aspirin, will require monitoring over spans longer than a single day for a given treatment administration time.

Background: Although weekly variations with a peak on Monday have been reported in the incidence of cardiovascular events, few studies have investigated weekly variations in blood pressure (BP)., Methods: One hundred and thirty-five community-dwelling subjects had 24-h ambulatory BP monitoring for 7 days. We calculated the mean awake, asleep, morning (during the first 3 h after awaking) BP, and morning BP surge (mean morning systolic BP minus mean asleep systolic BP) for each day., Results: Monday surge in BP was found in the awake and morning BP (awake BP: 128.8 +/- 15.4/79.1 +/- 9.2 v 131.5 +/- 16.3/80.7 +/- 10.0 mm Hg, P < 0.01, respectively; morning BP: 127.3 +/- 17.8/78.8 +/- 11.4 v 132.5 +/- 18.2/81.2 +/- 10.0 mm Hg, P < 0.01, respectively) but was not found in the asleep BP (112.7 +/- 18.3/68.4 +/- 10.7 v 113.1 +/- 17.6/68.7 +/- 10.5 mm Hg, P = NS, respectively). The morning BP surge on Monday was higher than on the other days of the week except for Tuesday (Monday: 19.7 +/- 13.3 mm Hg v Friday: 16.4 +/- 12.9 mm Hg, P < 0.05; v Saturday: 14.7 +/- 13.3 mm Hg, P < 0.01 v Sunday: 13.7 +/- 12.0 mm Hg, P < 0.01; v Wednesday: 15.5 +/- 14.3 mm Hg, P < 0.01)., Conclusion: Morning BP surge was the greatest on Monday in a community-dwelling population. This may be in accord with clinical evidence that cardiovascular events more frequently occur in the morning on Monday.

Half-hourly systolic (S) and diastolic (D) blood pressure (BP) and heart rate (HR) monitoring with gaps demonstrates transient elevations of unknown origin of the chronome (time structure)-adjusted mean, the MESOR, M, of BP, and of the circadian double amplitude of BP of TS, a clinically healthy-appearing engineering student who was 27 years of age at the start of the study. An assessment of large and small arterial vessel elasticity was in keeping with no detection of functional or structural alteration in her vasculature. The recovery of normality in BP endpoints at the time of this report is speculatively associated with a weight loss of 40 pounds and the formation of a friendship by correspondence. Whatever the underlying mechanisms of a long series of abnormal records may be, a 'baseline' can include weeklong spans of abnormality and is best replaced by comparisons with chronomic reference values.

A test of the relative merits of timed melatonin for the treatment of cardiac ischemia as well as hypertension refractory to other drugs is documented against the background of earlier chronobiological studies on blood pressure (BP), disease risks, circadian hyper-amplitude-tension and melatonin effects broadly.

Even when the daily blood pressure mean is acceptable, too large a circadian amplitude of blood pressure largely increases cardiovascular disease risk. Autogenic training (N = 11), a non-pharmacologic intervention capable of lowering an excessive blood pressure variability, may be well-suited for MESOR-normotensive patients diagnosed with circadian-hyper-amplitude-tension (CHAT). Not all anti-hypertensive drugs affect blood pressure variability. Accordingly, long-acting carteolol (N = 11) and/or atenolol (N = 8) may be preferred to captopril retard (N = 13), nilvadipine (N = 8), or amlodipine (N = 7) for midline-estimating statistic of rhythm (MESOR)-hypertensive patients with CHAT. Prospective outcome studies are needed to assess whether the relative merits of these treatments are in keeping with their effects on blood pressure and blood pressure variability.

We propose to initiate the automatic self-assessment of wear and tear as "stress and strain" by the time structures of blood pressure (BP) and heart rate (HR), in order to arrive eventually at an individualized timely and timed routine of life and to early preventive intervention as soon as needed. The routine may involve physiological scheduling of physical and mental activities and meals, and if need be of non-drug or drug treatment for stress amplification, e.g., by exercise, and/or strain (not stress) relief by relaxation. In so doing, we recognize the circulation as a pillar and marker of preventive and active neuroimmunomodulation (NIM), suggesting that some concerns of a vasculo- and broader NIM can be quantified by transdisciplinary chronobiology using its cartography--chronomics--of time structures, i.e., chronomes, from chronos = time and nomos = rule. Thus, we are introducing the chronomics of BP, HR and of other variables in the historical context of pioneers who were indispensable to experimental medicine. We build upon their contributions, but we must point out when, in the past, by necessity rather than choice, the giants provided rationalizing truisms that are no substitute for systematic serial data collection and appropriate computer analysis. A time-unspecified spotcheck as a baseline is much better than no measurement, but very often it is not enough, and it is always insufficient when an estimate of variability constitutes the information needed. For dynamic cycles, there are only reference cycles as a routine, although when maps are available, single timed spotchecks can be invaluable. With reference to their historical context, here we rely only upon data which necessity, rather than philosophy, compels us to collect.

Objectives: To review mechanisms of circadian variations in heart rate variability (HRV) and blood pressure variability (BPV) and mortality and morbidity due to cardiovascular diseases (CVD)., Methods: Results from 7-day/24-h HRV and BPV are interpreted by gender and age-specified reference values in the context of a Medline search., Results: Abnormal HRV and BPV measured around the clock for 7 days provides information on the risk of subsequent morbid events in subjects without obvious heart disease and without abnormality outside the conventional (in the sense of chronobiologically unquantified) physiological range. Meditation, beta-blockers, ACE inhibitors, n-3 fatty acids and estrogens may have a beneficial influence on HRV, but there is no definitive outcome-validated therapy. Low HRV has been associated with a risk of arrhythmias and arrhythmic death, unstable angina, myocardial infarction, progression of heart failure and atherosclerosis. BPV may be characterized by treatable circadian-hyper-amplitude-tension (CHAT), which can be transient '24-h CHAT' or '7-day-CHAT', MESOR-hypertension and/or an unusually-timed (odd) circadian acrophase (ecphasia), all associated with an increased risk of stroke, stroke death, myocardial infarction, and kidney disease., Conclusions: Precise insight into the patho-physiology in time of HRV and BPV is needed with development of a consensus on best measures of HRV for clinical purposes and to determine when a 7-day record interpreted chronobiologically suffices and when it does not, for detection within as well as outside the conventional normal range, for diagnostic clinical practice and to direct therapy of risk greater than that associated with hypertension, smoking or any other risk factor.

Early awakening and early to bed as well as good conduct, thought, diet, interpersonal dealings and physical activity have been suggested for healthy life in Ayurveda. Circadian rhythms, coordinated in part by the parietal hypothalamic-pituitary and adrenal mechanisms, have been reported in almost all variables examined thus far, including the circulation. It is possible that all metabolic functions undergo circadian rhythms. It remains to be explored whether these rhythms may be optimized by Ayurvedic practices. The onsets of myocardial ischemia, unstable angina, acute myocardial infarction, sudden cardiac death, and strokes have been reported to exhibit a circadian variation, with increased frequency in the second quarter of the day. An increased physical and mental load caused by an attempt to prepare for the day may be important in triggering acute cardiovascular events. Depending on their timing, meditation (Ayurvedic practice), n-3 fatty acids, coenzyme Q10, beta-blockers and estrogens may have beneficial effects, whereas progestins and mental load may have adverse effects on heart rate and blood pressure variability, which may be expressed by different circadian patterns. Around the clock serial recordings of blood pressure and heart rate during usual activities and lifestyles may be recorded and may be analyzed by computer-implemented curve fitting to assess the about 24-hour (circadian) variation, among other rhythmic, chaotic, and trend components of the time structure (chronome) of these variables. The new disease risk syndrome circadian hyper-amplitude-tension (CHAT), a condition characterized by an excessive circadian amplitude of blood pressure, cannot be ascertained on the basis of single casual blood pressure measurements. The International Chronome Ecological Study of Heart Rate (and blood pressure) Variability in various ethnic groups aims at collecting further evidence regarding the role of blood pressure and heart rate variability in the pathogenesis of cardiovascular events, while also examining any role played by ethnicity and lifestyle-associated factors.

Featured Application: Resolving the complexity of heliogiomagnetic effects on human physiology by considering several rules, including their bell-shaped dose-responses for health maintenance, should contemplate "chronobioethics", a resonance of biological rhythms, brain plasticity, and psychological resilience. This investigation reviews how geomagnetic activity affects the circadian variation in blood pressure (BP) and heart rate (HR) and their variabilities of clinically healthy individuals. A small study in Alta, Norway (latitude of 70.0° N), serves to illustrate the methodology used to outline rules of procedure in exploring heliogeomagnetic effects on human physiology. Volunteers in the Alta study were monitored for at least 2 days between 18 March 2002 and 9 January 2005. Estimates of the circadian characteristics of BP and HR by cosinor and the Maximum Entropy Method (MEM) indicate an increase in the circadian amplitude of systolic (S) BP on geomagnetic-disturbance days compared to quiet days (p = 0.0236). Geomagnetic stimulation was found to be circadian-phase dependent, with stimulation in the evening inducing a 49.2% increase in the circadian amplitude of SBP (p = 0.0003), not observed in relation to stimulation in the morning. In two participants monitored for 7 days, the circadian amplitude of SBP decreased by 23.4% on an extremely disturbed day but increased by 50.3% on moderately disturbed days (p = 0.0044), suggesting a biphasic (hormetic) reaction of the circadian SBP rhythm to geomagnetics. These results indicate a possible role of geomagnetic fluctuations in modulating the circadian system. [ABSTRACT FROM AUTHOR]

Recent studies have revealed 2 peaks in the onset of cardiovascular events, 1 in the morning and another in the evening. We evaluated whether blood pressure (BP) also rises in the morning/evening and identified the determinants of evening BP rise using 24-hour ambulatory BP monitoring for 7 consecutive days. We identified 2 BP peaks, 1 in the morning (0-3 hours after waking) and 1 in the evening (9-12 hours after waking). Subjects were subclassified according to the extent of evening BP rise: those in the top quartile (≥6.45 mm Hg, n = 34; ER group) vs all others. After adjustment for age, sex, and 24-hour systolic BP, evening BP rise was associated with the use of antihypertensive medications [odds ratio (OR), 3.57; 95% confidence interval (CI), 1.46-8.74; P = .01] and estimated glomerular filtration rate (OR, 0.96; 95% CI, 0.93-0.99; P = .04), confirming its association with antihypertensive medication use and renal dysfunction. [ABSTRACT FROM AUTHOR]

Research at the Halberg Chronobiology Center focused to a large extent on the monitoring of blood pressure (BP) and heart rate (HR). Self-measurements and later ambulatory BP monitoring yielded new knowledge of interest to basic science and clinical practice. After a brief review of BP measurement, we outline developments in methods of data analysis that paralleled technological advances in the measurement of BP. We review work done in cooperation with colleagues worldwide to illustrate how a chronobiological approach led to the mapping of spontaneous circadian and other rhythms for the derivation of refined reference values and to the assessment of response rhythms underlying chronotherapy. BIOCOS members work in different fields, spanning from cardiology and nutrition to obesity, diabetes, exercise physiology and rehabilitation, but all strive for "pre-habilitation". The early recognition of increased risk can prompt the timely institution of prophylactic intervention. As technology continues to improve, studies on groups are complemented by longitudinal self-surveillance for health maintenance. Longitudinal records serve for the investigation of environmental influences on human physiology, the topic of chronomics. As current advances in technology and wireless communication will likely impact the future of healthcare, chronobiological methods and concepts should be an integral part of this seachange. [ABSTRACT FROM AUTHOR]

Aim To present practical predictors for the difficulty of carrying out basic activities of daily living ( ADL) among the old-old during a 2-year period. Methods Assessment was carried out using data obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey on geriatric functions in the elderly. Predictor variables measured at baseline included age; sex; height; weight; blood pressure; oxygen saturation; neurobehavioral functions, such as Mini-Mental State Examination, Kohs Block Design test, Timed Up and Go test, button score, functional reach test, geriatric depression scale, cardio-ankle vascular index, ankle brachial pressure index; and blood chemical results, such as hemoglobin, fasting blood sugar, hemoglobin A1c, serum lipids, serum albumin and serum creatinine. The outcome variable was the presence of difficulties while carrying out basic ADL after 2 years. Results Age of ≥85 years, Timed Up and Go test of ≥15 s, button score of >17 s and presence of knee pain were independent predictors of difficulty in carrying out basic ADL after 2 years. Elderly individuals who have had at least two positive findings out of these four variables were likely to have impaired basic ADL during a 2-year period with a positive predictive value of 52.0%, negative predictive value of 90.2%, sensitivity of 70.3% and specificity of 80.8%. Conclusions Assessment of age, Timed Up and Go test, manual dexterity, and presence of knee pain is a useful and relevant way to identify patients who should be informed about their likelihood of developing difficulties in carrying out basic ADL. Geriatr Gerontol Int 2016; 16: 214-222. [ABSTRACT FROM AUTHOR]

Timing can greatly affect the response to a stimulus, including antihypertensive medications. Herein, we assess the response of 30 patients to losartan/hydrochlorothiazide (L/H), administered for at least 1 month at a given circadian stage to each patient, this stage being changed during consecutive spans to cover six treatment times from awakening to bedtime at approximately 3-hour intervals. At the end of each stage, each patient underwent a 7-day around-the-clock ambulatory blood pressure (BP) profile, analyzed chronobiologically. A larger reduction of the midline estimating statistic of rhythm (MESOR; a rhythm-adjusted mean) of diastolic BP was achieved by L/H administration in the early morning for more patients ( P < .05), while treatment upon awakening was the best choice for most patients to reduce the circadian amplitude of BP the most ( P < .01). The optimal treatment time varied considerably among patients, however. Special attention should be given to the effect on the circadian amplitude since treatment can increase it above a threshold, beyond which there is a marked increase in cardiovascular disease risk. The results indicate the desirability to individualize the optimization of the antihypertensive effect of L/H by timing along the circadian scale. [ABSTRACT FROM AUTHOR]

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no .significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subject with hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed lo morning surges in BP and/ or trough levels of antihypertensive drugs. [ABSTRACT FROM AUTHOR]

A few puzzles relating to a small fraction of my endeavors in the 1950s are summarized herein, with answers to a few questions of the Editor-in-Chief, to suggest that the rules of variability in time complement the rules of genetics as a biological variability in space. I advocate to replace truisms such as a relative constancy or homeostasis, that have served bioscience very well for very long. They were never intended, however, to lower a curtain of ignorance over everyday physiology. In raising these curtains, we unveil a range of dynamics, resolvable in the data collection and as-onegoes analysis by computers built into smaller and smaller devices, for a continued self-surveillance of the normal and for an individualized detection of the abnormal. The current medical art based on spotchecks interpreted by reference to a time-unqualified normal range can become a science of time series with tests relating to the individual in inferential statistical terms. This is already doable for the case of blood pressure, but eventually should become possible for many other variables interpreted today only based on the quicksand of clinical trials on groups. These ignore individual differences and hence the individual's needs. Chronomics (mapping time structures) with the major aim of quantifying normalcy by dynamic reference values for detecting earliest risk elevation, also yields the dividend of allowing molecular biology to focus on the normal as well as on the grossly abnormal. [ABSTRACT FROM AUTHOR]

The article discusses a study of a comprehensive geriatric assessment (CGA) of elderly people in a rural community in Japan which focused on the association between cognitive status and cardiovascular indicators including blood pressure.

Abstract: The aim of this study was to determine whether an artificial magnetic field with an amplitude and frequency equivalent to those of geomagnetic pulsations during geomagnetic storms could affect physiology and psychology. Three healthy volunteers wore an ambulatory BP monitor and an ECG recorder around the clock for 12 consecutive weekends in Winnipeg, Manitoba, Canada. In a room shielded against ELF and VLF waves, they were exposed for 8 hours per week to either a 50 nT 0.0016 Hz or a sham magnetic field at one of six circadian stages. Real exposure randomly alternated with sham exposure. They provided saliva and recorded mood and reaction time every 4 hours while awake. Systolic (S) and diastolic (D) blood pressure (BP), and heart rate (HR) were recorded every 30 minutes. Spectral analysis of HR variability (HRV) was performed using the maximum entropy method and a complex demodulation method. For these variables, daily means were compared between real and sham exposure, using paired t-tests. Their circadian MESOR, amplitude, and acrophase were analyzed and summarized using single cosinor and population-mean cosinor. Circadian rhythms were demonstrated for HR, SBP, DBP for sham exposure, salivary flow rate, positive affect, vigor, and subjective alertness (p&#60;0.001, ∼0.02). One participant showed higher HR, lower LF, HF, and VLF powers, and a steeper power-law slope (p&#60;0.005, ∼0.0001) in an early night exposure to the real magnetic field, but not in other circadian stages. There was no significant difference between circadian responses to real and sham exposure in any variable at any circadian stage. [Copyright &y& Elsevier]

Taking the heart rate (HR) for one cycle, whether to examine behavior in the region of periods of 1 s, 1 day, 1 week, 1.3 or 10.5 years, etc., is hazardous. Replications, when possible are mandatory for examining altered variability, whatever the period(s) involved may be. This replication in the individual, and across individuals when the periods are long, measured in decades, may serve for diagnosis and treatment. This rule applies in particular to a seemingly transient circadian hyper-amplitude-tension (CHAT), an over peer-threshold variability in blood pressure (BP), based on the fit of a 24-h cosine curve to time series of appropriate length, rather than to a mere snapshot covering just a single day or week. Transient CHAT may turn into intermittent CHAT, as determined in two cases presented herein. One case of transient CHAT could be so named after a successful treatment (Rx) change eliminated CHAT as an effect validated by monitoring at 30-min intervals for a 7-day span on a new treatment. CHAT disappeared for over 300 consecutive half-hourly measurements, but thereafter it reappeared. During the ensuing nearly continuously monitored 5 years, CHAT continued to appear and disappear sometimes without a treatment change. In another case, which was responsive to a change in the timing of medication, CHAT also disappeared and thereafter reappeared. In a short-term perspective of weeks or months of monitoring, CHAT seemed to be transient, but further monitoring again revealed it to be intermittent. Cases of intermittent CHAT require follow-up for outcomes by comparison with the population at large. Miniaturized instrumentation for their detection should be a high priority, but it must be realized that the automatic ambulatorily functioning monitors, available at 10% of the regular price through a BIOCOS project (corne001@umn.edu), already signify great progress, as compared to previously used manual measurements made around the clock by hypertensive opinion leaders in medicine from diagnosis to death. On automatically collected time series of BP and HR, gliding pergressive spectral windows as such, or such pergressive windows aligned further with global spectral windows, visualize the changing dynamics involved in health and disease, in the steps of Werner Menzel and Paolo Scarpelli. [Copyright &y& Elsevier]

We assess circadian (CD) and circaseptan (CS) changes in the blood pressure (BP) response to a 1–min immersion of the hand into ice water, the cold pressor test (CPT). An about 8 mmHg BP increase in the CPT reported by others for health and an elevation >25 mmHg for patients with “hypertension” have been viewed as predisease, but variables related to the vascular system exhibit prominent CD, CS and circannuals, among other components of their genetically anchored time structure or chronome, and may also have to be considered. Hence, a 16-year-old adolescent (ML) immersed her hand into ice water every 2–4 h for 2 days and once daily in the morning thereafter for 1 week (N = 25), as did, only for <2 days (≥24 h), four adults 20–66 years of age. BP and heart rate (HR) were monitored automatically around the clock at 15–min intervals and at 1–min intervals before and immediately after the CPT. Data were analyzed by cosinor. The difference between the first post-CPT BP value and the mean of the last seven values prior to the CPT was a measure of CPT response (at 1–min). Overall, ML’s systolic (S) BP increased by 8.2 ± 1.4 mmHg and her diastolic (D) BP by 6.2 ± 0.9 mmHg (P < 0.001). Increases were found in 96% of the tests for SBP, 92% for DBP and 20% for HR. There was only one tie for HR (4%), resulting in a HR decrease in 76% of CPTs. The BP response to CPT at 1 min was CS-dependent. The CS double amplitudes are 12.5 ± 4.1 for SBP (P = 0.019) and 7.8 ± 2.8 mmHg for DBP (P = 0.030), with acrophases occurring on late Sunday, early Monday (at –50° and –67° from 00:00 h from Saturday to Sunday for SBP and DBP, respectively, with 360° ≡ 1 week). The response of HR did not allow the detection of a CS rhythm (P = 0.969). The CD response peaked in the early morning hours; with 24 h ≡ 360° and 0° = local midnight, the acrophase (φ) for SBP is at –80° and for DBP at –113°, in keeping with earlier results from four adult subjects (SBP: –37°; DBP: –42°), individual differences notwithstanding. The average timing of the largest overall response of BP to CPT coincides with the timing of the response to other stimuli. The CS acrophases coincide with the times of increased morbidity/mortality from vascular diseases. Chronomes, time structures broader than circadian, notably their about-weekly components, should be considered, not only at the extremes of life when the CS and about-half-weekly rhythms are particularly prominent in BP and HR but also in interpreting BP responses as a gauge of vascular disease status in adolescents. [Copyright &y& Elsevier]

In order to re-examine the extent to which secular circulatory variation can be resolved into possibly accountable, if not yet predictable behavior, the 15–year record of blood pressure and heart rate of an adult male cardiologist (Y.W.) is reanalyzed. Gliding spectral windows with an interval of 4 years progressively displaced throughout the data series examine monthly means from August 1987 to August 2002. A circannual variation is only intermittent and appears to drift for years. A circasemiannual variation is consistent and prominent, yet only for a fraction of the record examined. By contrast to the circadian rhythm in blood pressure and heart rate, which is reliably detectable in most subjects in clinical health, the circannual variation in the human circulation is inconsistent and hence should be monitored, as in this case for its assessment as one goes, a conclusion that also applies to the circasemiannual variation, prominent for years but not detected thereafter. The results prompt the search for interactions between the photic, thermic and societal effects of the seasons that, if solely pertinent, should yield a consistent 1–year spectral component. That non-photic effects may also play an important role may point to modulation by solar cycle stage and solar cycle number, perhaps mediated by the solar wind. This conclusion is extended in proof to the role played by the most recently discovered transannual component in human blood pressure and heart rate, which is a probable further signature of the solar wind. The beating of the transannual and circannual components documented on another data series may contribute to the lack of a consistent 1-year synchronized circannual variation in this case and many others. [Copyright &y& Elsevier]

Abstract: A 26-year-old white woman had an ablated sino-atrial node and ventricular pacemaker as an unusual feature of a pheochromocytoma-compatible history. Her status quo included, on three occasions, elevated 24-hour urinary epinephrine and metanephrine excretion. She monitored her blood pressure (BP) and heart rate (HR) at 15- to 60-minute intervals over several days, with interruptions, before and after the institution of 10 mg phenoxybenzamine per os every 12 hours (between 7:30 and 8:00 and between 19:30 and 20:00), with continued monitoring over several months. Her data were summarized for consecutive 3-day intervals by sphygmochron. Circadian parameters and original data are compared with gender- and age-specified reference values, yielding also non-parametric endpoints, such as the percentage time elevation, the extent of excess, and the timing of excess, that all can be acceptable for some days but unacceptable for other days. In her broader time structure, or chronome, cosinor analyses revealed a prominent and statistically significant circadian rhythm in BP and HR before and during the 12-hourly therapy. The 12-hour component of BP was more prominent during therapy than prior to it. A statistically significant decreasing trend occurred before therapy, and recurred during treatment. Chronomically interpreted monitoring revealed: 1) the persistence of a statistically significant circadian rhythm during 12-hourly phenoxybenzamine treatment; 2) days-long changes in BP MESOR, the duration of which could not be previously determined based on spotchecks; 3) changes in the circadian amplitude of BP, which can be either very small or very large, compatible with the diagnosis of intermittent circadian hyper-amplitude-tension (CHAT); and 4) a very wide range of BP and HR values, so that occasional (casual) measurements fail to convey the dynamics that may underlie this infrequently found clinical condition of an elevated catecholamine excretion compatible with a pheochromocytoma. All findings support the need for long-term monitoring of BP and HR that may account for controversy in earlier publications. [Copyright &y& Elsevier]

Abstract: Longitudinal records of blood pressure (BP) and heart rate (HR) around the clock for days, weeks, months, years, and even decades obtained by manual self-measurements (during waking) and/or automatically by ambulatory monitoring reveal, in addition to well-known large within-day variation, also considerable day-to-day variability in most people, whether normotensive or hypertensive. As a first step, the circadian rhythm is considered along with gender differences and changes as a function of age to derive time-specified reference values (chronodesms), while reference values accumulate to also account for the circaseptan variation. Chronodesms serve for the interpretation of single measurements and of circadian and other rhythm parameters. Refined diagnoses can thus be obtained, namely MESOR-hypertension when the chronome-adjusted mean value (MESOR) of BP is above the upper limit of acceptability, excessive pulse pressure (EPP) when the difference in MESOR between the systolic (S) and diastolic (D) BP is too large, CHAT (circadian hyper-amplitude tension) when the circadian BP amplitude is excessive, DHRV (decreased heart rate variability) when the standard deviation (SD) of HR is below the acceptable range, and/or ecphasia when the overall high values recurring each day occur at an odd time (a condition also contributing to the risk associated with ‘non-dipping’). A non-parametric approach consisting of a computer comparison of the subject''s profile with the time-varying limits of acceptability further serves as a guide to optimize the efficacy of any needed treatment by timing its administration (chronotherapy) and selecting a treatment schedule best suited to normalize abnormal patterns in BP and/or HR. The merit of the proposed chronobiological approach to BP screening, diagnosis and therapy (chronotheranostics) is assessed in the light of outcome studies. Elevated risk associated with abnormal patterns of BP and/or HR variability, even when most if not all measurements lie within the range of acceptable values, becomes amenable to treatment as a critical step toward prevention (prehabilitation) to reduce the need for rehabilitation (the latter often after costly surgical intervention). [Copyright &y& Elsevier]