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Chronobiologically Interpreted Ambulatory Blood Pressure Monitoring in Health and Disease

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                                 RevIew

                                 Chronobiologically Interpreted Ambulatory Blood Pressure
                                 Monitoring in Health and Disease
                                 Franz Halberg, MD, Dr hc mult; Germaine Cornélissen, PhD; Dewayne Hillman, PhD; Larry A. Beaty, BS; Shiyu Hong;
                                 Othild Schwartzkopff, MD, FAAP; Yoshihiko Watanabe, MD; Kuniaki Otsuka, MD; Jarmila Siegelova, MD


         Author Affiliations     ABstRACt                                                 (C-ABPM) may detect the anteced-                                保持健康,但仅有这些要素或许
Franz Halberg, MD, Dr hc
                                 To detect vascular variability anoma-                    ents of these types of events. C-ABPM                           不够。可在就医时或在运动课程
mult, is professor of labo-
        ratory medicine and      lies (VVAs), a blood pressure and                        is of interest in preventive cardiology,                        之前测量血压,同时称体重并进
       Pathology; Germaine       heart rate profile around the clock for                  since it reveals new diagnoses as vas-                          行体检。疾病在显现之前很久便
   Cornélissen, PhD, is pro-     at least 7 days is a start. As a mini-                   cular variability anomalies (VVAs)                              已埋下种子,而传统观点所认为
fessor of integrative biol-
   ogy and physiology and
                                 mum, measurement every 60 or pref-                       and renders previous conventional                               的正常情况实际上可能并不正
          director; Dewayne      erably 30 minutes for a week is need-                    diagnoses more reliable, such as that                           常。生理机能的隐性变化被身体
 Hillman, PhD, is a consul-      ed, to be continued if abnormality is                    of an elevated BP. These VVAs include                           强大的适应能力掩盖,但可由新
 tant; Shiyu Hong is a stu-
                                 found, to assess the about 24-hour                       MESOR (midline-estimating statistic                             的时间生物学诊断和治疗方法揭
       dent of statistics; and
      Othild Schwartzkopff,
                                 (circadian) variability that exists in all               of rhythm)-hypertension, an eleva-                              示,从而展现可能隐藏的异常情
 MD, FAAP, is an assistant       individuals. As a first dividend, one                    tion of the MESOR, which is diag-                               况。时间生物学工具还可能带来
 clinical professor of pedi-     then also obtains a glimpse of 2 of the                  nosed, like all other VVAs, only after 1                        其他好处,例如检测与压力和压
   atrics, all at the Halberg
                                 very many longer-than-circadian                          or preferably several replications of                           力释放有关的生理“负荷”,及
 Chronobiology Center at
            the University of    periodicities, the biological half-week                  7-day around-the-clock BP monitor-                              太空天气对个人事件(如心脏猝
 Minnesota, Minneapolis.         and week. Certainly if we can have                       ing with available, affordable, and                             死)、社会事件(如恐怖主义和
  Larry A. Beaty, BS, is the     sensors and computer chips in our                        unobtrusive instrumentation. The                                战争)以及自然灾害的不利影
      senior member of the
      Phoenix Study Group,
                                 cars that continuously monitor the                       recommendation for continuous                                   响。从时间生物学角度解释的动
   composed of volunteer-        pressure over a tire’s life, we should                   C-ABPM recognizes several princi-                               态血压 (BP) 和心率 (heart rate,
ing members of the Twin          be able to do the same job for our-                      ples that constitute inseparably inter-                         HR) 监测 (C-ABPM) 可能会查出
                Cities chapter
                                 selves for diagnostic and therapeutic                    twined contributors to severe cardio-,                          这些事件的前因。C-ABPM 有助于
        (Minneapolis) of the
 Institute of Electrical and     decisions. Healthcare today empha-                       cerebro-        and      renovascular                           预防心脏病,因为其可显示血管
      Electronics Engineers.     sizes wellness with recommenda-                          diesase. C-ABPM gauges wear and                                 变异异常           (vascular variability
      Yoshihiko Watanabe,        tions for exercise and a proper diet,                    tear of genetics, physical loads, and in                        anomalies, VVA) 等新诊断,并使
   MD, is an associate pro-
     fessor and cardiologist
                                 yet these evaluations may not be                         particular mental stress placed upon                            先前的传统诊断(如血压 (BP)
and Kuniaki Otsuka, MD,          adequate. BP may be measured at a                        individuals from “womb to tomb” by                              升高)更加可靠。VVA 包括高血
  is a professor and hospi-      visit to the doctor or before an exer-                   daily life, including weather in extra-                         压 MESOR(midline-estimating sta-
       tal president, both at
                                 cise session, along with measuring                       terrestrial space as well as that on                            tistic of rhythm,即调整中值),
  Tokyo Women’s Medical
          University, Medical
                                 body weight and performing a physi-                      earth, as a continuous surveillance                             即 MESOR 升高,如同其他所有
         Center East, Japan.     cal exam. The seeds of disease are                       paradigm preventing us from flying                              VVA 一样,其仅可通过使用价格
 Jarmila Siegelova, MD, is       planted long before they are visible,                    blind to a change from less than 5%                             合理且普通可用的测量仪器进行
     professor and head of
         the Department of
                                 and what appears to be normal from                       to near 100% in the risk of a stroke                            7 天昼夜不停的血压 (BP) 测,
      Functional Physiology      a conventional point of view may in                      within 6 years.                                                 得到一次或(最好是)几次证实
      and Rehabilitation, St     fact be abnormal. Hidden alterations                                                                                     后作出诊断。关于持续 C-ABPM
   Anna Hospital, Masaryk        of physiological function, masked by                                                                                     的建议确认了几项要素,这些要
            University, Brno,
             Czech Republic.
                                 the body’s remarkable adaptive capa-                     摘要                                                              素紧密结合并互相作用,促成心
                                 bilities, may become visible through                     对于血压等看似简单的问题,仅                                                  脏、大脑和肾血管疾病。包括日
         Correspondence          a new diagnostic and therapeutic                         仅衡量药物乃至饮食和运动的影                                                  常生活在个体的整个一生中对个
      Franz Halberg, MD,
                                 realm—chronobiology—that reveals                         响是不够的:而需要至少 7 天昼                                                体基因、身体负荷和精神压力的
              Dr hc mult
      halbe001@umn.edu           hitherto unseen abnormalities. The                       夜不停地仔细衡量,以准确描述                                                  损耗,其中包括地球以外空间及
                                 tools of chronobiology may yield                         众多个体身上出现的 24 小时(                                                地球上的天气。
                Citation         additional dividends, such as the                        全天)变化。由此带来的首要好
Global Adv Health Med.
       2012;1(2):66-123.
                                 detection of physiological “loads”                       处是,可以简要了解很多超过一
                                 related to stress and stress relief and                  个昼夜时长的两个时段(即生物                                                  sInoPsIs
                Key words        the undesirable effects of space                         半周和生物周)的情况。当然,                                                  La mejor medición de los efectos de
           Chronobiology,        weather upon personal events such                        既然我们的汽车可以装传感器和                                                  los fármacos e incluso de la dieta y
         ambulatory blood
                                 as sudden cardiac death, societal                        电脑芯片,在轮胎寿命期内对轮                                                  del ejercicio físico en algo aparente-
  pressure, hypertension,
     circadian, coherence,
                                 events like terrorism and war, and                       胎压力进行持续监测,那么我们                                                  mente tan simple como la presión
  C-ABPM, stress, vascular       natural disasters. Chronobiologically                    自己应该也能采取相同的做法,                                                  arterial no es suficiente: necesita
       variability anomaly,      interpreted automatic ambulatory BP                      以作出诊断和治疗决定。如今的                                                  medirse prestando atención detenida
       disorder, syndrome
                                 and heart rate (HR) monitoring                           医疗注重建议运动和合理饮食以                                                  al tiempo, durante las 24 horas al


               66                Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                         Review
                                          AMBULATORY BLOOD PRESSURE MOnITORInG




menos 7 días, para caracterizar de        realidad, anormal. Las alteraciones       cos, como las anomalías de la variabi-
forma precisa la variabilidad durante     ocultas de la función fisiológica,        lidad vascular (vascular variability
24 horas (circadiana), que existe en      enmascaradas por la notable capaci-       anomalies, VVA), y convierte los
muchas personas. Como primer              dad adaptativa del cuerpo, pueden         diagnósticos convencionales anteri-
resultado, se vislumbran también          hacerse visibles mediante un nuevo        ores en más fiables, tales como los
dos de los muchos periodos largos         entorno diagnóstico y terapéutico         que muestran una PA elevada. Estas
circadianos, el biológico de media        (de modo cronobiológico), lo que          VVA incluyen la hipertensión de esti-
semana y el de una semana.                puede revelar anomalías que podrían       mación de línea media estadística del
Ciertamente, si nuestros coches           estar ocultas. Los instrumentos de        ritmo (midline-estimating statistic of
pueden tener sensores y chips infor-      cronobiología podrían reportar ben-       rhythm, MESOR), una elevación de
máticos, que monitorizan continua-        eficios adicionales, tales como la        MESOR, que se diagnostica, como el
mente la presión de los neumáticos,       detección de “cargas” fisiológicas rel-   resto de las VVA, solamente después
deberíamos ser capaces de conseguir       acionadas con el estrés y la liberación   de una o preferiblemente varias répli-
lo mismo con respecto a las decisio-      de estrés, así como los efectos indese-   cas del control constante de la PA las
nes diagnósticas y terapéuticas. La       ables asociados al tiempo espacial en     24 horas del día durante 7 días medi-
atención médica actual enfatiza el        los acontecimientos personales,           ante instrumentos que estén dis-
bienestar con recomendaciones de          como la muerte súbita cardiaca, los       ponibles, sean asequibles y no causen
practicar ejercicio físico y llevar una   acontecimientos sociales, como el         molestias. La recomendación para un
dieta apropiada, aunque estas valor-      terrorismo y la guerra, y los desastres   continuo C-ABPM reconoce varios
aciones puede que no sean las adec-       naturales. El control (chronobiologi-     principios, los cuales constituyen fac-
uadas. La presión arterial puede          cally interpreted automatic ambula-       tores entrelazados e inseparables que
medirse cuando se visita al médico o      tory blood pressure monitoring,           contribuyen a las enfermedades
antes de una sesión de ejercicio, con-    C-ABPM) automático y ambulatorio          graves cardiovasculares, cerebrovas-
juntamente con el peso corporal y un      de la presión arterial (PA) y la fre-     culares y renovasculares. Estos
examen físico. Las semillas de las        cuencia cardiaca (FC) interpretados       incluyen el desgaste genético, las car-
enfermedades se plantan mucho             de forma cronobiológica podría            gas físicas y el estrés mental, que
antes del momento en que las enfer-       detectar los antecedentes de este tipo    soportan las personas continua-
medades se hacen visibles y lo que        de acontecimientos. El C-ABPM es          mente en la vida diaria, incluido el
parece normal desde un punto de           interesante en la cardiología preven-     tiempo en el espacio extraterrestre,
vista convencional puede que sea, en      tiva, ya que revela nuevos diagnósti-     así como en la tierra.




C
        hronobiologically interpreted automatic ambu-          and laboratory animals used for research. Those interest-
        latory blood pressure monitoring (C-ABPM)              ed in measurement and self-tracking have innumerable
        yields marker rhythms for vascular and/or other        tools for measurement. By lifelong monitoring, we also
aspects of physiology, including mental functions and          gain new objective quantifiable perspectives of how seem-
thus provides a quantifiable measure of stress, as a vas-      ingly unconnected events such as space weather affect us
cular variability anomaly (VVA). When a VVA persists           and arrive at new diagnoses in a personalized, societal,
in successive 7-day records, it becomes a vascular vari-       and environmental sense that in turn leads to a unified
ability disorder (VVD) as an index of strain. When sev-        science based on “big data” (continuous time series, each
eral VVDs persist and accumulate, they become a vas-           covering years, eventually decades and even lifetimes).
cular variability syndrome (VVS). The risk of an adverse       Beyond healthcare, we can start to think globally and act
outcome within 6 years increased from less than 5% to          locally in space and can also be “glocal” in time, both with
nearly 100% in a study on 297 patients with hard out-          a view of the historical cycles that mold us and in the
comes by Kuniaki Otsuka. These adverse outcomes had            practice of automatically analyzing time series for contin-
a confirmatory follow-up on a much larger number of            ued surveillance.
subjects with a proxy outcome of the left ventricular               Big data from C-ABPM serve us with repeated passes
mass index (LVMI) and were further in keeping with a           over time as they accumulate both as a whole at a given
study followed up for over 4 decades. C-ABPM further           time (globally) and further in sections systematically var-
reveals a new transdisciplinary spectrum with novel            ied in length (locally) with a view of the cycles that char-
infradian (longer than 28-h) components that contrib-          acterize them. This requirement of “glocality” in concept
ute to other personal and societal health risks, includ-       and as an analytical method can be demonstrated, among
ing sudden cardiac death, suicide, and homicide.               others, by the fruits of analyzed C-ABPM data, yielding a
      Those who regard the proposition of lifelong ABPM        marker for the human mind as well as for the circulation.
as utopian may reconsider when they realize that we can        In so doing, it reveals our intimate associations with our
attach to our health, the same attention as we do for secu-    cosmos. In the language of frequencies, the odds ratio for
rity on the road when we continuously measure tire pres-       the number of periods shared by human mental function
sure in our cars. This technological opportunity can be        and geomagnetics more than matches that between the
made available to our bodies as well as to our automobiles     magnetisms of the interplanetary field and the earth.


Review                                                                          www.gahmj.com • Volume 1, Number 2 • May 2012   67
                                                                        GLOBAL ADVANCES IN HEALTH AND MEDICINE




                 self-suRveIllAnCe                                                                 implemented on a large scale by an international multi-
                       Healthcare stakeholders are slowly beginning to                             lingual analytical and educative website (Figure 1)1,4 on a
                 realize that the current costly, disease-oriented health                          larger than the currently ongoing small-scale endeavor.
                 service provided to an individual after the onset of dis-                         The emphasis on wellness can be augmented when pre-
                 ease can be complemented by programs for “wellness”                               vention is desired. We need no longer fly blind, ignorant
                 with self help–based care utilizing ongoing surveillance                          to the circadian and the many other variabilities within
                 and early actions whenever warranted. A cost-effective                            us and around us, as soon as we have in this generation a
                 C-ABPM system (around the clock at 30-min intervals for                           system instituted where such a service can be offered
                 all ages) is immediately available, worldwide, on a small                         freely, such as in community libraries or pharmacies. In
                 scale. It is provided with free analyses for all from a proj-                     the next generation, everyone can be trained in self-
                 ect on The BIOsphere and the COSmos, BIOCOS. This                                 monitoring in earliest schooling.9 Today, we have a Zeo
                 project constitutes a validation test for an international                        Sleep Coach that monitors the brain’s electrical waves,
                 website (www.2011.geocataclysm.org) recommended by                                the Fitbit that tracks the number of steps you take each
                 a World Forum on “Natural Cataclysms and Global                                   day (you need 10 000 steps a day), body scales that mea-
                 Problems of the Modern Civilization,” held September                              sure your weight and body-fat readings and send them to
                 19-21, 2011, in Istanbul, Turkey, that extended the scope                         your computer, blood pressure (BP) monitor jacks into
                 of prior consensus conferences. Thus, responses to Sir                            your smart phones, and motion sensors that allow you to
                 William Osler’s “wear and tear,” putative harbingers of                           track how often you brush your teeth or how many times
                 severe disease,1-4 are detected as gauges of loads,4-8                            a day you use the bathroom or open the refrigerator door.
                 prompting preventive action. Eventually, this task can be                         C-ABPM is no longer out of the ordinary.

                           1. Preventive and Curative Self-help-based Individual Healthcare
                                                                                                                                        3. Ever-evolving Diagnostic Tests &
                                                                                                                                           Improved Reference Standards
           Home

                                                                                                                                       4. Scrutiny of Space Weather Effects
                                     Personal
                                  (Institutional)                                                  Multilingual Analysis
                                    Data Base                                                            Database
                                                                         Secure                                                           Physiological-          Ecological
                                                                         Website                                                           Sociological            Database
                                                                                                                                            Database

      ABPM Wearer                                                                                        Repository of
                                                                      Ever-improved                     encrypted data
                                                                                                                                                  Research Database
        Manual or                                                      software for
        preferably                                                       analyses
        automatic
       ambulatory                                                                                                                                             Chronobiologic
       monitoring                                                                                 2. Education of the Public                                    Researches
                                     Home
          device                   computing                          Sphygmochron                and of Care Professionals
                                     device                            (summary)**



                        School
                                                                    Sequential
                                                                      testing
                                                                                                                                                Research Database


                                                                                                                                                               Medical
                                                                                                                                                               Record
                                                                                                                                                               System
                                                                                                                                       Care Providers
                                                                                                                                        5. Eventually: Societal Health Care

figure 1 Preventive and curative healthcare can yield the dividend of biomecial monitoring of space weather by time-structural analyses of ambulatory blood
pressure and heart rate series.* Physiological, other biological, notably epidemiological, and sociological as well as physical and environmental data collection
and analyses in the project on The BIOsphere and the COSmos, BIOCOS, are ongoing worldwide on a very small scale, yielding the data of this paper and some
of those cited from our team. They constitute a validation test underlying a proposal by a World Forum on “natural Cataclysms and Global Problems of the
Modern Civilization,” held September 19-21, 2011, in Istanbul, Turkey (www.2011.geocataclysm.org), for a manned international multilingual website, provid-
ing analyses for all comers, and saving the data, beyond both the medical community (bottom right) and physical environmental science concerned about space
weather effects (upper right), also for the self-surveilling public at large, notably for those interested in science and art, a unified transdisciplinary chronous-
phere. The Phoenix Project of volunteering members of the Twin Cities chapter of the Institute of Electrical and Electronics Engineers (http://www.phoenix.tc-
ieee.org) is planning to develop an inexpensive, cuffless automatic monitor of blood pressure and to implement the concept of a website for a service providing
automatic analyses in exchange for the data that in turn are to be used for refining methods for monitoring psychophysiological effects of space weather.
*By aligning longitudinal and linked cross-sectional biomedical with (whenever possible also local and global) physical environmental monitoring for transdisciplinary sci-
ence—while safeguarding anonymity, privacy, and security with lifelong follow-up.
**If abnormal, participants are advised to allow data and analyses transfer to care providers for surveillance, diagnosis, optimization of treatment, if and as need be, and for
ascertaining continued efficacy.



 68              Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                         Review
                                                                AMBULATORY BLOOD PRESSURE MOnITORInG




               what Can Be Done today                                                  monitor if it shows abnormality (Figure 4, p 71).
                    In a forthcoming book for the lay public advising                        In looking at Figure 2 in 2012, some readers who rely
               patients found to have a BP that is too high or too low, a              on current official guidelines11 may infer that CH, the
               colleague asked the authors whether he could repro-                     60-year-old man, had a larger swing in BP and may be the
               duce Figure 2, published in 198410 as an example of                     healthier of the 2. Many more may recognize CH, the
               interindividual differences among 24-hour profiles. At                  subject whose data are shown on the left of Figure 2, as an
               the time of the original publication, we had not yet for-               excessive “dipper,” a very common diagnosis based on a
               mulated VVAs or VVDs (Figure 3, pp 70-71) that are not                  single 24-hour profile associated with undesirable out-
               generally known, a long series of consensus meetings                    comes, on a population basis.12-15 This majority in turn
               notwithstanding1-4 and of course had no reference val-                  should not only question a record length of 24 hours as a
               ues for them. Mostly not implemented as yet is the                      basis of a diagnosis (Figure 2)5,16-18 but can compare the
               detection of circadian and approximately 7-day (circa-                  utility of a classification of dipping with the chronobio-
               septan) BP periodicities documented over a century ago                  logic diagnosis: eg, of a circadian overswing, CHAT
               that is immediately available for diagnostic and thera-                 (short for circadian hyper-amplitude-tension; Figure
               peutic use in 2012. As to diagnosis, let us start by asking             3)4,19 associated with a high risk of stroke (Figures 5A-5C,
               this question: Who in Figure 2 is at the greater risk of a              pp 72-73).4 It must be realized that a diagnosis based on
               cerebral stroke or other severe cardiovascular disease?                 the single measurement of BP (Figures 6A-6C, pp 74-75),
               The important answer, contrary to current worldwide                     like that relying on a single 24-hour record, as in the case
               practice, is this: We can’t tell; the record is too short. We           of Figure 2 and others, is a spotcheck rather than a plati-
               need a 7-day record as a start and must continue to                     num standard (Figure 7, p 75).2

                                       Subject 1 (CH, 60 y)                                                      Subject 2 (LA, 44 y)

             175                Ø = 14:57                                                              Ø = 13:38

                                                                             60.2 = 2A = 16.2




             150


                        M=                                                                        M=
                        130.3                              A = 30.1                               130.9
SBP (mmHg)




             125                                                                                                           A=
                                                                                                                           8.1



                                       “Best-Fitting”
                                        24-h Cosine
             100




                                  Original data at 7.5-minute                                                                           M = MESOR
                                  intervals for 24 hours                                                                                A = Amplitude
                                                                                                                                        Ø = Acrophase


               0

                   00            06            12                18            00         00              06             12              18              00
                                                                            Time (clock hours)


               figure 2 Different circadian patterns of systolic blood pressure (SBP) in 2 clinically healthy men. Twenty-four–hour profiles of blood pres-
               sure (BP) variation in 2 clinically healthy men were described in 198410 as revealing interindividual differences. In the interim, reference
               values from clinically healthy subjects with outcomes have demonstrated that a double amplitude of 60 mmHg in CH, 60 years of age, is
               compatible with a diagnosis of 24-hour CHAT (circadian hyper-amplitude-tension, a circadian overswing; see Figure 3) found on occasion
               in certain individuals as a physiological event (response) under routine conditions. If CHAT persists (is not smoothed out) in the 24-hour
               cosine fit to a 7-day around-the-clock record, the diagnosis of “7-day CHAT,” like that of “1-day CHAT,” is no more than an indication for
               further chronobiologically interpreted automatic ambulatory blood pressure (BP) and heart rate (HR) monitoring (C-ABPM). Two patients
               whose BP averages (here the MESORs, midline-estimating statistics of rhythm) are practically identical differ in terms of their psychophysiol-
               ogy, here gauged by the circadian amplitude of BP. Longer monitoring is indicated to arrive at an assessment of stress or load by a vascular
               variability anomaly (VVA), or a gauge of strain, a vascular variability disorder (VVD), and thus to assess the risk of developing, among other
               severe diseases, a stroke within 6 years. As compared to the risk associated with high BP, a risk of systolic CHAT doubled that risk.




               Review                                                                                      www.gahmj.com • Volume 1, Number 2 • May 2012        69
                                                                                              GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                                                                                 I. MESOR-Hypertension




      Blood pressure (mmHg)
                                                                                             Upper limit of acceptable MESOR                                             Excessive MESOR




                                               MESOR, M



                                                                        90% Prediction interval for
                                                                        M based on data from healthy
                                                                        peers matched by gender and age

                                       00:00           04:00    08:00     12:00      16:00      20:00     00:00                   00:00      04:00     08:00       12:00      16:00     20:00     00:00

                                                                                       II. CHAT (Circadian Hyper-Amplitude-Tension)
        Blood pressure (mmHg)




                                                                                                  Upper limit of acceptable amplitude
                                               90% Prediction interval
                                               for A based on data from                                                     Excessive amplitude
                                               healthy peers matched




                                                                                 Amplitude, A



                                         00:00         04:00    08:00     12:00      16:00      20:00     00:00                   00:00      04:00      08:00      12:00      16:00     20:00     00:00



                                                                    III. Ecphasia                                                                    IV. Ecfrequentia*

                                                                                                                                                                         Reference interval
                                                                         90% Prediction interval for φ
                                                                                                                                    (f=1/τ; τ≠24h)                       for the period
                                                                         based on data from healthy peers
                                                                         matched by gender and age
      Blood pressure (mmHg)




                                                Acrophase, φ


                                                                                                                                                   Period (τ) = 24 hours


                                                                                                        φ outside
                                                                                                        reference range

                                                                                                                                                              τ > 24 hours

                                                                                                                                                                 Period outside
                                                                                                                                                                 reference range

                                    00:00              04:00    08:00     12:00      16:00      20:00     00:00                   00:00    06:00      12:00      18:00       00:00     06:00     12:00


                                                           V. Excessive Pulse Pressure                                                VI. Deficient Heart Rate Variability

                                                  Upper limit of acceptability
                                                  for PP = SBP-M – DBP-M
                                                                                                                                                                                                SD
                       Blood pressure (mmHg)




                                                                        SBP
                                                                                                                     Heart rate




                                                                                                        High PP




                                                                 DBP
                                                                                                                                                       Standard deviation (SD) of HR
                                                                                                                                                       is below acceptable threshold

                                               00:00       12:00          00:00         12:00           00:00               00:00         04:00    08:00       12:00     16:00       20:00     00:00
                                                                                                         Time (clock hours)




70   Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                                                        Review
                                                       AMBULATORY BLOOD PRESSURE MOnITORInG




figure 3 (opposite) Six vascular variability anomalies (VVAs) or disorders (VVDs—if present in several repeated weeklong profiles), validated
by chronobiologic analysis of around-the-clock 1-day/24-hour records of measurements at 1-hour or shorter intervals, interpreted in the light
of time-specific reference standards qualified by gender and age. Definitions and abstract illustrations of circadian VVAs, for systolic blood
pressure (SBP), mean arterial (MA), or diastolic blood pressure (DBP) or a combination of the foregoing when the confidence interval (95% CI)
of the period, τ, overlaps 24 hours for I to III. I to IV are diagnosed by cosinor10 with reference to gender- and age-specified reference limits (RL)
with a CI of the amplitude (A) not overlapping zero and the characteristic(s) M (MESOR), A and ϕ (acrophase) within the corresponding RL:
I. MESOR (M)-hypertension (MH), an elevation of the M above RL, can be S-MH, D-MH, MA-MH or a combination thereof, demonstrated by M,
from curve-fitting complemented by stacking along the 24-hour scale by a measure of load, the hyperbaric index and by percentages and times
of abnormal values.4
II. Circadian hyper-amplitude (A)-tension (CHAT), an elevation of the 24-hour A above RL, which can also be systolic (S-CHAT), diastolic (D-
CHAT), mean arterial (MA-CHAT), or a combination of the foregoing. D-CHAT represents a 720% increase in risk of ischemic stroke.
III. SBP-, DBP- or MAP-ecphasia (when persisting and associated with illness, circadian dysphasia), an odd timing outside RL of the circadian
rhythm of BP but often not of that in HR.
IV. Circadian ecfrequentia (when persisting and associated with illness, circadian dysfrequentia), 1 or several circadian periods, τ, with a CI not
overlapping RL.
V. Excessive pulse pressure (EPP) when the difference in the MESORs of SBP and DBP for adults exceeds 60 mmHg.
VI. A deficient HR variability (DHRV), defined as a standard deviation of HR <7.5 beats/minute.

Threshold values remain to be replaced by RL. All RLs remain to be improved by restriction to those of disease-free long-lived peers specified by
gender, age, ethnicity, and geography.
*Ecfrequentia: short for frequency (f) alteration (eg, desynchronization) that can be dysfrequentia when associated with symptoms and/or persisting in repeated con-
secutive 7-day records.


                                                                          Circadian Double                                            Circadian Acrophase (˚)
                   MESOR (mmHg)                                          Amplitude (mmHg)                                              360˚ ≡ 24h; 0˚ = 00:00
 160                                                          40                                                         -405
                  Trouble                                                Trouble                   Bad day                                Trouble at work
                                                                         at work                                                                                   00:00
                  at work       Bad day                                                            at work               -360
                                at work                                     Emotion                                                       Emotion Bad day
                                                                                                        Grief                             (”Bad   at work
                   Emotion                                                  (”Bad                                        -315
 150                                                          30            memories”)                                                    memories”)                Grief
                   (”Bad
                   memories”)                                                                                            -270
                                            Grief
                                                                                                                         -225
 140                                                          20
                                                                                                                         -180

                                                                              Daily                                      -135
                  Daily                                                     Circadian
 130              MESOR                                       10            Amplitude                                      -90

                           21 Days                                                                                         -45
                                                                                                                                                                   00:00
    0                                                          0                                                            0
         0    4        8        12    16   20   24                 0    4       8        12    16      20       24               0    4        8        12    16   20       24
                                                              Time (calendar date in February 1995)

  160                                                         40                                                          -405
                                                                                                                                                                    00:00
                                                                                                                          -360

                                                                                                                          -315
  150                                                         30
                                                                             Upper 95%                                    -270
                                                                            prediction limit
                                                                                                                          -225
  140                                                         20
                                                                                                                          -180

                                                                                                                          -135                   Daily
                                                              10                                                                               Circadian
  130                                                                                                                      -90                 Acrophase

                                                                                                                           -45
                           11 Days                                                                                                                                 00:00
     0                                                         0                                                             0
         10       12       14        16    18   20                 10    12         14        16      18    20                   10       12       14        16    18       20

                                                                Time (calendar date in April 1995)

figure 4 Infradian systolic blood pressure (SBP) variability associated with psychophysiologic responses.* At the start of monitoring, CHF, a
woman in presumably good health, was 60 years of age. She monitored her blood pressure (BP) and heart rate (HR) around the clock with
a TM-2421 monitor from A&D (Tokyo, Japan). The reliability of the TM-2421 monitor had been documented. This monitor measures BP and
HR according to the oscillometric and the auscultatory method. As a rule, with the instrument used, oscillometric readings are more reliable
than auscultatory measurements. The monitor gives a beep as a warning to stand still (eg, if the user is walking or engaged in some other
activity) or remain seated or recumbent, as the case may be. After the beep, the cuff inflates automatically, taking and storing a measurement
of systolic and diastolic BP and HR. If so set at half-hourly intervals, automatic measurements are taken and stored for up to 2.5 weeks if the
instrument is recharged at 3-day intervals, by being plugged into an electrical outlet for several minutes.
     Monitoring sessions were repeated at intervals of weeks or months during 6 years. CHF kept a thorough diary at the time of monitoring,
which allowed the association of spans when her BP was found to be deviant with the presence of strong emotions such as grief, conflict,
and concern, albeit not in association with annoyance by particular measurements. Irrespective of the duration of a given monitoring session,
analyses were carried out in repeated scans of the same data for separate subspans of (1) at least 24 h, (2) a week, (3) longer spans, sections of


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                                                                                                       GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                               figure 4 (cont) the data such as (4) only nightly readings or (5) readings without those accompanied by a note indicating annoyance by measure-
                                               ment; (6) in particular, interest such as concern for several weeks about a diagnosis of ovarian cancer in her daughter (showing gross abnormality)
                                               and (7) including analyses on all her data accumulated at certain times during the 6 years.
                                                    Each data series was analyzed using a curve-fitting and a stacking approach, with analyses of the long series confirming that CHF was
                                               24-h synchronized; the CI (95% confidence interval) of her period, τ, overlapped 24 h. A model was fitted by least squares, which consisted
                                               of cosine curves with periods of 24 and 12 h. This model for most people accurately approximates the circadian waveform in BP and HR. The
                                               parameters are the MESOR, M, a rhythm-adjusted mean; the amplitude, A (of each of the 2 components), which is a measure of half the
                                               predictable extent of change within a cycle; and the acrophase, ϕ (also of each of the 2 components), a measure of the timing of overall high
                                               values recurring in each cycle, were computed. The circadian amplitude and acrophase, together with the MESOR, are interpreted in the
                                               light of reference values obtained from databases on clinically healthy subjects matched by gender and age. These reference intervals are
                                               calculated as 90% prediction limits. When the MESOR exceeds the upper 95% prediction limit, MESOR-hypertension is diagnosed; when the
                                               circadian amplitude exceeds the upper 95% prediction limit, the condition of CHAT is diagnosed; and when the ϕ or period lies outside the
                                               90% prediction interval, ecphasia or ecfrequentia, respectively, is diagnosed, as apparent from Figure 3.
                                                    In the stacking approach, the data as a whole, averaged over an idealized 24-h cycle, are compared by computer with the time-specified
                                               reference limits (derived from databases obtained independently on clinically healthy subjects). These reference standards are again calculated
                                               as 90% prediction limits over 1-h intervals that are displaced by half an hour throughout the 24-h day. The reference values are thus specified
                                               as a function of clock-hour, gender and age (for 24-h synchronized subjects only, not for JF in Figure 28D during episodes of depression). CHF’s
                                               data are compared with the upper limit of standards, called chronodesms. Whenever the subject’s data exceed the upper limit of the chro-
                                               nodesm, BP deviation is diagnosed. The amount of time when the data are above the reference limit represents the percent time elevation.
                                               The area delineated between the subject’s curve when the data are excessive and the upper limit of acceptability delineates the hyperbaric
                                               index in the case of BP and the tachycardic index in the case of HR. As an area under the curve, this index has the units of mmHg x h during 24
                                               h for BP and of beats/min x h during 24 h for the case of HR.
                                                    The center of gravity of the area of excess is also calculated to represent the time of overall excess, which usually is informative for specifying
                                               the timing of treatment administration when it is needed. Cosine fit- and stacking-derived indices were computed for each profile as a whole as
                                               well as for spans of about 24 hours so as to determine the extent of day-to-day variability in the circadian variation and any deviation in relation
                                               to chronobiologic norms. The limitation of a profile of 24 hours is seen as intermittent black excesses above the upper limit of the chronodesm in
                                               daily summaries in the first record yet missing (with one initial exception) in the second record, each record covering weeks.
                                                    MESOR-hypertension was then detected for the first 5 days but not for the next 16 days in February (top left). The circadian amplitude
                                               was acceptable for the first 3 days in February but was intermittently excessive in February (top middle) but not in April (bottom middle). The
                                               circadian acrophase was deviant only at the beginning of the record in February (top right) and is invariably acceptable in April (bottom right).
                                               These results suggest the desirability to monitor for much longer than 24 hours to obtain a reliable diagnosis. Abnormality can occur while
                                               most or all measurements lie within acceptable limits insofar as they are neither too high nor too low on the average.
                                               *Day-to-day variability of CH (a 60-year-old woman) may mislead diagnostic and treatment decisions. Another 11-day monitoring in July 1995 found no BP deviation.




                                                       20                                                                                             4-fold increase in risk
                                                                                                                                                  with an elevated BP mean


                                                       10
                                                                                                                                                                                                                 8.2
          Relative Risk (95% Confidence Interval)***




                                                                                                                                                                                                      6.2
                                                        5                                                                                                        4.7
                                                                                                                                                                                  4.1


                                                                                                               2.5             2.6              2.7
                                                                                                                                                                                                               Diastolic
                                                        2                                      1.7                                                                                                                BP
                                                                                                                                                                                                    Systolic
                                                                                                                                                                                                      BP
                                                                               1.0
                                                        1

                                                                0.6                                                                                                                                    Swingers
                                                                                                              Equal risk
                                            1/2                                                                                                                                              6- or 8-fold increase
                                                                                                                                                                                                in risk with an
                                                                                                                                                                                            exessive circadian BP-A


                                            1/5

                                                               BMI*           High           Gender                        Family history                        Age         SBP-MESOR               BP-A > 90th
     Risk Factor:                                           > 25 kg/m2     cholesterol       (male)       Drinking**         of high BP       Smoking         > 60 years     > 130 mmHg               Percentile
     N of patients
       Risk Present:                                           88              148             152             102              207              80              52                176                  32/25
            Absent:                                            209             149             145             195              90               217             245               121                 265/272

                                               figure 5A An excessive circadian amplitude of diastolic blood pressure raises the risk of ischemic stroke by 720% (see last column on
                                               right). Original data of Kuniaki Otsuka.
                                               *BMI (body mass index) correlates positively with BP-MESOR.
                                               **Drinking increases BP-A.
                                               ***Relative risk (RR) is risk of patients with risk factor (eg, smoking or excessive BP-A) present relative to risk of patients with risk factor absent (whose
                                               RR=1) computed as a ratio of incidences.




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                                                                                                               AMBULATORY BLOOD PRESSURE MOnITORInG


                                                                                                              5-fold increase in risk with an elevated BP mean


                                              20



                                              10
            Relative Risk (95% Confidence Interval)***




                                                                                                                                                                                                                                                6.9
                                                                                                                                                                                                              5.5
                                                                                                                                                                                                                                    5.3
                                                         5                                                                                                                                 4.8
                                                                                                                                             3.8                          3.8
                                                                                                                           3.5
                                                                                                        2.7


                                                         2                                                                                                                                                                                 Diastolic
                                                                                                                                                                                                                                              BP
                                                                                                                                                                                                                                   Systolic
                                                                                          1.3                                                                                                                                         BP
                                                                         0.9
                                                         1
                                                                                                                                                                                                                                       Swingers
                                                                                                        Equal risk
                                                                                                                                                                                                                             5- or 7-fold increase
                                    1/2                                                                                                                                                                                    in risk with an excessive
                                                                                                                                                                                                                                 circadian BP-A




                                    1/5

                                                                         BMI*       High                          Family history                              Age                         Gender     SBP-MESOR                     BP-A > 90th
Risk Factor:                                                          > 25 kg/m2 cholesterol        Smoking         of high BP          Drinking**         > 60 years                     (male)     > 130 mmHg                     Percentile
N of patients
  Risk Present:                                                          88               148           80                 207                102                          52              152                176                     32/25
       Absent:                                                           209              149           217                90                 195                          245             145                121                    265/272



                                        figure 5B Excessive circadian amplitude of diastolic blood pressure raises the risk of nephropathy by 590% (see last column on right).
                                        Original data of Kuniaki Otsuka.
                                        *BMI (body mass index) correlates positively with BP-MESOR.
                                        **Drinking increases BP-A.
                                        ***Relative risk (RR) is risk of patients with risk factor (eg, smoking or excessive BP-A) present relative to risk of patients with risk factor absent (whose
                                        RR=1) computed as a ratio of incidences.




                                                             Ischemic Stroke                                                                                                    Nephropathy

          1000                                                                                                                                                 1000
                                                                                      Systolic (S) BP                Diastolic (D) BP                                                                               Systolic (S) BP                      Diastolic (D) BP


                          100                                                                                                                                                      97.5
                                                                                                                                                                          100             71.9     Mean and 95% CI
                                                               23.2
                                                                                                                                                       Relative Risk***
  Relative Risk***




                                                                       16.3                                            13.5
                                              10                                                                6.4              8.0     9.0
                                                                                      5.0                                                                                  10                                                                      5.7
                                                                               3.0              3.4 3.4                                                                                                              4.5     4.5                                    3.9
                                                                                                                                                                                                                                          2.3                2.7
                                                                                                                                                                                                   0.8    1.3
                                                         1                                                                                                                  1

                                                                                                Equal risk
                                    0.1                                                                                                                                   0.1


SBP-MESOR:                                                       < 130         130 - 140        140 - 150       150 - 160           > 160            SBP-MESOR:                      < 130         130 - 140         140 - 150            150 - 160            > 160
(mmHg)                                                                                                                                               (mmHg)
N of Patients:                                                    121                99            39                 20                18           N of Patients:                       121            99             39                    20                   18



                                        figure 5C An excessive circadian blood pressure (BP) amplitude (A)* is a risk factor for ischemic stroke and nephropathy independent
                                        from the 24-hour mean (MESOR)** note high relative risk at lowest average blood pressure. Original data of Kuniaki Otsuka.
                                        *Above 90th percentile of peers.
                                        **Results of 6-year follow-up study of 297 patients.
                                        ***Relative risk (RR) is risk of patients with an excessive circadian BP-A relative to risk of patients with an acceptable circadian BP-A (whose RR=1).




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                                                                          GLOBAL ADVANCES IN HEALTH AND MEDICINE



                  185
                                Acrophase, φ                                              CI                                             140
                                                                                                                                                                              MESOR-Hypertension?

                                   Hypertension?
                                                                                                                                         135                          Daily MESOR




                                                                                                                         SBP-M (mmHg)
                                                                                                                                         130
                  155
                                     MESOR,
                                       M                                                                                                 125


                                                                                                                                         120
     SBP (mmHg)




                  125                                                                                                                    115
                                                                                                              CI                                                              MESOR-Normotension?

                                                                                                                                                  0
                                                                                                                                                          Sun           Tue         Thu                Sat
                                                                                          CI
                                                                                                                                                                  Time (days of the week)

                                                            Normotension?
                                                                                                                                                  40
                   95




                                                                                                                               2A of SBP (mmHg)
                                                                            Double amplitude, 2A
                                                                                                                                                                                              CI
                                                    Hypotension?                                                                                  20
                                                                                                         CI
                                                         Period, τ

                    0                                                                                                                              0
                                                                                                                                                                                 Circa-
                        00:00       04:00           08:00       12:00      16:00            20:00         00:00                                                   -dian         -septan      -trigintan
                                                        Time (clock hours)                                                                         τ (days):         1             7             30

                   figure 6A Hypertension and normotension at same clock-hour or even in 24-hour average on same day of week.* need for systematic
                   long-term surveillance by C-ABPM for subject JCM, a clinically healthy neurosurgery resident who had a systolic value of 160 mmHg on
                   each of 2 occasions while giving blood.
                   *Systolic blood pressures (SBP) at 30 or 60 minutes for 30 days (n = 782) over idealized day (left) or week (top right) reveal relative prominence of circadian
                   vs infradian components (bottom right); JCM (33-year-old male, untreated); CI = 95%.




                                              August 16, 1994 (n = 13)                                                                    September 28, 1994 (n=12)
                                                                                      ClAssIfICAtIon foR BP

                        SBP                                                                               SBP
                                            < 120        120-129       130-139        ≥ 140                                       < 120                        120-129        130-139        ≥ 140
                     DBP mmHg                                                                          DBP mmHg
                                                     O             n          Hn                H                                                        O               n           Hn                 H
                          < 80              15%           15%           47%                                   < 80
                                                     n             n          Hn                H                                                        n               n           Hn                 H
                          80-84                                                        8%                  80-84
                                                    Hn          Hn            Hn                H                                                       Hn            Hn             Hn                 H
                          85-89                                                       15%                  85-89                                                                             63%
                                                     H             H             H              H                                                        H               H              H               H
                          ≥ 90                                                                                ≥ 90                                                                           37%
                   Totals: n = 77%                                                     H = 23%                                      n = 0%                                                   H = 100%

                                                     normotension?                     stAges of HIgH BP                                                 Hypertension?

                        SBP                                                                               SBP
                                            < 140        140-159       160-169        180-...                                     < 140                        140-159        160-169        180-...
                     DBP mmHg                                                                          DBP mmHg
                                                     n          h1               h2         h3-4                                                         n               h1             h2         h3-4
                          < 90              77%           23%                                                 < 90                                              63%
                                                    h1          h1            h2            h3-4                                                         h1           h1                h2         h3-4
                          90-99                                                                            90-99                                                25%            12%
                                                    h2          h2               h2         h3-4                                                        h2            h2                h2         h3-4
                         100-109                                                                         100-109
                                                h3-4          h3-4          h3-4            h3-4                                                       h3-4         h3-4           h3-4            h3-4
                         110-...                                                                          110-...


                   figure 6B A single 24-hour blood pressure profile: fool’s gold, not gold standard.* Sometimes, as in JCM, 23 days of monitoring are not
                   enough for a diagnosis.
                   *Measurements during simulated office hours (09:00-17:00) with ambulatory monitor by 33-year-old man (JCM) on 2 different days. O = optimal; n = nor-
                   mal; Hn = high normal; H = high in classification of BP for adults aged 18 years and older; n = no high BP; h1-h4 = hypertension stage 1-4 in classification of
                   stages of high BP for adults aged 18 years and older according to nIH-nHLBI, 5th report of the Joint national Committee on detection, evaluation, and
                   treatment of high BP (nIH Publication no 93-1088). Measurements by ABPM-630 Colin Medical Instruments (Komaki, Japan).




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                                                       AMBULATORY BLOOD PRESSURE MOnITORInG




                     Classification for BP in Population                                                      (JCM, % class)

       SBP                                                                            SBP
                         < 120         120-129        130-139        ≥ 140                           < 120        120-129        130-139         ≥ 140
    DBP mmHg                                                                       DBP mmHg

      < 80            Optimal          normal        High normal     High              < 80            11            16             14             6

      80-84              normal        normal        High normal     High             80-84                           1             10             10

      85-89         High normal      High normal     High normal     High             85-89                           1              3             14

      ≥ 90               High           High            High         High              ≥ 90                                                        14

                                                                                                                                            44%
                                                                                  Total High: ________________________________________ ____________
                                 stages of High BP

       SBP                                                                            SBP
                         < 140        140-159        160-179       180-...                           < 140        140-159        160-179         180-...
    DBP mmHg                                                                       DBP mmHg

      < 90               no HBP          1              2            3-4               < 90           56%            29              1

      90-99                1             1              2            3-4              90-99                          11              3

     100-109               2             2              2            3-4             100-109

      110-...             3-4           3-4            3-4           3-4              110-...


figure 6C Flipping a coin: Of 230 ambulatory blood pressures (BP) measured automatically during 23 days, about half are acceptable
(56%) and half unacceptable (44%).*
*Subject is a 33-year-old man (JCM), right. Interpretation by prevailing criteria (left) of nIH-nHLBI (no HBP = no high blood pressure; 1-4 = hypertension
stage 1-4), 5th report of the Joint national Committee on detection, evaluation, and treatment of high BP (nIH Publication no 93-1088). Measurements by
ABPM-630 Colin Medical Instruments (Komaki, Japan) from 09:00 to 17:00 during weekdays to simulate office hours.


     Interpretation by 140/90 mmHg (systolic/Diastolic) limit of Automatic Ambulatory Blood Pressure Measurements on JCM, M, 33 yrs*
                Acceptable                            08/16/94                         09/28/94                              over 23 Days
                   Yes                                  77%                               0%                                      56%
                   no                                   23%                              100%                                     44%
          Treatment (Rx)?                               no                                Yes                   non-drug Rx with further monitoring

figure 7 There is an alternative to flipping a coin and finding 0% or 100% acceptable values, namely a systematic chronobiologic blood
pressure self-surveillance, notably in “borderline” hypertension. The current gold standard must go, just like the single blood pressure at
the provider’s office.
*During office hours only (09:00-17:00 on weekdays).



urgency and feasibility of lifelong Monitoring, starting                          with additional evidence accumulating since the avail-
at the Diagnosis of Blood Pressure Abnormalitya                                   ability of automatic BP monitoring (Figure 9C, p 77).
     In 1904, Theodore C. Janeway of Johns Hopkins                                     Frederic C. Bartter reached the following conclusion
University,20 then the opinion leader, did not wish to                            after having his patient studied in the clinical center23,24:
see a patient before collecting sufficient data to assess
periodicities. (The plural was justified since by 1880                                 By conventional standards, this patient is clear-
and 1881, Ignaz Zadek in Berlin had collected suffi-                                   ly normotensive every morning. Yet the BP
ciently long time series to document 24-h, 84-h, and                                   determined each day at 6 in the afternoon pro-
168-h rhythms [Figure 8, p 76].)21,22 In 1974, Frederic C.                             vides especially convincing evidence that this
Bartter, of Bartter syndrome fame, then head of the                                    patient is a hypertensive. . . . My plea today,
Hypertension-Endocrine Branch at the US National                                       first made in 1974, is that information con-
Institutes of Health (NIH) and later the director of the                               tained in such curves [cosinor fits; see Figures
Clinical Center at the NIH,b recognized that the reason                                2 and 3: our addition] become a routine mini-
his patient was diagnosed differently by 2 physicians                                  mal amount of information accepted for the
who saw him at different times of day stemmed from                                     description of a patient’s blood pressure. The
circadian changes in BP (Figure 9A, p 76). His foresight                               analysis of this information by cosinor should
was later illustrated in the abstract (Figure 9B, p 77),                               become a routine. It is essential that enough
                                                                                       information be collected to allow objective char-
a Dr Howard Levine, the late head of medical education at the new Britain

(Connecticut) General Hospital and professor of medicine at the University of
                                                                                       acterization of a periodic phenomenon, to wit,
Connecticut, implemented self-measurements of blood pressure, heart rate, and          an estimate of M [the time structure or chro-
other performance variables, including grip strength, around the clock from the
time of a chronobiologic diagnosis of MESOR-hypertension until the end of his
                                                                                       nome-adjusted mean, or MESOR] . . . an esti-
life from amyotrophic lateral sclerosis, his weakness notwithstanding.                 mate of [the amplitude] A itself, and finally an
b
                                                                                       estimate of acrophase, ϕ [a measure of timing,
 Dr Bartter also self-measured BP around the clock from the time of diagnosis
until a fatal stroke.                                                                  Figure 10A, p 78: our addition 24 ]. In this


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                                                     GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                                                                                                  .01
                                                                                                                  .01
                                                                                                                  .01




                                                                                                                               Amplitude
                                                                                                                  .00
                                                                                                                  .00
                                                                                                                  .00
                                                                                                                         ABC




                                                               Population Mean Cosinor
      Key                  P value               n       PR          Mesor ± se           Amplitude                       Acrophase (0)
      A 168 h              < .001                4       6           117.7512.08          0.98 (.92 1.05)                 –237° (–199 –274)
      B 84 h               .018                  4       11          117.5612.09          0.59 (.24 3.56)                  –83° (–2 –166)
      C 24 h               < .001                4       30          115.8112.38          0.98 (.91 1.39)                 –238° (–192 –280)


      figure 8 Results from 4 subjects φ in degrees 360° equated to period length (168, 84, or 24 hours). By 1880-1881, Ignaz Zadek had enough
      data on 4 patients to allow the demonstration by cosinor of daily, half-weekly, and weekly rhythms, seen with cosinor diagrams by error
      ellipses around the tip of vectors that do not overlap the center of the graph (pole) with the length of the directed line indicating the
      amplitude and its direction the acrophase.24

                                                                    Complete BP Record

     190
     180
     170
     160
     150
     140
     130
     120
     110
     100
      90
      80
      70
      60
                4     5       6      7       8       9         10      11     12     13     14        15    16      17           18        19      20
                                                              Time (calendar date in November 1964)


      figure 9A Blood pressure (BP) of Frederic C. Bartter’s patient, a 61-year-old man, who had been diagnosed as normotensive by 1 physician
      seen in the morning and as hypertensive by another provider seen in the afternoon. BP measurements were taken 6 times each day for
      17 days at nIH. Reprinted with permission from Bartter FC.23




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                                                                                        AMBULATORY BLOOD PRESSURE MOnITORInG




                                                                                                                               130
                                 BP During Office Hours Is >140/90 mmHg 44% of the Time
                                                MESOR of BP: 130/80 mmHg

                        160                                                                                                    120
                                                 Hypertension

                                                                                                                               110                                 Patient’s Profile
                        140
                                                                                                                                                                                        1 SE of y
Blood Pressure (mmHg)




                                                                                                                               100
                        120                                                               Systolic BP           WHO




                                                                                                                         DBP (mmHg)
                                                                                                                Limits
                                                                                                                                      90
                                                    Normotension
                        100
                                                                                                                                                                       Mean, y
                                                                                                                                      80
                                                                                                                                                                90% Prediction Limits
                        80
                                                                                                                                      70
                                                                                        Diastolic BP

                        60                                     Office Hours
                                                                                                                                      60


                         0                                                                                                            50       3-Hourly
                              00:00                  08:00                    16:00                     00:00                                  Fractionated
                                                                                                                                               Excess:          113 mmHg x h during 24 h
                                                         Time (clock hours)                                                            0
                                                                                                                                       00:00            06:00        12:00             18:00        00:00
                                 figure 9B Limitation of fixed limits for a circadian rhythmic                                                               Time (Clock hours)
                                 function: fixed (horizontal) limits must go. We are reminded of
                                 outmoded laws and guidelines, still on the books in many states,                    figure 9C Odd-time diastolic blood pressure (DBP) excess (dark
                                 intended to protect horses and mules at a time when automo-                         section of diagram) for DJ (78-year-old man) taking “daily” 10
                                 biles (read chronobiologic monitors) were regarded as noisy toys,                   mg Vasotec (ACE inhibitor). Daytime office or dense waking
                                 imposing obligations on motorists, such as “In the event that a                     self-measurements would have missed very high blood pressures
                                 horse refuses to pass a car on the road, the owner must take his                    by night. Reliance on office or self-measurements only during
                                 car apart and conceal the parts in the bushes.”                                     waking must go.



                                        way, a patient can be compared with himself at                               ond as assessing only a single cycle can now be extend-
                                        another time [Figure 10B, p 79: our addi-                                    ed to the physiological counterparts of a half-year and of
                                        tion 25], or under another treatment, and the                                the seasons and to periods shorter than 6 months, the
                                        patient can be compared with a normal [Figure                                cis-half-year (on this side of the period = cis) or longer
                                        2: our addition] or with another patient.23                                  than 12 months, the transyear (beyond = trans). Like the
                                                                                                                     11-year (undecennian) or decadal period of the sun-
                                 what to Do with 24-hour CHAt or with other                                          spots, they are all reflected in the human circulation
                                 Records Covering a single Cycle                                                     (Figures 11A-11C, pp 80-82).28-30 Whether it is normal
                                       Turning back to Figure 2, by using “clinically”                               or abnormal, neither a 24-hour nor a single 10- or
                                 healthy in its title rather than just “healthy” in 1984, we                         11-year record can eventually remain the basis of a diag-
                                 implied that we had no outcome data on the subjects                                 nostic, therapeutic, or etiologic decision. In any case,
                                 investigated but were not aware of any abnormality.                                 the need remains for further lifelong C-ABPM and for
                                 We still lack outcomes for CH, but have (we emphasize                               continued epidemiological data collection and analysis,
                                 tentative) gender- and age-specified reference standards                            the purpose of the website. When the 24-hour record
                                 (RS) for whites, among others.26 We can make a diagno-                              happens to be abnormal, it constitutes no more than an
                                 sis of 24-hour CHAT27 specifically in the light of now-                             indication of the urgency of C-ABPM to assess a possibly
                                 available acceptability limits for the 24-hour amplitude,                           acceptable physiological response. Reliance on data
                                 still to be improved by restriction to long-lived disease-                          covering less than a solar cycle length has led to contro-
                                 free individuals. Having diagnosed 24-hour CHAT, we                                 versy31,32 and has retarded recognition of heliobiology
                                 must realize the limitations of the record’s brevity.5,16-18                        in the West (Figures 12A-12D, pp 83-85).32,33
                                 Taking a 24-hour profile to assess a single circadian                                     A record of the beating heart for a minute or 2 may
                                 cycle being equivalent to taking the pulse for 1 second                             be compatible with diagnosing death vs life, but it is
                                 to gauge just a single cardiac cycle was recognized long                            hardly recommended when a full 24-hour record can
                                 ago.27,a The analogy of taking the pulse for only 1 sec-                            fail to reveal abnormality that is present during each of
                                                                                                                     11 subsequent days and of course vice versa.
                                 a Halberg et al wrote in 1997, “Even a single heartbeat, however faint, will
                                 rule in at least a glimmer of life. The taking of the pulse for only a second or    A 1-week CHAt
                                 two then provides valuable information as to the merits of further efforts in
                                 resuscitation. But if the pulse were routinely taken for only a second or so, a
                                                                                                                         A diagnosis of 24-hour CHAT, of an excessive circadi-
                                 bradycardic athlete in the best of health might be presumed dead!”27                an swing, can be physiologically associated in certain


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                                                                                         GLOBAL ADVANCES IN HEALTH AND MEDICINE



                                 115

                                                                         Mean ±1 SE




                                  99

                                                              Systolic



                                                                                                                                    68%
                                  83                                                                                          Prediction Limits
                                                          Rest-Activity Schedule




                                                                         Diastolic
                                  67
     Blood pressure (BP, mmHg)




                                   0                                                                                                                                                    Rest-Activity
                                                                                                                                                                                          Schedule
                                       00      04        08         12          16       20         00

                                                                Systolic BP                                                                            Diastolic BP


                                 170
                                                                                                           90%
                                                                                                     Prediction Limits

                                                                                                                         92


                                 130



                                                                                                                         78



                                 110



                                                                                                                         64



                                  80



                                                                                                                         50



                                   0                                                                                     0

                                       00      04        08         12          16        20        00                        00       04         08         12         16         20        00

                                                                                                          Time (clock hours)


                                  Patient’s Characteristics
                                  Variable                        MESOR                        Double Amplitude                    Acrophase*                     Reference Limits
                                  SBP (mmHg)                       104                               14.8                             -76°                        -222° (-177; -265)
                                  DBP (mmHg)                        64                                9.0                             -63°                        -206° (-167; -252)
                                  HR (beats/min)                    97                                6.6                            -108°                        -209° (-176; -260)


                                  figure 10A Circadian ecphasia of cardiovascular variables in diabetic pregnancy. BP and HR monitoring of an 18-year-old, gravida 1, para
                                  0, with type I brittle diabetes treated by an insulin pump during the 23rd week of pregnancy reveals not only a low BP and a high HR ME-
                                  SOR, but also ecphasia (actually a delayed acrophase, ie, epiphasia) by reference to peer group limits (68% prediction intervals). Results
                                  from Maggioni C, Halberg F, Cornélissen G, Work BA. nocturnal heart rate and blood pressure peaking quantified as circadian ecphasia in
                                  a diabetic pregnancy. Chronobiologia. 1987;14:201.

                                  *0° = local midnight; 360° = 24 hours (n = 131; P < .001 in each case).
                                  Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; HR, heart rate; MESOR, midline-estimating statistic of rhythm; SBP, systolic blood pressure.




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                                                                                    AMBULATORY BLOOD PRESSURE MOnITORInG




                                                                Fulminant CHAT With Myocardial infarction 4 Months Later (BR, 35-year old man)


                                                                                                 PARAMETRIC APPROACH
                                                 Profile: 1 (Weekend), Dec 2-3, 1995                                                 Profile: 2 (Weekdays), Dec 20-21, 1995
                                 210

                                                                                                                                                       P < .013



                                                                                                                                                              Excessive A
                                 180



                                                                      Excessive A


                                 150


                                                                                                                                                                           90%
                                                                                                                                                                        Prediction
                                                                                                                                                                         Interval
                                                                                                        P < .001                    Elevated                               for A
                                 120                                                                                                 MESOR




                                  0
Systolic Blood Pressure (mmHg)




                                   00:00                      00:00                             00:00               00:00                            00:00                           00:00
                                              12/2/95                           12/3/95                                          12/20/95                              12/21/95
                                                                                                   Time (calendar Date)



                                                    MESOR/A: 130/20.1                                                                   MESOR/A: 144/30.8
                                            Acrophase/P value: -238° (15:52)/<.001                                              Acrophase/P value: -226° (15:03)/<.001

                                                                                               NON-PARAMETRIC APPROACH

                                 210
                                                 HBI: 29 mmHg x h during 24 h                                                                   230 mmHg x h during 24 h




                                 180


                                                                                 90%
                                                                           Prediction Limits

                                 150




                                 120




                                  90




                                   0
                                       00   08          16     00          08             16     00                     00     08          16         00          08         16       00

                                                                                                   Time (clock hours)



                           figure 10B Excessive circadian blood pressure amplitude is a more sensitive warning ( ) than a conventional stress test. Presence of
                           circadian hyper-amplitude-tension (CHAT) found in 2 consecutive short records from a 35-year-old man precededing by a few months
                           the occurrence of a heart attack while a stress test, carried out following the abnormal alarming BP monitoring results, found no
                           abnormality. Even if warning was justified, sampling must not be restricted to actual spans of monitoring as short as those in BR.
                           *In BR, even on a weekend, several months before an actual myocardial infarction.
                           **Even if warning was justified sampling must not be restricted to actual spans of monitoring as short as those in BR.

                           Abbreviations: CHAT, circadian hyper-amplitude tension; A, circadian amplitude.




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                                                           GLOBAL ADVANCES IN HEALTH AND MEDICINE




                   SBP
                                                                                    τ: 11.8 (11.4, 12.1) years                                      150




                                                                                                                                                     MESOR (mmHg)
       60
                                                                                                                                                    100
       2A (mmHg)




                                                                                 τ: 11.0 (10.5, 11.5) years
           0                                                                                                                                        50




                   DBP                                                    τ: 14.5 (13.8, 15.1) years                                                90




                                                                                                                                                      MESOR (mmHg)
       50


                                                                                                                                                    55
      2A (mmHg)




                                                                                    τ: 10.4 (10.1, 10.8) years
           0                                                                                                                                         20




                   HR                                                τ: 29.9 (27.4, 32.3) and 7.6 (7.4, 7.9) years
                                                                                                                                                       80




      35                                                                                                                                             MESOR (mmHg)

                                                                                                                                                       40
      2A (mmHg)




                                   τ: 26.4 (20.4, 32.4) and 5.2 (5.0, 5.4) years
        0                                                                                                                                             0
       7/20/87                                                             7/2/98                                                               6/14/09
                                                                    Time (calendar date)


     figure 11A Different decadal and/or multidecadal periods in different variables of the same elderly man (FH) treated with hypotensive
     drugs. Periods,* τ, characterizing average (MESOR; blue) and circadian double amplitude (2A; red) of systolic (S; top) and diastolic (D;
     middle) blood pressure (BP) and heart rate (HR; bottom) of FH.**

     *Period, τ, with 95% confidence interval from nonlinear cosinor determined in intervals of 48 hours displaced in increments of 24 hours.
     **FH, 68-year-old man at start of ~half-hourly automatic measurements with gaps.




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                                                                 AMBULATORY BLOOD PRESSURE MOnITORInG




                                                                                                                                                         154
                                                                           τ: 10.25 (8.38, 12.11) years added to a cubic polynomial




                 40




                                                                                                                                                                      MESOR (mmHg)
                                                                                                                                                         102
  Amplitude (mmHg)
   Double Circadian




                             τ: 19.36 (13.96, 24.77), 7.61 (7.14, 8.08) years                                                                  SBP
                         0                                                                                                                               50



                                                                                                                                                          95
                                                                  τ: 34.8 (25.1, 44.5), 10.6 (8.2, 13.0)




                 22




                                                                                                                                                               MESOR (mmHg)
 Amplitude (mmHg)




                                                                                                                                                         50
  Double Circadian




                                        τ: 21.3 (15.1, 27.4) years
                                                                                                                                                DBP
                  4                                                                                                                                       5
                  8/27/91                            5/24/97                          2/20/03                           11/17/08                     8/16/14




                                                                                                                                                          94
                                                                                         τ: 29.4 (26.2, 49.1); 11.8 (7.3, 16.4) years



               26
                                                                                                                                                                 MESOR (beats/mn)
 Amplitude (beats/min)
   Double Circadian




                                                                                                                                                          52




                               τ: 27.0 (20.8, 33.0); 7.04 (6.22, 7.86) years
                                                                                                                                                 HR
                0                                                                                                                                        10
                8/26/87                               5/23/93                          2/19/99                           11/16/04                  8/15/10

                                                                                Time (calendar date)


figure 11B Different decadal and/or multidecadal periods in different variables of YW, a man untreated for his developing MESOR-
hypertension. Periods, τ, characterizing average (MESOR) and double circadian amplitude (2A) of systolic (SBP) and diastolic (DBP)
blood pressure and heart rate of YW.*

*YW is a 57-year-old man; interval analyzed, 21 days; increment, 21 days.




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                                                                                                       GLOBAL ADVANCES IN HEALTH AND MEDICINE



                     24                                                                                           160                                       18                                                                                         85




                                                                                                                                                                                                                                                             MESOR (mmHg)
                           SBP         32.1 (28.1,36.1), 6.32 (6.06,6.58), 2.47 (2.41, 2.52) y                                                                      HR 21.0 (12.2, 29.9), 6.65 (5.11, 8.20),




                                                                                                                        MESOR (mmHg)
                                                                                                                  140                                       16         4.33 (3.43, 5.22), 0.98 (0.95, 1.00) y
                     20                                                                                                                                                                                                                                75
                                                                                                                  120                                       14

                     16                                                                                                                                     12                                                                                         65
                                                                                                                  100
                                                                                                                                                            10
                     12                                                                                           80                                                                                                                                   55
7-Day-Cycle Double




                                                                                                                                           7-Day-Cycle Double
Amplitude (mmHg)




                                                                                                                                           Amplitude (mmHg)
                                                                                                                                                                8
                                                                                                                  60
                      8                                                                                                                                         6                                                                                      45
                                                                                                                  40
                                                                                                                                                                4
                      4                                                                                                                                                                                                                                35
                                                                                                                  20
                                                                                                                                                                2
                                                           12.9 (10.2, 15.6) y +12                                                                                        9.93 (6.75, 13.1) y
                      0                                                                                           0                                           0                                                                                       25
                     16                                                                                           100                                       2.8                                                                                       158
                           DBP     16.7 (15.2, 18.3), 8.09 (7.44, 8.75), 4.51 (4.30, 4.72), 2.48 (2.42, 2.55) y                                                     BW 25.9 (23.2,28.7), 13.8 (12.7,14.8), 6.39 (6.19, 6.59), 3.89 (3.77, 4.00),




                                                                                                                        MESOR (mmHg)
                     14                                                                                           90                                                           2.94 (2.85, 3.04), 1.97(1.94, 2.00), 1.70 (1.67, 1.74),                156
                                                                                                                                                            2.4
                                                                                                                                                                                                 1.04 (1.02, 1.05) y




                                                                                                                                                                                                                                                                MESOR (lbs)
                                                                                                                  80                                                                                                                                  154
                     12
                                                                                                                  70                                        2.0
                                                                                                                                                                                                                                                      152
                     10                                                                                           60
                               40.7 (28.5, 52.9) y
                                                                                                                                                            1.6                                                                                       150
                      8                                                                                           50
7-Day-Cycle Double




                                                                                                                                       7-Day-Cycle Double
Amplitude (mmHg)




                                                                                                                                                                                                                                                      148




                                                                                                                                         Amplitude (lb)
                                                                                                                  40                                        1.2
                      6
                                                                                                                  30                                                                                                                                  146
                      4                                                                                                                                     0.8
                                                                                                                  20                                                                                                                                  144
                      2                                                                                           10                                        0.4
                                                                                                                                                                                                                                                      142
                      0                                                                                          0                                                        10.9 (9.19, 12.6) y +t
                     4/30/78              3/31/87                3/1/96               1/30/05               1/1/14                                          0.0                                                                                        140
                                                                                                                                                            4/30/78                3/31/87              3/1/96              1/30/05                1/1/14

                                                                                                                  Time (calendar date)


                                         figure 11C Different decadal and/or multidecadal periods in different variables of WRB, a man treated for high blood pressure. Periods
                                         characterizing average (MESOR) and 7-day cycle double amplitude during 35 years of self-measured systolic (S, upper left) and diastolic
                                         (D, lower left) blood pressure (BP), and heart rate (HR, upper right) and body weight (BW, lower right) of WRB, a man 52 years old at
                                         start; increment and interval analyzed: 14 days.




                                         individuals, with events such as the arrival of welcome                                                                average (MESOR) was 115 mmHg (Figure 16, p 91)4 and
                                         visitors (Figure 13, p 85)5 or any other pleasant tasks (not                                                           the cost of ignoring variability approximated $1 million
                                         necessarily loads) such as giving a party5 or discussing                                                               US for the case of a very premature baby.
                                         important-seeming topics with a friend or even with a                                                                       A chronobiologic approach works when a dipping
                                         dear family member or without any obvious reason but                                                                   classification can fail19,37,38 or dipping misleads39 on a
                                         perhaps one hidden in space weather.34,35 When a                                                                       small-group basis. It seems the more important to realize
                                         24-hour cosine curve is fitted to a 7-day series as a whole                                                            that dipping cannot be recommended for the diagnosis
                                         (rather than to a 24-hour profile, as in Figure 2), a few                                                              of individuals, even for 7-day records because it is not
                                         days of CHAT may be smoothed out and the record as a                                                                   equivalent to C-ABPM,4,40,41 in keeping with Einstein’s
                                         whole may be acceptable (Figure 14A, p 86) or at least the                                                             admonition to “make everything as simple as possible
                                         number of weeks with CHAT is reduced (Figure 14B, p                                                                    but no simpler.” Dipping is “simpler.”
                                         87).36 On a population basis, the high risk of severe                                                                       When the diagnosis of MESOR-hypertension is
                                         events associated with CHAT (Figures 5A-5C) and more                                                                   made, the dose prescribed is preferably varied, starting
                                         so with coexisting VVDs is clearly demonstrated (Figures                                                               with a time preceding the peak by several hours.
                                         15A and 15B, pp 88-90).4 A VVA for a single day should                                                                 Hence, the circadian acrophase of BP as a marker pre-
                                         invariably prompt, as a follow-up, at least an added 7-day                                                             ceded by an interval whose length depends on the
                                         C-ABPM. In a case of fulminating CHAT (Figure 10B, p                                                                   chronopharmaceutics of the drug(s) involved is a pro-
                                         79),25 this recommendation was not fully implemented,                                                                  cedure that has yielded a faster desired response, with
                                         albeit a second short record was even more abnormal                                                                    fewer side effects compared to traditional therapy
                                         than the first. The patient took a conventional stress test                                                            (Figure 17, p 91) in the hands of Rina Zaslavskaya, MD,
                                         instead, which was normal, and hence nothing else was                                                                  the leading chronocardiologist.42,43 If needed, the tim-
                                         done. Some months later, he returned asking for an                                                                     ing of the drug can next be varied empirically to find
                                         implanted BP sensor. We asked why, and he told us that                                                                 the optimum (Figures 18A and 18B, p 92).44 This is the
                                         in the interim he had had a myocardial infarction.25                                                                   more important since the same dose of the same drug
                                         C-ABPM was also ignored in a single case of CHAT dur-                                                                  in the same patient tested at 6 different circadian stag-
                                         ing pregnancy (but not in other cases with this diagnosis                                                              es, for approximately 1 month at each time (at clock
                                         in the same investigation). In that case, the systolic BP                                                              hours after awakening 3 h apart) can induce or enhance


                      82                 Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                                                   Review
                                                                         AMBULATORY BLOOD PRESSURE MOnITORInG



                                                                                 Time (Solar cycle number)
                                                                    19                         20                         21
                                                           200
                                                                                No                                       Yes

                                                           150
                                                                                               USA              Russia



                            Solar Activity (Wolf Number)
                                                           100



                                                           50



                                                             0
                                                           200
                                                                          Yes                             Yes

                                                           150                                                                             Yes
                                                                                     Russia          Israel

                                                           100                                                                          Minnesota,
                                                                                                                                           USA

                                                           50


                                                            0
                                                             1960        1965           1970          1975         1980          1985        1996


figure 12A Geographic as well as temporal differences in the association of the incidence pattern of myocardial infarction and magnetism in
the United States, Israel, and Russia (where the original studies were done). An excess of death at peak solar activity can be demonstrated in
sufficiently (29-year) long series. Time-varying associations revealed by also changing phase synchronizations and coherences readily account for
site- and time-specific results. Controversy can be avoided when aeolian time- and site-specific changes are anticipated and documented in time
series covering the length of several critical cycles characterizing the data.
       The limitation of a blood pressure measurement over a single circadian cycle comes to mind: such a spotcheck may lead to a lifetime of
unneeded treatment (when, in several repeated sessions, the patient was excited and the spotchecks showed “hypertension,” not the “white-
coat effect,” which in a group examined was hypertension in the morning and hypotension in the evening. A hypertensive patient may be
caught on several measurements with occasional normotensive values and hence will not be treated until a stroke or other severe event occurs.
Furthermore, an individual with blood pressure overswinging limited to the normal range may not be recognized as being at a very high risk of
stroke by limitation of a record to a single cycle. Likewise, studies that cover a single solar cycle may not be conclusive and may miss a relation
that can be documented in the same solar cycle elsewhere or over 3 solar cycles (in Minnesota, United States). Taking evidence over a single
solar cycle, just like relying on a single circadian cycle, is equivalent to taking the pulse for 1 second.
       Association of magnetic storms and mortality from myocardial infarction (MI) not detected in the United States (1962-1966 daily data and
only monthly to 1971) but detected in Russia (including morbidity) in 1979-1981 (top) and earlier. Bottom: association also detected in 1962-
1968 in Russia and in 1974-1976 in Israel, at minima of Schwabe (~10.5-y) and Hale (~21-y) cycles, unless data in the late 1960s in Russia contrib-
ute the outcome at the preceding minimum. Minnesotan data over several solar cycles (1968-1996) document excess of 220 MI/year during solar
maxima vs solar minima (black horizontal arrow along abscissa).



an existing CHAT at 1 test time or at another remove                                                 Multiple Circadian Rhythms and Beyond
CHAT and lower BP, as intended (Figure 19, p 93).45,46                                                    Time series collected and accumulating for the
Sometimes, a single change in the timing of a medica-                                                goal of self-surveillance, once aligned with physical
tion can correct abnormality (Figure 20, p 94).2                                                     environmental time series, enlarge the scope of
Continued surveillance is indicated (Figure 21, p 95).2                                              Vladimir Ivanovich Vernadsky’s noösphere,49,50 the
The many millions receiving hypotensive drugs need                                                   sphere of the human mind by a chronosphere, a trans-
not fly blind, concerning risks in Figures 9A and 9B (pp                                             disciplinary spectrum of cycles congruent insofar as
76-77), while for security on the road we routinely                                                  their periods in us and around us have overlapping
automatically measure the pressure in automotive                                                     confidence intervals (CIs 95%) (Figures 28A-28H,
tires. Moreover, if we monitor ourselves continuously                                                pp103-109).51-54 Our inclusion of the moon in Figure
and automatically, we may learn about a new world of                                                 28B (p 104) is in keeping with studies on his own
infradian rhythms that reflect physical environmental                                                heart55 by Miroslav Mikulecky, emeritus head of inter-
counterparts and relate to sudden cardiac death (Figure                                              nal medicine and professor of statistics at Comenius
22, p 96), suicide (Figures 23A-23D, pp 97-99), homi-                                                University in Bratislava, Slovakia, and organizer of
cide (Figure 24, p 100), and terrorism (Figures 25 and                                               meetings on this and related topics.56-60 It is here
26, pp 100-101). We may even find, on a population                                                   prompted by the first patient encountered by us who
basis, the antecedents (Figure 27, p 102)30,47 as well as                                            shows the double period of tides61 averaging 24.8
the consequences48 of a tsunami accompanying an                                                      hours, repeatedly in the computer output (not input) of
earthquake at some distance from its epicenter.                                                      analyses of time series.


Review                                                                                                                   www.gahmj.com • Volume 1, Number 2 • May 2012   83
                                                                                                          GLOBAL ADVANCES IN HEALTH AND MEDICINE


                                                           Myocardial Infarction (MI)                                           Stroke (St)                                                         Blood Pressure (BP) and Heart Rate (HR)
                                                   1        2        3         4        5       6              1       2             3      4          5    6                                  1          2            3         4            5         6

                     110                                                                                                                                                                                                                          SBP
                                                                                                                      P < 0.05 (Ho: Mean = 100%)
                                                                                                                                                                                                                                                  MAP
                                                                                                                                                                                                                                                  DBP
     Incidence (%)




                                                                                                                                                                                                                                                  HR


                     100




                         0
                                                   -2       -1       Bz ≥     Bz ≤          1       2          -2      -1           Bz ≥   Bz ≤         1   2                                  -2        -1        Bz ≥          Bz ≤         1         2
                                                                 1.0 nT -1.5 nT                 Interval (Days)                 1.0 nT -1.5 nT                                                                     1.0 nT -1.5 nT

                                                              Southward Bz turn                                       Linear Planetary Index of                                                           Forbush Decrease in Cosmic
                                                        (≥ 4h IBI ≥ 8 nT and Bz ≤ -6 nT)                            Geomagnetic Activity (AA) > 60                                                         Ray Intensity (FD) (≥ 1.5%)
                     116


                                                                                                                                                                                                              MI
                     112
         Incidence (%)




                                                                                                                           MI
                                                            MI
                     108                                                                                                                           St
                                                                            Confirmation                                                                                                                                                 St


                     104


                                                                                     St
                     100
                                                                 *                 NS                                           *                 NS                                                               *                 *
                          0
                                              Means ± SE (versus all other days ≡ 100%: horizontal line); *: P < 0.05; NS; P > 0.05


                                              figure 12B Meta-analyses in Minnesota on diagnoses made in response to a set of ambulance calls in Moscow are confirmed and extended by Vil-
                                              loresi G, Breus TK, Iucci n, Dorman LI, Rapoport SI. The influence of geophysical and social effects on the incidences of clinically important patholo-
                                              gies (Moscow 1979-1981). Physica Medica. 1994;10:79-91. Top: Southward turns of the vertical component (Bz) of the interplanetary magnetic field’s
                                              induction vector and prior changes (for BP) affect pathology and physiology: Halber et al, 1991. Bottom: Confirmation of Bz effect and extension to
                                              AA and FD effects on pathology: Villoresi et al, 1994. Means ± SE (vs all other days = 100%: horizontal line); *P < .05; nS: P > .05.



                                                                         Original Data                                              Detrended Data                                                                         Solar Activity
                                              30                                                          30                                                                                   300



                                              25                                                                                                                                               250
                                                                                                          25
                                                                                                                                                                Wolf Number (Adjusted N/day)
                         MI (Incidence/day)




                                              20                                                                                                                                               200
                                                                                                          20

                                              15                                                                                                                                               150

                                                                                                          15
                                              10                                                                                                                                               100


                                                                                                          10
                                               5                                                                                                                                                50



                                               0                                       0                                                                                                            0
                                               1965 1970 1975 1980 1985 1990 1995 2000 1965 1970 1975 1980 1985 1990 1995 2000                                                                      1965 1970 1975 1980 1985 1990 1995 2000
                                                                                                                                 Time (calendar year)


                                              figure 12C Demonstration of about 10.5-year cycle in mortality from myocardial infarction in Minnesota (1968-1996) after removal
                                              of decreasing linear trend, aligned with about 10.5-year solar activity cycle. Fitted curves represent fundamental component as a first
                                              approximation that does not account for the asymmetry of the solar activity cycle considered in Figure 12D. Minnesota data on myo-
                                              cardial infarction and solar activity (Figure 12A) reveal association of the latter with the former (Figure 12D).




84                                            Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                                               Review
                                                              Solar Cycle (~10.5 year) Pattern
                                                                                                                        JF is a woman, 61 years of age, at start of a years-long
                                                                                                                   around-the-clock study, including C-ABPM, with a
       4600
                                                                                                                   20-year history of twice-yearly adynamic depression,
                                                                                                                   each lasting 2 to 3 months. During “downtimes,” JF is
                                                                                                                   unable to get out of bed and to keep synchronized with a
                                                                                                                   24-hour periodic sleep-wake schedule. Her sleep pattern
                                                                                                                   scans the hours of the day during her episodes. She self-
                                                                                                                   rated vigor-wellness while claiming sensitivity to the
                                                                                                                   moon. In the first months of the first two adynamic epi-
       4500                                                                                                        sodes investigated, we found a double tidal period of 24.8
                                                                                                                   hours supporting her impression of selenosensitivity. JF
Incidence (N/year)




                                                                                                                   self-measured BP and HR for 5 initial months and for >16
                                                                                                                   months thereafter (Figure 28D, p 106). At least 2 circadi-
                                                                                                                   an periods coexist most of the time (Figure 28E, p 107).
                                                                                                                   She also collected saliva at 4-hour intervals around the
                                                                                                                   clock for the determination, in 11 702 assays, of cortisol,
                                                                                                                   aldosterone, dehydroepiandrosterone, estradiol, testos-
       4400
                               Excess of 220 cases/year                                                            terone, and melatonin (Figure 28F, p 107), showing mul-
                                at maximum (P = .023)                                                              tiple recurring circadian endocrine as well as vascular
                                                                                                                   ecfrequentia. Several circadian periods were also present
                                                                                                                   in her outside downtimes during relative wellness,62 sug-
                                                                                                                   gesting a “wrangling” of the tides with society and natu-
                                                                                                                   ral and artificial light. We may speculate whether the
                                                                                                                   tides act via gravity and magnetism, a view shared with
                                                                                                                   physicist-chemist Dr Vladimir Evstafyev63 and Prof
                                                                                                                   Mikulecky (their personal communications), acting by
                     0
                                                                                                                   mechanisms considered by Friedemann Freund.64 In any
                       Maximum                                   Descending         Minimum          Ascending
                     (1968, 69, 80,                           (1970-74, 82-84,     (1975, 76,        (1977-79,     event, in JF, this tug of war yields (compromise?) periods
                       81, 90, 91)                                 92-95)         85, 86, 96)          87-89)      between 24.0 and 24.8 hours except that during some of
                                                                    Solar Cycle (stage)                            the first months of an adynamic desynchronized epi-
                                                                                                                   sode, a precise average double-tidal period prevails. The
     figure 12D During years of maximal solar activity, there is an about
     5% excess mortality (220 cases per year) from myocardial infarction                                         diagnosis in JF of dysfrequentia, visualized by a compari-
     in Minnesota (1968-1996) as compared to years of minimal solar                                              son with an age- and gender-matched control in Figures
     activity. Twenty-nine years of data allow detection of differing mor-                                       28G and 28H (pp 108-109) can be made by C-ABPM (but
     tality from myocardial infarction associated with solar cycle stages.
     Further analyses in Figures 32B-32D.
                                                                                                                 not by self-measurement, a highly motivated JF notwith-
                                                                                                                 standing, in keeping with earlier results65).
                                                                                      Visitor #1                       Visitor #2
                                                              195                                                                                          120
                                                                                                                                                     SBP
                                                                                                                                                     DBP
                                                              175                                                                                    HR
                                                                                                                                                           100
                                      Blood Pressure (mmHg)




                                                              155
                                                                                                                                                                Heart Rate (beats/min)




                                                                                                                                                           80
                                                              135


                                                              115                                                                                          60


                                                               95
                                                                                                                                                           40

                                                               75

                                                                                                                                                           20
                                                               55


                                                               35                                                                                          0
                                                                3/7/10       3/8/10         3/9/10   3/10/10     3/11/10     3/12/10       3/13/10     3/14/10
                                                                                                        Time (calendar date)

     figure 13 Original data underlie an association of circadian hyper-amplitude-tension (CHAT; fit not shown) with visitors who were friendly,
     one a prospective collaborator, the other an earlier provider of important data for analysis. FH, an elderly man, was unaware of the fact that
     the arrival on March 7 of one and of the other on March 10 was preceded by spikes in BP by hours or a day, respectively. All results were
     within the acceptable range, yet the swing within that range was excessive. CHAT was present while the visitors were around.




     Review                                                                                                                            www.gahmj.com • Volume 1, Number 2 • May 2012     85
                                                           GLOBAL ADVANCES IN HEALTH AND MEDICINE



                                             200                                                                              MH
                                             180                                                  MESOR based on
                                                                                                  24-hour intervals
                                             160                                                                              Yes
                                             140
                                                                                                                               No




                                SBP (mmHg)
                                             120
                                             100
                                                   Upper 95% prediction limits of                                            CHAT
                                              80   gender-, age-, and geography-           Double CIRCADIAN amplitude
                                                      matched healthy peers                 based on 24-hour intervals
                                              60
                                              40                                                                              Yes
                                                                                                                               No
                                              20
                                               0
                                             200                                                                              MH
                                             180                                                 MESOR based on
                                                                                                 168-hour intervals
                                             160
                                                                                                                              Yes
                                             140
                                SBP (mmHg)




                                                                                                                               No
                                             120
                                             100                                                                             CHAT
                                                   Upper 95% prediction limits of
                                              80   gender-, age-, and geography-            Double CIRCADIAN amplitude
                                                      matched healthy peers                  based on168-hour intervals
                                              60
                                              40                                                                              Yes
                                                                                                                               NO
                                              20
                                               0
                                                           2004                                      2005
                                                                       Time (calendar years)

     figure 14A Consecutive averages (above) and circadian swings (below) of SBP during ~2-year alternate between mostly acceptable and
     rarely unacceptable. A 24-hour cosine fit to 7-day data sections removes the occasional abnormality (bottom) found in analyses of 24-
     hour data sections (top) in an elderly woman. Results from non-overlapping 1-day (top) and 7-day (bottom) intervals in serial sections
     on half-hourly around-the-clock data; OS (an 81-82-year-old woman) on atenolol treatment. When 1-day intervals are used, occasional
     unacceptable results occur.
     Abbreviations: CHAT: circadian hyper-amplitude-tension, MH: MESOR-hypertension; SBP, systolic blood pressure.


          Cycles in us, such as the physiological week, among                       ping51,54,71-74 but also by the subtraction and/or addition
     others, led to natural geomagnetic near-weeks (Figures                         approach44,75 (or preferably by the remove-and-replace
     29A and 29B, p 110).51 Reports of new cycles by physi-                         approach implemented by the sun), notably for those in
     cists prompted our discovery of coperiodic biospheric                          healthcare interested in the effects of space weather.34
     signatures of the cosmos such as approximately 5 or 16
     months long (Figures 30A-30C, pp 111-112)34 and other                          DIsCussIon
     cycles (Figures 31A-31C, pp 113-115).53,54 There are fur-                           In confronting congruent cycles in us and around us,
     ther cross-spectral coherences54,66-68 and phase synchro-                      the biospheric cycles when they are coded in our genes
     nizations68 between endpoints around us, such as Bz, Kp,                       may reflect what goes on and went on outside us from the
     Wolf number, or coronal mass ejection or cosmic rays                           origins of living matter more reliably than the relatively
     and urinary variables or the decades-long monitored BP                         recently recorded corresponding physical cycles. The
     of individuals. Associations are also seen from cross-                         dynamics of the cosmos almost certainly went on for a
     wavelets and coherence between myocardial infarctions                          very long time and have left their mark in our makeup.
     of populations or the incidence of terrorism on the one                        We have just begun to scratch the surface of measure-
     hand and space weather on the other hand (Figures 32A-                         ment. A record of polar lights and sunspots traces only a
     32D, pp 115-117). We trust that with Figures 33 and 34
     (pp 118-119), among others, a chronouspherea emerges,                          a From Greek chronos, time; Attic Greek nous, mind; and Greek sphairos,

                                                                                    globe. We used nous in the portmanteau’d chronousphere to credit
     consisting of many infradians with periods longer than                         Vladimir Ivanovich Vernadsky, Pierre Teilhard de Chardin, and Edouard le
     28 hours up to myriadennians.69,70 For some of the infra-                      Roy, who used the derivation of noosphere from noos, recognizing the
                                                                                    need for a sphere of the human creative mind or broader culture, coura-
     dian pairs of periods, the disappearance or reappearance                       geously extrapolating beyond the sphere of available data (criticized by
     of the environmental (eg, solar) or interplanetary com-                        Hagemeister M. In: Rosenthal BG, editor. The occult in russian and Soviet
                                                                                    culture. Ithaca: Cornell University Press; 1997. p. 185-202, yet endorsed
     ponent entails corresponding biospheric consequences                           with extensive study by Ertel S. Stud Psychol. 1996;38:3-22). Cosmism’s pio-
     (Figures 34-36, pp 119-121).44,61,62 The approach by                           neers as yet did not have the means (computers and satellites) for detect-
     removal of a gland and replacement of its hormone                              ing and documenting the pervading transdisciplinary spectrum of solar,
                                                                                    interplanetary, geopheric, and biospheric cycles and the consequences in
     started endocrinology and eventually chronobiology.71                          the human mind of the aeolian disappearance and/or reappearance of
     Investigation seems indicated not only by map-                                 nonphotic rhythms.




86   Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                      Review
                                                    AMBULATORY BLOOD PRESSURE MOnITORInG




                                200
                                                                           Daily averages           MESOR based on
                                180                                                                 24-hour intervals

                                160

                                140
                   SBP (mmHg)   120

                                100                                                         Double CIRCADIAN amplitude
                                                                                             based on 24-hour intervals
                                80
                                        Upper 95% prediction limits of gender-,
                                60     age-, and geography-matched healthy peers

                                40

                                20

                                  0
                                200
                                                                            MESOR based on
                                180                                         168-hour intervals
                                160

                                140
                   SBP (mmHg)




                                120

                                100
                                                                                             Double CIRCADIAN amplitude
                                 80                                                           based on168-hour intervals
                                        Upper 95% prediction limits of gender-,
                                 60    age-, and geography-matched healthy peers

                                 40

                                 20

                                  0
                                      1990                    1995                   2000                          2005
                                                               Time (calendar years)


figure 14B Consecutive averages (above) and circadian swings (below) of systolic blood pressure (SBP) during ~16-year alternate between
mostly acceptable and rarely unacceptable. A 24-hour cosine fit to 7-day data sections reduces the extent of abnormality (bottom) found
in analyses of 24-hour data section (top) in an elderly man. Results from non-overlapping 1-day (top) and 7-day (bottom) intervals in serial
sections on half-hourly around-the-clock data; FH (a 71-87-year-old man) on varying treatments.


millennium or less; time series of sun-related, interplan-                     The “increased power of connected intention and con-
etary, lunar, or geomagnetic variables cover a much                            sciousness,” also a topic of interest in Michael
shorter span; recordings by satellites of interplanetary,                      Persinger’s78,79 and Hans Wendt’s80 research already
solar, and cosmic variables are still more recent. None of                     explored at atomic and quantum81 levels, should all
them, however, matches in density or length the dynamic                        prompt attempts to seek better measures of coherence
information provided by cycles in living matter.                               beyond those used herein from macroscopic physics
     In this context, the cycles of the biosphere, mim-                        and time series analysis. Perhaps the language of fre-
icking those of the cosmos, constitute another novel                           quencies within them and far outside Schumann’s reso-
way of dating and certainly serve to validate, as magne-                       nances is pertinent, that yielded Figure 23 and remove-
tometers or cosmometers, the relatively recent physical                        and-replace approaches in arriving at Figures 24 to 26
counterparts.52 This dating by mapping reveals a set of                        constitute a step in that direction.
transdisciplinary cycles pervading all disciplines, each                             It seems the more important to assess the status quo
a sphere of the human mind (also Attic Greek nous)                             of information measured as tangible “coherence,” the
yielding a novel time structure. We can get much infor-                        topic of this paper. From this viewpoint, C-ABPM, while
mation about such a chronousphere by monitoring                                worth implementing for immediate health benefit, once
ourselves with repeated passes over the accumulating                           it is aligned with physical environmental monitoring
data as a whole (globally) and in sections of varying                          provides marker rhythm information concerning both
lengths (locally)—that is glocally in time and glocally                        environmental magnetism and other nonphotic factors
in space, eventually from the womb to the tomb in the                          competing with oscillations in the visible range.
individual and in the population.                                                    The findings herein of a largely novel spectrum of
     In the first issue of Global Advances in Health and                       transdisciplinary components—the chronosphere and
Medicine, McCraty et al,76 and in another journal,                             its entry into the noösphere (ie, the chronousphere)—
McCraty and Childre,77 presented the Global Coherence                          constitute a complement to work by a great many oth-
Initiative aimed at a shift from “competition” to “great-                      ers.82-89 Most pertinent are Alexander Leonidovich
er cooperation” in a coherent planetary standing wave.                         Chizhevsky’s heliobiology and Vladimir Ivanovich


Review                                                                                              www.gahmj.com • Volume 1, Number 2 • May 2012   87
                                                                                                 0
                                                                                                       0           1          2                              3
                                                       15                                                   No. of Additional VVDs
  Conventionally                                                                                 GLOBAL ADVANCES IN HEALTH AND MEDICINE
                                                     (5.1%)
   undiagnosed
ESOR-Normotensives)
                          3
                       (1.0%)                        5
                                                  (1.7%)
                                                           De cient Heart Rate Variability (DHRV)
                                                           15
                                                         (5.1%)                          1003
                                                                                         (1.0%)               MESOR-Hypertension (MH)




                                                                      Morbidity Incidence (%)
                                                                                          80

                                                                                                60                                             100




                                                                                                                          Morbidity Incidence (%)
                                                                                                40                                                  80

                                        55                                                      20                                                  60
               8                     (18.5%)
            (2.7%)                                                                                                           40
                                                            5                                    0               103
                                                         (1.7%)                                        0           1
                                                                                                               (34.7%)        2                              3
                                                                                                                             20
                                                                                                             No. of Additional VVDs
                                                                                                                                                     0
           Key: No. of additional VVDs                                                                                                                   0             1           2      3
                                                                                                                                                                 No. of Additional VVDs
                      Alone
                                                               3
                      +1                                    (1.0%)
                      +2                                                                     0
                                                                                           (0%)             Excessive Pulse Pressure (EPP)
                      +3
                                           13
                                         (4.4%)                                                                                                100




                                                                                                                          Morbidity Incidence (%)
                                                                                                                                                    80

                                                                                                                                                    60

                                                                                                                                                    40
                                                                                                                35                                  20
                                                                                                             (11.8%)
                                                                                                                                                     0
                                                                                                                                                         0             1          2       3
                                                                                                                                                                 No. of Additional VVDs

                                                               3
                                                            (1.0%)                                         Circadian Hyper-Amplitude-Tension (CHAT)

                                                                                                               7
                                                                                                            (2.4%)
                                                                                                       100
                           figure 15A (Above and opposite) Percentages of vascular variability disorders (VVDs) or rather vascular variability anomalies
                                                                                                                          Morbidity Incidence (%)




                           (VVAs) and vascular variability syndromes (VVSs) missed in current prac¬tice. The incidence of VVDs in this graph is assessed in a
                                             9                                                           80
                           clinic population of 297 patients. BP and HR of each subject were moni¬tored around the clock for 2 days at 15-minute intervals
                                          (3.0%)
                           at the start of study. Each record was analyzed chronobiologically and results interpreted in the light of time-specified reference
                                                                                                         60
                           limits qualified by gender and age. On this basis, MESOR-hypertension (MH, diagnosed in 176 patients), excessive pulse pressure
                           (EPP), circadian hyper-amplitude-tension (CHAT), and deficient heart rate40    variability (DHRV) were identified and their incidence
                           related to outcomes (cerebral ischemic attack, coronary artery disease, nephropathy, and/or retinopathy). Outcomes, absent at
                                                                                                         20
                           the start of study in these nondiabetic patients, were checked every 6 months for 6 years to estimate the relative risk associated
                           with each VVD alone or in combination with 1, 2, or 3 additional VVDs, shown in columns complementing each circular display of
                                                                                                          0
                           incidences of variability disorders.                                                   0            1          2        3
                                                                                                                        No. and of nephropathy
                                 Earlier work showed that CHAT was associated with a risk of cerebral ischemic event of Additional VVDs higher than MH
                                Conventionally                                           15
                           and that the risks of CHAT, EPP, and DHRV were mostly (5.1%)independent and additive. It thus seemed important to determine the
                                 undiagnosed
                           incidence of each VVD, present alone or in combination with one or more additional VVDs. Results from this investigation are
                            (MESOR-Normotensives)
                           summarized in this graph.
                                 Results related to MH are shown in the upper section of the graph. The 176 patients with MH are broken down into 103
                                                          3
                                                         population of 297 patients) 5
                           (34.7% of the whole study(1.0%)                           with uncompli¬cated MH, 55 (18.5%) with MH complicated by 1 additional
                                                                                 (1.7%)
                                                                                           De cient Heart Rate Variability (DHRV)
                           VVD (EPP, CHAT, or DHRV), and 15 (5.1%) and 3 (1.0%) with MH complicated by 2 or 3 additional VVDs. In the latter group, all
                           3 patients had a morbid outcome within 6 years of the BP monitoring. Am¬bulatory BP monitoring over only 48 hours, used for
                           diagnosis, is much better than a diagnosis based on casual clinic measure¬ments, yet its results apply only to groups. With this
                                                                                                       100
                           qualification, of the 176 patients with MH, 73 (42.2%) have additional VVDs that further increase their vascular disease risk and
                                                                                                                          Morbidity Incidence (%)




                           that are not considered in the treatment plan of these patients since current practice does not assess these VVDs. This proportion
                                                                                                         80
                           may be smaller in a 7-day record (available for CHAT).
                                                                                                         60
                                 Results related to EPP (second row), CHAT (third row), and DHRV (bottom) illustrate that these conditions can be present in
                           the absence of MH in as many as 12 (4.0%) of the 297 subjects. Since they do not have MH, it is unlikely that these subjects would
                                                                                                         40
                           be treated from a conventional viewpoint even though their vascular disease risk can be as high as or even higher than MH.
                           Evidence suggests that treatment of these conditions may trans¬late into a reduction in morbidity and/or mortality from vascular
                                                                                                         20
                                               8
                           disease. Another lesson from these results is that around-the-clock monitoring of BP and HR interpreted chronobiologically is
                                            (2.7%)
                           needed, even in the absence of MH, to detect vascular disease risk associated with VVDs such as CHAT and DHRV that cannot be
                                                                                           5              0
                           assessed on the basis of casual clinic measurements so that nonpharmacologic and/or pharmacologic intervention can be insti-
                                                                                        (1.7%)                    0            1          2        3
                                                                                                                         No. of Additional VVDs
                           tuted in a timely fashion before the occurrence of adverse outcomes. Once implemented across the board rather than in selected
                           patient populations, vascular disease could be curbed to a much larger extent at relatively low cost if the monitoring is offered
                                           public and care providers
                           directly to the Key: No. of additional VVDs become involved only after detection of a VVD. A website has to be built to interest
                           many people and to provide cost-free analyses in exchange for the data, as is now provided worldwide by the BIOCOS project on
                           a small scale.             Alone
                                                      +1
                                                    +2
                                                    +3
             88            Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                      Review
                                                                       Morbidity In
                                                                                                 40
                                           AMBULATORY BLOOD PRESSURE MOnITORInG
                                                        35                                       20
                                                         (11.8%)
                                                                                                  0
                                                                                                      0          1          2          3
                                                                                                           No. of Additional VVDs

                                   3
                                (1.0%)                 Circadian Hyper-Amplitude-Tension (CHAT)

                                                            7
                                                         (2.4%)
                                                                                           100




                                                                       Morbidity Incidence (%)
                9                                                                                80
             (3.0%)
                                                                                                 60

                                                                                                 40

                                                                                                 20

                                                                                                  0
                                                                                                      0           1          2         3
                                                         15                                                No. of Additional VVDs
    Conventionally
                                                       (5.1%)
     undiagnosed
(MESOR-Normotensives)
                            3
                         (1.0%)                       5
                                                   (1.7%)
                                                            De cient Heart Rate Variability (DHRV)


                                                                                          100
                                                                       Morbidity Incidence (%)
                                                                                                 80

                                                                                                 60

                                                                                                 40

                                                                                                 20
                 8
              (2.7%)
                                                           5                                      0
                                                        (1.7%)                                        0           1          2         3
                                                                                                            No. of Additional VVDs

             Key: No. of additional VVDs

                        Alone
                        +1
                        +2
Vernadsky’s even broader noösphere. Bernhard and                    cycles is the mandate of the health department, of the
                        +3
               90 Harlan True Stetson,91 Alexander P.
Traute Düll,                                                        World Health Organization and of the United Nations;
Dubrov,84 Frank A. Brown Jr,85 and Rutger Wever86                   analyses of epidemiological data are their job. Here, gov-
pioneered in the field, as did Sergei M. Chibisov87 and             ernmental action is required to place as a minimum the
Tamara Breus,88 contributing a review of the status quo             data into the public domain and as an optimum to have
in Russia.89                                                        health departments realize the need for retrospective and
     Many tasks remain to reach two goals: (1) a minia-             ongoing analyses. The biggest hurdle, however, is the
turized, unobtrusive, and ambulatorily functional                   attitude of well-meaning teachers currently prevailing in
C-ABPM device that is affordable to all and communi-                medical schools, where the majority are unaware that
cates with (2) an also automated, manned website provid-            continued reliance on a single BP measurement or a sin-
ing analyses of several kinds of incoming data flows such           gle 24-hour profile will leave many people who need
as (a) physiological, to start with of BPs and HRs; (b) epi-        treatment untreated, and equally regrettable, many peo-
demiological, to start with of natality, morbidity, and             ple who may not need treatment will be treated. The
mortality; and (c) sociological, to start with military,            proposition that it would be best to perhaps give an
political, and criminological (time series). The feasibility        antihypertensive drug to everybody reaching a certain
of a device costing less than $100 has been demonstrat-             age is the best documentation of the fact that concern
ed,92 as well as the ability of glocal analyses in space and        about “do no harm” is forgotten and the need to diagnose
time of all 3 kinds of time series (a, b, c) as steps in concept    variability disorders leading to personal severe disease
validation and feasibility demonstration.4,53 For the epi-          (such as stroke) and to other social disasters (such as
demiological data analyses, which should be ongoing as              crime or terrorism) or to natural cataclysms (such as
natality, morbidity, and mortality data accumulate, state           earthquakes) is ignored. An alternative is available in the
health departments constitute a major hurdle: a few offer           project on The BIOsphere and the COSmos, BIOCOS.
to sell these data or just refuse to provide them in the
United States, as was the case in 45 of 48 states to which          ConClusIon
requests for data were sent. The time has come for realiz-             The BP cuff in the healthcare provider’s office
ing that replacing baselines for all statistics with mapped         must go for the moment to the homes of each individ-


Review                                                                                                    www.gahmj.com • Volume 1, Number 2 • May 2012   89
                                                        GLOBAL ADVANCES IN HEALTH AND MEDICINE




            Circadian Hyper-Amplitude-Tension (CHAT)                                                      Excessive Pulse Pressure (EPP)
                        6                                                                                   10
                     (0.9%)                                                                                                            13
                                                Key: No. of                            Key: No. of        (0.9%)                     (1.1%)
                                              additional VVDs                        additional VVDs
       17                                             Alone                                  Alone
     (1.4%)                                           +1                                     +1
                                                      +2                                     +2
                                                      +3                                     +3


                                                                            *           35
                                                                                      (3.0%)


                                                          34
                                                        (2.9%)
                                                                                                                                                 30
                                                                                                                                               (2.6%)

            31
          (2.6%)


               Ecphasia (odd timing of BP but not HR)                                                    De cient Heart Rate Variability (DHRV)

                                    5                  Key: No. of                Key: No. of     20                        9
                                 (0.4%)              additional VVDs            additional VVDs (1.7%)                   (0.8%)
        17
                                                             Alone                       Alone
      (1.4%)
                                                             +1                          +1
                                                             +2                          +2
                                                             +3                          +3




                                                             48                            37
                                                           (4.1%)                        (3.1%)
       26
     (2.2%)                                                                                                                                  87
                                                                              10
                                                         37                                                                                (7.4%)
                                                                            (0.9%)
                                                       (3.1%)
                                                                                                    Key: No. of
                                                                                                  additional VVDs
                                                                                                          Alone
                                                                                                          +1
                                                                                                          +2
                                                                                                          +3




                                                90                                                   152
                                              (7.7%)                                               (12.9%)




      figure 15B Top 4 pie charts: incidence of a given vascular variability disorder (VVD) alone or in combination with other VVDs in a study popu-
      lation. Bottom pie chart: incidence of MESOR-hypertension alone or in combination with other VVDs in a study population. VVDs or rather
      vascular variability anomalies (VVAs) (lightest shading) are complicated to a differing extent by one or more added VVDs (darker shading). In
      this graph, MESOR-hypertension (MH) is diagnosed in a total of 289 subjects, representing 24.6% of the 1177 untreated, presumably normo-
      tensive subjects included in the study. Among these 289 subjects, as many as 137 (47.4% of those diagnosed with MH) have at least 1 addi-
      tional VVD that is not part of the current screening but increases the vas¬cular disease risk beyond that associated with MH alone. The 4 graphs
      illustrate that VVDs other than MH occur in the absence of MH in very few patients with excessive pulse pressure (EPP) and in more patients
      with circadian hyper-amplitude-tension (CHAT) and in yet more with ecphasia and in 87 patients with deficient heart rate variability (DHRV),
      that is for a total of 182 subjects, representing 15.5% of the study population. In this study, BP and HR data available hourly for only 24 hours
      were complemented by an assessment of the left ventricular mass index as a sur¬rogate outcome measure. In addition to MH, EPP, CHAT, and
      DHRV summarized from another earlier study, ecphasia was assessed. The great limitation of a record covering only 24 hours is not overcome
      by the relatively large study population of 1177 subjects not treated with antihypertensive agents, yet results in keeping with those obtained
      in a clinic population of 297 patients suggest that MH is to be recognized as a VVD and that its risk can be very greatly increased when other
      VVDs combine into vascular variability syndromes that escape current diagnostics. none of the 1177 untreated subjects had 4 additional VVDs.
      *Conventionally undiagnosed (MESOR-normotensives).




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                                                                                                           IMPROVING HEALTHCARE OUTCOMES WORLDWIDE



                                                                                     150
                                                                                                          Upper 95% prediction limit for A for
                                                                                                          non-pregnant and pregnant women                      30

                                                                                     140

                                                                                                                                                               20

                                                    Systolic Blood Pressure (mmHg)   130




                                                                                                                                                                    Amplitude, A (mmHg)
                                                                                                                                                               10

                                                                                     120

                                                                                                                                                               0

                                                                                     110

                                                                                                                                                               10

                                                                                     100

                                                                                                                                                               20

                                                                                      90                                                                                                  MESOR: 115 mmHg
                                                                                                                                                                                          Double Amplitude: 41 mmHg
                                                                                                                                                               30                         Acrophase: -202° (13:29)
                                                                                                                                                                                          P value: <.001
                                                                                       0
                                                                                                 01                        02                    03
                                                                                                              Time (calendar date in Dec 1988)

figure 16 An unheeded chronobiologic warning: eclampsia followed overswinging or circadian hyper-amplitude-tension (CHAT). Eight
weeks later, convulsions began, and a boy in the 27th gestational week was delivered. The cost-accounted care during his first 13 months
totals US $615 000; 26-month hospitalization may have increased the cost to about US $1 million. By sole reliance on the average blood
pressure (of 115 mmHg systolic), disregarding our strong advice for bed rest and treatment in view of CHAT, a particular obstetrician did not
prevent a very premature delivery, which happened to be avoided in all other deliveries in a national Institutes of Health–sponsored study in
which chronobiologic advice usually resulted in bed rest and/or drug treatment without incurring major cost.



                                                                                     Mean, y      1 SE of y                                           (mg)                                                        (g)
                                                                                                                                                       4
                100




                                                                                                                                                                                                                       Dose (2-week course)
                                                                                                            (g)
                                                                                                                                                                                                                  10
                                                  Rx:                                                         1                                        3
                                                        TT                                                                                                   Less with medication
Dose (%)




                                                       CT
                             50                                                                                                                        2
                                                                                                                                                                                                                  .5
                                                                                                              .5
                                                                                                                                                       1


                                           SBP                                       DBP                             SBP        DBP                             SBP                          DBP
                                 0
                                                                                               P < .001                                    P < .001                                                    P < .001
  Blood Pressure Decreases (%)




                             10


                                                                                                                                       Increased efficacy



                             20
                                     Rx:         Propranolol                                                               Clonidine                               α-Methyldopa


figure 17 Efficacy, safety, and cost effectiveness of chronotherapy vs traditional therapy with 3 antihypertensive drugs. There were 20
patients per group; hypotensive effect was more pronounced on CT than TT (P < .05). The chronocardiologist Rina Zaslavskaya was first to
demonstrate a longer desired effect, by comparison to conventional therapy, by timing hypotensive treatment prior to the circadian peak in
blood pressure, on a group basis, with less medication and fewer complications. Minnesotan meta-analysis.
Abbreviations: CT, chronotherapy; DBP, diastolic blood pressure; SBP, systolic blood pressure; TT, traditional therapy.




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                                                                 GLOBAL ADVANCES IN HEALTH AND MEDICINE



         8.8

                       NoRx      Rx 00:00        Rx 04:00        Rx 08:00      Rx 12:00       Rx 16:00        Rx 20:00

         4.4



         0.0
     CUSUM




        -4.4


                     Estimated time effect
        -8.8              took place                  Effect detected



     -13.2
                                         NoRx→Rx at 00:00


     -17.6
         9/26/04           10/10/04      10/24/04     11/7/04     11/21/04   12/5/04      12/19/04      1/2/05        1/16/05      1/30/05    2/13/05    2/27/05
                                                                             Time (calendar date)

     figure 18A Monitoring the mean seems successful, but what happens to the amplitude? Changing timing of medication (ΔRx) during con-
     secutive spans shows efficacy of treatment. An empirical approach to chronotherapy: immediately after diagnosis, one should ascertain that
     the treatment is effective. Optimization of treatment effects by timing can be achieved for the individual patient by systematically changing,
     eg, advancing the time of treatment (in relation to hours after awakening). Successful treatment of MESOR-hypertension assessed by a self-
     starting cumulative sum control chart. To optimize his hypotensive treatment (Rx), a just-diagnosed 24-year-old individual (TT) switched his
     Rx first every 17 days by 4 h and then mostly at shorter intervals. note statistically significant decrease in MESOR, evidenced by the breakout
     outside the decision interval of the negative CUSUM line. With continued Rx, the blood pressure MESOR leaves the decision interval, indicat-
     ing a statistically significant decrease in overall blood pressure. (J Appl Biomed. 2006;4:73-86.)



                 8.8
                          NoRx        Rx 00:00      Rx 04:00      Rx 08:00     Rx 12:00      Rx 16:00      Rx 20:00


                 4.4



                 0.0
             CUSUM




                -4.4

                                                                                                                 Effect detected

                -8.8                                                                        Estimated
                                                                                            time effect
                                                                                            took place

             -13.2

                                           NoRx→Rx at 00:00

             -17.6
                 9/26/04      10/10/04     10/24/04    11/7/04     11/21/04   12/5/04   12/19/04     1/2/05       1/16/05       1/30/05   2/13/05   2/27/05
                                                                          Time (calendar date)

     figure 18B Monitoring the circadian amplitude shows an otherwise silent putative large risk. Changing timing of medication (ΔRx) during
     consecutive spans shows risk of iatrogenic CHAT (Circadian Hyper-Amplitude-Tension). An empirical approach to chronotherapy: immedi-
     ately after diagnosis, one should ascertain that one does not induce CHAT by inappropriate timing of anti-hypertensive medication. In this
     24-year old man (TT) who advanced the time of treatment by 4 hours every 17 days initially and at shorter intervals thereafter, treatment
     in the evening was associated with an increase in circadian amplitude, raising the question whether the risk of MESOR-hypertension may
     not have been traded for the even higher risk of stroke that CHAT represents. Iatrogenic CHAT, induced by treatment is silent to office
     visits. One must not inadvertently trade benefit (lowering of the MESOR of blood pressure) for something worse (circadian overswinging
     of blood pressure). This danger applies to some hypertensives (who tend to have a large circadian amplitude of blood pressure) to whom
     treatment time is not specified by the care provider, as was the case for TT (or is specified for bedtime). A few others who took hypertensive
     medication at bedtime were also found to have CHAT. The figure also shows the assessability of otherwise undetected harm by as-one-goes
     sequential analysis.




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                                                    IMPROVING HEALTHCARE OUTCOMES WORLDWIDE




               30                                           HARM
                                                                                                 1-way ANOVA: F = 6.555; P < .001
                                                                                                 Cosinor: PR = 39%; P < .001
                                                        CHAT exacerbated

               25
                                                                                                               No treatment:
                                                                                                              CHAT diagnosed

               20
SBP-A (mmHg)




                                                                                                             Treatment effect
               15

                                Upper limit of acceptability
                                for SBP-A based on clinically
               10                healthy peers matched by
                                      gender and age
                                                                                        CHAT eliminated


                5                                                                                          BENEFIT


                                                                DO NO HARM                                  TREAT
                0
                                               AW               +3h            +6h             +9h          +12h            +15h




               20
                     Upper limit of acceptability
                                                                      Iatrogenic CHAT
                    for DBP-A based on clinically
                     healthy peers matched by
                          gender and age
               16                                                                             1-way ANOVA: F = 4.406; P =.003
                                                                                              Cosinor: PR = 32%; P < .001


                                                                                                                          No treatment
DBP-A (mmHg)




               12

                                                                                                              Treatment effect


                8




                4                                                                                    CHAT eliminated



                                                                DO NO HARM                                  TREAT

                0
                                               AW               +3h            +6h             +9h           +12h           +15h
                                                                      Time (hours from awakening)



figure 19 A popular drug, if prescribed without personalised surveillance, can induce a vascular variability disorder (VVD) such as Circadian
Hyper-Amplitude-Tension (CHAT). A change in the time when the drug is taken can make the same dose of the same drug in the same
person beneficial or vice versa. At one administration time (before noon), Hyzaar induces CHAT in diastolic blood pressure and exacerbates
a preexisting CHAT in systolic blood pressure (red). At another time of administration, Hyzaar eliminates a pre-existing VVD (green). These
opposite effects were found in tests at 6 medication times, each administered for about a month, with half-hourly surveillance of BP during
the last week of each span. These differences occur as a function of the timing of the drug’s use along the scale of 24 h. Original study of
Yoshihiko Watanabe of a 66-year-old man treated with Losartan (50 mg) and hydrochlorothiazide (12.5 mg). Each point represents 1 week
of half-hourly around-the-clock monitoring after ~1 month on a given treatment time. After this graph was completed, treatment at AW +
15h yielded a SBP-A of 10.36 ± 2.09 mmHg and a DBP-A of 8.69 ± 1.85 mmHg. By cosinor, a circadian stage-dependent response to treatment
could be shown to account, with statistical significance for both endpoints, for 39% and 32% of the overall variance, respectively.




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                                                                                              GLOBAL ADVANCES IN HEALTH AND MEDICINE




Monitoring Span in 1995:                                   January 24 - February 5                                                                                February 5 - 27
No. of Hourly Measurements:                                          210                                                                                                 439

                       180
                                                                         Mean, y
                                                                                                  1 SE of y
                                    F = 7.253;                                                                                        F = 5.934;
                                    P < .001                                                                                          P < .001


                       160                                                                                                               MESOR and
                                                                                                                                          95% CI
  Systolic BP (mmHg)




                       140




                       120




                         0

                             00         04            08            12             16            20           00       00                   04             08            12              16             20              00
                                                                                                           Time (clock hours)
                         M ± SE:                                147.7 ± 2.1                                        P = .017                                          141.7 ± 1.0
                         2A ± SE:                                34.2 ± 6.0                                        P = .039                                           19.6 ± 3.0
                         SD:                                         23                                                                                                   17

                                    figure 20 Individualized blood pressure chronotherapy. Lower circadian double amplitude (2A) and MESOR (M) after switching treatment
                                    time from 08:30 (left) to 04:30 (right).* The usefulness of a chronobiologic approach is supported by the demonstration that treatment with
                                    antihypertensive drugs can be optimized by timing. The same dose of the same drug can have different effects on the MESOR and circadian
                                    amplitude of the same patient’s blood pressure when it is administered daily at a different circadian stage as seen by the naked eye and
                                    documented by parameter tests.
                                    *240 mg Diltiazem HCI taken daily by 75-year-old man (FH) after getting up (left) or during an interruption of sleep (right).




                                    ual. In the 1960s and 1970s, it seemed worthwhile to                                           variabilities constituting risks greater than hypertension: with an illustrative
                                                                                                                                   case report. In: Mitro P, Pella D, Rybar R, Valocik G, editors. Proceedings of the
                                    plead, as Frederic C. Bartter also did, for moving the BP                                      2nd Congress on Cardiovascular Diseases; 2002 April 25-27; Kosice, Slovakia.
                                    cuff from the providers’ offices to everybody’s (includ-                                       Bologna: Monduzzi Editore; 2002. p. 223-58.
                                    ing his own) office by day and home by night. This                                        4.   Halberg F, Cornelissen G, Otsuka K, et al; BIOCOS project. Extended consensus
                                                                                                                                   on need and means to detect vascular variability disorders (VVDs) and vascular
                                    recommendation holds until a system of C-ABPM                                                  variability syndromes (VVSs). Geronto-Geriatrics: Int J Gerontology-
                                    becomes affordably available to everybody. Bartter                                             ChronomeGeriatrics 2008;11(14):119-46.
                                    advocated this as head of the Hypertension-Endocrine                                      5.   Halberg F, Cornélissen G, Halberg F, Kessler T, Otsuka K. Measuring mental
                                                                                                                                   strain by duration of blood pressure overswing (CHAT): case report. World
                                    Branch at the US National Institutes of Health (NIH)                                           Heart J. 2010;2(2):47-73.
                                    and later as head of the NIH’s Clinical Center. In 2012,                                  6.   Halberg F, Cornélissen G, Spector NH, et al. Stress/strain/life revisited.
                                                                                                                                   Quantification by blood pressure chronomics: benetensive, transtensive or
                                    self-measurements at home have detected an effect of
                                                                                                                                   maletensive chrono-vasculo-neuro-immuno-modulation. Biomed
                                    the great earthquake in Japan, proving their value.48                                          Pharmacother. 2003 Oct;57 Suppl 1:136s-63s.
                                    They confirmed, if not the finding of antecedents30,47                                    7.   Maschke C, Harder J, Cornélissen G, Hecht K, Otsuka K, Halberg F.
                                                                                                                                   Chronoecoepidemiology of “strain”: infradian chronomics of urinary cortisol
                                    at least the consequences of the same quake found on                                           and catecholamines during nightly exposure to noise. Biomed Pharmacother.
                                    a small scale yet worldwide in a de facto validation test                                      2003 Oct;57 Suppl 1:126s-35s.
                                    of an ongoing C-ABPM system, serving for cost-free                                        8.   Halberg F. Organisms as circadian systems; temporal analysis of their physio-
                                                                                                                                   logic and pathologic responses, including injury and death. In: Symposium on
                                    analyses of self-surveillance data by all comers.                                              medical aspects of stress in the military climate. Washington DC: US
                                                                                                                                   Government Printing Office; 1965. p. 1-36.
                                    RefeRenCes                                                                                9.   Halberg F, Smith HN, Cornélissen G, Delmore P, Schwartzkopff O;
                                      1. International Congress: Natural Cataclysms and Global Problems of the                     International BIOCOS Group. Hurdles to asepsis, universal literacy, and chro-
                                         Modern Civilization; 2011 September 19-21; Istanbul, Turkey.                              nobiology—all to be overcome. Neuro Endocrinol Lett. 2000;21(2):145-60.
                                      2. Halberg F, Cornélissen G; International Womb-to-Tomb Chronome                    10.      Halberg F, Drayer JI, Cornélissen G, Weber MA. Cardiovascular reference data-
                                         Initiative Group. Resolution from a meeting of the International Society for              base for recognizing circadian mesor- and amplitude-hypertension in appar-
                                         Research on Civilization Diseases and the Environment; 1995 March 17-18;                  ently healthy men. Chronobiologia. 1984 Jul-Sep;11(3):275-98.
                                         Brussels, Belgium.                                                               11.      Whitworth JA; World Health Organization, International Society of
                                      3. Halberg F, Cornélissen G, Otsuka K, et al. Chronomics detects altered vascular            Hypertension Writing Group. 2003 World Health Organization (WHO)/




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                                                                                                 IMPROVING HEALTHCARE OUTCOMES WORLDWIDE




                                                                              Systolic BP                                                                                      Diastolic BP
                                 6
                                                                                                                                                                                            Upper limit signalling
                                                                                                                                                                                             increase in MESOR

                                                                                             Trans (7-) meridian                                                                                          Increase
                                                                                                W     E    W
                                 3                                                                   Trip                                                                                                 Decrease
Decision Interval (N of SDs)**




                                 0




                                 -3




                                                                           Lower limit signalling
                                 -6
                                                                            decrease in MESOR

                                                Rx*** at                                                                                            Rx*** at
                                                 ~08:30                  ~00:00                                                                      ~08:30                ~00:00


                                 -9
                                        2/28             3/10          3/20           3/30          4/10            4/20                     2/28          3/10          3/20           3/30          4/10           4/20
                                                                                                                  Time (Calendar date in 1995)

                                  figure 21 Control chart assesses individualized anti-MESOR-hypertensive chronotherapy.* The chronobiological approach includes inferential
                                  statistical methods for the rigorous assessment of intervention effects applicable to the individual patient, eg, detecting whether the lower-
                                  ing in the MESOR of systolic (left) and diastolic (right) blood pressure can be associated with the time when the change in treatment timing
                                  was instituted.
                                  *Blood pressure MESOR lowering by change in timing Diltiazem HCI (240 mg/day) assessed by self-starting CUSUM.
                                  **Standard deviation from CUSUM; if there is significant displacement of 1 SD, it would be diagnosed by a slope of 1 – 0.5 =) 0.5 SD.
                                  ***After awakening (~08:30) or at bedtime (~00:00).


                                            International Society of Hypertension (ISH) statement on management of                     sure. Medtronic continuing medical education seminars. 4th ed. Minneapolis:
                                            hypertension. J Hypertens. 2003 Nov;21(11):1983-992.                                       Medtronic Inc; 1988.
                                      12.   Verdecchia P, Porcellati C, Schillaci G, et al. Ambulatory blood pressure. An        25.   Cornélissen G, Halberg F, Gubin D, et al. Carpe diem mensuratem: Fulminant
                                            independent predictor of prognosis in essential hypertension. Hypertension.                CHAT, its recognition a chronobiologic path to preventing a myocardial infarc-
                                            1994 Dec;24(6):793-801. Erratum in: Hypertension. 1995 Mar;25(3):462.                      tion? Abstract, 4° Convegno Nazionale, Società Italiana di Cronobiologia,
                                      13.   O’Brien E. Dipping comes of age: the importance of nocturnal blood pressure.               Gubbio; 1996 June 1-2; Perugia, Italy.
                                            Hypertension. 2009 Mar;53(3):446-7.                                                  26.   Hillman DC, Cornélissen G, Scarpelli PT, et al; International Womb-to-
                                      14.   Stolarz K, Staessen JA, O’Brien ET. Night-time blood pressure: dipping into the            Tomb Chronome Initiative Group. Chronome maps of blood pressure and
                                            future? J Hypertens. 2002 Nov;20(11):2131-3.                                               heart rate. University of Minnesota/Medtronic chronobiology seminar
                                      15.   Staessen JA, Bieniaszewski L, O’Brien E, et al. Nocturnal blood pressure fall on           series #2; 1991 December.
                                            ambulatory monitoring in a large international database. The “Ad Hoc”                27.   Halberg F, Cornélissen G, Otsuka K, et al. Rewards in practice from ‘recycling’
                                            Working Group. Hypertension. 1997 Jan;29(1 Pt 1):30-9.                                     heart rate, ectopy, ischemia and blood pressure information. J Med Eng
                                      16.   Halberg F, Cornélissen G, Schwartzkopff O. In memoriam— Howard Burchell:                   Technol. 1997 Sep-Oct;21(5):174-84.
                                            Lifetime chronobiologically-interpreted (C-) ABPM for strain assessment for          28.   Halberg F, Hillman D, Cornélissen G, et al. Putative solar signatures can differ
                                            everybody, with diagnostic dividends. World Heart J. 2010;2(3):177-96.                     among variables and circadian endpoints and in individuals vs populations.
                                      17.   Fiser B, Havelkova A, Siegelova J, et al. Night-to-day blood pressure ratio during         International Congress: Natural Cataclysms and Global Problems of the
                                            seven-day ambulatory blood pressure monitoring. Noninvasive Methods in                     Modern Civilization; 2011 September 19-21; Istanbul, Turkey.
                                            Cardiology; 2010 September 16-17; Brno, Czech Republic.                              29.   Watanabe Y, Cornélissen G, Hillman D, Otsuka K, Halberg F. Long periods in 23
                                      18.   Siegelova J, Havelkova A, Fiser B, et al. Day and night blood pressure variability         years of around-the-clock automatic measurements of human blood pressure
                                            during seven-day ambulatory blood pressure monitoring. Noninvasive                         and pulse. International Congress: Natural Cataclysms and Global Problems of
                                            Methods in Cardiology; 2010 September 16-17; Brno, Czech Republic.                         the Modern Civilization; 2011 September 19-21; Istanbul, Turkey.
                                      19.   Otsuka K, Cornélissen G, Halberg F. Predictive value of blood pressure dipping       30.   Halberg F, Cornélissen G, Schwartzkopff O, et al. Preventive cardiology con-
                                            and swinging with regard to vascular disease risk. Clin Drug Invest.                       cerns avoidance of personal and societal health-related and natural cataclysms.
                                            1996;11(1):20-31.                                                                          Noninvasive Methods in Cardiology; 2011 October 17; Brno, Czech Republic.
                                      20.   Janeway TC. The clinical study of blood pressure. New York: D. Appleton              31.   Feinleib M, Rogot E, Sturrock PA. Solar activity and mortality in the United
                                            & Co; 1904.                                                                                States. Int J Epidemiol. 1975 Sep;4(3):227-9.
                                      21.   Zadek I. Die Messung des Blutdrucks am Menschen mittelst des Basch’chen              32.   Lipa BJ, Sturrock PA, Rogot E. Search for correlation between geomagnetic dis-
                                            Apparates [medical dissertation]. Berlin: Schumacher; 1880.                                turbances and mortality. Nature. 1976 Jan 29;259(5541):302-4.
                                      22.   Zadek I. Die Messung des Blutdrucks am Menschen mittelst des Basch’chen              33.   Halberg F, Bakken EE, Katinas GS, et al. Chronoastrobiology: Vernadsky’s future
                                            Apparates. Z klin Med. 1881;2:509-51.                                                      science? Benefits from spectra of circadians and promise of a new transdisci-
                                      23.   Bartter FC. Periodicity and medicine. In: Scheving LE, Halberg F, Pauly JE, edi-           plinary spectrum of near-matching cycles in and around us. International
                                            tors. Chronobiology. Tokyo: Igaku Shoin Ltd; 1974. p. 6-13.                                Conference: Civilization Diseases in the Spirit of V.I. Vernadsky; 2005 October
                                      24.   Halberg F, Cornélissen G, Halberg E, et al. Chronobiology of human blood pres-             10-12; People’s Friendship University of Russia, Moscow.




                                  Review                                                                                                                 www.gahmj.com • Volume 1, Number 2 • May 2012                      95
                                                                            GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                              Geographic and time-varying differences in the spectrum of sudden cardiac death*




           Latvia
             Y
                                           Lithuania
                                              Y, cY/2                                                                                  Minnesota
                                                                                                                                         T, c Y/2
                                                                                                    Tokyo
                                                  Georgia
     Czech Rep.                                                                                     TY, cY/2
                                                    Y
      T, c Y/2*,Y
                              Hungary                                                      Hong Kong
                                                                                               Y                                  Arkansas                                      South
                                cY/2
                                                                                                                                    T, Y                                       Carolina
                                                                                                                                                                                  Y




               Czech Republic c Y/2 :

                            Not detected                                     Detected




             figure 22 Geographic and time-varying differences in the spectrum of sudden cardiac death. A curtain of uncertainty, because of limited
             available data, hides any time- and geographic (geomagnetic or dip-magnetic) site-specificity of various spectral aspects of sudden cardiac
             death. Thus, we find a transyear (T) in Minnesota with a cis-half-year (cY/2) and both a calendar year (Y) and a transyear in Arkansas and the
             Czech Republic: at the latter site, a cis-half-year, corresponding in length to an also-transient period of hard solar flares, is detected after but
             not before 1999. Whether other geographic differences in sudden cardiac death may also relate to any magnetic latitude deserves scrutiny.
             It is noteworthy in any event that cardiac arrhythmias can also transiently reveal a transyear or a cis-half-year, each in a different Horrebow-
             Schwabe sunspot cycle stage.
                    note site-specificity in the frequency domain displayed by patterns of sudden cardiac death worldwide. Time-specificity is seen at bot-
             tom left in the Czech Republic. Rhythms (spectral components) with one or several widely differing periods are found even when focusing
             solely upon the United States. (A phase difference of changes mirroring a didecadal [Hale sunspot bipolarity] cycle in newborns’ body weight
             in Minnesota vs Denmark is documented by millions of cases; it shows that the local setting on earth, while depending upon input from the
             sun, also plays a major role.)
                    note differences within United States and vs Europe, Middle East (Georgia), and Asia (Hong Kong).
             *T, transyear; Y, calendar year; cy/2, cis-half-year.


              34. Halberg F, Cornélissen G, McCraty R, al-Abdulgader A. Time structures (chro-                Evidence-based Holistic Approach to Health; 2010 June 3; Krakow, Poland.
                  nomes) of the blood circulation, populations’ health, human affairs and space           42. Zaslavskaya RM. Chronodiagnosis and chronotherapy of cardiovascular diseas-
                  weather. World Heart J. 2011;3(1):73-114.                                                   es. 2nd ed. Moscow: Medicina; 1993. In English.
              35. Vallot J, Sardou G, Faure M. De l’influence des taches solaires: sur les accidents      43. Güllner HG, Bartter FC, Halberg F. Timing antihypertensive medication.
                  aigus des maladies chroniques. Gazette des Hôpitaux. 1922;904-5.                            Lancet. 1979 Sep 8;2(8141):527.
              36. Schwartzkopff O, Halberg F, Katinas G, et al. Strain tests: gauging variability in a    44. Halberg F, Cornélissen G, Katinas G, et al; International BIOCOS Group.
                  day, week, year or decade. 59th Annual Meeting, Japan Society of                            Chronobiology’s progress: season’s appreciations 2004-2005. Time, frequency,
                  Neurovegetative Research; 2006 November 1-3; Tokyo, Japan.                                  phase, variable, individual, age- and site-specific chronomics. J Appl Biomed
              37. Cornélissen G, Halberg F, Otsuka K, Singh RB, Chen CH. Chronobiology pre-                   2006;4:1-38.
                  dicts actual and proxy outcomes when dipping fails. Hypertension. 2007                  45. Watanabe Y, Cornélissen G, Halberg F, et al. Harm vs. benefit from losartan with
                  Jan;49(1):237-9.                                                                            hydrochlorothiazide at different circadian times in MESOR-hypertension or CHAT.
              38. Gupta AK, Greenway FL, Cornélissen G, Pan W, Halberg F. Prediabetes is associ-              Noninvasive Methods in Cardiology; 2008 October 4-7; Brno, Czech Republic.
                  ated with abnormal circadian blood pressure variability. J Human                        46. Halberg F, Cornélissen G, Wilson D, et al. Chronobiology and chronomics:
                  Hypertension. 2008 Sep;22(9):627-33.                                                        detecting and applying the cycles of nature. Biologist (London).
              39. Cornélissen G, Halberg F, Beaty L, et al. Cugini’s syndrome in statu nascendi.              2009;56(4):209-14.
                  Oratio contra morem prevalentem et pro chronobiologica ratione ad pressione             47. Watanabe Y, Halberg F, Otsuka K, Cornelissen G. Physiological changes in rela-
                  sanguinis curandam. A plea against the prevailing custom and in favor of a                  tion to the 2011 East Japan earthquake. International Congress: Natural
                  chronobiological approach to treating blood pressure. Clin Ter.                             Cataclysms and Global Problems of the Modern Civilization; 2011 September
                  2009;160(2):e13-24.                                                                         19-21; Istanbul, Turkey.
              40. Müller-Bohn T, Cornélissen G, Halhuber M, Schwartzkopff O, Halberg F. CHAT              48. Satoh M, Kikuya M, Ohkubo T, Imai Y. Acute and subacute effects of the great
                  und Schlaganfall. Deutsche Apotheker Zeitung. 2002 Jan 24;142:366-70.                       East Japan earthquake on home blood pressure values. Hypertension. 2011
              41. Müller-Bohn T, Cornelissen G, Halberg F, Halhuber M, Delea CS. Blood pressure               Dec;58(6):e193-4.
                  variability gauged by circadian overswing (CHAT) and lifespan. Time Series              49. Vernadsky VI. Some words about the noösphere. 21st Century Sci Technol.
                  (not spotcheck) 1st International Workshop of the TsimTsoum Institute:                      2005; Spring:16-21.




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                                                                           IMPROVING HEALTHCARE OUTCOMES WORLDWIDE



                                  0.120

                                                                                     1.0y
                                  0.100                16.93y
                                                                                        0.5y
                                                   [14.25, 19.60]

                                                               1.276y
                                  0.080                    [1.252, 1.300]
             Amplitude (N/day)




                                                                                                                                                    0.283
                                                    9.85y                      1.002y                       0.501y                              [0.282, 0.285]
                                                [8.05, 11.64]              [0.984, 1.020]               [0.497, 0.504]
                                  0.060



                                  0.040



                                  0.020



                                  0.000
                                       0.0                              1.0                           2.0                              3.0                            4.0
                                                                                                Frequency (cycles/year)


                                  0.050

                                                                                     1.0y
                                                        23.8y
                                                     [19.2, 28.3]
                                  0.040                                                1.5y

                                                               1.073y
              Amplitude (N/day)




                                                            [1.06, 1.09]
                                                                                                                          0.372y
                                  0.030                                           1.020y                              [0.369, 0.374]
                                                           1.428y
                                                                              [1.003, 1.037]
                                                       [1.389, 1.467]
                                                                                                   0.499y
                                                                                               [0.494, 0.504]
                                  0.020




                                  0.010




                                  0.000
                                          0.0                           1.0                            2.0                             3.0                            4.0
                                                                                                Frequency (cycles/year)


figure 23A Daily incidence of suicide by day of death in the 2 genders in Minnesota (1979-2007). Top: Signatures of the seasons (1.0 y),
geomagnetics (0.5 y), and solar dynamics (~17, ~9.8, ~1.3, and ~0.28 y); men, n = 11 371. Bottom: Hale (~24-y) and extra-annual and extra-
semiannual components with periods of ~1.43, ~1.07, ~1.02, and ~0.37 years; women: n = 2794. In addition to a circannual and circasemian-
nual variation, a far-transyear is detected by least squares spectra, with a slightly different period in males (~1.28 years) and females (~1.43
years). A near-transyear is detected in females but not in males.


 50. Bailes KE. Science and Russian culture in an age of revolutions: V.I. Vernadsky                       56. Mikulecky M, editor. Sun, moon and living matter. Bratislava, Slovakia.
     and his scientific school, 1863-1945. Bloomington/Indianapolis: Indiana                                   Bratislava: Slovak Medical Society; 1994.
     University Press; 1990.                                                                               57. Mikulecky M, editor. Chronobiology and its roots in the cosmos. High
 51. Halberg F, Cornélissen G, Sothern RB, Katinas GS, Schwartzkopff O, Otsuka K.                              Tatras; 1997 September 2-6; Bratislava, Slovakia.
     Cycles tipping the scale between death and survival (=“life”). Progr Theor Phys                       58. Mikulecky M, Florida PL. Daily birth numbers in Davao, Philippines, 1993-
     Suppl. 2008;Suppl 173:153-81.                                                                             2003: Halberg’s transyear stronger than year. 26th Seminar: Man in His
 52. Halberg F, Cornélissen G, Schack B, et al. Blood pressure self-surveillance for                           Terrestrial and Cosmic Environment; 2005 May 17-19; Upice, Czech Republic.
     health also reflects 1.3-year Richardson solar wind variation: spin-off from                          59. Kovac M, Mikulecky M. Secular rhythms and Halberg’s paraseasonality in the
     chronomics. Biomed Pharmacother. 2003 Oct;57 Suppl 1:58s-76s.                                             time occurrence of cerebral stroke. Bratisl Lek Listy. 2005;106(2):423-7.
 53. Halberg F, Cornélissen G, Regal P, et al. Chronoastrobiology: proposal, nine confer-                  60. Kovac M, Mikulecky M. Time sequence of epileptic attacks from the point of
     ences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and                          view of possible lunisolar connections. International Conference on the
     ontogenetic memories. Biomed Pharmacother. 2004 Oct;58 Suppl 1:S150-87.                                   Frontiers of Biomedical Science: Chronobiology; 2006 September 24-26;
 54. Halberg F, Breus TK, Cornélissen G, et al; International Womb-to-Tomb Chronome                            Chengdu, China.
     Initiative Group. Chronobiology in space. 37th Annual Meeting Japan Society for                       61. Doodson AT. The harmonic development of the tide-generating potential. Proc
     Aerospace and Environmental Medicine; 1991 November 8-9; Nagoya, Japan.                                   Roy Soc Lond A. 1921;100(704):305-29.
 55. Mikulecký M. Paroxysmal tachyarrhythmia and moon. Chronobiologia. 1990                                62. Halberg F, Cornélissen G, Hillman D, et al. Multiple circadian periods in a lady
     Jan-Mar;17(1):71-3.                                                                                       with recurring episodes of adynamic depression: case report. Noninvasive




Review                                                                                                                           www.gahmj.com • Volume 1, Number 2 • May 2012                    97
                                                                                                   GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                                             Seasons’ (1.0 year) and Geomagnetcis’ (0.5 year) Singatures in Men Joining Solar 9.2- and 0.42-year*
                         0.3

                                                                                                   1.0 Year
                                                                                                              0.5 Year                                      1/3 Year
                                          9.16Y                                  1.004Y
                                       [8.50, 9.82]                          [0.997, 1.010]

                                                         1.99Y
                         0.2                          [1.94, 2.03]
                                                                                                                                                 0.421Y
     Amplitude (N/day)




                                            5.50Y                                                                                            [0.418, 0.423]
                                         [5.18, 5.82]
                                                                                                                               0.502Y
                                                                                                 0.741Y                    [0.499, 0.505]                    0.397Y
                                                                1.718Y
                                                            [1.681, 1.754]                   [0.734, 0.748]                                              [0.394, 0.399]



                         0.1




                         0.0
                                0.0       0.2         0.4       0.6        0.8     1.0       1.2     1.4        1.6      1.8       2.0      2.2    2.4        2.6      2.8   3.0   3.2   3.4    3.6
                                                                                                               Frequency (cycles/year)




                                      Extra-annual and Extrasemiannual Putatively Solar About 0.56-year, a 1.21-[trans] Year and a 9.2-year Component in Women*


                         0.12                                                                      1.0 Year
                                          9.16Y
                                      [8.37, 10.01]                                                           0.5 Year                                      1/3 Year


                         0.10                 3.300Y
                                          [3.188, 3.412]

                                                                                                                      0.563Y
                                                                                                                  [0.560, 0.567]
     Amplitude (N/day)




                         0.08                                             1.214Y
                                                                      [1.193, 1.236]
                                                                                                                                                          0.385Y
                                                                                                        0.685Y
                                                                                                                                                      [0.382, 0.387]
                                                                                                    [0.678, 0.692]
                         0.06



                         0.04



                         0.02



                         0.00
                                0.0       0.2         0.4       0.6        0.8         1.0   1.2      1.4        1.6     1.8       2.0      2.2    2.4        2.6      2.8   3.0   3.2   3.4    3.6
                                                                                                               Frequency (cycles/year)




                                figure 23B Suicides in Australia by day of death and gender, 1968-2001. Top: Seasons’ (1.0 y) and geomagnetics (0.5 y) signatures in men
                                joining solar 9.2- and 0.42-year.* Bottom: Extra-annual and extrasemiannual putatively solar about 0.56-year, a 1.21-[trans]year and a
                                9.2-year component in women.** The circannual component is prominent in males but not in females. A far-transyear is detected for both
                                genders, albeit with different periods.
                                *Data detrended (removal of linear trend). no. of cases: 50 169.
                                **Original data of Michael Berk. no. of cases: 15 859.




98                              Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                  Review
                                                                                                      IMPROVING HEALTHCARE OUTCOMES WORLDWIDE




                                                                               0.4                             M                     Period                    Amplitude
                                                                                                             1.178 [1.100 1.256] 15.46 [12.00 18.91]               0.29        [0.21 0.37]
                                                                                                                                   1.00                            0.37        [0.29 0.45]
                                                                                                                                   0.50                            0.08        [0.00 0.16]




                                                       Amplitude (N/100 000)
                                                                               0.3                          On residuals from above model
                                                                                                                                  4.114 [3.39 4.84 ]               0.06        [-0.01 0.13]
                                                                                                                                  1.478 [1.42 1.54]                0.09         [0.02 0.16]
                                                                                                            Separately on same residuals
                                                                               0.2
                                                                                                                                  0.436 [0.43 0.44]                0.05        [-0.00 0.12]



                                                                               0.1




                                                                               0.0
                                                                                 0.0                1.0           2.0            3.0            4.0                   5.0               6.0
                                                                                                                        Frequency (cycles/year)


figure 23C Suicides in Bulgaria by day of death (1929-1945). In addition to the prominent year, the half-year, a transyear, and a cis-half-year
are also detected.




                                                      1.0 y                                        0.5 y
                                    ~7.5 y
                                8
                                                                                     0.73 y
                                                                                                                   ~0.42 y
                                             ~2.2 y
                                7


                                6
Suicides (n/1,000 000 births)




                                5


                                4


                                3


                                2


                                1


                                0
                                    0                 10                                      20             30                 40                  50                    60                   70                   80
                                                                                                           Frequency (cycles per 12 years)


figure 23D Suicides in England and Wales by day of birth reveal a different spectrum without the transyears found in Minnesota by
day of death.


         Methods in Cardiology; 2011 October 17; Brno, Czech Republic.                                                               short rhythms. Neuro Endocrinol Lett. 2003 Oct;24(5):355-80.
     63. Evstafyev VK. How solar activity influences earth’s molecular processes. Open                                           69. Cornélissen G, Bakken EE, Sonkowsky RP, Halberg F. A 38-million-year cycle
         Biol J. 2009;2:38-41.                                                                                                       among myriadennians in the diversity of oceanic genera. International
     64. Freund F. Toward a unified solid-state theory for pre-earthquake signals. Acta                                              Conference: Civilization Diseases in the Spirit of V.I. Vernadsky; 2005 October
         Geophys. 2010;58(5):719-66.                                                                                                 10-12; People’s Friendship University of Russia, Moscow.
     65. Stinson SM, Cornélissen G, Scarpelli PT, Halberg F. Self-measurement and                                                70. Sonkowsky RP, Cornélissen G, Chibisov SM, Schwartzkopff O, Sampson M,
         ambulatory monitoring of blood pressure: a subject’s chronobiological per-                                                  Halberg F. Myriadennian, including perhaps millionennian or the shorter
         spective. Biomed Pharmacother. 2002;56 Suppl 2:333s-8s.                                                                     megennian—a choice to be made: invitation for comment. International
     66. Hillman DC, Siffre M, Milano G, Halberg F. Free-running psycho-physiologic                                                  Conference: Civilization Diseases in the Spirit of V.I. Vernadsky; 2005 October
         circadians and three-month pattern in a woman isolated in a cave. New Trends                                                10-12; People’s Friendship University of Russia, Moscow.
         Exp Clin Psychiatry. 1994;10:127-33.                                                                                    71. Halberg F, Cornélissen G, Katinas G, et al. Transdisciplinary unifying implica-
     67. Hillman DC. Physiologic 7- and 3.5-day patterns in health and disease revealed                                              tions of circadian findings in the 1950s. J Circadian Rhythms. 2003 Oct 29;1(1):2.
         by free-run and single-stimulus induction. Doctoral Thesis, May 1993.                                                   72. Cornélissen G, Halberg F, Gheonjian L, et al. Schwabe’s ~10.5- and Hale’s ~21-
     68. Halberg F, Cornélissen G, Bingham C, et al. Chronomics: imaging in time by                                                  year cycles in human pathology and physiology. In: Schröder W, editor. Long-
         phase synchronization reveals wide spectral-biospheric resonances beyond                                                    and short-term variability in sun’s history and global change. Bremen: Science




Review                                                                                                                                                   www.gahmj.com • Volume 1, Number 2 • May 2012                    99
                                                                                                    GLOBAL ADVANCES IN HEALTH AND MEDICINE



                                               12                                             Homocides in USA                                                      Fitted model



                                               10



                                                8                                                                    Yearly value
                       Homocides (N/100 000)




                                                6



                                                4


                                                              Fitted model, consisting of cosine curves with trial periods of 50 and 21 years
                                                2             6.713 + 2.85 cos (360t/53.260 - 264) + 0.97 cos (360t/20.349 - 26)




                                                0
                                               1900          1910           1920             1930          1940           1950                                      1960           1970        1980         1990     2000

                                                                                                                  Time (Calendar year)

                         figure 24 The Kondratiev and Hale cycles are mirrored in US homicides (1900-1998). national Center for Health Statistics (Homicide rates
                         from the vital statistics: http://www.ojp.usdoj.gov/bjs/glance/hmrt.htm).


                                                    Solar Cycles                                                                                                                           Solar Cycles N
                                                                                                           A                                                                                                            B
                21                                      22             23                                                                                                           21              22         23
                                                                               Period
 Solar wind speed                                                              (years)                                                                       SWS
                                                                                                                                                                                                                             -210
                                                                                 2.00
                                                                                                                                                                                                                             -150

                                                                                 1.33                                                                                                                                         -90
                                                                                                                                                                                                                              -30
                                                                                 1.00                                                                                                                                        -330
                                                                                 0.83                                                                                                                                        -270
                                                                                                                                                                                                                             -210
                                                                                 0.70


                                                                                                                                                             aa
                                                                                                                            Acrophase and Limits (degrees)




  Geomagnetism                                                                                                                                                                                                               -210
                                                                                 2.00
                                                                                                                                                                                                                             -150

                                                                                 1.33                                                                                                                                         -90
                                                                                                                                                                                                                              -30
                                                                                 1.00
                                                                                                                                                                                                                             -330
                                                                                 0.83
                                                                                                                                                                                                                             -270
                                                                                 0.70                                                                                                                                        -210


                                                                                                                                                             MIPT
  Terrorism                                                                                                                                                                                                                  -180

                                                                                 2.00                                                                                                                                        -120
                                                                                                                                                                                                                              -60
                                                                                 1.33
                                                                                                                                                                                                                             -360

                                                                                 1.00                                                                                                                                        -300
                                                                                                                                                                           lag                    lag
                                                                                 0.83                                                                                                                                        -240
                                                                                                                                                                                                                             -180
                                                                                 0.70
                                                                                                                                                     1968                   1978             1988           1998         2008
             1980     1985     1990     1995                            2000             0   25 50 75 100                                                                                 Time (Years)
                     Time (Calendar years)                                                   Relative Amplitude
1972                                                                            2007




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                                                                  IMPROVING HEALTHCARE OUTCOMES WORLDWIDE




figure 25 (opposite, bottom) A gliding (local, left) and aligned overall (global, right) spectral window (A, left) show similarities in the para-
annual region, a transyear around 1.33 years in solar wind speed (SWS, top), the antipodal geomagnetic disturbance index (aa, middle),
and in the incidence of terrorism in the MIPT’s (Memorial Institute for the Prevention of Terrorism) 39-year-old database (bottom). Phases
of chronomic serial sections are shown for the transyear at the average period for the three variables (B, right). The transyear is observed to
be particularly prominent in all three variables during solar cycle 22, as seen from the darker shading at a frequency of 1 cycle in about 1.33
years. Changes with time of the phase of the transyear component indicate further that statistical significance for terrorism relatively shortly
follows (with only a lag) that in solar wind speed and geomagnetism and that it may persist, in terrorism for quite a while, after statistical
significance is lost for the two environmental variables. Despite some expected wobbliness, the transyear appears to be relatively stable in
all variables during most of solar cycle 22. The fact that a predictable cycle characterizing the incidence of terrorism is also present in the
physiology of individuals renders it amenable to monitoring by a population marker rhythm for further scrutiny and for the eventual design
of rational countermeasures against undesirable effects of the cosmos. Gliding spectra prepared by Professor George S. Katinas.


                       4




                       3
   Incidence (N/day)




                       2




                       1




                       0
                       1968           1972           1976       1980        1984        1988        1992            1996    2000       2004         2008
                                                                                 Time (Calendar year)
                      0.2
                                                                                                                               *Components fitted
                                                                                                                                   concomitantly
                                      26.65y
                                  [23.47, 29.82]*
                                                                            1.0 year             0.5 year


                                   9.81y
                               [9.00, 10.62]
                      0.2
  Amplitude (N/day)




                                       2.86y
                                    [2.78, 2.94]


                                                          1.34y                                               0.495y
                                                      [1.32, 1.37]*                                        [0.49, 0.50]

                      0.1




                      0.0
                         0.0                   0.5                    1.0               1.5                   2.0               2.5                 3.0
                                                                                Frequency (Cycles per year)


figure 26 In data then available from the Memorial Institute for the Prevention of Terrorism’s (MIPT) Terrorism Knowledge Base (1968-2008)
(http://www.tkb.org/) (top), a transyear of ~ 1.3 years is detected in the absence of a calendar year component, suggesting that space weath-
er (gauged by magnetism) is more important than any (absent) effect of the seasons. From February 1968 to March 2007, daily incidence
computed from monthly totals (adjusted for differences in the number of days per month).




Review                                                                                                         www.gahmj.com • Volume 1, Number 2 • May 2012   101
                                                                                                          GLOBAL ADVANCES IN HEALTH AND MEDICINE



                                                                                                                                                                                    105




                                                                                                                    4000
                                                                                                                                                                                                                                            105
                                                          Mag. 8.0 Earthquake
                                                                                                                                                                                    103                                                     103




                                                                                                                                                                SBP-M (% of mean)
                                                                                                                    Activity of Mouse (Numbers of turns/day)
                                                                                                                                                                                    101                                                     101




                                                                                                                                                  3000
                                                                                                                                                                                     99                                                      99

                                                                                                                                                                                     97                                                      97

                                                                                                                                                                                     95                                                      95
                                                                                                                                                                                          Day-3 Day-2 Day-1 EQ Day+1 Day+2 Day+3                  Day-3 Day-2 Day-1 Day+1 Day+2 Day+3




                                                                                                                                      2000
                                                                                                                                                                                    105                                                     105




                                                                                                                                                               SBP-M (% of mean)
                                                                                                                                                                                    103                                                     103

                                                                                                                                                                                    101                                                     101




                                                                                                                        1000
                                                                                                                                                                                     99                                                      99

                                                                                                                                                                                     97                                                      97




                                                                                                                    0
                                                                                                                                                                                     95                                                      95
                                                                                                                                                                                          Day-3 Day-2 Day-1 EQ Day+1 Day+2 Day+3                  Day-3 Day-2 Day-1 Day+1 Day+2 Day+3
                            B18
                            B17
                            B16
                            B15
                            B14
                            B13
                            B12
                            B11
                            B10
                            B09
                            B08
                            B07
                            B06
                            B05
                            B04
                            B03
                            B02
                            B01
                              0
                            A01
                            A02
                            A03
                            A04
                            A05
                            A06
                            A07
                            A08
                            A09
                            A10
                            A11
                            A12
                            A13
                            A14
                            A15
                            A16
                            A17
                            A18
                            A19
                                                                                                                                                                                                        Time (Days)                                           Time (Days)
                                                               Time (Days)


                      1.0
                             Human counter-      Model [95% CI] (1-parameter for A)
                             parts exist for
                             all periods                                                                                                                                                                                                               Period
                      0.8                                                                                                                                                                               Natality - USA                                                             95%
Incidence (N/month)




                             9-month running                                                                                                                                                                                                                                   confidence
                             means                                                                                                                                                               Length at birth - Girls                                                         interval

                      0.6         Fitted model                                                                                                                                                   Length at birth - Boys
                                                                                                                                                                                    Stroke incidence - Czech Republic
                                                                                                                                                                                          Stroke incidence - Minnesota
                      0.4                                                                                                                                                                            Homicides - USA
                                                                                                                                                                                          Index of wars - International     (2556 years)

                      0.2                                                                                                                                                                    Earthquakes (1900-2010)
                                                                                                                                                                                                Tsunamis (1900-2010)
                                                                                                                                                                                           Wolf Numbers (1900-2010)
                      0.0
                        1900 1910 1920 1930 1940 1950 1960 1970 1980 1990 2000 2010                                                                                                                                    30       35     40         45     50      55       60        65      70
                                                     Time (Calendar years)                                                                                                                                             Nonlinear Period Estimate (τ) and 95% Confidence Interval (Years)



                                            figure 27 Proposed biospheric contributions to the understanding, if not prediction of earthquakes. Upper left: Locomotor activity of some
                                            of the mice telemetered around the clock was statistically significantly decreased starting 3 days prior to the magnitude 8.0 earthquake in
                                            Chengdu, China on 12 May 2008. Upper right: Human systolic blood pressure started increasing 2 days prior to the magnitude 9.0 earth-
                                            quake in Sendai, Japan on 11 March 2011, documented on the basis of weeklong records of around-the-clock ambulatorily obtained data
                                            from 13 Japanese. Similar records from longitudinal and transverse controls differ in their time course, suggesting that the trend observed
                                            before the earthquake was related to it rather than being a feature of an anticipated weekly pattern. Lower left: The monthly incidence of
                                            major earthquakes since 1900 is characterized by the presence of cycles with periods of about 49.3, 12.2, 1.44, and 0.41 year(s), given with
                                            their uncertainties in parentheses. Lower right: The prominent about–50-year cycle is also documented in physiology, pathology, societal
                                            upheavals and space weather. nonlinearly estimated periods are displayed with their 95% confidence intervals shown as the length of cor-
                                            responding horizontal bars. n = 331.


                                                   Edition; 2000. p. 79-88.                                                                                                               82. Tchijevsky AL. de Smitt VP, translator. Physical factors of the historical process.
                                               73. Hrushesky WJ, Sothern RB, Du-Quiton J, Quiton DF, Rietveld W, Boon ME.                                                                     Cycles. 1971 Jan 22:11-27.
                                                   Sunspot dynamics are reflected in human physiology and pathophysiology.                                                                83. Sigel F, Dreier W. Schuld ist die Sonne. Frankfurt am Main: Deutsch Harri
                                                   Astrobiology. 2011 Mar;11(2):93-103.                                                                                                       GmbH; 1979.
                                               74. Sello S, Halberg F, Cornélissen G. Human babies: a slow-to-read, sensitive popu-                                                       84. Dubrov AP. Sinclair FL, translator. The geomagnetic field and life: geomagneto-
                                                   lation magnetometer, also read by wavelets. Noninvasive Methods in                                                                         biology. New York: Plenum Press; 1978.
                                                   Cardiology; 2011 October 17; Brno, Czech Republic.                                                                                     85. Brown FA Jr. A unified theory for biological rhythms. In: Aschoff J, editor.
                                               75. Cornélissen G, Halberg F, Wendt HW, et al. Resonance of about-weekly human                                                                 Biological clocks. Amsterdam: North-Holland Publishing Co; 1965. p. 231-61.
                                                   heart rate rhythm with solar activity change. Biologia (Bratisl). 1996                                                                 86. Wever RA. The circadian system of man: results of experiments under tem-
                                                   Dec;51(6):749-56.                                                                                                                          poral isolation. New York: Springer-Verlag; 1979.
                                               76. McCraty R, Deyhle A, Childre D. The Global Coherence Initiative: creating a                                                            87. Chibisov SM, Cornélissen G, Halberg F. Magnetic storm effect on the circula-
                                                   coherent planetary standing wave. Global Adv Health Med. 2012;1(1):62-74.                                                                  tion of rabbits. Biomed Pharmacother. 2004 Oct;58 Suppl 1:S15-9.
                                               77. McCraty R, Childre D. Coherence: bridging personal, social, and global health.                                                         88. Breus TK, Cornélissen G, Halberg F, Levitin AE. Temporal associations of life
                                                   Altern Ther Health Med. Jul-Aug 2010;16(4):10-24.                                                                                          with solar and geophysical activity. Ann Geophys. 1995;13:1211-22.
                                               78. Persinger MA. On the possible representation of the electromagnetic equiva-                                                            89. Breus TK, Chibisov SM, Baevsky RM, Schebzuhov KV. The chronostructure
                                                   lents of all human memory within the Earth’s magnetic field: implications for                                                              of heart biorhythms under effects of external environment factors. Moscow:
                                                   theoretical biology. Theoret Biol Insights. 30 Sep 2008;1:3-11.                                                                            Russian University of People’s Friendship, Polygraph Service; 2002.
                                               79. Persinger MA, Koren SA, Lafreniere GF. A neuroquantologic approach to how                                                              90. Düll B, Düll T. Erd- und Sonnenphysikalische Vorgänge in ihrer Bedeutung für
                                                   human thought might affect the universe. Neuroquantology. 2008;6(3):262-71.                                                                Krankheits- und Todauslosung. Nosokomeion. 1938;9:103-20.
                                               80. Wendt HW. Interplanetary magnetic field (IMF) polarity, collective emotions                                                            91. Stetson HT. Sunspots in action. New York: Ronald Press Co; 1947.
                                                   and entropy changes of random event generators. 8th International Congress:                                                            92. Beaty L, Cornélissen G. Towards inexpensive ambulatory blood pressure vari-
                                                   Health and Education Millennium; 2007 November 14-17; Moscow, Russia.                                                                      ability monitors for home use: a first experiment using off-the-shelf devices as
                                               81. Ulmer W, Cornélissen G, Halberg F. Physical chemistry and the biologic week                                                                the basis for ABPMs. 2008. www.phoenix.tcieee.org/0001_
                                                   in the perspective of chrono-oncology. In Vivo. 1995 Jul-Aug;9(4):363-74.                                                                  Bibliography/20081221beat_FirstHomemadeABPM.pdf. Accessed April 4, 2012.




                            102             Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                                                                              Review
                                              IMPROVING HEALTHCARE OUTCOMES WORLDWIDE




figure 28A Frame on lower right half lists some components of the transdisciplinary set of cyclic components found in the bio- and/or in the
litho-, hydro-, atmo-, iono-, helio-, magneto- and cosmospheres, underlying a time-structured sphere of the human mind (Attic Gk nous), the
chronousphere.




Review                                                                                     www.gahmj.com • Volume 1, Number 2 • May 2012       103
                                                              GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                                                    COSMOS




                                     Sun                                                               Earth




                                                                         B1



                                                                                                                     Actor*




              Modulator*
                                               A                                                       B2




      C
                      IMF


                                                                                                                          D2         Moon




                                                                                                                   D1


                                                Reactor*                           Organism                                       Back-up*




          figure 28B Chronousphere: genetically coded biospheric resonance including terrestrial luni-solar and/or cosmic cycles. Signatures of the
          cosmos with validated statistical significance of anticipated periods characterize (1) dozens of decades-long time series of human blood pres-
          sure and heart rate; (2) other physiology and psychology, including human mental functions; (3) religious proselytism; (4) suicide; (5) sudden
          cardiac death; (6) terrorist activity for the past 39 or 41 years; (7) 2556 years of international battles compiled by Raymond Holder Wheeler; (8)
          military expenditures for training in non-medical science; (9) degrees earned; (10) Gallup Polls; and (11) political and military actions in nearly
          200 years, meta-analyzed from the much broader treasure of data compiled by Alexander Leonidovich Chizhevsky. While chance can never
          be ruled out, it would be further greatly reduced by systematic lifetime monitoring of physiology in health, of pathology and disease, notably
          in archives to separate effects of sun, tides, and earth, many of which are beneficial. Other effects such as extreme cold and heat or extreme
          light can be met by countermeasures such as housing, heating and air conditioning. The task remains to develop countermeasures to those
          nonphotic effects that can be documented as harmful. While the earth is the immediate actor, and for that action the sun is the modulator,
          the biosphere reacts directly, yet sometimes selectively to only 1 (or both) terrestrial and lunisolar factors, the tides, as well as natural and
          artificial light competing with each other under certain circumstances, as seen in patient JF (Figures 28C-28G). There may be other more subtle
          effects of synchronized human action upon the earth. Effects of the moon, contributing about two-thirds of the tides, are thus also demon-
          strated (Figures 25C-25G). The roles of actor, reactor and modulator are continuously changing. In the greenhouse effect, organisms are the
          actors, as shown by a double-headed arrow (B2). Original compilation by Mary Sampson.
          *Roles played interactively and interchangeably.

          Abbreviation: IMF, interplanetary magnetic field.




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                                                                                                                                                                     100               Period
                                                                                                                                                                                       (hours)




                                                                                                                                                                       Chonogram
100                                                                                                                                                                  0
Amplitude and MESOR




                                                                                                                                                                                        168.0




             0
                                                                                                                                                                        (-90)
                                                                                                                                                                        -360
Acrophase and Limits




                                                                                                                                                                        -270

                                                                                                                                                                        -180

                                                                                                                                                                            -90         24.0
                                                                                                                                                                                   0

                                                                                                                                                                     (-270)
                                                                                                                                                                       >.50
 P Value




                                                                                                                                                                          .05
                                                                                                                                                                        (-90)
                                                                                                                                                                        -360
   Acrophase and Limits




                                                                                                                                                                        -270

                                                       24.838                                                                                                           -180
                                                   (24.53, 25.14)                                                                           24.866
                                                                                                                                        (24.28, 25.46)                      -90
                                                                                                                                                                                        24.8
                                                                                                                                                                                   0

                                                                                                                                                                     (-270)
                                                                                                                                                                       >.50
 P Value




                                                                                                                                                                             .05

                                                                                                                                                                               70
  Data/Interval




                                                                                                                                                                               30


                          1   2          3            4           5           6          7           8            9          10          11        12    13     14
              3/7/09                                                               Time (Lunar cycles)                                                        4/1/10


            figure 28C Replicated lunar synchronization of JFF’s vigor during first month (shaded) of (2-month-long) adynamia episodes.* Chronomic
            serial section of self-rated vigor-wellness of JF, a woman aged 61 years at start of study during the first 14 lunar months of investigation,
            revealing extreme changes in vigor and mostly a lack of statistical significance of 24.0-h (row 4) and 24.8-h (row 6) cosine fits. Lunar cycles 4
            and 11, the first months of the first two episodes of depression investigated, are characterized by a delaying acrophase when a 24-h cosine
            is fitted and, as anticipated, by a more or less horizontal time course with a 24.84-h cosine fit (rows 3 and 5 respectively). Each first month of
            an adynamic episode in nonlinear analyses is characterized by a 24.8-h period twice in succession, never found by us earlier (also further in
            other variables of JF during adynamic episodes).
            *Dashed vertical lines: full moons (JF reports sensitivity to the moon). n data: 2820; interval: 168 hours; increment: 12 hours.




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                                                                 GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                                                                                                                                           170.00




                                                                                                                                                            Chronogram
      150                                                                                                                                                  60.00
      Amplitude and MESOR




      100
                                                                                                                                                            (-90)

                                                                                                                                                            -360


                                                                                                                                                            -270
      Acrophase and Limits




                                                                                                                                                            -180


                                                                                                                                                            -90


                                                                                                                                                            0


                                                                                                                                                            (-270)
                                                                                                                                                            >.50
      P value




                                                                                                                                                            0.05
      Data/Interval




                                                                                                                                                            250


                                                                                                                                                            0


                             1   2   3   4   5   6   7   8   9    10   11 12     13 14      15    16   17 18       19    20    21 22       23 24   25 26
                                                                                 Time (Days)


      figure 28D Self-measurements of systolic blood pressure of JF, from lunar cycles (vertical dashed lines) 4 to 8 inclusive, followed by auto-
      matic monitoring in lunar cycle 8. Original data on top reveal lack of lower values during rest/sleep. The lower curve in the second row is
      the circadian average (MESOR), which is higher during measurements restricted to wakefulness. The circadian amplitude, the distance be-
      tween the 2 curves in the second row, is small and not statistically significant, as seen from the penultimate row of P values for test of the
      zero 24-hour amplitude assumption in cycles 4 through 8. note acrophases in row 3, shown with 95% confidence interval when statistical
      significance is reached (ie, as soon as automatic measurements start in lunar cycle 9 to the end). Their time course continues in alternation
      horizontally (during wellness) and upward diagonally (during adynamia), thereby indicating a changing dominance between the 24-hour
      synchronized and desynchronized circadian components of variation, a wrangling of the tides with society in JF.
      Period: 24 h; Interval: 168 h; Phas ref: 01/01/09; Start time: 03/01/09; End time: 04/15/09; no. of data: 10 078; Increment: 12 h.




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                                                          SBP                                                 DBP                                               HR
                                                                                                  Period Estimate and 95% CI
                                28                                                    28                                                    28


                                26                                                    26                                                    26


                                24                                                    24                                                    24


                                22                                                    22                                                    22


                                20                                                   20                                                    20
                                10/24/09              4/10/10                  9/25/10                       4/10/10                      10/24/09              4/10/10            9/25/10

                                                                                               Amplitude Estimate and 95% CI
                                25                                                   20                                                     15

                                20
                                                                                     15
                                                                                                                                            10
                                15
                                                                                     10
                                10
                                                                                                                                             5
                                                                                       5
                                 5

                                 0                                                    0                                                     0
                                10/24/09              4/10/10                  9/25/10                      4/10/10                       10/24/09            4/10/10             9/25/10
                                                                                                    Time (calendar date)


                                figure 28e Coexisting societal-light 24-hour (dots) and tidal 24.8-hour (diamonds) components dominating during wellness and illness,
                                respectively, in JF’s (a 62-year-old woman) blood circulation.
                                Abbreviations: CI, confidence interval; DBP, diastolic blood pressure; HR, heart rate; SBP, systolic blood pressure.



                                              Wellness                      Adynamia                                      Wellness                                   Adynamia
                              25.4




                              24.8                                                                                                                                        Tides
Best-Fitting Period (Hours)




                              24.2


                                                                                                                                                                  24-hour
                                                                                                                                                                Society, Light



                              23.6



                                                                Cortisol                                      DHEA                                     Melatonin
                                                                Testosterone                                  Estradiol                                Aldosterone
                                                                SBP                                           DBP                                      HR
                              23.0
                               10/24/09                  12/19/09                    2/13/10                   4/10/10                     6/5/10              7/31/10                9/25/10

                                                                                                         Time (calendar date)


                                figure 28f Competition of 24.0-hour (light and society) and 24.8-hour (tides) periods in JF’s endocrines with 24-hour dominance during
                                wellness and the tides pulling most during illness. n = 11 700 salivary hormonal assays (JF: 61-62-year-old woman; 20 years of adynamic
                                episodes lasting 2-3 months and recurring half-yearly).
                                Abbreviations: DBP, diastolic blood pressure; DHEA, 5-Dehydroepiandrosterone; HR, heart rate, SBP, systolic blood pressure.




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                                                                     JF (recurrent ecfrequentia)




                                 SBP
                                                      Out of
                                                       sync
                                                                                                         Out of
                                                                                                          sync




                                 DBP
                                 HR
                                 Data/Interval




                                                                                                                       200
                                                                                                                        0

                                                 1     2      3      4     5      6      7     8       9   10     11
                                                     Time (In days; vertical dashed lines indicate full moons)

                                                                      GC (24-hour synchronization)
                                                                                                                       (-90)
                                                                                                                       -360
                                                                                                                  ↓    -270
                                    SBP




                                                                                                                       -180
                                                                                                                       -90
                                                                                                                       0
                                                                                                                       (-270)
                                                                                                                       (-90)
                                                                                                                       -360
                                                                                                                       -270
                                    DBP




                                                                                                                       -180
                                                                                                                       -90
                                                                                                                       0
                                                                                                                       (-270)
                                                                                                                       (-90)
                                                                                                                       -360
                                                                                                                       -270
                                   HR




                                                                                                                       -180
                                                                                                                       -90
                                                                                                                       0

                                                                                                                       (-270)
                                                                                                                       500
                                                                                                                       100

                                                 1     2       3     4     5      6     7      8     9       10   11
                                                     Time (In days; vertical dashed lines indicate full moons)


      figure 28g Chronobiologically interpreted automatic ambulatory blood pressure (BP) and heart rate (HR) monitoring (C-ABPM) monitors
      circadian ecfrequentia of JF (top) by comparison to a gender- and age-matched control, GC. Circadian acrophases of systolic blood pressure
      (SBP), diastolic blood pressure (DBP) and heart rate (HR) from 11/03/09 to 10/12/10 for both subjects. Fit of 24-hour cosine curve to data in
      168-hour intervals, displaced in 12-hour increments for consecutive analyses. Acrophases are doubly plotted (top) when nearing midnight,
      indicated by horizontal dashed lines at 0° and 360°. More or less horizontal time course = 24-hour synchronization. ↓ indicates brief trans-
      meridian roundtrip across 8 time zones.



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 Predominantly 24-hour Rather than 24.8-hour synchronization Histograms of                                                              Period and Interval estimations in Recurring Adynamia Associated with
Point estimates of Circadian Period of systolic (sBP) and Diastolic Blood Pressure                                                    variable-dependent sequences of frequency De- and Resynchronization (Jf)
    (DBP) and Heart Rate (HR) of a Clinically Healthy woman in 270 Mostly                                                                                      and Healthy Control (gC)*
                           weekly Records (2004-2010)

         60
                                                                                                               N=270
                                                                                                                                                                                       24.84 Hours
         50
                                                                                                                                                                                               Two Adynamia
                                                                                                                                                        JF (F, 62y)                            episodes
         40
SBP: N




         30
                                                                                                                                                  GC (F, 54-60y)
                                                                                                        0%                                         13τ < 24h                            Systolic Blood Pressure
         20                                                                                                                                         2τ > 24h
                                                                                                                                                   255τ = 24h

         10


          0
              23.0 23.1 23.2 23.3 23.4 23.5 23.6 23.7 23.8 23.9 24.0 24.1 24.2 24.3 24.4 24.5 24.6 24.7 24.8 24.9 25.0 25.1




         50
                                                                                                               N=270
                                                                                                                                                                                       24.84 Hours
         40                                                                                                                                        JF (F, 62y)


         30
                                                                                                                               Time
DBP: N




                                                                                                      0.74%
                                                                                                                                            GC (F, 54-60y)
         20                                                                                                                                   2τ < 24h                                   Diastolic Blood Pressure
                                                                                                                                              0τ < 24h
                                                                                                                                             268τ = 24h

         10



          0
              23.0 23.1 23.2 23.3 23.4 23.5 23.6 23.7 23.8 23.9 24.0 24.1 24.2 24.3 24.4 24.5 24.6 24.7 24.8 24.9 25.0 25.1



         60
                                                                                                                N=270

         50                                                                                                                                                                             24.84 Hours
                                                                                                                                                    JF (F, 62y)

         40
HR: N




         30
                                                                                                       0.37%
                                                                                                                                                GC (F, 54-60y)
                                                                                                                                                 27τ < 24h                                 Heart Rate
         20
                                                                                                                                                  5τ < 24h
                                                                                                                                                 268τ = 24h
         10


          0
               23.0 23.1 23.2 23.3 23.4 23.5 23.6 23.7 23.8 23.9 24.0 24.1 24.2 24.3 24.4 24.5 24.6 24.7 24.8 24.9 25.0 25.1             18.0              21.0             24.0             27.0            30.0
                                                         Period (Hours)                                                                              Period, τ (hours) [and 95% Confidence Interval]


              figure 28H Distribution of period estimates, τs (histograms on left, individual results on right, shown with their 95% confidence intervals [CIs]) displayed
              as a function of time (upward) along the ordinate for a 54-60-year-old woman (GC), based on around-the-clock ~24-hour/7-day records at 30-minute
              intervals. Monthly summaries of a patient’s (JF’s) τ and CI during “downtimes” (shaded) and outside such episodes of loss of vigor are shown (right, top
              of each section). The first winter adynamia (shaded) is characterized for SBP by 2 consecutive τs longer than 24.8 hours for JF, a finding not seen in GC.
              For all 3 of GC’s variables, desynchronized τs are rare and are absent in a sequence, while in JF’s second upper adynamic episode, based on automatic
              measurements, desynchronization from society is the rule: the CIs of τs invariably fail to cover 24 hours.

              *JF (above dashed lines): estimates during consecutive lunar cycles; GC (below dashed lines): circadian rhythm invariably detected (P < .05) in about week-long (rather
              than month-long) spans.




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                                                                                            7.00 d              Point estimation
                                                                                                                               6.78 d
                                           Solar wind’s (SW)
                                           speed
                                                                                        7.03 d
                                       Dst


                                       Ap


                                       Kp
                                                                                                                      95% CI**

                                       Heart rate (HR)
                                                                                           7.01 d                      6.82 d

                                       Systolic Blood
                                       Pressure (SBP)

                                       Diastolic Blood
                                       Pressure (DBP)


                                                                   7.20          7.10        7.00            6.90          6.80          6.70
                                                                                             Period (days, d)


      figure 29A Congruence in certain environmental circaseptan spectral components and in some cardiovascular counterparts during
      1998-2005.*Selective transdisciplinary congruence in the spectral region around 1 week.
      *All peaks are statistically significant (P < .001) by linear-nonlinear least squares cosinor spectra (not corrected for multiple testing). HR, SBP, and DBP (n =
      124 263 each) – half hourly records of GSK, a 72-year-old-man at start of around-the-clock monitoring, Data: SW (n = 68 845) hourly values from http://
      omniweb.gsfc.nasa.gov/ Dst, Ap, and Kp 3-hourly data (n = 23 376 each ) from http://spidr.ngdc.noaa.gov/.
      **CI = confidence interval.
      ***Two separate spectral peaks without CI-overlapping.
      ****All available daily SW data during 1963-2005.




                                                                  7.50


                                                                  7.00
                                       Period ( τ )




                                                                  6.77

                                                                                                                                             Cycle
                                                                  6.00                                                                      fitted
                                                                                                                                            (days)
                                                                  -360
                                       Acrophase (φ, 360° ≡ τ )




                                                                  -180
                                                                                                                                                6.77
                                                                    0


                                                                  -360

                                                                  -180
                                                                                                                                                7.00
                                                                    0


                                     Jun 1997                             1998             2000              2002                 2004          Dec 2005
                                                                                             Time (calendar years)



      figure 29B Combination of gliding spectral window (top) with special focus on the behavior of 2 selected periods (chronomic serial sec-
      tions, middle and bottom), with the time course of the phase validating the 6.77-day period by a more or less horizontal trajectory of
      phases bracketed by CIs (dots) indicating statistical significance in only part of the record, but invalidating a precise 7-day periodicity since
      with this fit no dots bracket any horizontal time course of phases, and the small initial section with dots shows a gradual advance (rather
      than being horizontal).
            Data from http://omniweb.gsfc.nasa.gov/html/ow_data.html. In gliding spectral window, interval = 1 year, increment = 1 week;
      shaded areas show percentage of rhythm (from 1.2% to 6.8%). Statistical significance seen as 95% confidence intervals of φs shown as
      dots bracketing curves (middle and bottom). Reference time: 00:00 on December 21, 1997. Dotted arrows indicate correspondence be-
      tween circaseptan components in the phase (middle and bottom) and period (top) domains. Twenty-third solar cycle began in May 1996;
      its maximum was in April 2000, and the cycle still continued descending after the end of record.




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                                                                            Monthly Mean Flare Index
                                                                              Jan 1976 - Dec 1998                                                                                                                         Time (calendar date)
                                                       30                                                                                                                                   1.0                                                                              D
                                                                                                                           A                                                                                                           3.16 y
                                                                                                                                                                                            0.8




                                                                                                                                                            Cross-Correlation Coefficient
                                                       20
                                                                                                                                                                                            0.6
                                   Solar Flare Index



                                                                                                                                                                                                                                                      r=0.79
                                                       10                                                                                                                                   0.4
                                                                                                                                                                                            0.2
                                                        0
                                                                                                                                                                                            0.0
                                                  -10                                                                                                                                       -0.2
                                                                                                                                                                                            -0.4
                                                  -20
                                                                                                                                                                                            -0.6
                                                  -30                                                                                                                                       -0.8
                                                            1976 1978 1980 1982 1984 1986 1988 1990 1992 1994 1996 1998
                                                                                                                                                                                            -1.0
                                                                                  North      South (*-1)
                                                                                                                                                                                              -18 -15 -12        -9   -6     -3    0       3     6        9   12      15    18
                                                                                 Wolf Numbers                                                                                                                                 Lag (years)
               250                                                                                                              B

               200
                                                                                                                                                                                                                                  COSMOS
Sunspots (N)




               150                                                                                                                                                                                                                                                           E
                                                                                                                                                                                                                   Sun                               Earth

               100

                                                                                                                                                                                                                                    B1
                     50
                                                                                                                                                                                                                                                              Actor
                       0
                     2.0                                                                                                        20                                                                        Modulator
                                                                                                                           C                                                                                          A                              B2
                                                                                                                                        Total Solar Flares (index)
                                                                                  0.41 year
                     1.6                                                                                                        16
  HR-A (beats/min)




                     1.2                                                                                                        12                                                                    C
                                                                                                                                                                                                                                                                   IMF
                     0.8                                                                                                            8                                                                  IMF

                     0.4                                                                                                            4

                                                                                                                                                                                                                   Reactor                 Organism
                     0.0                                                                                                            0
                     12/31/69                               12/31/77            12/312/77          12/31/93         1 2/31/01




                                figure 30A Waxing and waning of the aeolian ~5-month (~0.41-year) cycle in solar flares (top), sunspots (middle), and with a lag in the heart
                                rate of a clinically healthy man (RBS). Concomitant changes occur in sudden cardiac death incidence not here shown. Influence of solar flares
                                (SF, A, x in C) and sunspots (B) on human heart rate amplitude (HR-A, φ in C) in cis-half-year window suggested by shared ~11-year cycle
                                andhigh cross-correlation (HR-A vs SF) with 3.2-year lag (D): a helio-geo-bio-feedsideward (E).
                                *In frequency windows (not shown), predicted theoretically, some components already validated transdisciplinarily.

                                Abbreviation: IMF, interplanetary magnetic field.




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                                                       1. Solar magnetism

                                                       2. SW speed (SWS)

                                                      3. Sigma of SWS

                                                          4. Proton density of SW

                                                            5. North-South c of IMF, Bz

                                                           6. Geomagnetic aa-index

                                                    7. Acetabularia

                                                        8. Autism, California

                                                            9. 17-Ketosteriods in urine
                                                                   10a. Systolic blood pressure, ~4.8 y

                                                                   10b. Systolic blood pressure, ~6.5 y

                                                                   10c. Systolic blood pressure, ~7.0 y


                                                                                                      0.95        1.00           1.05           1.10           1.15
                                                                                                                               Period (years)




                             figure 30B near-transyears around us (rows 1-6) and in living matter (rows 7-10).




                  1.0                     1.1                         1.2                      1.3                       1.4                           1.5                     1.6
             0


                                                                                                                                          Physical variables
             10

                                                                                        MI

             20




             30
Series (N)




             40         43 records of blood
                        pressure and heart
                        rate from 13 subjects

             50




             60



                                                                       Point and 95% confidence interval (CI)
             70



                             figure 30C Far-transyears around us (top 10 rows), incidence of myocardial infarctions in Minnesota and in 43 blood pressure and heart
                             rate records from 13 subjects who each provided longitudinal records covering several years. The trans-year (a ~1.3-year component) in the
                             cosmos (top 10 rows), pathology (myocardial infarction), and physiology (bottom 43 rows)—all differing by non-overlapping 95% CIs from
                             the precise calendar year and many differing among each other, a putative hint of endogenicity. Similar results found for another man
                             providing 3 additional series.




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                 aa
                                                                                    Environment
      Kp
                                                                                                                                                1
                                                                                                                                                2
      WN                                                                                                                                        3
                                                                                                                                                4
                                                                                                               Computed hale                    5
       -Dst                                                                                                    bipolarity cycle
                                                                 Microbiology
                                                                                                                                                6

                                                               Eukaryotic unicell
                                                                                                                                                7

                                                               Human physiology
                                                                                                                                                8
                                                                                                                                                9
                                                                                                                                               10
                                                                                                                                               11
                                                                                                                                               12
                                                                                                                                               13
                                                                                                                                               14
                                                                                                                                               15
                                                                                                                                               16
                                                                                                                                               17
                                                                                                                                               18

                                                              Human pathology
                                                                                                                                               19
                                                                                                                                               20
                                                                                                                                               21

                                                              Anthropometry
                                                           Body weight at birth

                                                                                                                                               22
                                                                                                                                               23
                                                                                                                                               24
                                                                                                                                               25
                                                                                                                                               26
                                                                                                                                               27
                                                                                                                                               28
                                                                                                                                               29
                                                                                                                                               30
                                                                    Body length at birth
                                                                                                                                               31
                                                                                                                                               32
                                                                                                                                               33
                                                                                                                                               34
                                                                                                                                               35
                                                                                                                                               36
                                                                  Head circumference at birth
                                                                                                                                               37
                                                                                                                                               38
                                                               Demography
         Natality                                                                                                                              39

                                                               Motivation                                          Religious activity
              Jehovah’s Witnesses                                                                                                              40

                                                                Criminality                                Homicide
                                                                                                                                               41

                                                                    Wars
                                                                              International battles                                            42

       7               9            11       13          15            17             19              21          23              25    27




figure 31A Paradecadals and paradidecadals, ~10.5- and ~21-year cycles similar in length to the Schwabe and Hale solar activity cycles char-
acterize a host of biological variables, from micro-organisms to human physiology, pathology, anthropometry, and sociology, assessed from
population statistics, yet critically dependent upon also-available individual “pilot studies.” Such self-experimentation is indispensable for a
scrutiny of mechanisms underlying population cycles.




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                                                                        GLOBAL ADVANCES IN HEALTH AND MEDICINE



                                                          Chronomics: ~10.5- and ~21-year cycles in and around us

                                                                                        Period (years)
                                                                               lower        Best         upper      series duration      number       geographic
                                                                               limit*        fit         limit*     Dates       Years    of data         site

environment            1    aa = Antipodal Geomagnetic Index                   10.12        10.63        11.13    1890-1999     110      1 / year
                       2    Kp = Planetary Geomagnetic disturbance             10.32        10.58        10.85    1932-1999      68     1 / month
                       3    WN = Wolf relative sunspot number                  10.37        10.54        10.70    1890-1999     110      1 / year
                       4    -Dst = Equatorial geomagnetic disturbance           8.75        10.85        12.96    1973-1999      27          "
                                                                               10.48        10.51        10.55    1700-1999     300          "
                       5    Bipolarity "Hale Cycle" **                         20.86        21.10        21.26    1890-1999     110          "
                                                                               21.42       21.428        21.43    1700-1999     300          "
Biology                6    Prokaryotes: Air Bacterial Sectoring                9.12        9.45          9.81    1970-1982      13        3744          Italy
                       7    Eukaryotes: Unicellular Algal O2 Production         7.79        9.24         11.87    1980-1991     11          324        Germany
Physiology***          8    Mood (RBS)                                         10.11       11.50         13.41    1966-1998     33       ~5 / day        USA
                       9    Time (1-Minute) Estimation (RBS)                    9.38       10.29         11.37    1966-1998     33           "             "
                      10    Urinary 17-ketosteroid excretion (CH)               8.70        9.30          9.90    1948-1963     15        1 / day      Denmark
                      11    Peak Expiratory Flow (RBS)                         10.36       11.74         13.11    1966-1998     33       ~5 / day        USA
                      12    Respiratory Rate (RBS)                             10.13       12.50         17.32    1966-1998     33           "             "
                      13    Systolic Blood Pressure - SBP (RBS)                 9.05       10.21         11.36    1966-1998     33           "             "
                      14    Standard Deviation of SBP (YW)                      8.85       10.43         12.76    1987-1998     11      ~48 / day       Japan
                      15    Diastolic Blood Pressure - DBP (RBS)               10.09       10.98         11.87    1966-1998     33       ~5 / day        USA
                      16    Standard Deviation of DBP (YW)                     6.18         7.82         10.02    1987-1998     11      ~48 / day       Japan
                      17    Heart Rate - HR (YW)                               9.54        12.93         17.91    1987-1998     11           "             "
                      18    Standard Deviation of HR (YW)                      8.27        11.52         16.22    1987-1998     11           "             "
Pathology             19    Myocardial Infarction                              10.00       10.80         11.70    1960-1996     37       129 205         USA
                      20    Leptospirosis                                      9.40        10.80         12.40    1949-1995     47         2907        Slovakia
                      21    Diabetes                                           7.70        10.40         13.30    1985-1995     11         1369            "
Anthropometry               Body Weight        Boys
at birth              22                         Minnesota                     19.53        23.19        27.67    1963-1998      36     2 136 745        USA
                      23                         Alma-Ata Russians             14.99        17.17        20.07    1946-1998      53        9056       Kazakhstan
                      24                              "       Kazakhs          18.39        21.24        24.05    1946-1998      53        3459           "
                      25                         Moscow                                     10.49                 1874-1985     112        5987         Russia
                                               Girls
                      26                         Minnesota                     20.58        23.46        26.83    1963-1998      36     1 039 464        USA
                      27                         Alma-Ata Russians             15.21        17.75        21.06    1946-1998      53        9105       Kazakhstan
                      28                              "       Kazakhs          15.44        21.45        27.45    1946-1998      53        3448           "
                      29                         Moscow                        9.70         10.29        11.01    1874-1985     112        5840         Russia
                                               Both genders
                      30                         Denmark                       14.71        17.94        22.68    1973-1994      22     1 166 206      Denmark
                           Body Length         Boys
                      31                         Alma-Ata Russians             15.82        18.58        22.38    1946-1998      53        9026       Kazakhstan
                      32                         Moscow                        18.76        20.28        21.86    1874-1985     112        5976         Russia
                                               Girls
                      33                         Alma-Ata Russians             16.13        19.20        23.39    1946-1998      53       9105        Kazakhstan
                      34                              "       Kazakhs          15.72        19.60        25.40    1946-1998      53       3485            "
                      35                         Moscow                        19.05        20.76        22.78    1874-1985     112       5976          Russia
                                               Both genders
                      36                         Denmark                                    23.55        26.55    1973-1994      22     1 166 206      Denmark
                           Head Circumference
                      37                       Boys            Moscow          17.71        19.23        20.75    1874-1985     112       5976          Russia
                      38                       Girls              "            18.42        20.73        23.95    1874-1985     112       5820            "
Demography            39   Birth rate                                           8.63         9.43        10.23    1940-1996     57         57            USA
                                                                               17.61        21.33        25.05    1940-1996
Motivation            41 Religious activity of Jehovah’s Witnesses             17.52        20.44        24.45    1950-1999      50      328 572#     Worldwide
                                                                                                                                        5 653 987##
Criminality           40 Homicide                                               8.99        10.58        12.16    1900-1998      99         99           USA
                                                                               19.23        20.35        21.62
wars                  42 International battles                                 21.87        21.96        22.06    599BC-1957    2556       2556       Worldwide


* 95% confidence limit; not shown if cycle is not statistically significant.
** Computed by changing the sign of WN at each WN minimum.
***RBS - Dr. Robert B. Sothern, CH - Dr. Christian Hamburger, YW - Dr. Yoshihiko Watanabe.
 # in 1950, ## in 1999, pool of 103 plus other unspecified number of sites.


figure 31B Key to Figure 31A.



114            Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                            Review
                                                                   IMPROVING HEALTHCARE OUTCOMES WORLDWIDE



                                                     τ                                                                                        7                       3.5
                                                                                                              1
         Natality:
            USA                                                                                                                   Micturition interval
  Length at birth:                                                                                                                Urine execretion rate
                                                                                                             0.8
             Girls                                                                                                                 Caffeine metab. ratio                      Coh (.05)=.728
  Length at birth:
             Boys




                                                                                                 Coherence
Stroke incidence:                                                                                            0.6
  Czech Republic
Stroke incidence:
      Minnesota                                                                                              0.4
       Homicides:
              USA
   Index of Wars:                                                                                            0.2
     International
                     42    45                   48   51            54         57         60
                                                                                                              0
                Nonlinear Period Estimate (τ) and 95% Confidence Interval (years)                                  0                    0.1             0.2          0.3       0.4             0.5
                                                                                                                                                     Frequency (cycles/day)
                 figure 31C Kondratiev cycle beyond economics in the biosphere.
                 Transdisciplinary mapping of about 5-year spectral components.                               figure 32A Coherence at a period of about 3.5 days is found between the daily
                                                                                                              standard deviation of hourly neutron monitor courses from Dourbes, Belgium,
                                                                                                              and daily values for the inter-micturition interval, urine excretion rate and
                                                                                                              caffeine metabolite ratio of a woman (VLG) during social isolation in a cave.
                                                                                                              The coherence values are 0.90 (P = .001), 0.85 (P = .006) and 0.77 (P = .029) for
                                                                                                              each variable, respectively, calculated by standard approximate χ2. At a period
                                                                                                              of about 7 days, similar agreement is found among the three variables, albeit
                                                                                                              coherence with the environmental variable is not statistically significant.

                                                                                                                                                      edf = 25
                                               1.0       τ = 26.94
                                                                                                    τ = 3.77
                                                              τ = 14.75
                                                                                                                       τ = 3.15
                                               0.8                         τ = 7.68
                                   Coherence




                                               0.6

                                                                                                                                                                 P = .05
                                               0.4



                                               0.2



                                                0
                                                             0.1                0.2              0.3               0.4                                  0.5
                                                                     Frequency (f = 1 in cycles per day; τ = period)
                                                                                    τ
                                                                                                                                                     edf = 50
                                            1.0



                                            0.8

                                                                                                                       τ = 3.17
                                                         τ = 26.95
                                            0.6
                                Coherence




                                                                                                                                          τ = 2.52

                                                                                                                                                                 P = .05
                                            0.4



                                            0.2



                                               0
                                                             0.1                   0.2           0.3                              0.4                  0.5
                                                                     Frequency (f = 1 in cycles per day; τ = period)
                                                                                    τ
           figure 32B Cross-spectral coherence between daily incidence of myocardial infarctions* and the Bz-GSE component of the interplanetary
           magnetic field (1979-1981). Multiple coherence findings depend, of course, upon resolution used.
           *Determined in Moscow (USSR) as reson for ambulance call. Edf = equivalent number of degrees of freedom. Analyses performed after removing mean,
           with 5% cosine taper.




           Review                                                                                                                 www.gahmj.com • Volume 1, Number 2 • May 2012                      115
                                                                                                                  GLOBAL ADVANCES IN HEALTH AND MEDICINE




                                  Sunspot Number                                                                                                                                 Myocardial Infarctions
20                                                                                                                                    20
18                                                                                                                                    18
16                                                                                                                                    16
14                                                                                                                                    14
12                                                                                                                                    12
10                                                                                                                                    10
 8                                                                                                                                     8
 6                                                                                                                                     6
 4                                                                                                                                     4
 2                                                                                                                                     2
 0                                                                                                                                     0
     0         21   43       64         86       107      128                                                 150       171                0           21     43     64            86     107       128   150      171
                                  Frequency (cycles/year)                                                                                                                       Frequency (cycles/year)



                                                                                                           Significant Phase Synchronization: MI/SN


                                                                   20

                                                                   40
                                       Frequency (cycles/year)




                                                                   60

                                                                   80

                                                                   100

                                                                   120

                                                                   140

                                                                   160

                                                                   180
                                                                                                  50        100         150         200        250          300     350
                                                                                                                              Time (days)


                    figure 32C Cross-spectral coherences are time-varying. Commentary to the example phase synchronization between the sunspot number
                    and myocardial infarction:
                    • Phase synchronization does not depend on the amplitudes of rhythms. It appeals also for rhythms with low amplitudes.
                    • Phase synchronization signals a strong phase coupling between different oscillators. Thus, it is an indicator for a common time regime of
                    different processes.
                                                                             Wolf Numbers




                                                                                               400
                                                                                               300
                                                                                               200
                                                                                               100
                                                                                                 0
                                                                                                1/1/1968   1972      1976     1980      1984      1988      1992   12/13/1996
                                                                                                                                 Wavelet Analysis
                                                                                         0.006
                                                                                               0.01
                                                                                                                                                                           256
                                                                                   7 days                                                                                  128
                                                                                                                                                                           64
                                                                                               0.04                                                                        32
                                                                                                                                                                           16
                                                                              Period (Years)




                                                                                               0.09                                                                        8
                                                                                                                                                                           4
                                                                                               0.18                                                                        2
                                                                                                                                                                           1
                                                                                               0.35                                                                        1/2
                                                                                                                                                                           1/4
                                                                                               0.70                                                                        1/8
                                                                                                  1                                                                        1/16
                                                                                               1.40                                                                        1/32
                                                                                                                                                                           1/64
                                                                                               2.81                                                                        1/128
                                                                                                                                                                           1/256
                                                                                               5.61
                                                                                         11.22
                                                                                           1/1/1968        1972      1976     1980      1984      1988      1992   12/31/1996
                                                                                                                               Time (Calendar years)
                                                                          MI Detrented




                                                                                                40
                                                                                                20
                    figure 32D (Above and opposite) Cross-wavelet coherence with Wolf numbers (Wn, gauging solar activity, above) differs between the
                                                           0
                    incidence of myocardial infarctions (MI) in Minnesota (next page, left column) and the incidence of international terrorist acts (TA, from the
                                                         -20
                                                           1/1/1968 right
                    total Global Terrorism Database, next page, 1972 column). Whereas a low-frequency component is visible in the wavelet spectra of all
                                                                           1976   1980    1984    1988     1992     12/31/1996
                    3 variables (left) and in the cross-wavelets of MI and TA with Wn (middle), only MI (but not TA) shows coherence in this region.
                                                                                                                               Period (Years)               Wolf Numbers - MI Detrended
                                                                                                                               Wavelet Analysis
                                                                   0.07                  0.006                                                                                  0.006
                                                                                                                                                                            32   0.01
                                                                   0.13                        0.01
                                                                                                                                                                            16 7 days
                                                                   0.23           7 days
                                                                                                                                                                            8    0.04
                                                                   0.53                        0.04
                                                     od (Months)




                                                                                                                                                                            4
                                                                           od (Years)




         116                              1.05      0.09
                    Volume 1, Number 2 • May 2012 • www.gahmj.com                                                                                                                0.09                     Review
                                                                                                                                                                            2
                                                                   2.10                        0.18                                                                              0.18
                                                                                                                                                                            1
                                                                   4.21                        0.35                                                                              0.35
                                                                                  7 days                                                                            32
                                                                                                                                                                    16    1.05 128 0.09                                                                                                            0.09




                                                                                                                                                                     Period (Mon




                                                                                                                                                                                                Period (Year
                                                                                                                                                                               64




                                               Period (Years)
                                                                0.09                         0.04                                                                   8                                                                                                                      2
                                                                                                                                                                    4     2.10 32 0.18                                                                                                             0.18
                                                                                                                                                                               16                                                                                                          1
                                                                0.18                                                                                                2




                                                                            Period (Years)
                                                                                             0.09                                                                   1     4.21 8     0.35                                                                                                          0.35
                                                                0.35                                                                  IMPROVING HEALTHCARE         OUTCOMES 4
                                                                                                                                                                    1/2        WORLDWIDE                                                                                                   1/2
                                                                                             0.18                                                                   1/4 8.42   2     0.70                                                                                                          0.70
                                                                                                                                                                    1/8        1        1                                                                                                  1/4
                                                                0.70                                                                                                                                                                                                                                  1
                                                                                             0.35                                                                   1/16 16.83 1/2 1.40                                                                                                            1.40
                                                                   1                                                                                                           1/4                                                                                                         1/8
                                                                1.40                                                                                                1/32       1/8 2.81
                                                                                             0.70                                                                   1/64 33.67                                                                                                                     2.81
                                                                                                1                                                                   1/128      1/16                                                                                                        1/16
                                                                2.81                         1.40                                                                              1/32
                                                                                                                       MI                                           1/25667.33 1/64 5.61                                                            tA                                     1/32    5.61
                                                                5.61                         2.81                                                                              1/128
                                                                                                                                                                                    11.22
                                                                                                                                                                        123.92 1/256                                                                                                              11.22
                                                             11.22                        5.61                                                                                                                  1/1/1968 1972        1976    1980        1984    1988       1992   12/31/1996       1/1/1968
                                                               1/1/1968                   1972      1976        1980        1984       1988     1992       12/31/1996                                                                       Time (Calendar years)
                                                                                         11.22
                                                                                           1/1/1968 1972        Time (Calendar years)1984
                                                                                                                   1976    1980                   1988      1992                      12/31/1996
                                                                                                                                                                                                                80
                                         MI Detrented




                                                                 40
                                                                                                                              Time (Calendar years)                                                             60
                                                                 20
                                                                       MI Detrented


                                                                                              40                                                                                                                40
                                                                  0                           20                                                                                                                20
                                                                -20                            0                                                                                                                 0
                                                                  1/1/1968                   1972      1976     1980        1984       1988     1992       12/31/1996                                        1982 1986 1990 1994 1998 2002 2006 12/13/2010 Cross-wavele
                                                                                                                                                                                                                1/1/1970 1974 1978
                                                                                             -20
                                                                                                                                                                       Period (Years)                   Wolf Numbers - MI Detrended
                                                                                                                                                                                                                        Wavelet Analysis                  Period (Years)
                                                                                               1/1/1968 1972      1976    1980
                                                                                                                 Wavelet Analysis       1984      1988      1992       12/31/1996                                                                                                      C
            0.07                                        0.006                                                                                                             0.006
                                                                                                                                                                         0.07        0.006                                                                  0.006          0.006
                                                                                                                                                                                    Period (Years)                 Wolf Numbers - MI Detrended                          Period (Years)
2      12/13/1996                                                                                                             Wavelet Analysis                      32 0.130.01       0.01                                                                    0.01 256 0.006
            0.13                                      0.01
                                                      0.07      0.006                                                                                                                  0.006                                                                                 0.01
                                                                                                                                                                    16 7 days 32 7 days                                                               64 7 days 128
            0.23                                    7 days                                                                                                               0.23           0.01                                                                                days
                                                                                                                                                                                                                                                                      64 7 0.01
    1988      1992                                   12/13/1996 0.01
                                                      0.13
                                                                                                                                                                    8
                                                                                                                                                                                                                                                      32
                                                                                                                                                                                                                                                              0.04 6432 7 days
            0.53                                      0.04                                                                                                                            0.04
                                                                                                                                                                         0.53 16 7 days
                                                                                                                                                                           0.04                                                                       16              16     0.04
                                                      0.23     7 days




                                                                                                                                                                    Period (Months)
          Period (Months)




ysis                                                                                                                                                                4                                                                                 8             32
                                                                                                                                                                         1.05 8 0.09                                                                          0.09 168




                                                                                                                                                                                               Period (Years)
            1.05256                                                                                                                                                                                                                                                          0.09
                                                                                                                                                                                                                                                                            0.04
                                            Period (Years)




                128                                   0.09
                                                      0.53       0.04                                                                                                      0.09         0.04                                                          4               4
                                        Period (Months)




                                                                                                                                                                    2    2.10 4 0.18
                            2.1032
                                  64                            0.18                                                                                                       0.18                                                                       2       0.18 8 2       0.18
                                                                                                                                                                                                                                                                            0.09
                                                                        Period (Years)




                                                                1.05                         0.09                                                                                       0.09                                                                        41
                                  16                         256                                                                                                    1    4.21 2 0.35                                                                  1                      0.35
                            4.218                               0.35
                                                             128 0.18                                                                                                      0.35         0.18                                                                  0.35 2 1/2 0.18
                                                             64
                                                                2.10                                                                                                1/2 8.42 1 0.70                                                                   1/2
                          4
                      8.422                         0.70     32 0.35                                                                                                       0.70         0.35
                                                                                                                                                                                          1                                                           1/4     0.70 1 1/4 0.35 1
                                                                                                                                                                                                                                                                             0.70
                                                    4.211    16                                                                                                     1/4 16.83 1 1/2 1.40                                                              1/8
                                                                                                                                                                                                                                                                      1/8
                                                                                                                                                                                                                                                                  1 1/2
                          1
                                                    1.40     8 0.70                                                                                                        1.40                                                                               1.40 1/41/16 1.40
                     16.831/2                       8.42                                                                                                            1/8 33.67 1/4 2.81  0.70                                                          1/16            1/32 0.70
                          1/4                                4      1                                                                                                                                                                                                        2.81
                     33.671/8                       2.81     2 1.40                                                                                                        2.81              1                                                        1/32 2.81 1/8   1/64
                                                                                                                                                                                                                                                                                 1
                          1/16                     16.83     1                                                                                                      1/1667.33 1/8 5.61  1.40
                                                                                                                                                                                                                                                      1/64          1/16 1.40
                                                                                                                                                                                                                                                                      1/128 5.61
                     67.331/32                      5.61     1/2 2.81                                                                                                      5.61         2.81                                                                  5.61 1/32 2.81
                                                                                                                                                                                                                                                                      1/256
                          1/64                     33.67     1/4                                                                                                    1/32         1/16 10                                                                                       10
                    123.921/128                    11.22     1/8 5.61                                                                                                  175.24
                                                                                                                                                                          11.22      14.60                                                                  11.22 1/64 14.605.61
                          1/256                    67.33     1/16
                                                       1/1/1968 1972
                                                             1/32          1976                                 1980        1984       1988      1992      12/31/1996            1/32 5.61
                                                                                                                                                                            1/1/1968 1972         1976   1980     1984     1988     1992   12/31/1996          1/1/1968      1972
                                                  123.92        11.22
                                                             1/64                                                                                                                       1/1/1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010 11.22
                                                                                                                                                                                       11.22                                                                                  1/1/1970
                                                             1/128 1/1/1968 1972                               Time (Calendar years) 1984
                                                                                                                  1976      1980                  1988       1992       12/31/1996       1/1/1968 1972     Time (Calendar years)
                                                                                                                                                                                                            1976     1980 (Calendar years)
                                                                                                                                                                                                                      Time    1984    1988    1992      12/31/1996            1/1/1968
                                                             1/256
2       12/31/1996        80                                      Time (Calendar years)                                                                          Time (Calendar years)
                          60
                                       80
  1988       1992         40
                       12/31/1996      60
                          20
ears)                                  40
                           0
                                       20
                          1/1/1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010
                                        0
                                                                                                                                                Terrorist Acts - Wolf Numbers                                  Crosswavelet Coh
                                                            1982 Analysis
                                       1/1/1970 1974 1978 Wavelet1986 1990 1994 1998 2002 2006 12/13/2010
2     12/31/1996
           0.07       0.006                                                                                    0.006 Cross-wavelet Coherence Between Myocardial Infractions in Minnesota                0.006
                                                                                                                                                             Terrorist Acts - Wolf Numbers                                   Crossw
                                                                       Wavelet Analysis                 Period (Years)                       (Detrended) and Wolf Numbers
           0.13 Period (Years) 0.006
                       0.01
                        0.07
                                                    Wolf Numbers - MI Detrended                           256
                                                                                                                0.01         0.006
                                                                                                                                                                                                   256 0.01
                                                                                                                                                                                                                      0.006
  1988       1992 0.00612/31/1996                                                                          0.006
                                                                                                          128                                                                                      128
           0.2332    7 days                                                                               64 7 days 256                                                                                 Minnesota
                                                                                                                                          Cross-wavelet Coherence Between Myocardial Infractions in 7 days 256 0.01
                                                                                                                                                                                                   64
                        0.13         0.01                                                                                      0.01
                     0.01           Period (Years)                 Wolf Numbers - MI Detrended            320.01        128Period (Years)                      (Detrended) and Wolf Numbers        32
                                                                                                                                                                                                          0.04 128 7 days
s          0.53        0.04
                        0.23      7 days                                                            64 7 days0.04 64 7 0.006                                                                       16
               16 7 days                                                                                  16                  days                                                                               64
         Period (Months)




                                       0.006
           1.05        0.09                                                                         32 8        0.09 32                                                                            8      0.09 32
                                           Period (Years)




               8        0.53     32 0.040.01                                                                                   0.04
                                                                                                                               0.01                                                                                     0.04
                                                                                                    16 4 0.04           16                                                                         4             16
                                       Period (Months)




           2.10      0.04
                       0.18                                                                                                                                                                               0.18 8
                        1.05     16 0.09                                                                  2     0.18 64 7 0.09
                                                                                                                        8      days                                                                2                    0.09
                                                                       Period (Years)




               4                      7 days                                                        8
                     0.09
                       0.35                                                                               1 0.09        4
                                                                                                                       32                                                                          1      0.35 4
           4.21         2.10     8 0.18                                                             4           0.35 2         0.18                                                                                     0.18
               2                                                                                          1/2                  0.04                                                                1/2           2
           8.42      0.18
                       0.70
                                        0.04                                                        2       0.180.70 16
                                                                                                          1/4                                                                                      1/4    0.70 1
               1        4.211    4 0.35                                                             1                  81      0.35
                                                                                                                               0.09                                                                1/8       1 1/2      0.35
                                        0.09                                                              1/8
                                                                                                            0.35     1 1/2
          16.83
               1/2
                     0.35
                       1.40
                        8.42     2 0.70                                                             1/2 1/16 1.40 41/4 0.70                                                                        1/16 1.40 1/4        0.70
          33.67      0.70
                       2.81             0.18
                                         1                                                          1/4 1/32 2.81 21/8
                                                                                                            0.70               0.181                                                               1/32 2.81 1/8           1
               1/4    16.83
                          1      1 1.40                                                             1/8   1/64 1       11/16 1.40                                                                  1/64          1/16 1.40
          67.33        5.61
                     1.40               0.35                                                                1.40               0.35                                                                1/128 5.61 1/32 2.81
               1/8    33.67      1/2 2.81                                                           1/16 1/128 5.61 1/2 1/32 2.81
                                                                                                                                                                                                   1/256
                     2.8110             0.70                                                        1/32 1/256 10 1/4
                                                                                                            2.81
                                                                                                                        1/64 0.70                                                                           10 1/64 5.61
                      67.33
         175.241/16 14.60        1/4 5.61 1                                                                             1/128 5.611                                                                              1/128
                                                                                                    1/64       14.60 1/8                                                                                 14.60 1/256
                     5.61
               1/32 175.24       1/8 10
                                        1.40                                                                5.61       1/16 1.40
                                                                                                                        1/256
                                                                                                                                 10                                                                                       10
                                   14.60 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010
                         1/1/1970 19742.81                                                                        1/1/1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010
                                                                                                                       1/32 14.60
                                                                                                                               2.81                                                                         1/1/1970 1974 1978
                                                                                                                                                                                                                       14.60
                    11.22        1/16                                                                      11.22
2     12/31/1996                                              (Calendar years) 1994 1998 2002 2006 1/1/19681/64
                                      1/1/1970 1974 1978Time 198419861988                                     12/13/2010 19721/1/1970 1974 1978 Time (Calendar years) 1994 1998 12/31/1996 12/13/2010
                      1/1/1968 1972 5.61 1976        1980 1982           1990 1992       12/31/1996                            5.61 1976        1980 19821984         1988
                                                                                                                                                              1986 1990          1992      2002 2006                      1/1/1970
                                 1/32
                                       11.22                        Time (Calendar years)
                                                       Time (Calendar years)                                                  11.22                               Time (Calendar years)
                                                                                                                                                  Time (Calendar years)
  1988       1992      12/31/1996        1/1/1968 1972     1976     1980      1984     1988      1992      12/31/1996            1/1/1968   1972       1976       1980        1984     1988     1992       12/31/1996
ars)                                                                                                                               Time (Calendar years)                                                                                            Time (Calendar years)




    2006 12/13/2010
                                                        Terrorist Acts - Wolf Numbers                                  Crosswavelet Coherence Between Total Terrorist Acts and Wolf Numbers
4 1998                     2002
                   2006 12/13/2010
                        0.006                                                                                   0.006
                                   Cross-wavelet Coherence Between Myocardial Infractions in Minnesota
                  256
                  Period (Years)                                                                           256 0.01                      Crosswavelet Coherence Between Total Terrorist Acts and Wolf Numbers
ysis              128
                         0.01                           (Detrended) andTerrorist Acts - Wolf Numbers
                                                                          Wolf Numbers                     128
                  64 0.006
                       7 days             0.006                                                            64 7 days              0.006
                  32 0.01            256                                                                   32                256 0.01
                         0.04              0.01                                                            16
                                                                                                                  0.04
                  16                 128                                                                                     128
               64 8 7 days           64 7 days                                                             8      0.09       64 7 days
               32 4      0.09
                                     32                                                                    4                 32
               16 2    0.04
                         0.18              0.04                                                            2      0.18       16
                                                                                                                                    0.04
                                     16
               8 1 0.09              8     0.09                                                            1      0.35       8      0.09
                         0.35                                                                              1/2
               4 1/2                 4                                                                                       4
                                           0.18                                                            1/4    0.70              0.18
               2 1/4 0.180.70        2
                                                                                                                     1
                                                                                                                             2
                                                                                                           1/8
               1 1/8 1.40     1      1
                                           0.35                                                            1/16 1.40
                                                                                                                             1      0.35
                       0.35
               1/21/16
                  1/32 2.81
                                     1/2
                                     1/4                                                                   1/32 2.81
                                                                                                                             1/2
                                                                                                                             1/4    0.70
               1/41/64 0.70                0.70
                                     1/8        1                                                          1/64              1/8       1
               1/81/128 5.61
                       1.40
                            1        1/16 1.40                                                             1/128 5.61        1/16 1.40
               1/16
                  1/256              1/32 2.81                                                             1/256    10       1/32 2.81
               1/32 2.81   10        1/64                                                                                    1/64
               1/64     14.60        1/128 5.61                                                                  14.60       1/128 5.61
 2006 12/13/2010       5.61          1/256 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010
                           1/1/1970 1974                                                                                     1/256
                                                                                                                    1/1/1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010
                                                                                                                                      10
                                             10
                      11.22               14.60             Time (Calendar years)                                                  14.60           Time (Calendar years)
    12/31/1996           1/1/1968     1972        1976     1980       1984      1988     1992      12/31/1996
4 1998 2002 2006 12/13/2010                  1/1/1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010                         1/1/1970 1974 1978 1982 1986 1990 1994 1998 2002 2006 12/13/2010
years)                                                       Time (Calendar years)(Calendar years)
                                                                              Time                                                                                 Time (Calendar years)




                                            Crosswavelet Coherence Between Total Terrorist Acts and Wolf Numbers
                                      0.006
                                  256 0.01
                                  128
                                  64 7 days
                                  32
                                      Review                                                                                                                                                                        www.gahmj.com • Volume 1, Number 2 • May 2012                       117
                                  16
                                       0.04
                                  8    0.09
                                                                   GLOBAL ADVANCES IN HEALTH AND MEDICINE



                1000
                                                   Congruence with Antipodal Geomagnetic Disturbance Index aa




                            100
      Odds Ratio (95% CI)




                              10




                               1




                              0.1




                                                                                                                    +.05 < P < .10 *.01 < P < .05 **P < .01
                    0.01
                                    DBP    Temp            HR             SBP           Vigor         Mood            1MTE
                                                            Biological Variables Congruent with aa

                1000


                                                                 Congruence with Solar Wind Speed (SWS)


                            100
        Odds Ratio (95% CI)




                              10




                               1




                              0.1




                                                                                                                    +.05 < P < .10 *.01 < P < .05 **P < .01

                     0.01
                                    DBP    Temp            HR             SBP           Vigor         Mood           1MTE

                                                                Biological Variables Congruent with aa


                 figure 33 Anticipated influence of the antipodal index of geomagnetic disturbance “aa” (top) and of the non-photic environment (gauged
                 by solar wind speed, an approximation of interplanetary magnetism) on human psychophysiology was assessed by means of the congruence
                 of periods of their spectral components (defined by overlap of the 95% confidence intervals of the periods, Δs, in the frequency range of
                 one cycle in 2.5 years to 3 cycles per year). The biological data stem from 40 years of self-measurements of oral temperature (Temp), systolic
                 blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) and of ratings of mood and vigor and the estimation of 1-minute by
                 counting (1MTE), performed about 5 times a day by a clinically healthy man, Dr Robert B. Sothern. Congruences (assessed by means of odds
                 ratios based on the noncentral hypergeometric distribution) found for 1MTE and for several other variables more than equal that of the
                 known association of helio- and geo-magnetism (bottom, last column on right). Mental functions (full red) show higher congruence than
                 somatic functions (green). Among the latter, SBP is responsive, perhaps constituting a seemingly acceptable proxy for the mental functions.
                 P values are based on the non-central Fisher hypergeometric distribution, with 95% confidence intervals computed using Fisher’s exact test,
                 used since the null hypothesis was rejected in some but not all cases.



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                                          A      B        C            D                 E             F           G

                            2.0                                                                                                             SWS


                            1.3


                            1.0




                            0.7
                                                                                               Delay

                                                                                                           E’



                            2.0                                                                                                             SBP


                            1.3


                            1.0




                            0.7
           Period (years)




                            2.0                                                                                                             DBP


                            1.3


                            1.0




                            0.7




                                                                                                                                            HR
                            2.0


                            1.3

                            1.0




                            0.7
                                   1994                   1996                               1998                          2000
                            1989                                  Time (Calendar date)                                                     2005




figure 34 The transyear can prominently characterize solar wind speed, as shown in the top gliding spectral window by the wide dark
band around 1.3 years (vertical scale are frequencies in the range of 1 cycle in 2 to 0.7 y). This component, however, is Aeolian in nature, its
characteristics (frequency and amplitude) changing as a function of time. This is exemplified around 1998 (E) when its amplitude is consider-
ably decreased (the darker the band, the larger the amplitude). After E, the transyear is no longer detected in solar wind speed. A transyear
is also found to characterize systolic blood pressure (SBP) of a man (FH) who monitored himself around the clock for more than 23 years
(with interruptions), as seen in the gliding spectral window (row 2). With a lag (at E’), the transyear in FH’s SBP is dampened but remains
detectable, suggesting that the frequencies characterizing the solar wind may still drive us and may be built into us since they persist in the
absence of a counterpart in the Sun. Somewhat similar results are suspected by some viewers for diastolic blood pressure (DBP, row 3) and
heart rate (HR, row 4), but they are most clearly apparent only for SBP.




Review                                                                                         www.gahmj.com • Volume 1, Number 2 • May 2012       119
                                                        GLOBAL ADVANCES IN HEALTH AND MEDICINE




                     Subject ID (gender, age)
                                                                               Reduction in HR CSD*




                             RS (M, 28y)                                                                                            P = .017




                             HL (M, 59y)




                             EK (F, 43y)




                             EH (M, 48y)




                             MH (F, 81y)




                               Mean ± SE
                                P < .05




                                                               -50                            -25                             0
                                                                                        Change in CSD
                                                                                       HR-A Ratio (%)**
                                   CSD in presence of
                                   Solar Circaseptan




      figure 35 A ~7-day spectral component in the heart rate of 5 men is less prominent when the solar wind loses its counterpart of correspond-
      ing length. Implied, but not shown, is the persistence in the biosphere of a ~7-day component that can be amplified (driven) by a reciprocal
      component in solar activity.
      7-day/1-day amplitude (A) ratio (CSD**):
      1. Is dampened in the absence of a solar counterpart (blue, still driven after subtraction of solar wind) yet (not shown)
      2. It persists (since it is genetically anchored).
      *CSD: circaseptan (7-day)-to-circadian (1-day) A ratio
      **When 7-day component in sunspot area has no 7-day componenet (as analyzed by YS Vernova et al, Geomagnetism and aeronomy. 1983;23:425-7).




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                                                                                              Solar activity doing the “removal” (middle) and the “replacement” (bottom)




                                          “Remove”                                                                    Mortality from Myocardial Infarction
                                                                                             1.0
                          160                                                                                                     1980-1982

                          140
                                                                                                                7 days

                          120                                                                0.5

                          100
     Wolf Number




                              80
                                                                                              0
                              60


                              40
                                                                                             1.0
                                                                                                                                  1984-1987
                              20                                                                                                                             “Remove”
                                                                     Amplitude (event/day)




                               0

                                                    “Replace”                                0.5
                              1.0

                              0.9

                              0.8
                                                                                              0
                              0.7
     Amplitude (events/day)




                              0.6
                                                                                             1.0
                                                                                                                                  1989-1992
                              0.5                                                                                                                            “Replace”

                              0.4
                                                                                                                7 days
                              0.3
                                                                                             0.5
                              0.2

                              0.1

                               0
                                       81 83 85 87 89 91                                       0
                                    1980 82 84 86 88 90 92
                                                                                                                                  Period (days)


                                          Time (years)



                                                                                               Mortality from Myocardial Infarction




figure 36 About-weekly (circaseptan) resonance of human mortality from myocardial infarction with solar circaseptans demonstrated by
“remove and replace” approach.* This approach focuses on a weekly component by investigators from the Republic of Georgia who built a
clinical facility to study effects of geomagnetism.
*Results from Republic of Georgia (Tbilisi; geographic coordinates: 41.43° n, 44.48° E; geomagnetic coordinates: 36.02° n, 123.12° E). Khomeriki O,
Paatashvili T, Gheonjian L, Kapanadze n. The influence of 7-day variations of interplanetary magnetic field on the frequency of myocardial infarctions. Bull
Georgian Acad Sci. 1998;158(1):123-6. For a similar effect on human heart rate, see Biologia. 1996;51:749-56.




Review                                                                                                                      www.gahmj.com • Volume 1, Number 2 • May 2012   121
                                                               GLOBAL ADVANCES IN HEALTH AND MEDICINE




      ADDenDuM
      Germaine Cornélissen, PhD


           The Spiegel Online (http://www.spiegel.de/inter-                           loads (ie, strain) and is informed as to their associa-
      national/) by Philip Bethge on May 5, 2012, was titled                          tions that can provide clues for stress relief; one also
      “A Future of Self-Surveillance? Tech Pioneers Track                             detects changes in the risk of severe disease and dis-
      Bodily Functions Day and Night.” Accordingly, the                               ease-related events, such as stroke (within 6 years,
      authors of the foregoing article (Halberg et al) trust                          from <5% to near 100%, in one cited study); those
      that those concerned with self-tracking will include                            treated for high blood pressure will not fly blind to
      the self-surveillance of blood pressure and heart rate,                         risks induced by the medication (Figure A) that can-
      analyzed chronobiologically in repeated passes over                             not be detected by office visits. As a dividend, one
      the accumulating data at systematically selected                                even learns about the effects of space weather on
      times during their entire lifespans. In this endeavor,                          human mental functions (Figure B) that may lead to
      they can focus on vascular variability disorders as a                           a better understanding and countermeasures against
      first step. Thereby, one immediately gauges undue                               sudden cardiac death, suicide, crime, terrorism, war,



                                 30                                     HARM
                                                                                              1-way ANOVA: F = 6.555; P < .001
                                                                   CHAT exacerbated           Cosinor: PR = 39%; P < .001

                                 25
                                                                                                             No treatment:
                                                                                                            CHAT diagnosed
                                 20
                  SBP-A (mmHg)




                                                                                                          Treatment effect
                                 15
                                               Upper limit of acceptability
                                               for SBP-A based on clinically
                                 10             healthy peers matched by
                                                     gender and age                     CHAT eliminated

                                  5                                                                       BENEFIT

                                                                        DO NO HARM                         TREAT
                                  0
                                                              AW          +3h         +6h        +9h         +12h       +15h




                                 20
                                       Upper limit of acceptability       Iatrogenic CHAT
                                      for DBP-A based on clinically
                                        healthy peers matched by
                                             gender and age                                     1-way ANOVA: F = 4.406; P = .003
                                 16
                                                                                                Cosinor: PR = 32%; P < .001

                                                                                                                    No treatment
                  DBP-A (mmHg)




                                 12

                                                                                                          Treatment effect

                                  8



                                  4                                                               CHAT eliminated


                                                                        DO NO HARM                         TREAT
                                  0
                                                              AW          +3h         +6h      +9h           +12h       +15h
                                                                        Time (hours from awakening)


       figure A “First do no harm” to some of the many millions of treated hypertensives whose VVAs are currently undetected.




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                                              1000
                                                                 SWS: Solar Wind Speed
                                                                 aa: antipodal geomagnetic disturbance index
           Odds Ratio (OR) [95% Confidence Interval, CI]                                                                                                     **


                                                                                                                               **
                                                           100           Point estimate of Mood-SWS association is above
                                                                                   95% CI of aa-SWS association

                                                                            *                              *


                                                           10
                                                                                         CI
                                                                           OR




                                                            1                                                                                                P = .05

                                                                      REFERENCE                          PROXY                              MOOD self-rated ~6/day
                                                                     Purely Physical              for Mental Functions                for 43.5 years (data of RB Southern)
                                                                       Standard                     Including Mood


                                                                                                                                                    *.01 < P < .05 **P < .01
                                                           0.1
                                                                       aa vs. SWS                     SBP vs. SWS          Mood vs. SWS                  Mood vs. aa




figure B The influence of space weather on the human mind more than matches the well-known association of interplanetary and
earth magnetism. Moreover, systolic blood pressure can be automatically monitored during sleep as well as waking as a proxy for
mental functions.

Mood (red) is more congruent (similar in terms of its frequency structure) to magnetism of space (SWS) and earth (aa) than SWS and aa are to each other
(blue). Systolic blood pressure (SBP, green) may serve as proxy for mental functions.



and possibly natural disasters such as earthquakes.
Those advised to reduce sodium intake could check
whether salt lowers or increases the blood pressure
mean or leaves it unaltered. Those diagnosed with
cancer could collect saliva to survey their cancer
markers, chronobiologically analyzed, for cycles and
thus guide treatment by the characteristics of a host
of rhythms, etc.




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