100 or 30 years after Janeway or Bartter, Healthwatch helps avoid 'flying blind'.

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

Hurdles to asepsis, universal literacy, and chronobiology-all to be overcome.

A joining of chronobiology and endocrinology was achieved in 1974 at a symposium focusing on the critical role of the hypothalamic-pituitary-adrenal network on the basic side and on the first drug to carry timing in its name. The next step is a section on chronobiology in this neuroendocrinology journal. An account of the problems encountered before both asepsis and universal literacy became the law of the profession and of the land serves here as background to endeavors in behalf of chronobiologic literacy. A step toward the latter goal is the use of systematically collected measurements of heart rate and blood pressure evaluated by computer against reference standards from peers of corresponding age, gender and ethnicity. Thereby, an illustrative, clinically relevant aspect of everyday physiology is resolved within the otherwise neglected normal range, and disease risk syndromes are detected so that preventive treatment can be instituted before catastrophic disease occurs. The scope of this chronobiology section of the Neuroendocrinology Letters is to map the time-qualified feedsideward interactions within the neuroendocrines, in the rest of an organism and in the environment. Thereby, we replace time-unqualified feedbacks and feedforwards, along imaginary axes, by neuroendocrine and cellular networks operating predictably insofar as rhythmically within the range of everyday physiology. Subtle effects are thus found that are otherwise covered by the curtain of ignorance drawn over the normal range. More important, feedsidewards account for opposite effects that recur rhythmically, and thus help clarify mechanisms that may underlie the difference between stimulating or inhibiting a malignancy and thus shortening or lengthening the lifespan.

Engineering and governmental challenge: 7-day/24-hour chronobiologic blood pressure and heart rate screening: Part I.

This review provides evidence that the bioengineering community needs to develop cost-effective, fully unobtrusive, truly ambulatory instrumentation for the surveillance of blood pressure and heart rate. With available instrumentation, we document a disease risk syndrome, circadian blood pressure overswinging (CHAT, short for circadian hyper-amplitude-tension). Circadian hyper-amplitude-tension is defined as a week-long overall increase in the circadian amplitude or otherwise-measured circadian variability of blood pressure above a mapped threshold, corresponding to the upper 95% prediction limit of clinically healthy peers of the corresponding gender and age. A consistently reduced heart rate variability, gauged by a circadian standard deviation below the lower 5% prediction limit of peers of the corresponding gender and age, is an index of a separate yet additive major risk, a deficient heart rate variability (DHRV). The circadian amplitude, a measure of the extent of reproducible variability within a day, is obtained by linear curve-fitting, which yields added parameters: a midline-estimating statistic of rhythm, the MESOR (a time structure or chronome-adjusted mean), the circadian acrophase, a measure of timing of overall high values recurring in each cycle, and the amplitudes and acrophases of the 12-hour (and higher order) harmonic(s) of the circadian variation that, with the characteristics of the fundamental 24-hour component, describe the circadian waveform. The MESOR is a more precise and more accurate estimate of location than the arithmetic mean. The major risks associated with CHAT and/or DHRV have been documented by measurements of blood pressure and heart rate at 1-hour or shorter intervals for 48 hours on populations of several hundred people, but these risks are to be assessed in a 7-day/24-hour record in individuals before a physical examination, for the following reasons. (1) The average derived from an around-the-clock series of blood pressure measurements, computed as its MESOR, the proven etiopathogenetic factor of catastrophic vascular disease, can be above chronobiologic as well as World Health Organization limits for 5 days or longer and can be satisfactory for months thereafter, as validated by continued automatic monitoring. The MESOR can be interpreted in light of clock-hour-, gender-, and age-specified reference limits and thus can be more reliably estimated with a systematic account of major sources of variability than by casual time-unspecified spot checks (that conventionally are interpreted by a fixed and, thus, rhythm, gender-, and age-ignoring limit). With spot checks, in a diagnostically critical range of "borderline" blood pressures, an inference can depend on the clock-hour of the measurement, usually providing a diagnosis of normotension in the morning and of hypertension in the afternoon (for the same diurnally active, nocturnally resting patient!). Long-term treatment must not be based upon the possibility of an afternoon vs a morning appointment. Moreover, the conventional approach will necessarily miss cases of CHAT that are not accompanied by MESOR hypertension. (2) Circadian hyper-amplitude-tension indicates a greater risk for stroke than does an increase in the around-the-clock average blood pressure (above 130/80 mm Hg) or old age, whereas (3) CHAT can be asymptomatic, as can MESOR hyptertension. (4) Deficient heart rate variability, the fall below a threshold of the circadian standard deviation of heart rate, an entity in its own right, is also a chronome alteration of heart rate variability (CAHRV). Deficient heart rate variability can be present together with CHAT, doubling the relative risk of morbid events. In each case--either combined with CHAT or as an isolated CAHRV--a DHRV constitutes an independent diagnostic assessment provided as a dividend by current blood pressure monitors that should be kept in future instrumentation designs. CHAT and DHRV can be screened by systematic focus on variability, preferably by the use of automatic instrumentation and analyses, which are both available (affordably) for research in actual practice, in conjunction with the Halberg Chronobiology Center at the University of Minnesota.