Impeachment & Recommendations

Abstract prepared by invitation for the meeting in Ferrara, Italy, of the New York Academy of Sciences, September 10-12, 1995, amplified by reference to a table and figures in this resolution, prepared with Patrick Delmore, Director of Communications, Medtronic Inc., Minneapolis, Minnesota (phone 612-574-3725; fax 612-574-4563), to whom requests for reprints may be addressed

The about 40% error in diagnosis associated with the current approach to BP likely stems 1) from reliance on one or a few readings taken in the physician's office when the within-hour standard deviation of BP is of the order of 7 mm Hg [1] and the within-day change exceeds 50 mm Hg (Figures 1 and 2) and 2) from the interpretation of BP records in the light of fixed limits such as 140/90 mm Hg (systolic, S/diastolic, D BP) when built-in circadian and infradian rhythms of large amplitude (A) have been documented (7). Fixed thresholds (best replaced by chronodesms) can render the office BP measurement equivalent to flipping a coin (Table 1 and Figure 14). Estimating parametric (Figure 1) (MESOR, A and acrophase of major anticipated rhythmic components and of their harmonics) and non-parametric (percent time elevation, hyperbaric index and timing of excess) endpoints, even for MESOR-normotensive patients, is desired in view of the association of an enlarged circadian BP-A with 1) familial antecedents of high BP and related vascular complications [2]; 2) morphologic changes in the heart revealed by echocardiography in adulthood [3] and also after the in utero exposure to betamimetics, observed in neonates [2] and in adolescence [4]; and 3) actual adverse outcomes (Figures 9-11). A chronobiologic approach based on manual if not on automatic self-measurements is useful since certain behavioral interventions as well as certain antihypertensive agents, when given at the appropriate time, can lower the circadian (and circaseptan) BP-A [5]. Its practicality lies in the availability of statistical methods, notably control charts based on self-starting cumulative sums for the individualized assessment of intervention effects (Figures 16 and 17). Longitudinal monitoring is needed so that 1) reference values from low-risk individuals become widely available; 2) the earliest rhythm alteration can be picked up early before there is target organ damage; 3) timely intervention is instituted when needed and is targeted in time (Figure 12) for highest efficacy with minimal side effects; and 4) infradian BP variability associated with psychophysiologic responses (see inside back cover) or with unusually prominent circannual variation (Figure 5d) is recognized. Reference values for circadian and infradian rhythm parameters require systematic longitudinal monitoring and software for the windowing, compacting and recycling of information (Figure 18), readily achieved for the experimental animal, yet still awaiting the design of unobtrusive monitoring instrumentation for use in the much larger human being.

1. Cornélissen G.: Instrumentation and data analysis methods needed for blood pressure monitoring in chronobiology. In: Chronobiotechnology and Chronobiological Engineering, Scheving L.E., Halberg F., Ehret C.F. (eds.), Martinus Nijhoff, Dordrecht, The Netherlands, 1987, pp. 241-261.

2. Halberg F., Cornélissen G., Bakken E. Caregiving merged with chronobiologic outcome assessment, research and education in health maintenance organizations (HMOs). Progress in Clinical and Biological Research 341B: 491-549, 1990.

3. Kumagai Y., Shiga T., Sunaga K., Cornélissen G., Ebihara A., Halberg F. Usefulness of circadian amplitude of blood pressure in predicting hypertensive cardiac involvement. Chronobiologia 19: 43-58, 1992.

4. Syutkina E.V., Cornélissen G., Halberg F., Grigoriev A.E., Abramian A.S., Yatsyk G.V., Morozova N.A., Ivanov A.P., Shevchenko P.V., Polyakov Y.A., Bunin A.T., Safin S.R., Maggioni C., Alvarez M., Fernandez O., Tarquini B., Mainardi G., Bingham C., Kopher R., Vernier R., Rigatuso J., Johnson D. Effects lasting into adolescence of exposure to betamimetics in utero. Clinical Drug Investigation 9: 354-362, 1995.

5. Tamura K., Kohno I., Saito Y., Wakasugi K., Achiwa S., Imanishi Y., Cugini P., Halberg F. Antihypertensive individualized therapeutic strategy. Difesa Sociale 6: 109-124, 1991.