CC BY
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THE DIAGNOSTIC VALUE OF THE SPHYGMOCHRON IN THE EARLY DIAGNOSIS OF PRE-HYPERTENSION AND HYPERTENSION.
*Cornelissen G., **Chibisov S.M., **Kharliskaya E.V.,
*Halberg F., **Ertueva M., ***Zaslavskaya R.M. **Agarwal R.K.
*Halberg Chronobiology Center, University of Minnesota, Minneapolis, MN, USA **People's Friendship University of Russia, Moscow, Russia *** The Moscow clinical hospital № 60, Russia
Introduction
The likelihood of stroke or cardiac death can be immediately reduced by chronobiologically assessing blood pressure and heart rate variability and by optimizing the efficacy of timed treatment rather than relying on an unacceptable and often inaccurate spotcheck and treating by convenience rather than pertinence. Needed are: detection of nocturnal abnormality when medication may no longer be effective (or is too effective) neither seen during office visits by day; detection of circadian hyperamplitude-tension (CHAT) associated with a risk of stroke and kidney disease greater than other risks (including “hypertension” when all risks are assessed concomitantly); detection of CHAT as high risk among normotensives who may not need anti-hypertensive medication; individualized inferential statistical testing to determine whether a drug or non-drug intervention such as autogenic training (relaxation) is effective and for how long (detecting any initial and later success or failure), some of which conditions otherwise are not found without chronobiology; individualization of treatment timing, since the same dose of the same medication can further lower the subject's blood pressure average and circadian amplitude when the timing of daily administration is optimized, as ascertained by sequential testing and parameter tests.
Method
A 19-year-old female student provided two 7-day profiles of automatic around-the-clock blood pressure and heart rate measurements at 30-minute intervals, assessed chronobiologically by sphygmochron (1-3), allowing a comparison of the cosinor with a classification by dipping (4-9). The former, but not the latter, are consistent on a weekly basis, in keeping with earlier results (2). Once abnormality is detected, continuous vascular monitoring is indicated (1).
Time (calendar date)
1А IB
Figure 1A. Sphygmochron of a 19-year-old student, ME. © Halberg.
Figure 1B. Original data: systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) of ME in a first 7-day profile.
© Halberg.______________________________________________
Sphygmochron 1 in Figure 1A summarizes the original data shown in Figure 1B. As seen in bold in the upper parametric section of Figure 1A, the MESOR, M, is just slightly above the PI, the upper 95% prediction limit derived from clinically healthy peers matched by gender and age. The circadian double amplitude, 2A, is clearly elevated above its PI, also derived from data on clinically healthy gender- and age-matched peers. In the nonparametric section, the hyperbaric index, also in bold, is above the threshold of 50 mm Hg x hour during 24 hours. Figures 2A-C show data stacked along a 24-hour scale with best-fitting two-component models consisting of cosine curves with periods of 24 and 12hours.
Original data stacked over , Single 24-h cosine fit
idealized 24-h day i
-_____ CHAT
Time (Clock Hours)
2А
200 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 2В
Time (Clock Hours)
Figure 2A. Systolic blood pressure of ME in a first 7-day profile, stacked over an idealized 24-hour span, with corresponding averages and a model of 24-hour and 12-hour cosine
curves fitted to them. © Halberg.________________________
Figure 2B. Diastolic blood pressure of ME in a first 7-day profile, stacked over an idealized 24-hour span, with corresponding averages and a model of 24-hour and 12-hour cosine
curves fitted to them. © Halberg.________________________
Figure 2C. Heart rate of ME in a first 7-day
profile, stacked over an
idealized 24-hour
span, with corresponding
averages and a
model of 24-hour and 12-
hour cosine curves
fitted to them. © Halberg.
Figures 3A-C visualize the parameters obtained by cosinor and Figure 3D those for day-night ratios (DNR), revealing their variability on a daily basis and the overall results from the entire 7-day record. For the cosinor, the characteristics are also given in the parametric top section of the sphygmochron in Figure 1A. The outcome overall for DNR in Figures 3D and 3E is not consistent with the daily assessment, since the abnormalities cancel each other out, as may previously have been the case in the outcome of a different study of Cugini's pre-hypertension (10). By contrast, results from the chronobiologic approach by sphygmochron are consistent, CHAT being diagnosed overall as well as on 6 of 7 consecutive days, Figure 3E.
60
50
40
S0
S 70
100
90
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Time (calendar date)
Daily Day-Night Ratios of Systolic Blood Pressure
u. 10 z ° 0 Ш
W -10
-20
-30
Extreme Dipping
З4ббТ
Time (day of monitoring)
3D
Daily 24-hour Amplitudes of Systolic Blood Pressure
3В
1 2 3 4 5 6 7
Time (day of monitoring)
SPAN
Day1
Day2
Day3
Day4
Day5
Day6
Day7
Overal
Works
?
DN
R
21.6
6
23.1
2
32.0
3
30.7
8
42.2
6
29.6
2
24.0
2
19.5
4
Diagnosis
ExtremeDi 1__________
ExtremeDi 1__________
ExtremeDi 1__________
ExtremeDi p__________
ExtremeDi p__________
ReverseDi
p
ExtremeDi
P_________
Dipping
NO
24h
-A
13.
7
21.
9
29.
2
22.
0
34.
0
34.
1
17.
5
19.
1
24h
-f
213
259
233
236
239
338
222
253
Diagnosi
s
OK
CHAT
CHAT
CHAT
CHAT
CHAT,
ecf
CHAT
3E
CHAT
YES
* To be doubled for comparison with the BP-2As listed in parametric section of the sphygmochron_
Daily Circadian Acrophases of Systolic Blood Pressure
а
Т
f 6 о
* 5
о
E
■s 4 >
а з ! 2 1
90% Prediction Limits
Acrophase, 1
9.00 12.00 15.00
Acrophase (clock hours)
3С
Figure 3A. Cosinor analyses on a daily basis of ME in a first profile. © Halberg.
Figure 3B. Daily circadian amplitudes of systolic blood pressure in a first profile of ME. Note normality during the first day, followed by abnormality (CHAT, short for Circadian Hyper-Amplitude-Tension) during 6 subsequent days. © Halberg.
Figure 3C. Daily acrophases showing an odd systolic blood pressure timing only in one (on day 6) of the s even 24-hour profiles, without altering the diagnosis of CHAT in contrast to an altered DNR in that profile in Figure 3D. © Halberg.
09
3D
0 —
0.00
3.00
6.00
21.00
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Figure 3D. Day-night ratios (DNR) on a daily basis in first profile of ME. All are abnormal, but with no consistent diagnosis (one profile shows reverse dipping). Note acceptable overall DNR in this clearly abnormal set of daily results. © Halberg.
Figure 3E. The very large variability in DNR cancels out changes demonstrated
in the preceding figure, so that overall there is dipping with no abnormality
detected by contrast to the overall CHAT, missing just on one day, and
complicated by circadian ecphasia on another day. © Halberg. ______________________________________________
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Figure 4A. Second profile of ME. © Halberg.
Figure 4B. Original data in second profile of ME. © Halberg.
Figure 4C. Data stacked for systolic blood pressure in second profile of ME. © Halberg.
Figure 4D. Data stacked for diastolic blood pressure in second profile of ME. © Halberg.
4E
Time (Clock Hours)
Figure 4E. Data stacked for heart rate in second profile of ME. © Halberg.
Results from a second monitoring are summarized in Figures 4A-E and 5A-E, now revealing a diagnosis of both systolic and diastolic CHAT. The extent of day-to-day variability is visualized in Figures 4A-E and 5A-C for the chronobiologic approach and in Figure 5D for the DNR. The latter figure and Figure 5E reveal the wide range of DNRs varying from -2.2 to +52.7. Moreover, by expressing changes in acrophase and amplitude in one number, the DNR cannot differentiate between changes in different parameters. In the second profile as in the first profile, the DNR is not consistent. It may mislead, being normal in a person who is clearly abnormal (Figures 3D and 3E, and 5D and 5E).
E
£ 190
40 11/23/09 0:00
0:00 0:00 0:00 Time (calendar date)
Daily Day-Night Ratios of Systolic Blood Pressure
Daily 24-hour Amplitudes of Systolic Blood Pressure
CHAT
З 4 5
Time (day of monitoring)
4 5 б
Time (day of monitoring)
5D
Diagnosis
ExtremeD ip________
ExtremeD ip________
ExtremeD ip________
Dipping
24h
-A
27.
4
25.
5
28.
1
10.
5
24h
-f
231
238
248
222
Diagnos
is
CHAT
CHAT
CHAT
OK
240
140
90
2
З
00
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Day5
Day6
Day7
Overal
Works
?
52.?
4
-2.2
ll.l
2
2?.0
б
ExtremeD ip________
ReverseDi P__________
Dipping
ExtremeD Ф_________
Not
consistent
З?.
?
lB.
9
l2.
9
22.
2
240
3l9
254
24?
CHAT
CHAT,
ecf
OK
CHA
5E
onsisten
t
(5/7
CHAT)
Daily Circadian Acrophases of Systolic Blood Pressure
___________________________________90% Prediction Limits
О
9.00 12.00 15.00
Acrophase (clock hours)
5C
Figure 5A. Variability in systolic blood pressure MESORs and circadian amplitudes in 7 consecutive days of second 7-day profile of ME.
© Halberg.
Figure 5B. Circadian amplitudes of systolic blood pressure of ME in the second 7-day profile assessed daily during 7 consecutive days. © Halberg.
Figure 5C. Circadian acrophases of systolic blood pressure of ME in the second 7-day profile. © H alberg.
Figure 5D. Daily assessment of the day-night ratio of ME’s systolic blood
pressure during 7 consecutive days and overall in her second 7-day profile.
© Halberg.
Figure 5E. Comparison of extent of consistency of diagnoses based on the day-night ratios (DNR) or on the circadian (24h) amplitudes (A) and acrophases (Q in the second profile of ME. Note the consistent diagnosis of overall CHAT, also found in 5 of 7 daily profiles in the presence of
the additional diagnosis of odd timing (circadian ecphasia) on day 6,
warranting follow-up monitoring with precise diaries and a physical
examination. © Halberg.___________________________________
Discussion
While the evidence from population studies with outcomes as morbid events (11) or with a proxy outcome, the left ventricular mass index (2, 12), deals with hundreds and thousands of patients, even relatively small studies sufficed to demonstrate that the sphygmochron can distinguish pre-diabetes from normoglycemia when the DNR fails to do so (13), and can actually mislead in pre-hypertension (10). In Figure 3D, the overall DNR misleads again. Figure 3D is particularly persuasive in showing that the current platinum standard, the 24-hour profile, is
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Q 3
0.00
3.00
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unsatisfactory: that is, it is misleading when after an acceptable result on the first day, all six subsequent daily results show abnormality. That even monitoring for 2, 3 or 4 days does not predict outcomes has also been shown (14).
Conclusion
Diagnoses, whether by DNR or sphygmochron, on consecutive days can vary greatly and can lead to different diagnoses with the DNR which confounds changes in phase and amplitude. The diagnoses based on the sphygmochron are more consistent and overall do not mislead as the overall DNR did in this case in one of two profiles.
