the variability of arterial pressure

The variability of arterial pressure

W. A. Littler, M.D., M.R.C.P.* M. J. West, M.B., Ph.D., M.R.A.C.P.** A. J. Honour, M.A., D.Phil.*** P. Sleight, M.D., F.R.C.P.**** Oxford, England

The decision to treat patients with high blood pressure depends largely on the level of pressure. It is therefore important to obtain data from the patient that is truly representative of his average arterial pressure. A major difficulty in evaluating such data is the great variability in the level of blood pressure.in any individual patient. Previous workers have attempted to solve the problem by the measurement of blood pressure under standard conditions: for example, at rest and on repeated occasions so as to obtain a representative pressure.’ The relationship between the indi- rectly obtained casual blood pressure and the average 24-hour blood pressure, sustained by the circulation over 24 hours, is unknown.

Over the last ten years there have appeared from this laboratory a series of publications describing the development and application of a system for continuously recording direct arterial pressure in unrestricted patients.‘, R It has now become possible to analyze data collected over a 24-hour period quantitatively in a great deal more depth than was hitherto possible and this paper describes our experience with the latest develop-

From the University Department of Cardiovascular Medicine, Univer- sity of Oxford, and Radcliffe Infirmary, Oxford, England.

Received for publication Sept. 16, 1976.

Accepted for publication Feb. 23, 1977. Reprint requests: Professor W. A. Littler, British Heart Foundation, Department of Cardiology, East Birmingham Hospital, Bordesley Green East, Birmingham B9 5ST, England.

*Lecturer, University Department of Cadiovascular Medicine, Univer- sity of Oxford and Radcliffe Infirmary.

**Research Fellow, University Department of Cardiovascular Medi- cine, University of Oxford and Radcliffe Infirmary. ***First Assistant, University Department of the Regius Professor of Medicine, University of Oxford and Radcliffe Infirmary.

****Professor, University Department of Cardiovascular Medicine, University of Oxford and Radcliffe Infirmary.

ment of this technique and its use in evaluating the variability of arterial pressure over a 24-hour period.

Patients and methods

Ten patients are included in this study. After informed consent all had their arterial pressure recorded over a 24-hour period, as previously described.3 The details of the ten patients are listed in Table I and all were asymptomatic and none was receiving drug therapy. All ten patients went about their normal, daily activities during the course of the study and they slept at home.

Tape analysis system. This system was devel- oped in conjunction with our Departments by the Engineering Division of AERE, Harwell, Berk- shire. The system consists of three separate units: (a) a tape replay unit, (b) a blood pressure histogram plotter, and (c) a multi-channel analyzer.

The histogram plotter accepts the output for the tape replay unit (speed set at 25 times the recording speed) and derives data in digital form of systolic, diastolic, and mean pressures and measures pulse interval all on a beat-to-beat basis. The data are held in four registers- which sequentially address the memory of the multichannel analyzer at the end of each beat. When the memory is addressed the contents stored at that address are incremented so that a frequency distribution histogram of each of the four param- eters builds. up. Each parameter is allocated 128 channels in the store of the multichannel analyzer. Each channel size representing 2.5 mm. Hg. When the analysis is complete the elements of the four frequency distribution histograms are discharged via a teletypewriter on to paper

180 February, 1978, Vol95, No. 2 0002-8703/78/0295-0180$00.70/O 0 1978 The C. V. Mosby Co.

Variability of arterial pressure

punch tape and these data are subsequently submitted to standard statistical analysis by computer program. For each histogram the mean, variance, and standard deviation were determined.’ It is important to scrutinize the complete 24-hour recording before feeding it through this system in order to avoid inaccurate information due to technical faults or error in the recording procedure. The accuracy of this automatic analysis was checked against the direct measurements of the records by two independent observers. These two observers agreed with one another with an accuracy of + or -4 per cent, and the within observer error was + or -1 per cent. Compared with this manual analysis the automatic system corresponded with an accuracy of + or -6 per cent for arterial pressure and hear trate and + or -3 per cent for the total number of beats analyzed. The degree of agreement between observer and machine was much greater during the period of sleep, when the error was reduced by approximately 50 per cent.

Analysis of individual records. Records of the ten individual patients were analyzed beat by beat on an hourly basis throughout the 24-hour period. In addition, the waking and sleeping periods were each averaged, sleep being taken as that period from the time that the subject indicated that he was in bed until the time that he was awake again.

Statistical methods. To test whether the variability of systolic pressure differed from that of diastolic pressure throughout the day and night the Wilcoxon matched-pairs signed-ranks test was employed.” Variability was determined from the standard deviation about the mean for each hour.

Results

Frequency distribution of blood pressure over 24 hours. The frequency distribution pattern of arterial pressure over 24 hours described a bi- modal curve (Fig. 1) in all but one patient (Case 10). The bi-modality was uninfluenced by the over-all average pressure. The lower mode was due predominantly to the fall of pressure which occurs during sleep (Fig. 2). The length of sleep was the single most important factor in determining the shape of the frequency distribution curve (Fig. 3).

The variqbility of arterial pressure. Variability

d 35 yrs.

6000 r

- Systolic 126.9 + 20.3 .-i- Diastolic 68.1 t 18.5

25 75 125 175 225

ARTERIAL PRESSURE mm Hg

Fig. 1. A frequency distribution curve of systolic and diastolic blood pressure in a 35-year-old normotensive individual (Case 8). Note the b&modality of both systolic and diastolic pressure and the ‘wide range of pressures covered throughout the 24- hour period.

Table I. Details of 10 patients selected to give a range of different levels of arterial pressure

1 F 53 1.8 2 M 60 1.8 3 F 28 1.8 4 M 26 1.9 5 F 32 1.5 6 F 23 1.5 7 F 44 1.5 8 M 35 2.0 9 M 21 1.8 10 M 20 1.7

2civ90 Normal LV+ Normal 180/105 Normal Normal Normal 160/110 Normal LV+ Normal 130/100 Normal Normal Normal 130180 Normal Normal Normal HO/110 Normal Normal Normal 160/100 Normal Normal Normal 120/70 Normal Normal Normal 130/90 Normal Normal Normal 165/110 Normal Normal Normal

*MA = body surface area; CXR = chest radiograph,

of arterial pressure was determined in ten patients from the standard deviation of pressure about the mean for each hour (example, Fig. 4). Throughout the 24-hour period systolic pressure variation was significantly greater than that in diastolic pressure in all but Case 3, in whom there was no difference. This variability was most acutely affected by physical exertion, although in individual instances there was marked change in pressure in response to psychological influences, During sleep systolic and diastolic pressures both

American Heart Journal 181

Littler et al.

900 -

800 -

700 -

600 -

3 500 - c ;

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400

300 -

200 +- :

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100 :

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\ 0 - I \ , I I

0 25 50 75 100 125 150

Mean arterial pressure mmHg

Fig. 2. A frequency distribution plot of mean arterial pressure for two separate hours in the day (Case 8). (i) A one- hour period during sleep and (ii) a one-hour period during waking when the patient was, for the majority of the time, sitting quietly and not engaged in physical activity. Note that during sleep pressure is lower and covers a smaller range than during the waking period.

Table Il. Summary of awake and asleep arterial pressures in the 10 patients whose records were analyzed on an hourly basis

Awake Asleep

Case Systolic S.D. Diastolic S.D. Mean S.D. Systolic S.D. Diastolic SD. Mean S.D.

1 216 26 108 12 145 15 122 13 70 7 92 7 2 140 15 109 12 127 11 110 8 so 7 102 8 3 138 18 91 9 106 9 112 8 79 5 92 6 4 144 29 63 22 94 20 105 14 49 16 75 15 5 182 26 115 15 141 16 132 11 81 7 103 8 6 131 13 124 11 132 11 109 7 92 7 105 7 7 99 14 72 21 86 17 79 7 40 9 58 7 8 188 20 88 11 122 13 170 12 72 6 109 8 9 180 14 126 10 14s 11 156 9 123 8 140 7

10 141 20 44 13 95 13 116 17 55 11 75 12

Mean 155.9 97.0 119.7 121.8 75.9 96.1

fell by an average of 20 per cent of the waking approximately every 90 to 120 minutes during firessure and were significantly less variable than sleep (Fig. 5) and accounted for the greatest during waking. During sleep systolic pressure was variability during this period being probably due still significantly more variable than diastolic to periods of rapid eye movement (REM) sleep. pressures. kn alternative explanation for this rhythmicity

Spontaneous fluctuations of pressure occurred could be that these fluctuations reflect the

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MEAN BP 10 PATIENTS

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CL: 4

40

20

01 I I I I I. I I I I I I I 10.00 12.00 14.00 16.00 18.00 20.00 22.00 24.00 02.00 04.00 06.00 08.00 10.00

TIME

Fig. 3. A plot of mean arterial pressure (diastolic pressure plus a third of the pulse amplitude) for ten patients. This emphasizes the fall in arterial pressure during sleep in all but one subject (Case 10) and this individual did not sleep very well during the period of study which is reflected in the arterial pressure which was maintained at a similar level to that during waking.

changes in arterial pressure produced by respira- tion.

Discussion

The development of systems for continuously recording arterial pressure has enabled us to obtain a more accurate characterization of an individual’s blood pressure during his normal daily activities and thus avoid the pitfalls that may occur due to the presence of the orientating or defence reflex.’ The automatic analysis system makes it possible to measure each individual beat during the 24-hour period and obtain quantitative data useful in the assessment of hypotensive therapy. The results in a group of patients studied before and after beta blockade will form the basis of a separate publication.” Since sleep produces similar percentage falls in pressure irrespective of the over-all level in arterial pressure, it is perhaps not surprising that drug therapy, which lowers

blood pressure, does not apparently alter this bimodality.? Patients who did not sleep very well or at all did not demonstrate this b&modality.

Systolic pressure shows much more variation during the day and night when compared with diastolic pressure and the higher the level of systolic pressure the greater was the variability. This may reflect the poorer baroreflex control found in hypertension.” Sokolow and associates,g using frequent semiautomatic blood pressure recordings taken by the ambulatory patient away from the medical environment, have shown that although the prevalence of hypertensive complications increases as the casual pressure increases, the portable diastolic pressure tends to be more predictive of severity class than does the casual diastolic pressure. Whether or not the variations in systolic pressure are, of themselves, important in determining the degree of target organ damage, cannot be answered by the present study and will


Littler et al.

HEART RATE

160 r

SYSTOLIC FREQUENCY OF BEATSOUTSIDE LIMITS

BLOOD PRESSURE mm Hg

200 r

DlASTOLlt FREQUENCY OF BEATS OUTSIDE LIMITS

100 r

1400 1600 1800 2000 2200 2400 0200 0400 0600 0800 1000

TIME

Fig. 4. A plot of systolic and diastolic pressure against time in an individual patient. Pressures have been averaged for each hour and plotted with its standard deviation. Note that during waking the pressure is higher and more variable (as indicated by the larger standard deviations) than during sleep. In addition, in this diagram the frequency of those beats above the arbitrary limits of 140 systolic and SO diastolic have also been plotted.

require longitudinal studies on the same patient over a large number of years. A recent report of the Framingham Studylo appears to confirm the importance of systolic hypertension as a risk factor in cardiovascular disease-systolic pressure being a stronger determinant for the risk of coronary heart disease than either diastolic or mean blood pressure in women and in men over 45 years of age. It appeared to be independent of other variables and to retain its importance when subjects with other risk factors for coronary artery disease were excluded from analysis. Kannel’O has suggested that systolic hypertension

may accelerate atherogenesis or may reflect an increased susceptibility to atherogenesis due to an altered state of the arterial wall, while Page and Sidd” have suggested an alternative explanation, that is, that it may simply reflect advancing atherogenesis in the absence of other known risk factors.

We have found that the casual blood pressures measured in outpatient clinics tended to be higher than the average 24-hour pressure recorded by our method in some 60 per cent of patients. This is not surprising since our average 24-hour figure would include the period while the patient was

184 February, 1978, Vol. 95, No. 2


Fig. 5. A record from a young woman (Case 6) obtained during sleep. It shows both the electrocardiogram and the arterial pressure. There are marked, spontaneous increases in arterial pressure occurring in rhythmic fashion during this period of sleep. Note the marked slowing associated with this rise in pressure. (This pattern, we believe, is an example of baroreflex activity during sleep buffering an initial sympathetically mediated rise in blood pressure.)

asleep and exclude the alerting response to an observer, whereas casual recordings are invari- ably taken during the waking period which neces- sitate the presence of an observer. This finding has been shown on several occasions previous-

ly. 2. 9. I2 Furthermore, Sokolow and colleagues” found that the presence of target organ damage related more closely to the average pressure for the 24 hours than to the casual blood pressure. We have not attempted such a comparison in our small group of patients reported here, but in a previous publication we have shown that the averaged 24-hour blood pressure in patients with high casual- levels and little evidence of target organ damage was significantly lower than the average casual readings over several months, and furthermore indicated the use of this type of assessment in patients who are difficult to diag- nose because of the great variability of their arterial pressure.13

Summary

Direct arterial pressure has been recorded continuously on magnetic tape in totally unrestricted patients going about their normal routine outside hospital for periods of 24 hours.

On replaying these tapes data are derived in digital form of systolic, diastolic, and mean pressure, plus pulse interval, all on a beat-by-beat basis; a computer program then performs averaging and statistical analysis of these data.

The frequency distribution of blood pressure over a 24-hour period was plotted and showed a bi-modal curve, the lesser mode being due predominantly to sleep. This bimodality was

unaffected by the average 24-hour pressure, but was modified by the length of sleep.

The variability of arterial pressure was determined from the standard deviation by averaging pressure over each hour in 10 patients (five men, five women). They were selected to give a range of different levels of arterial pressure and had never received drugs. Throughout the 24 hours the variability of systolic pressure was significantly greater than that in diastolic pressure. This variability was most acutely affected by physical exercise.

During sleep both systolic and diastolic pressure fell by an average of 20 per cent of the waking pressure and both were less variable than during waking. Spontaneous rhythmic changes of pressure occurring approximately every 90 to 120 minutes accounted for the greatest variability during sleep and were probably due to REM sleep.

REFERENCES

1.

2.

3.

4.

5.

6.

Pickering, G. W.: High blood pressure, London, 1968, J. & A. Churchill Ltd. Bevan, A. T., Honour A. J., and Stott, F. D.: Direct arterial pressure recording in unrestricted man, Clin. Sci. 36:329, 1969. Littler, W. A., Honour, A. J., and Sleight, P.: Continuous recording of direct arterial pressure and electrocardiogram in unrestricted man. Br. Med. J. 3:76, 1972. Snedecor, G. W., and Co&ran, W. G.: Statistical methods, Ames, Iowa, 1967, The Iowa State College Press, p. 81. Siegel, S.: Non-parametric statistics, New York, 1956, McGraw-Hill Book Company, p. 75. West, M. J.: Ambulatory monitoring of the intra-arterial blood pressure, application in the clinical trial of a new hypotensive agent. (Unpublished data)


Littler et al.

7. Littler, W. A., Honour, A. J., Carter, R. D., and Sleight, P.: Sleep and blood pressure, Br. Med. J. 3:346, 1975.

8. Gribbin, B., Pickering, T. G., Sleight, P., and Peto, R.: Effect of age and high blood pressure on baroreflex sensitivity in man, Circ. Res. 29:424, 1971.

9. Sokolow, M., Werdegar, D., Kain, H. K., and Hinman, A. T.: Relationship between level of blood pressure measured casually and by portable recorders and severity of complications in essential hypertension, Circulation 34:279, 1966.

10. Kannel, W. B.: Role of blood pressure in cardiovascular morbidity and mortality, Progr. Cardiovasc. Dis. 17:5, 1974.

11. Page, L. B., and Sidd, J. J.: Medical management of primary hypertension, N. Engl. J. Med. 287:10X$ 1972.

12. Irving, J. B., Kerr, F., Ewing, D. J., and Kirby, B. J.: Value of prolonged recording of blood pressure in assessment of hypertension, Br. Hrt. J. 36:859. 1974.

13. Littler, W. A., Honour, A. J., Pugsley, D. J., and Sleight, P.: Continuous recording of direct arterial pressure in unrestricted patients. Its role in the diagnosis and management of high blood pressure, Circulation 61: 1101, 1975.

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