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4. Burgess CD, Siebers RW, Purdie GL, Taylor C, Maling TJ. The relationship between the QT interval and plasma amiodarone concentration in patients on long-term therapy. Eur J Clin Pharmacol 1987;33:33:115-8. 5. Saarnivaara L, Lindgren L. Prolongation of QT interval during induction of anaesthesia. Acta Anaesth Stand 1983;27:12630. 6. Ahnve S, Vallin H. Influence of heart rate and inhibition of autonomic tone on the QT interval. Circulation 1982:65:

11.

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7. Fananapazir L, Bennett DH, Faragher EB. Contribution of heart rate of QT interval shortening during exercise. Eur Heart

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J 1983;4:265-71.

8. Rickards AF, Norman J. Relation between QT interval and heart rate; new design of physiologically adaptive cardiac pacemaker. Br Heart J 1981;45:56-61. 9. Roman0 M, Adinolfi L, Cotecchia M, Carella G, DiMaro T, Golia B, Chiariello M, Condorelli M. Correcting the QT interval for heart rate by a simple linear regression formula: applicability in clinical practice. Am J Noninvas Cardiol 1987;l: 356-9. 10. Boudoulas H, Geleris P, Lewis RP, Rittgers SE. Linear rela-

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tionship between electrical systole, mechanical systole, and heart rate. Chest 1981;80:613-8. Puddu PE, Jouve R, Mariotti S, Giampaoli S, Lanti M, Reale A, Menotti A. Evaluation of 10 QT prediction formulas in 881 middle-aged men from the Seven Countries Study: emphasis on the cubic root Fridericia’s equation. d Electrocardiol 1988;21:219-29. Sarma JS, Sarma RJ, Bilitch M, Katz D, Song SL. An exponential formula for heart rate denendence of QT interval during exercise and cardiac pacing’ in humans: reevaluation of Bazett’s formula. Am J Cardiol 1984;54:103-8. Ahnve S. Correction of the QT interval for heart rate: review of different formulas and the use of Bazett’s formula in myocardial infarction. AM HEART J 1985;109:568-74. Kawataki M, Kashima T, Toda H, Tanaka H. Relation between QT interval and heart rate. Applications and limitations of Bazett’s formula. J Electrocardiol 1984;17:371-5. du Ploody WJ, Schutte PJ. Compilation of regression equations employing the RR interval for the correction of systolic time interval measurements for heart rate in sheep. Cardiovast Res 1989;23:359-63.

blood pressure

in

It has been suggested that ambulatory blood pressure monitoring is superior to casual cuff methods in predicting cardiovascular events, but lack of reference data from a normal population seriously limits this method’s clinical applicability. We therefore performed 24-hour intra-arterial ambulatory blood pressure (BP) monitoring in 50 normal volunteers (cuff BP < 140190 mm Hg) whose ages ranged from 18 to 74 years. There were 30 men and 20 women in the study, but there was no significant difference between the sexes with respect to age, cuff BP, or body mass index. A diurnal variation in BP was observed, qualitatively similar to that seen in hypertensive individuals, including a prewaking BP rise. Mean daytime intra-arterial pressures differed little between the sexes (124174 mm Hg for women and 127176 mm Hg for men, p = NS), but was lower at night in women than in men (96152 versus 102159 mm Hg, respectively; p < 0.02 for diastolic pressure). Based on this group of subjects, we defined the upper limit of normal daytime BP in both men and women as 150/90 mm Hg and the upper limit of mean nighttime BP as 130/80 mm Hg for men and 115/65 mm Hg for women. The lower nighttime pressures in women compared with their male counterparts with similar daytime pressures may explain why women appear to tolerate similar levels of BP better than men. (AM HEART J 1990;120:160.)

Paul Broadhurst, MRCP, Geoffrey Brigden, MRCP, Prabir Dasgupta, MBBS, Avijit Lahiri, MD, and Edward B. Raftery, MD. Harrow, Middlesex, England

Hypertension is associated with an increased morbidity and mortality from cardiovascular diseases,l, 2 From the Department of Cardiology and the Section of Cardiovascular Diseases, Northwick Park Hospital & Clinical Research Centre. Received for publication Sept. 20, 1989; accepted Feb. 20, 1990. Reprint requests: Dr. E.B. Raftery, Northwick Park Hospital & Clinical Research Centre, Watford Road, Harrow, Middlesex HA1 3Ud, England. 4/1120452

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and it has been conclusively demonstrated that effective therapy reduces this risk.3 Traditional methods of blood pressure measurement using cuff sphygmomanometry have many limitations4-6 and can give only an approximate assessment of cardiovascular risk.7t ’ On the other hand, it has been suggested that ambulatory blood pressure monitoring is superior in predicting future cardiovascular eventsg* lo As a consequence, great interest is being

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10 12 14 16 18 20 22 24 2 4 6 8 10 12 Time of day (hours) Fig. 1. Mean and standard deviation hourly values for systolic and diastolic blood pressureand heart rate (n = 50).

focused on this method

of assessing the hypertensive patient. Despite this interest, little is known about what constitutes normal ambulatory blood pressure, and no epidemiologic evidence is available to indicate what level of ambulatory blood pressure should demand treatment. Noninvasive ambulatory bloodpressure monitors have provided some useful data,11-13 but these devices may show apparently random differences when their results are compared with intraarterial ambulatory recordings.14-l7 A normal range of ambulatory intra-arterial blood pressure has not yet been clearly defined for day or night. We therefore set out to produce such ranges and to study circadian blood pressure variation in a normal population. METHODS

Fifty-six subjects of Northern European origin volunteered to take part in the study. Each subject wasrequired

to fulfill the following criteria to be acceptedasa “normal” volunteer for the purpose of this study: (1) no history of cardiovascular diseaseor elevated blood pressureat any time; (2) normal cardiovascularexamination; (3) cuff blood pressureof 140/90 mm Hg, and in two subjects arterial access could not be obtained. Of the 50 subjects, 30 were men. Thirty-eight subjects were hospital workers, while the remaining 12 came from the local community. Their mean age was 44 (range 18 to 74) years and their mean (SD) body mass index was 23.8 (2.8) kg/m2. There was no significant difference in age or body mass index between men and women, nor in their respective duration of sleep (7.69 (0.92) hours versus 7.51(1.15) hours). The average systolic cuff blood pressure at initial screening was 125 (9.6) mm Hg and the average diastolic cuff pressure was 79 (6.9) mm Hg. Again, there was no significant difference between the sexes: for men the cuff pressure was 125 (10) mm Hg systolic, 79 (8) mm Hg diastolic; and for women the cuff pressure was 124 (9) mm Hg systolic and 79 (6) mm Hg diastolic. Fig. 1 shows the hourly mean intra-arterial pressures and heart rates for the whole group (n = 50). Blood pressure was stable throughout the day until late evening, when it fell to its nadir at 2 to 3 AM. Thereafter, blood pressure rose slowly once again until waking, whereupon it rose rapidly (Fig. 2, n = 49). Heart rate changes followed this pattern, but fell earlier in the evening and showed a later rise during the prewaking phase in the early hours of the morning. Fig. 3 shows circadian blood pressure and heart rate curves for men and women. There was no significant difference between sexes with respect to mean daytime pressure, but mean nighttime pressures were lower in women, the difference in diastolic pressures being significant. The only significant difference between the sexes with respect to hourly mean blood pressure during the daytime was in systolic pressure in the time between 9 and 10 AM. Heart rate was lower in women than in men for most of the day, but at night and in the morning there was little difference. We also examined the relationship between subject age and mean daytime, nighttime, and overall blood pressures as well as heart rate. We found no significant correlation except between age and male mean nighttime diastolic blood pressure (F = -0.37, p < 0.05).

significantly in its distribution from normal (applying the Kolmogerov-Smirnov test), we can thus define the upper limits of blood pressure from our group in terms of the mean plus two standard deviations. For men and women the upper limits during the day are therefore 149/92 and 152/92 mm Hg, respectively, and during the night the upper limits were 128/81 and 114/64 mm Hg, respectively. For mean overall pressure it is 140/86 mm Hg for men and 137/ 81 mm Hg for women. DISCUSSION

The principal aim of our study was to define the upper limits of intra-arterial ambulatory blood pressure in a population with normal casual cuff blood pressures. There are obvious limitations to our study since all subjects were volunteers, rather than being randomly selected, but this was necessary because of the invasive nature of the technique. Nevertheless, we have studied a population with a broad age range and one that contained an adequate number of subjects. It is likely that the distribution of ambulatory blood pressure in the population will describe the same kind of curve as that found with casual cuff measurements. Consequently, a clear distinction between normal and hypertensive individuals cannot really be made. However, approximate guidelines as to what constitutes a normal ambulatory blood pressure profile are of some value when making diagnostic or therapeutic decisions. We would therefore define daytime ambulatory blood pressure in both men and women as being less than 150/90 mm Hg (to the nearest 5 mm Hg); for nighttime, in men this value is 130/80 mm Hg, and in women it is 115/65 mm Hg. Our estimate of the upper limit for mean 24-hour pressure would be 140/85 mm Hg for men, and for women a little lower, at 135/80 mm Hg. These figures are for guidance only, and when interpreting individual 24hour blood pressure profiles, it is also important to take into account the activity level of the patient during the study. At first glance, the daytime pressures, with which we are all more familiar, seem rather high, but it must be remembered that these are based on true ambulant recordings and not on measurements taken in a clinic while the subject is seated or lying quietly. Pomidossi et a1.20recently studied 19 normotensive subjects using a similar technique and found lower mean daytime pressures. The most likely explanation for this is that their subjects were less active during the study. Nearly all of our volunteers went to work during the ambulatory recording period

July1990 American Heart Journal

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