Hypertension: Short Communications

are confidential to the trial participants. Patients are admitted to the trial on the basis of 3 succes­sive blood pressures of l70mm Hg (systolic) or 105mm Hg (diastolic) or above on separate days.

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(12.5mg) and Atenolol (50mg) in the Elderly

K. Siamopoulos, R. Wilkinson, R. Campbe/f and K.Boddy Department of Medicine and Nephrology, Freeman Hospital, Newcastle upon Tyne, UK

Diuretic therapy causes a reduction in mean plasma potassium (MRC, 1981) and in total body potassium (TBK) [Hollifield, 1981). This effect may be particularly marked in the elderly. Mild hypo-

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The criteria for exclusion are: heart block, atrial fibrillation, diabetes, bronchial asthma, severe as­sociated disease limiting the prospect of fruitful living, treatment of hypertension within the pre­vious 2 months, blood pressure greater than 280mm Hg (systolic) or 120mm Hg (diastolic).

Initiallyatenolol 100mg once daily is given, with the addition of bendrofluazide 5mg daily if control is unsatisfactory. Patients who are unable to take ate nolo I are given a-methyldopa 500mg at night. Random-zero sphygmomanometers are used to re­duce observer bias. ECGs are classified by Min­nesota Code by an independent assessor. Major end-points are adjudicated by an independent panel unaware of the treatment status of the patients. On the evidence ofthe incidence of events in the pilot stage of the trial, a target of 4000 patient-years has been set for the combined treatment and control groups. This should give a 90% power of demon­strating a one-third reduction in completed stroke, coronary artery attacks, and mortality. Analysis will be on an 'intention-to-treat' basis.

Results: A mean reduction in systolic pressure of about 25mm Hg and diastolic pressure of about lOmm Hg is being maintained over 6 years (fig. I). A self-filled questionnaire was given to the treat­ment and control groups, and a 1 in 5 sample of normotensive patients. No significant differences were found despite widespread complaints. 85% of patients are being maintained on atenolol and 95% on some form of antihypertensive therapy. 14 patients showing a fall of systolic blood pressure less than 10mm Hg had blood taken without prior warning and 12 showed evidence of recent inges­tion of atenolol.

kalaemia (plasma K+ 3.0-3.5 mmol/L) may lead to an increased incidence of arrhythmias following myocardial infarction (Cole et aI., 1981), itself more frequent in the elderly hypertensive than in the young. ~-Blocking drugs raise plasma potassium when given alone (MRC, 1981) and attenuate the reduction which occurs with thiazides (Sweet and Gaul, 1975). They also have an antiarrhythmic ef­fect independent of their effect on plasma potas­sium. The addition of a ~-blocker to diuretic therapy would therefore be expected to reduce hypokalaemia and the associated risk of arrhyth­mia.

The study objectives were to determine, in a group of elderly hypertensives, the effect on pla~ma K+, TBK, and cardiac rhythm (24-hour momtor)

Hypertension: Short Communications

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Fig. 1. Effect of chlorthalidone, atenolol and the combination preparation ('Tenoretic') on plasma potassium (a), total body potassium (b), plasma renin activity (c) and mean plasma aldosterone (d).

of treatment with chlorthalidone (12.5mg daily), atenolol (50mg daily), and a combination of chlor­thalidone (12.5mg) and atenolol (50mg) ['Tenor­etic'] given once daily. Six patients aged over 60 years with a diastolic BP between 100 and 115mm Hg with no recent myocardial infarction or stroke and who were in sinus rhythm, were included in the trial. The following measurements were made: TBK (whole body counter; 4°K), plasma renin ac­tivity and plasma aldosterone (by radioimmuno­assay), and cardiac rhythm by 24-hour monitoring.

Results: There was a similar response to chlor­thalidone, atenolol and the combination prepara­tion. Mean plasma potassium concentration fell from 4.35 mmol/L on placebo to 3.9 mmolfL on chlorthalidone, was 4.48 mmolfL on atenolol, and 4.22 mmol/L after 6 weeks and 4.1 mmol/L after 6 months' treatment with the combination prep­aration (fig. la). The mean values for total body

potassium fell to 93.5% of placebo level during chlorthalidone, was 96.5% on atenolol, and 97.5% initially and 92.5% after 6 months on the combin­ation (fig. Ib). The mean recumbent level of plasma renin activity rose from 7.5 pmol/L/min during placebo to 20 pmol/L/min with chlorthalidone, was 2.5 pmol/L/min with atenolol, and 9 pmol/L/min at 6 weeks and 8 pmol/L/min at 6 months with the combination. Corresponding values for am­bulant plasma renin activity were 9, 41 , 2, 27 and 13 pmolfL/min (fig. Ic). The mean recumbent level of plasma aldosterone was 110 pmol/L on placebo, 168 pmolfL on chlorthalidone, 114 pmolfL on atenolol, and 78 pmolfL at 6 weeks and 156 pmol/ L at 6 months on the combination preparation (fig. Id). Corresponding values during ambulation were 192, 184, 132, 90 and 114 pmol/L.

There was no change in 24-hour heart rate with chlonhalidone, but a marked reduction with at-

Hypertension: Short Communications

enolol which was sustained on the combination preparation. Ventricular ectopic complexes were infrequent in all except I patient in whom they were frequent on placebo (143jhour), increased to 220jhour with chlorthalidone, while plasma aldos­terone rose steeply accompanied by a fall in plasma K+ to 3.2 mmol/L and in TBK to 18% of the level on placebo. Atenolol reduced the ventricular ec­topic complexes, and this reduction was main­tained with the combination with reduction in plasma renin activity and plasma aldosterone, res­toration of plasma K+ to 4.3 mmol/L and of TBK to 93.7%.

Conclusions: In a group of elderly hyperten­sives, chlorthalidone 12.5mg, atenolol 50mg, and a combination of the two have similar effects on blood pressure. Chlorthalidone resulted in a re­duction in plasma K+ and TBK, possibly due in part to an increase in plasma aldosterone and ac­companied in I patient by an increase in ventric­ular ectopic complexes. The addition of atenolol to

Blood Pressure in Children and its Relevance to Adult Hypertension The Brompton Study

M. de Swiet, P.M. Fayers and E.A. Shinebourne Department of Paediatrics, Cardiothoracic Institute, Brompton Hospital, and the Medical Research Councii, Tubef'cuiosis and Chest Disease Uiiit, Brompton Hospital, London, UK

We set out to attempt to answer 2 questions: a) What is the normal blood pressure in childhood and what factors influence it? b) At what age do children assume a fixed position in the blood pressure distribution and therefore a likelihood of developing essential hypertension as they grow older?

Blood pressure was measured in 2000 infants, born consecutively at one .hospital (Farnborough, Kent), at ages 4 days, 6 weeks, 6 months, 1 year and yearly thereafter. Parks Doppler ultrasound system was used until age 4 years (only systolic

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chlorthalidone suppressed renin and aldosterone and was accompanied by an increase in plasma K+ and TBK and a reduction in ventricular ectopic complexes in the single patient in whom this was a problem. It seems reasonable to suggest from this small study that a combination of ~-blocker and diuretic may be preferable to diuretic alone in the treatment of hypertension in the elderly. It is, of course, necessary to extend the study to more patients in order to draw firm conclusions.

References Cole, A.G. et a1.: Royal Society of Medicine International Con­

gress and Symposium Series No. 44, pp.47-53 (Academic Press, London 1981).

Hollifield, J.W.: Royal Society of Medicine International Con­gress and Symposium Series No. 44, p.5 (Academic Press, London 1980).

Medical Research Council Working Party on Mild to Moderate Hypertension. Lancet 2: 539-543 (1981).

Sweet, C.S. and Gaul, S.L.: European Journal of Pharmacology 2:370-374 (1975).

blood pressure measured by Parks system), then conventional sphygmomanometry. The majority (70%) of initial measurements were made in hos­pital; between 6 weeks and 3 years these were made at home. After 5 years, all measurements were made at school.

The systolic blood pressure in infants, whether awake or asleep, rises rapidly during the first 3 weeks of life from a mean of 66mm Hg (asleep) at 2 days to 8lmm Hg at 3 weeks; the awake figures being 71mm Hg (2 days) to 90mm Hg (3 weeks). The percentile distribution to age 10 years is shown in figure 1. Although there were significant corre­lations between blood pressures measured earlier than I year and subsequent blood pressure meas­urements, these became much more marked after the age of 1 year. The correlation between blood pressure measured at 3 years and at 4 years (r = 0.47) is approaching the adult value for similar measurements (r = 0.7).

Blood pressure rises very rapidly in the first weeks oflife at a time when heart rate is also rising; this may represent increased sympathetic activity. Blood pressure remains stable from 6 months to at least 5 years. At age 4 to 5 years blood pressure is not affected by minor illness, place of measure­ment, time of day, time since previous meal or am-