John P. Cox

TWENTY-FOUR-HOUR AMBULATORY BLOOD PRESSURE IN MEN AND WOMEN AGED 17 TO 80 YEARS : THE ALLIED IRISH BANK STUDY

In order to determine reference values for ambulatory blood pressure, a sample of 815 healthy bank employees (399 men and 416 women), aged 17-79 years, were investigated. Ambulatory blood pressure was recorded over 24 h, taking measurements at 30-min intervals. Blood pressure was also measured by trained observers in the clinic. Ambulatory blood pressure in the 815 subjects averaged 118/72 mmHg over 24 h, 124/78 mmHg during the day (1000-2259 h) and 106/61 mmHg at night (0100-0659 h). Office blood pressure, measured by an observer, was 4/2 mmHg lower (p less than 0.0001) than daytime ambulatory pressure. The 95th centiles for the daytime ambulatory pressure in men were: 114/88 mmHg for the age group 17-29 years (n = 107); 143/91 mmHg from 30-39 years (n = 123); 150/98 mmHg from 40-49 years (n = 109); and 155/103 mmHg in 50-79 year old men (n = 60); for the corresponding age groups in women, the 95th centiles of the daytime pressure were: 131/83 mmHg (n = 174); 132/85 mmHg (n = 149); 150/94 mmHg (n = 55); and 177/97 mmHg (n = 38).

Ambulatory blood pressure monitoring in the evaluation of drug efficacy

Conventional clinic measurement of blood pressure is influenced by many factors that make the technique unsuitable for the assessment of antihypertensive drug efficacy. The major drawback of conventional measurement is that it cannot indicate the duration of drug effect or the influence of antihypertensive drugs on nocturnal blood pressure. Noninvasive 24-hour ambulatory blood pressure measurement has a number of advantages over conventional measurement: it provides a profile of blood pressure over the 24-hour period; it detects white coat responders; it is free of regression to the mean and the placebo response, thereby making it possible to consider efficacy studies which need not have a placebo phase; it enables considerably more observations than is possible with clinic measurement by increasing the power of studies, which may reduce significantly the numbers of patients needed for antihypertensive drug studies. Twenty-four-hour ambulatory blood pressure measurement offers the opportunity to study antihypertensive drugs in fewer patients with greater accuracy than is possible with conventional clinic measurement and should be a mandatory requirement for such studies.

Choice of drug treatment for elderly hypertensive patients.

It is generally agreed that moderate and severe hypertension in the elderly should be treated, but it is not clear which drug or drugs are most appropriate. Thiazide diuretics are inexpensive and effective, but they are associated with metabolic side effects that are becoming less acceptable as newer agents become available. Beta blockers are effective, but can be associated with central nervous system side effects and are often contraindicated by coexisting disease. Recently, attention has been focused on the newer agents, including calcium antagonists and angiotensin-converting enzyme inhibitors. The advantage of calcium antagonists is that they do not produce metabolic side effects. However, they are expensive and may cause vasodilatory side effects. The angiotensin-converting enzyme inhibitors are effective and relatively free of side effects and may be particularly useful for elderly hypertensive patients with congestive heart failure.

A double-blind evaluation of captopril in elderly hypertensives

To establish the role of angiotensin converting enzyme inhibitors in the management of hypertension in the elderly, 16 patients were treated with captopril in a randomized double-blind placebo-controlled cross-over study. Clinic blood pressure, ambulatory blood pressure, renal function and mental performance, with emphasis on mood and psychological well-being, were assessed. Twelve patients, aged 73 (+/- 4.4) years, completed the study. The doses of captopril used were 50 mg (11 patients) and 25 mg (one patient) twice daily for 4 weeks. Mean (+/- s.e.m.) clinic sitting blood pressure during captopril therapy was significantly lower than during administration of placebo (172 +/- 4.5/83 +/- 25 versus 188 +/- 4.4/89 +/- 3.4 mmHg; P less than 0.001/P less than 0.05). Mean ambulatory blood pressure was also significantly lower on captopril treatment than during administration of placebo (166 +/- 5.3/87 +/- 1.6 versus 179 +/- 5.1/94 +/- 2.4 mmHg; P less than 0.02/P less than 0.02) and this effect was sustained over the dosing interval. Renal blood flow and mental performance were unaltered by treatment. Gastrointestinal discomfort occurred in two patients, one of whom was withdrawn and cough developed in one patient. We conclude that captopril is effective as monotherapy in lowering blood pressure in the elderly.

Problems of drug treatment in the elderly.

N 1819 THE poet Shelley’s wife gave birth to their 3rd child, one year after they had left England accompanied by Byron’s mistress and her child. Four years later Shelley and 3 of the 4 children were dead. Mortality of this order reflects the prevailing death rates of the time, a situation quite different from that in Western society today, where improvement in Public Health over the last 150 years has resulted in a greatly extended average lfie span. This fact coupled with a declining birth rate has resulted in an increasing proportion of elderly patients in the community’. Figure 1 shows the percentage of person 65 years and over from 1900 onwards in a number of countries’. In the UK although the elderly represent only 12% of the population, they were dispensed twice as many prescriptions as the national average in 19803. In the USA, where it is estimated that about 11 % of the population are over 65 years the elderly spent 25% of the national total expenditure for drugs and sundries in 19764. It is not surprising with this large volume of drug consumption among the elderly that studies from the UK 5, USA , and Sweden’ have shown that adverse drug reactions increase with increasing age. A number of factors are responsible for the high incidence of adverse drug reactions in this population and have been the subject of a recent Report from the Royal College of Physicians’. Of importance however are the problems associated with polypharmacy for patients with multiple pathology, age related pharmacokinetic and pharmacodynamic changes, and poor compliance. ’